Research activity information

• Neoadjuvant FOLFOXIRI plus bevacizumab without radiotherapy for high-risk rectal cancer: multicentre phase II trial.

  Takeru Matsuda, Yoshiaki Nagatani, Yohei Funakoshi, Takahiro Tsuboyama, Yasuhiko Mii, Kunihiko Kaneda, Tomohiro Tanaka, Hiroshi Hasegawa, Kimihiro Yamashita, Naomi Kiyota, Hironobu Minami, Yoshihiro Kakeji

  BACKGROUND: The optimal neoadjuvant strategy for high-risk locally advanced rectal cancer (LARC) remains a matter of debate. This study evaluated the efficacy and safety of neoadjuvant FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan) plus bevacizumab without radiotherapy in patients with magnetic resonance imaging-defined high-risk LARC. METHODS: A prospective, multicentre, single arm phase II trial was conducted in four Japanese Institutions between 2018 and 2024, enrolling patients with rectal adenocarcinoma and at least one high-risk criterion: clinical T4, lateral pelvic lymph node metastasis, mesorectal fascia involvement, or positive extramural vascular invasion. Patients received four cycles of FOLFOXIRI plus bevacizumab, followed by two cycles of FOLFOXIRI alone, before total mesorectal excision. The primary endpoint was pathological complete response (pCR); secondary endpoints included the R0 resection rate, local recurrence (LR), recurrence-free survival (RFS), overall survival (OS), and safety. RESULTS: OF 50 eligible patients, 31 were enrolled before early trial closure due to a slow accrual (accrual rate 62%). All patients underwent surgery. The pCR rate was 10% (3 of 31) and R0 resection was achieved in 97% (30 of 31) of patients. The median follow-up was 36.7 months. The 3-year cumulative LR rate was 3%, with 3-year RFS and OS rates of 73 and 81%, respectively. Grade ≥ 3 neutropenia occurred in 29% of patients, with acceptable toxicity overall. No cases of gastrointestinal perforation were observed. Grade ≥ III postoperative complications occurred in seven patients (23%), with the most frequent events being anastomotic leakage in two patients (7%). CONCLUSIONS: In this phase II trial, although recruitment was suboptimal, neoadjuvant FOLFOXIRI plus bevacizumab achieved good local control without radiotherapy in patients with high-risk LARC. Although the pCR rate was modest compared with radiotherapy-based regimens, this chemotherapy-only approach may represent a reasonable option for select patients who are not suitable candidates for pelvic radiotherapy. Registration number: UMIN000037367 (https://www.umin.ac.jp/english/).

  Dec. 2025, BJS open, 10(1) (1), English, International magazine

  Scientific journal


• A phase II trial of nivolumab for patients with platinum-refractory recurrent or metastatic salivary gland cancer

  Yoshiaki Nagatani, Naomi Kiyota, Tomoko Yamazaki, Yukinori Asada, Masaaki Higashino, Hironaga Satake, Shogen Boku, Ari Nishimura, Hirokazu Uemura, Ichiro Ota, Katsunari Yane, Kaoru Tanaka, Takuma Onoe, Yuji Hirayama, Takahiro Tsujikawa, Hajime Fujiwara, Hikari Shimoda, Ken-Ichi Nibu, Yoshinori Imamura, Shiro Kimbara, Taiji Koyama, Yohei Funakoshi, Hironobu Minami

  Abstract Background Salivary gland cancer (SGC) is rare and has various histological types. This rarity and heterogeneity have hindered elucidation of the therapeutic contribution of systemic therapy, including immune checkpoint inhibitors, to recurrent or metastatic SGC (RM-SGC). The purpose of this trial was to investigate the efficacy and safety of nivolumab for platinum-refractory RM-SGC. Methods This phase II trial for platinum-refractory RM-SGC was conducted at nine centers. Nivolumab 240 mg was administered intravenously every 2 weeks. The primary endpoint was the objective response rate (ORR), and secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results Twenty-four patients were enrolled between March 2018 and January 2022. The main histological types were salivary duct carcinoma (n = 10), adenoid cystic carcinoma (n = 6), and adenocarcinoma not otherwise specified (n = 5). The ORR was 8.3% (2/24, 80% CI, 2.2–20.6), with two partial responses in patients with salivary duct carcinoma. The DCR was 29.2% (7/24), while all of the other 17 patients (70.8%) showed progressive disease on first disease evaluation at 12 weeks. With a median follow-up of 21.2 months, median PFS and OS were 3.0 months (95% CI, 2.8–3.2) and 25.0 months (95% CI, 10.9–39.1), respectively. There were no new safety concerns with nivolumab monotherapy. Conclusions This phase II trial of nivolumab for patients with platinum-refractory RM-SGC did not meet its primary endpoint of ORR. Although nivolumab may be worth further development in salivary duct carcinoma, these results may raise concerns over nivolumab monotherapy for RM-SGC.

  Oxford University Press (OUP), Dec. 2025, Japanese Journal of Clinical Oncology

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Negative Impact of Coronavirus Disease 2019 Pandemic on Gastric Cancer Care in Japan: A Tokushukai Real‐World Data Project 08 ( TREAD 08)

  Rai Shimoyama, Yoshinori Imamura, Kiyoaki Uryu, Takahiro Mase, Masataka Taguri, Tadahisa Okuda, Megumi Shiragami, Yoshiaki Fujimura, Maki Hayashi, Hironobu Minami

  ABSTRACT Aims Concerns regarding the adverse impact of coronavirus disease 2019 (COVID‐19) on cancer care survival have been raised; however, clear evidence remains limited. Therefore, we aimed to investigate the influence of the COVID‐19 pandemic on gastric cancer management in Japan using real‐world data from the Tokushukai Real‐World Data project. Methods and Results This retrospective cohort study was conducted across 46 Tokushukai Medical Group hospitals in Japan, identifying patients newly diagnosed with gastric cancer between January 2017 and December 2022. Patients with active double cancers or non‐epithelial tumors were excluded. We used data between January 2017 and March 2020 as the baseline (pre‐COVID‐19 period) to assess the changes in the number of diagnoses, screening detections, disease stage at diagnosis, and prognosis between April 2020 and December 2022 (mid‐COVID‐19 period). This study included 14 125 patients with 14 446 gastric cancer cases. Compared with the pre‐COVID‐19 period, the mid‐COVID‐19 period exhibited a 12% (95% confidence interval [CI]: 3%–20%) decrease in screening detections, a 9% (95% CI: 1%–18%) increase in metastatic stage detection, a 14% (95% CI: 7%–20%) decrease in curative surgery, and a 32% (95% CI: 19%–43%) decrease in radiation therapy. The analysis also revealed a 9.4% (95% CI: 2.0%–17.2%) increase in mortality in the mid‐COVID‐19 period compared with the pre‐COVID‐19 period. Conclusion This nationwide, real‐world study provides robust evidence that COVID‐19 has reduced survival rates for Japanese patients with gastric cancer by disrupting diagnosis and treatment.

  Wiley, Oct. 2025, JGH Open, 9(10) (10)

  Scientific journal


• Real-world evidence on the survival benefit of immune checkpoint inhibitors in combination with cytotoxic chemotherapy for patients with extensive-disease small-cell lung cancer: the Tokushukai Real World Data Project (TREAD) 06

  Tomoya Fukui, Yoshinori Imamura, Takuya Kakutani, Kiyoaki Uryu, Rai Shimoyama, Maki Hayashi, Tadahisa Okuda, Koshi Kataoka, Masataka Taguri, Hironobu Minami

  Springer Science and Business Media LLC, Aug. 2025, BMC Cancer, 25(1) (1)

  Scientific journal


• [Challenges and Prospects for Medical Oncology under the Emerging Infectious Disease Disaster].

  Sachi Morita, Noritoshi Kobayashi, Junji Tsurutani, Haruko Daga, Emiko Ohki, Takami Kashiwada, Kentaro Kawakami, Yoshiko Kitagawa, Masaki Maruta, Yasuhiro Fujiwara, Hironobu Minami

  The Japanese Society of Medical Oncology has conducted a questionnaire survey of its members over a 4-year period from 2020 to 2023 as part of the"Survey on the Impact of Anticancer Drug Therapy under the Spread of COVID-19 Infection". By summarizing the results of the questionnaire survey and reviewing the changes in cancer treatment in the aftermath of the COVID-19, focusing on the results of the 2023 survey which was conducted after the disease became category V infectious disease. It became clear that the COVID-19 not only had an impact on medical professionals and treatment choices but also had a significant impact on end-of-life care. This work was supported by MHLW Special Research Program (Grant Number JPMH20CA2046) and MHLW Research on Emerging and Re-emerging Infectious Diseases and Immunization(Program Grant Number JPMH21HA2011, JPMH23HA2011 and JPMH24HA2015).

  Aug. 2025, Gan to kagaku ryoho. Cancer & chemotherapy, 52(8) (8), 573 - 576, Japanese, Domestic magazine

  Scientific journal


• Humoral immunity after hematopoietic stem cell transplantation: evaluation by B-cell receptor repertoire analysis

  Sakuya Matsumoto, Yohei Funakoshi, Kimikazu Yakushijin, Takaji Matsutani, Yuri Okazoe-Hirakawa, Goh Ohji, Taiji Koyama, Yoshiaki Nagatani, Keiji Kurata, Shiro Kimbara, Naomi Kiyota, Hironobu Minami

  Abstract Immunity acquired before hematopoietic stem cell transplantation (HSCT) may decrease or disappear following HSCT, and it is unclear whether the first vaccination after HSCT in patients with an antigen exposure history before HSCT elicits a primary or secondary immune response. The Quantification of Antigen-Specific Antibody Sequence (QASAS) method enables real-time assessment of responses to SARS-CoV-2 antigen exposure through B-cell receptor (BCR) repertoire analysis. Using this method, we evaluated the disappearance of immunological memory after HSCT. First, in individuals without hematologic disorders, primary SARS-CoV-2 antigen exposure elicited no immune response at 7 days post-exposure but demonstrated activation between 14 to 21 days. In contrast, repeated exposure elicited early responses (secondary immune responses) at 7 days post-exposure. We then enrolled HSCT patients with pre-HSCT SARS-CoV-2 antigen exposure history and collected samples before and after vaccination. Despite prior exposure history, patients receiving their first vaccination after HSCT showed no response around 7 days post-exposure but responded at 14 days. In conclusion, even with pre-HSCT antigen exposure, the first vaccination after HSCT induced a primary immune response. This demonstrates that first vaccination after HSCT should be considered to induce a primary immune response, regardless of previous infection or vaccination history.

  Springer Science and Business Media LLC, Jul. 2025, International Journal of Hematology, 122(6) (6), 877 - 884

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Importance of E/e’ and BNP for early detection of late cardiotoxicity in long-term follow-up of childhood hematologic cancer survivors: a retrospective cross-sectional study

  Yuri Okazoe-Hirakawa, Kimikazu Yakushijin, Keiji Kurata, Sakuya Matsumoto, Hiroya Ichikawa, Rina Sakai, Taku Nose, Shiro Kimbara, Yoshiaki Nagatani, Taiji Koyama, Yumiko Inui, Yohei Funakoshi, Naomi Kiyota, Mitsuhiro Ito, Keiko Hatazawa, Hidekazu Tanaka, Nobuyuki Yamamoto, Hironobu Minami

  Abstract Background Childhood cancer survivors (CCS) often develop late complications after their primary disease is cured. Cardiovascular disease is one of the most frequent and serious complications that significantly affects prognosis and quality of life. Early detection and appropriate intervention are expected to improve their prognosis. However, the risk factors for late cardiotoxicity in CCS are not well defined, and biomarkers that can detect cardiac dysfunction prior to the development of heart failure have not yet been established. Methods Medical records of childhood hematologic cancer survivors referred to our department for transitional care between January 2016 and October 2023 were reviewed for this cross-sectional study. The relationships between the most recent cardiac function at the review and history of cancer treatment were analyzed. Results This study included 34 patients and the median elapsed time since cancer diagnosis was 16.5 years (range, 5–30 years). None of the patients had symptomatic cardiac complications. The E/e’ ratio was significantly higher in survivors with a history of hematopoietic stem cell transplantation (HSCT) than in those who did not undergo HSCT (median, 8.4% vs. 6.25%, P = 0.040), while no intergroup differences were observed in ejection fraction (EF), global longitudinal strain (GLS), or the brain natriuretic protein (BNP) level. In addition, the E/e’ ratio was positively correlated with years elapsed since cancer diagnosis (ρ = 0.38, P = 0.034). While there was no clear correlation between years since cancer diagnosis and the BNP level in the overall cohort, a strong correlation was found in patients with a history of HSCT (ρ = 0.73; P < 0.01). No significant differences were observed in EF, E/e’ ratio, GLS, and BNP level by cumulative anthracycline dose or history of chest irradiation. Conclusions In this study, no patient had late symptomatic cardiac complications. However, in those who had survived for a long time since their cancer diagnosis, particularly those with a history of HSCT, there were significant elevations in the E/e’ ratio and the BNP level. Continuous follow-up is required to determine whether these abnormalities lead to symptomatic cardiotoxicity and whether they serve as useful markers for the early detection of cardiac complications.

  Springer Science and Business Media LLC, Jun. 2025, Cardio-Oncology, 11(1) (1)

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A Rare Case of Pseudohypercalcemia Associated with Multiple Myeloma.

  Chiharu Mishima, Kimikazu Yakushijin, Hidenori Fukuoka, Ruri Takahashi, Yuri Okazoe, Miki Joyce, Sakuya Matsumoto, Rina Sakai, Yumiko Inui, Keiji Kurata, Hironobu Minami

  We report a rare case of pseudohypercalcemia associated with multiple myeloma in a 77-year-old woman. Despite elevated albumin-corrected calcium levels (12.6 mg/dL), ionized calcium levels remained normal (1.25 mmol/L). Differential diagnoses excluded common causes of hypercalcemia, and the findings suggested calcium binding to negatively charged immunoglobulins and confirmed pseudohypercalcemia due to IgG-type myeloma. Treatment with isatuximab plus dexamethasone normalized albumin-corrected calcium levels as IgG levels decreased. This report highlights the importance of recognizing pseudohypercalcemia to prevent misdiagnosis of true hypercalcemia due to myeloma. Measuring ionized calcium levels is crucial for accurate diagnosis when hypercalcemia is suspected without corresponding clinical symptoms.

  May 2025, The Kobe journal of medical sciences, 71(2) (2), E46-E49, English, Domestic magazine

  Scientific journal


• Ring Chromosomes 7 in Two Cases of Myelodysplastic Syndrome: Isolated Abnormality and Complex Karyotype Including idic(21)(p11.2) Duplication

  Katsuya Yamamoto, Keiji Kurata, Kimikazu Yakushijin, Hironobu Minami

  Wiley, May 2025, International Journal of Laboratory Hematology, 47(5) (5), 791 - 793

  Scientific journal


• Asciminib in combination with imatinib, nilotinib, or dasatinib in patients with chronic myeloid leukemia in chronic or accelerated phase: phase 1 study final results

  Jorge E. Cortes, Fabian Lang, Delphine Rea, Andreas Hochhaus, Massimo Breccia, Yeow Tee Goh, Michael C. Heinrich, Timothy P. Hughes, Jeroen J. W. M. Janssen, Philipp le Coutre, Hironobu Minami, Koji Sasaki, Daniel J. DeAngelo, Gessami Sanchez-Olle, Nathalie Pognan, Meng Cao, Matthias Hoch, Michael J. Mauro

  Springer Science and Business Media LLC, Apr. 2025, Leukemia, 39(5) (5), 1124 - 1134

  Scientific journal


• Asciminib monotherapy in patients with chronic myeloid leukemia in chronic phase without BCR::ABL1T315I treated with at least 2 prior TKIs: Phase 1 final results

  Andreas Hochhaus, Dong-Wook Kim, Jorge E. Cortes, Koji Sasaki, Michael J. Mauro, Timothy P. Hughes, Massimo Breccia, Moshe Talpaz, Hironobu Minami, Yeow Tee Goh, Daniel J. DeAngelo, Fabian Lang, Oliver Ottmann, Michael C. Heinrich, Valle Gomez Garcia de Soria, Philipp le Coutre, Gessami Sanchez-Olle, Meng Cao, Nathalie Pognan, Shruti Kapoor, Matthias Hoch, Delphine Rea

  Abstract Asciminib is the first approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP). The present final analysis of the phase 1, open-label, nonrandomized trial (NCT02081378) assessed the long-term safety, tolerability, and antileukemic activity of asciminib in 115 patients with chronic myeloid leukemia in chronic phase without the BCR::ABL1 ^T315I mutation who received asciminib 10–200 mg twice daily (BID) or 80–200 mg once daily (cutoff: March 14, 2023). Median exposure duration was 5.9 (range, 0–8.4) years; 60.9% of patients continued receiving asciminib through post-trial access. Grade ≥3 adverse events (AEs) occurred in 88 patients (76.5%). AEs led to treatment discontinuation, dose adjustment/interruption, or additional therapy in 15 (13.0%), 74 (64.3%), and 106 (92.2%) patients, respectively. Most first-ever AEs, particularly hematologic AEs, presented within the first year and no new safety signals emerged. Of 56 patients who achieved major molecular response, 50 maintained the response by cutoff; the Kaplan-Meier-estimated probability of maintaining this response for ≥432 weeks ( ≈ 8.3 years) was 88% (95% confidence interval, 78.2–97.0%). The recommended dose for expansion was determined at 40 mg BID. With up to 8.4 years of treatment, asciminib continued to demonstrate long-term safety and efficacy in this population.

  Springer Science and Business Media LLC, Apr. 2025, Leukemia, 39(5) (5), 1114 - 1123

  Scientific journal


• Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors

  Naruto Taira, Naomi Kiyota, Yuichiro Kikawa, Eiki Ichihara, Kyoko Kato, Kaoru Kubota, Ryosuke Tateishi, Akinobu Nakata, Keiichiro Nakamura, Yukiya Narita, Katsuyuki Hotta, Hiroji Iwata, Akihiko Gemma, Kojiro Shimozuma, Kei Muro, Tetsuya Iwamoto, Yuki Takumoto, Takeru Shiroiwa, Takashi Fukuda, Takuhiro Yamaguchi, Yasuhiro Hagiwara, Hironobu Minami

  Abstract Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase.

  Oxford University Press (OUP), Feb. 2025, Japanese Journal of Clinical Oncology, 55(5) (5), 547 - 555

  Scientific journal


• Public assistance and survival equality in patients with EGFR mutation-positive lung cancer

  Kiyoaki Uryu, Yoshinori Imamura, Rai Shimoyama, Takahiro Mase, Yoshiaki Fujimura, Maki Hayashi, Megu Ohtaki, Keiko Otani, Makoto Hibino, Shigeto Horiuchi, Tomoya Fukui, Ryuta Fukai, Yusuke Chihara, Akihiko Iwase, Noriko Yamada, Yukihiro Tamura, Hiromasa Harada, Asuka Tsuya, Takafumi Okabe, Masahiro Fukuoka, Hironobu Minami

  Abstract Background Disparities in public assistance or the urbanization level of a residential region can affect cancer treatment outcomes. This study aimed to investigate whether these factors affect the overall survival (OS) of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) using Tokushukai REAL World Data. Methods We analyzed the clinical data of consecutive patients with NSCLC receiving EGFR-tyrosine kinase inhibitors between April 2010 and March 2020 at 46 Tokushukai Medical Group hospitals in Japan. The patient’s insurance coverage status was extracted from electronic medical records, and the urbanization level of residential regions was classified as megalopolis or other according to the secondary medical region. Univariate and multivariate Cox regression analyses were performed to examine the associations between OS and patient/tumor/treatment/socioeconomic-related factors. Results In total, 758 patients (58.5% females) were included in the study; 41 patients (5.4%) received public assistance, and 442 patients (58.3%) were categorized under megalopolis in the secondary medical regions. In multivariate Cox regression analyses, there was no significant difference in the OS between non-recipients of public assistance and recipients [hazard ratio (HR) 1.084; 95% confidence intervals (CIs), 0.674–1.744]. There was also no significant difference in the OS between megalopolis and other regions in the secondary medical regions (HR 1.143; 95% CIs, 0.914–1.428). Conclusions Our findings suggest that neither the use of public assistance nor the urbanization level in the residential region significantly impacts the prognosis of Japanese patients with EGFR mutation-positive NSCLC.

  Oxford University Press (OUP), Dec. 2024, Japanese Journal of Clinical Oncology, 55(3) (3), 228 - 236

  Scientific journal


• Analysis of B-cell receptor repertoire to evaluate the immunogenicity of SARS-CoV-2 RBD mRNA vaccine: MAFB-7256a (DS-5670d)

  Goh Ohji, Yohei Funakoshi, Kimikazu Yakushijin, Takaji Matsutani, Tomoki Sasaki, Takahiro Kusakabe, Sakuya Matsumoto, Taiji Koyama, Yoshiaki Nagatani, Keiji Kurata, Shiro Kimbara, Naomi Kiyota, Hironobu Minami

  A monovalent Omicron XBB.1.5 mRNA RBD analogue vaccine, MAFB-7256a (DS-5670d), was newly developed and approved in Japan in the Spring of 2024 for the prevention of COVID-19. However, clinical efficacy data for this vaccine are currently lacking. We previously established the Quantification of Antigen-specific Antibody Sequence (QASAS) method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assays and the Coronavirus Antibody Database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of MAFB-7256a. We analyzed repeated blood samples using the QASAS method from three healthy volunteers before and after MAFB-7256a vaccination. BCR response increased rapidly one week post-vaccination and then decreased, as with conventional vaccine. Notably, the matched sequences after MAFB-7256a vaccination specifically bound to the receptor-binding domain (RBD), with no sequences binding to other epitopes. These results validate that MAFB-7256a is an effective vaccine that exclusively induces antibodies specific for the RBD, demonstrating its targeted immunogenic effect.

  Frontiers Media SA, Oct. 2024, Frontiers in Immunology, 15, 1468760 - 1468760, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 日常的に計算可能な臨床的指標と、類洞閉塞症候群(SOS/VOD)の病勢進行との関連

  市川 大哉, 藥師神 公和, 倉田 啓史, 岡副 結梨, 高橋 瑠理, 松本 咲耶, 坂井 里奈, 北尾 章人, 宮田 吉晴, 齊藤 泰之, 川本 晋一郎, 山本 克也, 伊藤 光宏, 村山 徹, 松岡 広, 南 博信

  (一社)日本血液学会, Oct. 2024, 日本血液学会学術集会, 86回, O2 - 3, English


• B細胞リンパ腫に対するマクロファージ標的療法のヒト化マウスモデルを用いた前臨床評価

  齊藤 泰之, Tania Afroj, 小森 里美, 高井 智子, 小谷 武徳, 船越 洋平, 村田 陽二, 藥師神 公和, 松岡 広, 南 博信, Markus Manz, 的崎 尚

  (一社)日本血液学会, Oct. 2024, 日本血液学会学術集会, 86回, O2 - 4, English


• Impact of First-Line Osimertinib and Other EGFR-Tyrosine Kinase Inhibitors on Overall Survival in Untreated Advanced EGFR-Mutated Non-small Cell Lung Cancer in Japan: Updated Data from TREAD Project 01

  Makoto Hibino, Yoshinori Imamura, Rai Shimoyama, Tomoya Fukui, Ryuta Fukai, Akihiko Iwase, Yukihiro Tamura, Yusuke Chihara, Takafumi Okabe, Kiyoaki Uryu, Tadahisa Okuda, Masataka Taguri, Hironobu Minami

  Springer Science and Business Media LLC, Sep. 2024, Targeted Oncology, 19(6) (6), 925 - 939

  Scientific journal


• Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer.

  Yoshiaki Nagatani, Naomi Kiyota, Yoshinori Imamura, Taiji Koyama, Yohei Funakoshi, Masato Komatsu, Tomoo Itoh, Masanori Teshima, Ken-Ichi Nibu, Kazuko Sakai, Kazuto Nishio, Manami Shimomura, Tetsuya Nakatsura, Daiki Ikarashi, Takayuki Nakayama, Shigehisa Kitano, Hironobu Minami

  AIM: Although immune checkpoint inhibitors (ICPi) for salivary gland cancer (SGC) have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) remain unclear. This research aimed to elucidate the TIME of SGC and its relationship with tumor mutation burden (TMB) and to explore the rationale for the applicability of ICPi. MATERIALS AND METHODS: We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEClow/high). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next-generation sequencing. RESULTS: ACC and MEChigh showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEClow showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3+CD8+ T cells in tumor and TMB (r = 0.647). CD3+CD8+ T cells in tumors showed a positive correlation with programmed cell death-ligand 1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3+CD4+Foxp3+ cells in tumors (r = 0.399). However, no correlation was observed between CD3+CD8+ T cells and CD204+ cells in tumors (r = -0.049). CONCLUSION: The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune-inflamed type, and this may support the rationale of ICPi for this pathological subtype.

  Sep. 2024, Asia-Pacific journal of clinical oncology, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Analysis of thromboembolism and prognosis in metastatic pancreatic cancer from the Tokushukai REAl‑world data project

  Rai Shimoyama, Yoshinori Imamura, Kiyoaki Uryu, Takahiro Mase, Megu Ohtaki, Keiko Ohtani, Megumi Shiragami, Yoshiaki Fujimura, Maki Hayashi, Nobuaki Shinozaki, Hironobu Minami

  Spandidos Publications, Aug. 2024, Molecular and Clinical Oncology, 21(4) (4)

  Scientific journal


• Effect of increase in heart rate after anthracycline chemotherapy on subsequent left ventricular dysfunction

  Masayuki Kintsu, Susumu Odajima, Kimikazu Takeuchi, Yasushi Ichikawa, Saki Todo, Eri Ota, Yuki Yamauchi, Hiroaki Shiraki, Kentaro Yamashita, Terunobu Fukuda, Eriko Hisamatsu, Hironobu Minami, Ken-ichi Hirata, Hidekazu Tanaka

  Elsevier BV, Aug. 2024, Journal of Cardiology, 84(2) (2), 119 - 125

  Scientific journal


• Analysis of B-cell receptor repertoire to evaluate immunogenicity of monovalent Omicron XBB.1.5 mRNA vaccines.

  Yohei Funakoshi, Kimikazu Yakushijin, Goh Ohji, Takaji Matsutani, Kazuhiko Doi, Hironori Sakai, Tomoki Sasaki, Takahiro Kusakabe, Sakuya Matsumoto, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Taiji Koyama, Yoshiaki Nagatani, Keiji Kurata, Shiro Kimbara, Yoshinori Imamura, Naomi Kiyota, Mitsuhiro Ito, Hironobu Minami

  Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen-specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA-1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS-CoV-2-specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS-CoV-2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023-2024 COVID-19 vaccination campaign.

  Aug. 2024, EJHaem, 5(4) (4), 661 - 668, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Corrigendum to ‘A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody’: [ESMO Open volume 9 issue 6 (2024) 103476] (ESMO Open (2024) 9(6), (S2059702924012456), (10.1016/j.esmoop.2024.103476))

  T. Koyama, N. Kiyota, S. Boku, Y. Imamura, N. Shibata, H. Satake, K. Tanaka, H. Hayashi, T. Onoe, Y. Asada, T. Yamazaki, T. Nose, S. Ohata, Y. Nagatani, S. Kimbara, Y. Funakoshi, M. Teshima, H. Shinomiya, H. Minami

  Aug. 2024, ESMO Open, 9(8) (8)

  Scientific journal

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• Near‐triploidy with four Philadelphia chromosomes in adult B‐lymphoblastic leukemia with BCR::ABL1 fusion

  Katsuya Yamamoto, Yuri Hirakawa, Sakuya Matsumoto, Kimikazu Yakushijin, Hironobu Minami

  Wiley, Jun. 2024, International Journal of Laboratory Hematology, 46(6) (6), 988 - 990

  Scientific journal

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• Long-term efficacy and safety of tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: final analysis of phase IIb results

  Shinya Rai, Won Seog Kim, Kiyoshi Ando, Ilseung Choi, Koji Izutsu, Norifumi Tsukamoto, Dai Maruyama, Kunihiro Tsukasaki, Junya Kuroda, Jun Ando, Michihiro Hidaka, Youngil Koh, Hisashi Kato, Toshiki Uchida, Deok Hwan Yang, Kenji Ishitsuka, Kenichi Ishizawa, Jin Seok Kim, Hong Ghi Lee, Hironobu Minami, Hyeon Seok Eom, Mitsutoshi Kurosawa, Jae Hoon Lee, Jong Seok Lee, Won Sik Lee, Hirokazu Nagai, Takero Shindo, Dok Hyun Yoon, Shinichiro Yoshida, Mireille Gillings, Hiroshi Onogi, Kensei Tobinai

  Ferrata Storti Foundation (Haematologica), Jun. 2024, Haematologica, 109(10) (10), 3357 - 3362

  Scientific journal


• A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody

  T. Koyama, N. Kiyota, S. Boku, Y. Imamura, N. Shibata, H. Satake, K. Tanaka, H. Hayashi, T. Onoe, Y. Asada, T. Yamazaki, T. Nose, S. Ohata, Y. Nagatani, S. Kimbara, Y. Funakoshi, M. Teshima, H. Shinomiya, H. Minami

  Jun. 2024, ESMO Open, 9(6) (6)

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 進行・再発・転移の固形腫瘍における血栓塞栓症と出血リスク PROVE-emboli試験post-hoc解析

  今村 善宣, 能勢 拓, 大幡 真也, 乙井 一典, 森 健太, 辻 高寛, 宮田 吉晴, 金原 史朗, 長谷 善明, 小山 泰司, 船越 洋平, 清田 尚臣, 南 博信

  (一社)日本血栓止血学会, May 2024, 日本血栓止血学会誌, 35(2) (2), 336 - 336, Japanese


• Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial)

  Hironobu Goto, Taro Oshikiri, Takashi Kato, Yoshiaki Nagatani, Yohei Funakoshi, Yasufumi Koterazawa, Ryuichiro Sawada, Hitoshi Harada, Naoki Urakawa, Hiroshi Hasegawa, Shingo Kanaji, Kimihiro Yamashita, Takeru Matsuda, Hironobu Minami, Yoshihiro Kakeji

  Background In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. Methods This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4–16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. Discussion To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

  Public Library of Science (PLoS), Apr. 2024, PLOS ONE, 19(4) (4), e0299742 - e0299742

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Prognostic impact of concomitant pH-regulating drugs in patients with non-small cell lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitors: the Tokushukai REAl-world Data project 01-S1

  Kiyoaki Uryu, Yoshinori Imamura, Rai Shimoyama, Takahiro Mase, Yoshiaki Fujimura, Maki Hayashi, Megu Ohtaki, Keiko Otani, Makoto Hibino, Shigeto Horiuchi, Tomoya Fukui, Ryuta Fukai, Yusuke Chihara, Akihiko Iwase, Noriko Yamada, Yukihiro Tamura, Hiromasa Harada, Nobuaki Shinozaki, Toyoshi Shimada, Asuka Tsuya, Masahiro Fukuoka, Hironobu Minami

  Springer Science and Business Media LLC, Apr. 2024, Cancer Chemotherapy and Pharmacology, 94(2) (2), 197 - 208

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 進行胃癌に対する免疫療法と分子標的治療の新展開 びまん性胃癌における遺伝子変異と腫瘍免疫微小環境から考える複合免疫療法

  長谷 善明, 船越 洋平, 南 博信

  (一財)日本消化器病学会, Mar. 2024, 日本消化器病学会雑誌, 121(臨増総会) (臨増総会), A51 - A51, Japanese


• 進行胃癌に対する免疫療法と分子標的治療の新展開 びまん性胃癌における遺伝子変異と腫瘍免疫微小環境から考える複合免疫療法

  長谷 善明, 船越 洋平, 南 博信

  (一財)日本消化器病学会, Mar. 2024, 日本消化器病学会雑誌, 121(臨増総会) (臨増総会), A51 - A51, Japanese


• The Efficacy of Bepotastine Besilate Compared With Hydroxyzine Pamoate for Preventing Infusion Reactions to the First Dose of Rituximab in Patients With Non-Hodgkin Lymphoma: Protocol for a Phase II, Double-Blind, Multicenter Randomized Trial.

  Yumi Kitahiro, Kazuhiro Yamamoto, Kimikazu Yakushijin, Takeshi Ioroi, Masaaki Tanda, Kotaro Itohara, Tomohiro Omura, Hironobu Minami, Ikuko Yano

  BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1-receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H1-receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion. OBJECTIVE: This study aimed to assess the efficacy of first- and second-generation histamine H1-receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma. METHODS: This is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1-receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H1-receptor antagonist-induced drowsiness using the visual analogue scale, with each patient providing their individual response. RESULTS: This study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026. CONCLUSIONS: This study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1-receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54882.

  Feb. 2024, JMIR research protocols, 13, e54882, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Irreversible Intrathecal Chemotherapy-induced Myelopathy in a Patient with Diffuse Large B-cell Lymphoma

  Yuri Hirakawa, Akihito Kitao, Marika Watanabe, Sakuya Matsumoto, Ryohei Komaki, Rina Sakai, Kohei Morimoto, Kimikazu Yakushijin, Hironobu Minami

  Intrathecal chemotherapy is often administered for prophylaxis and treatment of central nervous system involvement in hematological malignancies. However, it may rarely cause neurotoxicity as a side effect. We herein report a 74-year-old woman with diffuse large B-cell lymphoma including a spinal lesion. She received systemic and intrathecal chemotherapy. After five doses of intrathecal chemotherapy, she developed intrathecal chemotherapy-induced myelopathy. Intrathecal treatment was discontinued, and she was administered vitamin B12 and folic acid, along with steroid pulses. However, her symptoms did not improve. Intrathecal chemotherapy-induced myelopathy is rare, but may be irreversible; therefore, clinicians should be aware of this potential complication.

  Japanese Society of Internal Medicine, Feb. 2024, Internal Medicine, 63(4) (4), 547 - 551, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Utility of the refined EBMT diagnostic and severity criteria 2023 for sinusoidal obstruction syndrome/veno-occlusive disease

  Hiroya Ichikawa, Kimikazu Yakushijin, Keiji Kurata, Takahiro Tsuji, Naoko Takemoto, Miki Joyce, Yuri Okazoe, Ruri Takahashi, Sakuya Matsumoto, Rina Sakai, Akihito Kitao, Yoshiharu Miyata, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Tohru Murayama, Hiroshi Matsuoka, Hironobu Minami

  Abstract Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis of SOS/VOD is associated with improved clinical outcomes. In 2023, the refined European Society for Blood and Marrow Transplantation diagnostic and severity criteria (refined EBMT criteria 2023) have been advocated. The revision has introduced new diagnostic categories, namely; probable, clinical, and proven SOS/VOD. In addition, the Sequential Organ Failure Assessment (SOFA) score has been newly incorporated into the SOS/VOD severity grading. We performed a retrospective analysis to evaluate the utility of these criteria. We analyzed 161 cases who underwent allogeneic HSCT. We identified 53 probable, 23 clinical, and 4 proven SOS/VOD cases. Probable SOS/VOD was diagnosed a median of 5.0 days earlier (interquartile range: 2–13 days, P < 0.001) than that of clinical SOS/VOD. The development of probable SOS/VOD alone was associated with a significantly inferior survival proportion compared to non-SOS/VOD (100-day survival, 86.2% vs. 94.3%, P = 0.012). The SOFA score contributed to the prediction of prognosis. Consequently, the refined EBMT criteria 2023 demonstrated the utility of SOS/VOD diagnosis and severity grading. Further investigations and improvements in these criteria are warranted.

  Springer Science and Business Media LLC, Jan. 2024, Bone Marrow Transplantation, 59(4) (4), 518 - 525

  Scientific journal


• Preclinical evaluation of the efficacy of an antibody to human SIRPα for cancer immunotherapy in humanized mouse models

  Yasuyuki Saito, Rie Iida-Norita, Tania Afroj, Alaa Refaat, Daisuke Hazama, Satomi Komori, Shinya Ohata, Tomoko Takai, Okechi S. Oduori, Takenori Kotani, Yohei Funakoshi, Yu-Ichiro Koma, Yoji Murata, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami, Hiroshi Yokozaki, Markus G. Manz, Takashi Matozaki

  Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment and are considered potential targets for cancer immunotherapy. To examine the antitumor effects of agents targeting human TAMs in vivo, we here established preclinical tumor xenograft models based on immunodeficient mice that express multiple human cytokines and have been reconstituted with a human immune system by transplantation of human CD34⁺ hematopoietic stem and progenitor cells (HIS-MITRG mice). HIS-MITRG mice supported the growth of both human cell line (Raji)– and patient-derived B cell lymphoma as well as the infiltration of human macrophages into their tumors. We examined the potential antitumor action of an antibody to human SIRPα (SE12C3) that inhibits the interaction of CD47 on tumor cells with SIRPα on human macrophages and thereby promotes Fcγ receptor–mediated phagocytosis of the former cells by the latter. Treatment with the combination of rituximab (antibody to human CD20) and SE12C3 inhibited Raji tumor growth in HIS-MITRG mice to a markedly greater extent than did rituximab monotherapy. This enhanced antitumor effect was dependent on human macrophages and attributable to enhanced rituximab-dependent phagocytosis of lymphoma cells by human macrophages. Treatment with rituximab and SE12C3 also induced reprogramming of human TAMs toward a proinflammatory phenotype. Furthermore, the combination treatment essentially prevented the growth of patient-derived diffuse large B cell lymphoma in HIS-MITRG mice. Our findings thus support the study of HIS-MITRG mice as a model for the preclinical evaluation in vivo of potential therapeutics, such as antibodies to human SIRPα, that target human TAMs.

  Frontiers Media SA, Dec. 2023, Frontiers in Immunology, 14

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  Link to Kobe Univ. Repository (Kernel)


• Stepwise prolongation of overall survival from first to third generation EGFR-TKIs for EGFR mutation-positive non-small-cell lung cancer: the Tokushukai REAl-world Data project (TREAD 01)

  Kiyoaki Uryu, Yoshinori Imamura, Rai Shimoyama, Takahiro Mase, Yoshiaki Fujimura, Maki Hayashi, Megu Ohtaki, Keiko Otani, Makoto Hibino, Shigeto Horiuchi, Tomoya Fukui, Ryuta Fukai, Yusuke Chihara, Akihiko Iwase, Noriko Yamada, Yukihiro Tamura, Hiromasa Harada, Nobuaki Shinozaki, Asuka Tsuya, Masahiro Fukuoka, Hironobu Minami

  Abstract Objective The introduction of new-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has afforded promising overall survival outcomes in clinical trials for non-small-cell lung cancer. We aim to investigate the current adoption rate of these agents and the real-world impact on overall survival among institutions. Methods In a nationwide retrospective cohort study of 46 Tokushukai Medical Group hospitals in Japan, we analyzed clinical data of consecutive patients with non-small-cell lung cancer receiving EGFR-TKIs between April 2010 and March 2020. Univariate and multivariate Cox regression analyses examined the associations between overall survival and patient/tumor-related factors and first-line EGFR-TKIs. Results A total of 758 patients (58.5% females; median age, 73 years) were included. Of 40 patients diagnosed in 2010, 72.5% received gefitinib, whereas 81.3% of 107 patients diagnosed in 2019 received osimertinib as the first-line EGFR-TKI. With a median follow-up of 15.8 months, the median overall survival was 28.4 months (95% confidence interval, 15.3–31.0). In a multivariate Cox regression analysis, age, body mass index, disease status, EGFR mutational status and first-line epidermal growth factor receptor tyrosine kinase inhibitor were identified as significant prognostic factors after adjusting for background factors including study period, hospital volume and hospital type. The estimated 2-year overall survival rates for gefitinib, erlotinib, afatinib and osimertinib were 70.1% (95% confidence interval 59.7–82.4), 67.8% (95% confidence interval 55.3–83.2), 75.5% (95% confidence interval 64.7–88.0) and 90.8% (95% confidence interval 84.8–97.3), respectively. The median time to treatment failure of gefitinib, erlotinib, afatinib and osimertinib were 12.8, 8.8, 12.0 and 16.9 months or more, respectively. Conclusions Our real-world data revealed that the swift and widespread utilization of newer-generation EGFR-TKIs in patients with EGFR mutation-positive non-small-cell lung cancer, and that these newer-generation EGFR-TKIs can prolong overall survival regardless of hospital volume or type. Therefore, osimertinib could be a reasonable first choice treatment for these patients across various clinical practice settings.

  Oxford University Press (OUP), Nov. 2023, Japanese Journal of Clinical Oncology, 54(3) (3), 319 - 328

  Scientific journal


• Treatment of dermal ulcer with autologous fibrin glue: Two case reports of an exploratory prospective pilot study

  Shinichiro Kawamoto, Eriko Shinkawa, Susumu Fujiwara, Yoshiko Oda, Haruki Jimbo, Eiji Nakano, Takeshi Fukumoto, Ryusuke Ono, Takahiro Yasuda, Hironobu Minami

  Introduction: The healing of recurrent and refractory skin ulcers requires a long time, during which there is risk of infection, and hospital admission is occasionally required for surgical or daily conservative treatment. Therefore, the development of promising treatments that promote faster, uneventful healing is a must. Composed of cryoprecipitate and thrombin, fibrin glue has a history of surgical use for preventing bleeding and spinal fluid leakage. Moreover, in-house cryoprecipitates contain higher concentrations of coagulation factors and cytokines that may enhance wound healing than commercially available products. However, the efficacy of completely autologous fibrin glue (AFG) in tissue repair has not yet been fully demonstrated. Patient concerns: This study aimed to evaluate the efficacy of AFG in the treatment of refractory skin ulcers in comparison with the conventional treatment. Diagnosis: Two patients with skin ulcer on their lower extremities due to trauma or scleroderma who showed resistance to conventional treatment were included in the study. Both study participants were diagnosed with refractory skin ulcer and were ineligible for autologous skin transplantation. Interventions: AFG was prepared following autologous blood donation using a Cryoseal^® system. Subsequently, AFG was administered to 50% of the area of each ulcer and observed for 4 weeks in comparison with recombinant basic fibroblast growth factor with bucladesine sodium treatment that was administered to the rest of the ulcer. Outcomes: The skin ulcer after trauma in participant 1 showed better improvement in the AFG-treated area. Although AFG did not show superiority regarding the ulcer area of a patient with scleroderma, it guarded the continuous exudation from the edge of the swollen skin surrounding the ulcer. Conclusion: AFG showed effective and beneficial results for wound healing of refractory skin ulcer and prevented exudation without any severe adverse events.

  Ovid Technologies (Wolters Kluwer Health), Nov. 2023, Medicine, 102(46) (46), e36134 - e36134

  Scientific journal


• Efficacy and Safety of Synbiotics in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Randomized, Double-blinded, Placebo-controlled Pilot Study

  Yu Mizutani, Shinichiro Kawamoto, Michiko Takahashi, Hisayo Doi, Kumiko Wakida, Satoko Tabuchi, Masaaki Tanda, Akihiro Soga, Ruri Chijiki, Hidetomo Takakura, Koji Kawaguchi, Ako Higashime, Marika Watanabe, Hiroya Ichikawa, Sakuya Matsumoto, Rina Sakai, Hideaki Goto, Keiji Kurata, Seiji Kakiuchi, Yoshiharu Miyata, Kiyoaki Uryu, Yumiko Inui, Akihito Kitao, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  Japanese Society of Internal Medicine, Oct. 2023, Internal Medicine, 62(20) (20), 2949 - 2958

  Scientific journal


• Real-world treatment outcomes of metastatic biliary tract cancer patients in Japan: the Tokushukai REAl-world data project 04 (TREAD 04)

  Rai Shimoyama, Yoshinori Imamura, Kiyoaki Uryu, Takahiro Mase, Masataka Taguri, Tadahisa Okuda, Yoshiaki Fujimura, Maki Hayashi, Satomi Tanaka, Keiji Sawamukai, Hironobu Minami

  Abstract Objectives To investigate temporal trends in treatment patterns and prognostic factors for overall survival in patients with metastatic biliary tract cancer. Methods From the Tokushukai REAl-world Data project, we identified 945 patients with metastatic biliary tract cancer treated with gemcitabine, tegafur/gimeracil/oteracil, gemcitabine plus cisplatin, gemcitabine plus tegafur/gimeracil/oteracil or gemcitabine plus cisplatin and tegafur/gimeracil/oteracil between April 2010 and March 2022. Stratified/conventional Cox regression analyses were conducted to examine the association between overall survival and patient- and tumour-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimen. Using inverse probability of treatment weighting with propensity scores, overall survival was also compared between monotherapy and combination therapy groups. Results We enrolled 366 patients (199 men; median age, 72 years). Over a median follow-up of 5.2 months, the median overall survival was 7.0 months (95% confidence interval 6.2–9.0), and the median time to treatment failure was 3.5 months (95% confidence interval 3.1–4.5). Median overall survival and time to treatment failure for gemcitabine/tegafur–gimeracil–oteracil/gemcitabine plus cisplatin/gemcitabine plus tegafur–gimeracil–oteracil/gemcitabine plus cisplatin and tegafur–gimeracil–oteracil regimen were 6.2/6.6/7.9/16.2/15.1 and 2.8/3.4/4.1/15.3/7.4 months, respectively. Primary disease site, previous surgery, previous endoscopic procedures and hospital type were identified as significant prognostic factors. Inverse probability of treatment weighting analysis demonstrated that combination therapy had a significantly better prognosis than monotherapy (hazard ratio 0.61, 95% confidence interval 0.43–0.88, P = 0.006). Conclusions Our real-world data analysis showed that standard care for metastatic biliary tract cancer is widely used in hospitals throughout Japan and verified the survival benefits of combination therapy over monotherapy observed in prior clinical trials. Clinical trial number UMIN000050590 (http://www.umin.ac.jp/ctr/index.htm).

  Oxford University Press (OUP), Oct. 2023, Japanese Journal of Clinical Oncology, 54(1) (1), 70 - 80

  Scientific journal


• Phase III clinical trial of autologous CD34 + cell transplantation to accelerate fracture nonunion repair

  Ryosuke Kuroda, Takahiro Niikura, Tomoyuki Matsumoto, Tomoaki Fukui, Keisuke Oe, Yutaka Mifune, Hironobu Minami, Hiroshi Matsuoka, Kimikazu Yakushijin, Yoshiharu Miyata, Shinichiro Kawamoto, Tatsuo Kagimura, Yasuyuki Fujita, Atsuhiko Kawamoto

  Abstract Background We previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients. Methods CD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded. Results All fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16–6.85); moreover, no safety concerns were observed. Conclusions Our findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion. Trial registration UMIN-CTR, UMIN000022814. Registered on 22 June 2016.

  Springer Science and Business Media LLC, Oct. 2023, BMC Medicine, 21(1) (1), 386 - 386, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 血小板輸血不応の項を含む新診断基準による、類洞閉塞症候群(SOS)の早期診断

  市川 大哉, 藥師神 公和, 宮田 吉晴, 兼平 博史, ジョイス 美紀, 平川 結梨, 松本 咲耶, 長尾 茂輝, 坂井 里奈, 倉田 啓史, 北尾 章人, 齊藤 泰之, 川本 晋一郎, 山本 克也, 伊藤 光宏, 村山 徹, 松岡 広, 南 博信

  (一社)日本血液学会, Oct. 2023, 日本血液学会学術集会, 85回, 683 - 683, English


• 治療前CD163はニボルマブ+化学療法における予後不良因子(WJOG9917BTR)

  尾崎 由記範, 岩朝 勤, 北野 滋久, 山下 万貴子, 鶴谷 純司, 高橋 將人, 向原 徹, 増田 慎三, 二村 学, 南 博信, 松本 光史, 田辺 裕子, 川端 英孝, 吉村 健一, 高野 利実

  (一社)日本癌治療学会, Oct. 2023, 日本癌治療学会学術集会抄録集, 61回, O25 - 3, English


• 治療前CD163はニボルマブ+化学療法における予後不良因子(WJOG9917BTR)

  尾崎 由記範, 岩朝 勤, 北野 滋久, 山下 万貴子, 鶴谷 純司, 高橋 將人, 向原 徹, 増田 慎三, 二村 学, 南 博信, 松本 光史, 田辺 裕子, 川端 英孝, 吉村 健一, 高野 利実

  (一社)日本癌治療学会, Oct. 2023, 日本癌治療学会学術集会抄録集, 61回, O25 - 3, English


• ASO Visual Abstract: The Usefulness of Total Tumor Volume as a Prognostic Factor and in Selecting the Optimal Treatment Strategy of Chemotherapeutic Intervention in Patients with Colorectal Liver Metastases.

  Yuhi Shimura, Shohei Komatsu, Yoshiaki Nagatani, Yohei Funakoshi, Keitaro Sofue, Masahiro Kido, Kaori Kuramitsu, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Shinichi So, Hiroaki Yanagimoto, Hirochika Toyama, Hironobu Minami, Takumi Fukumoto

  Oct. 2023, Annals of surgical oncology, 30(11) (11), 6613 - 6614, English, International magazine

  Scientific journal


• ASO Author Reflections: Can the Total Tumor Volume be an Indicator for Optimal Treatment Strategy in Patients with Colorectal Liver Metastases?

  Yuhi Shimura, Shohei Komatsu, Hironobu Minami, Takumi Fukumoto

  Springer Science and Business Media LLC, Jul. 2023, Annals of Surgical Oncology, 30(11) (11), 6611 - 6612, English, International magazine

  Scientific journal


• The Usefulness of Total Tumor Volume as a Prognostic Factor and in Selecting the Optimal Treatment Strategy of Chemotherapeutic Intervention in Patients with Colorectal Liver Metastases

  Yuhi Shimura, Shohei Komatsu, Yoshiaki Nagatani, Yohei Funakoshi, Keitaro Sofue, Masahiro Kido, Kaori Kuramitsu, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Shinichi So, Hiroaki Yanagimoto, Hirochika Toyama, Hironobu Minami, Takumi Fukumoto

  BACKGROUND: Few reports have discussed the association between total tumor volume (TTV) and prognosis in patients with colorectal liver metastases (CRLM). The present study aimed to evaluate the usefulness of TTV for predicting recurrence-free survival and overall survival (OS) in patients receiving initial hepatic resection or chemotherapy, and to investigate the value of TTV as an indicator for optimal treatment selection for patients with CRLM. PATIENTS AND METHODS: This retrospective cohort study included patients with CRLM who underwent hepatic resection (n = 93) or chemotherapy (n = 78) at the Kobe University Hospital. TTV was measured using 3D construction software and computed tomography images. RESULTS: A TTV of 100 cm3 has been previously reported as a significant cut-off value for predicting OS of CRLM patients receiving initial hepatic resection. For patients receiving hepatic resection, the OS for those with a TTV ≥ 100 cm3 was significantly reduced compared with those with a TTV < 100 cm3. For patients receiving initial chemotherapy, there were no significant differences between the groups divided according to TTV cut-offs. Regarding OS of patients with TTV ≥ 100 cm3, there was no significant difference between hepatic resection and chemotherapy (p = 0.160). CONCLUSIONS: TTV can be a predictive factor of OS for hepatic resection, unlike for initial chemotherapy treatment. The lack of significant difference in OS for CRLM patients with TTV ≥ 100 cm3, regardless of initial treatment, suggests that chemotherapeutic intervention preceding hepatic resection may be indicated for such patients.

  Springer Science and Business Media LLC, Jun. 2023, Annals of Surgical Oncology, 30(11) (11), 6603 - 6610, English, International magazine

  Scientific journal


• Response to mRNA SARS-CoV-2 vaccination evaluated by B-cell receptor repertoire after tixagevimab/cilgavimab administration.

  Yohei Funakoshi, Kimikazu Yakushijin, Goh Ohji, Takaji Matsutani, Wataru Hojo, Hironori Sakai, Sakuya Matsumoto, Marika Watanabe, Akihito Kitao, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Taiji Koyama, Yoshiaki Nagatani, Shiro Kimbara, Yoshinori Imamura, Naomi Kiyota, Mitsuhiro Ito, Hironobu Minami

  The use of anti-SARS-CoV-2 antibody products like tixagevimab/cilgavimab represents an important strategy to protect immunocompromised patients with haematological malignancies from COVID-19. Although patients who receive these agents should still be vaccinated, the use of tixagevimab/cilgavimab can mask the production of anti-spike antibody after vaccination, making it hard to assess vaccine response. We have newly established a quantification method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the Coronavirus Antibody Database (CoV-AbDab). Repeated blood samples before and after vaccination were analysed for the BCR repertoire, and BCR sequences were searched in the database. We analysed the number and percentage frequency of matched sequences. We found that the number of matched sequences increased 2 weeks after the first vaccination and quickly decreased. Meanwhile, the number of matched sequences more rapidly increased after the second vaccination. These results show that the postvaccine immune response can be assessed at the mRNA level by analysing the fluctuation in matching sequences. Finally, BCR repertoire analysis with CoV-AbDab clearly demonstrated the response to mRNA SARS-CoV-2 vaccination even after tixagevimab/cilgavimab administration in haematological malignancy patients who underwent allogeneic haematopoietic stem cell transplantation.

  Jun. 2023, British journal of haematology, 202(3) (3), 504 - 516, English, International magazine

  Scientific journal


• HER2陰性転移再発乳癌に対するニボルマブ+ベバシズマブ+パクリタキセル併用療法の第II相試験(WJOG9917B)

  尾崎 由記範, 鶴谷 純司, 向原 徹, 岩朝 勤, 高橋 將人, 田辺 裕子, 川端 英孝, 増田 慎三, 二村 学, 南 博信, 松本 光史, 吉村 健一, 北野 滋久, 高野 利実

  (一社)日本乳癌学会, Jun. 2023, 日本乳癌学会総会プログラム抄録集, 31回, 65 - 65, English


• 再発乳癌とstage IV乳癌における免疫状態や免疫チェックポイント阻害薬に対する反応性の違い WJOG9917BTR

  尾崎 由記範, 北野 滋久, 山下 万貴子, 五十嵐 大樹, 鶴谷 純司, 岩朝 勤, 高橋 將人, 向原 徹, 増田 慎三, 二村 学, 南 博信, 松本 光史, 田辺 裕子, 川端 英孝, 吉村 健一, 高野 利実

  (一社)日本乳癌学会, Jun. 2023, 日本乳癌学会総会プログラム抄録集, 31回, 73 - 73, Japanese


• Early diagnosis of sinusoidal obstruction syndrome after hematopoietic stem cell transplantation, with modified diagnostic criteria including refractory thrombocytopenia

  Hiroya Ichikawa, Kimikazu Yakushijin, Yoshiharu Miyata, Hirofumi Kanehira, Miki Joyce, Yuri Hirakawa, Sakuya Matsumoto, Shigeki Nagao, Rina Sakai, Keiji Kurata, Akihito Kitao, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Tohru Murayama, Hiroshi Matsuoka, Hironobu Minami

  Abstract Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis for SOS can improve clinical outcomes significantly. Here, we performed a retrospective study to investigate the Cairo diagnostic criteria, in which SOS was defined as the development of two or more in seven events, including transfusion‐refractory thrombocytopenia. Among 154 cases of allogeneic HSCT, 10 cases of SOS using the European Society for Blood and Marrow Transplantation criteria (EBMT16) as the reference standard were identified. The original Cairo criteria could diagnose SOS 5 days earlier than any other established criteria, with some false‐positive results (sensitivity = 100.0%; specificity = 72.2%). When the cutoff was set to three events for the Cairo criteria, the diagnosis of SOS could be made 3 days earlier than that using the EBMT16 criteria, with comparable precision (specificity = 86.1%). The accuracy of the Cairo criteria improved further when the cutoff point was set to four (specificity = 93.8%). The fulfillment of the Cairo criteria was associated with high mortality. Based on our results, the Cairo criteria were also considered clinically useful, especially at three or four cutoff points. Further studies are required to validate and refine the criteria.

  Wiley, Jun. 2023, eJHaem, 4(3) (3), 695 - 704

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 進行・再発・転移の未治療固形がん患者における静脈血栓塞栓症の前向き観察研究の統合解析

  今村 善宣, 能勢 拓, 大幡 真也, 森 健太, 乙井 一典, 宮田 吉晴, 金原 史朗, 長谷 善明, 小山 泰司, 船越 洋平, 清田 尚臣, 南 博信

  (一社)日本血栓止血学会, May 2023, 日本血栓止血学会誌, 34(2) (2), 195 - 195, Japanese


• A Pathogenic <i>NRAS</i> c.38G>A (p.G13D) Mutation in <i>RARA</i> Translocation-negative Acute Promyelocytic-like Leukemia with Concomitant Myelodysplastic Syndrome

  Hideaki Goto, Kimikazu Yakushijin, Yoko Adachi, Hisayuki Matsumoto, Katsuya Yamamoto, Sakuya Matsumoto, Tomoe Yamashita, Ako Higashime, Koji Kawaguchi, Keiji Kurata, Hiroshi Matsuoka, Hironobu Minami

  An acute promyelocytic leukemia (APL) patient not demonstrating the retinoic acid receptor α (RARA) translocation is rare. A 76-year-old man was diagnosed with myelodysplastic syndrome (MDS). After a year, abnormal promyelocytes were detected with pancytopenia and disseminated intravascular coagulopathy. Morphologically, the patient was diagnosed with APL; however, a genetic examination failed to detect RARA translocation. Thereafter, whole-genome sequencing revealed an NRAS missense mutation [c.38 G>A (p.G13D)]. This mutation was not detected in posttreatment bone marrow aspirate, despite residual MDS. Few reports are available on similar cases. Furthermore, the NRAS c.38 G>A mutation may be a novel pathogenic variant exacerbating RARA translocation-negative acute promyelocytic-like leukemia.

  Japanese Society of Internal Medicine, May 2023, Internal Medicine, 62(9) (9), 1329 - 1334, English, Domestic magazine

  Scientific journal


• Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results

  Michael J. Mauro, Timothy P. Hughes, Dong-Wook Kim, Delphine Rea, Jorge E. Cortes, Andreas Hochhaus, Koji Sasaki, Massimo Breccia, Moshe Talpaz, Oliver Ottmann, Hironobu Minami, Yeow Tee Goh, Daniel J. DeAngelo, Michael C. Heinrich, Valle Gómez-García de Soria, Philipp le Coutre, Francois-Xavier Mahon, Jeroen J. W. M. Janssen, Michael Deininger, Naranie Shanmuganathan, Mark B. Geyer, Silvia Cacciatore, Fotis Polydoros, Nithya Agrawal, Matthias Hoch, Fabian Lang

  Abstract Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10–200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1 ≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population.

  Springer Science and Business Media LLC, Mar. 2023, Leukemia, 37(5) (5), 1048 - 1059

  Scientific journal


• Comparable efficacy and safety of COVID-19 vaccines for patients receiving tegafur–uracil as postoperative adjuvant chemotherapy

  Megumi Nishikubo, Yugo Tanaka, Suguru Mitsui, Takefumi Doi, Daisuke Hokka, Wataru Hojo, Hironori Sakai, Yohei Funakoshi, Kimikazu Yakushijin, Goh Ohji, Hironobu Minami, Yoshimasa Maniwa

  Abstract Purpose Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur–uracil (UFT) as postoperative adjuvant chemotherapy. Methods The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. Results The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. Conclusions The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. Clinical trial registration This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).

  Springer Science and Business Media LLC, Feb. 2023, Surgery Today, 53(9) (9), 1057 - 1063, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• がん関連静脈血栓塞栓症に対するアピキサバン療法の出血リスク予測 多施設共同第2相臨床試験副次的解析

  今村 善宣, 能勢 拓, 宮田 吉晴, 小山 泰司, 長谷 善明, 金原 史朗, 船越 洋平, 清田 尚臣, 藥師神 公和, 南 博信

  (一社)日本内科学会, Feb. 2023, 日本内科学会雑誌, 112(臨増) (臨増), 163 - 163, Japanese


• Biclonal Diffuse Large B-cell Lymphoma Commonly Characterized by Partial Trisomy 18q Involving <i>MALT1</i> and <i>BCL2</i>

  Katsuya Yamamoto, Shinichiro Kawamoto, Ruri Chijiki, Marika Watanabe, Sakuya Matsumoto, Akihito Kitao, Yu Mizutani, Kazuyoshi Kajimoto, Yoshitake Hayashi, Kimikazu Yakushijin, Hironobu Minami

  Japanese Society of Internal Medicine, Jan. 2023, Internal Medicine, 62(2) (2), 285 - 292

  Scientific journal


• Safety and Accuracy of Professional Continuous Glucose Monitoring in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

  Nagao S., Yakushijin K., Higashime A., Kawaguchi K., Watanabe M., Sakai R., Ichikawa H., Mizutani Y., Goto H., Kakiuchi S., Kurata K., Kitao A., Miyata Y., Imamura Y., Hirota Y., Takahashi M., Kawamoto S., Yamamoto K., Matsuoka H., Minami H.

  Asia-Pacific Blood and Marrow Transplantation Group, 2023, BLOOD CELL THERAPY / The official journal of APBMT, 6(2) (2), 54 - 60

  Scientific journal


• RUNX1 rearrangement in mature B-cell acute lymphoblastic leukemia with non-L3 morphology

  Katsuya Yamamoto, Akihito Kitao, Marika Watanabe, Hiroshi Kanehira, Miki Joyce, Yuri Hirakawa, Sakuya Matsumoto, Kimikazu Yakushijin, Hironobu Minami

  Japanese Society for Lymphoreticular Tissue Research, 2023, Journal of Clinical and Experimental Hematopathology, 63(4) (4), 240 - 245

  Scientific journal


• GSK3 inhibitor enhances gemtuzumab ozogamicin‐induced apoptosis in primary human leukemia cells by overcoming multiple mechanisms of resistance

  Aki Inase, Yimamu Maimaitili, Shiro Kimbara, Yu Mizutani, Yoshiharu Miyata, Shinya Ohata, Hisayuki Matsumoto, Akihito Kitao, Rina Sakai, Koji Kawaguchi, Ako Higashime, Shigeki Nagao, Keiji Kurata, Hideaki Goto, Shinichiro Kawamoto, Kimikazu Yakushijin, Hironobu Minami, Hiroshi Matsuoka

  Abstract In acute myeloid leukemia (AML), the heterogeneity of genetic and epigenetic characteristics makes treatment difficult. The prognosis for AML is therefore poor, and there is an urgent need for new treatments for this condition. Gemtuzumab ozogamicin (GO), the first antibody‐drug conjugate (ADC), targets the CD33 antigen expressed in over 90% of AML cases. GO therefore has the potential to counter the heterogeneity of AML patients. However, a major clinical problem is that drug resistance to GO diminishes its effect over time. Here, we report that the inhibition of glycogen synthase kinase 3 (GSK3) alone overcomes several forms of GO resistance at concentrations without antileukemic effects. The GSK3 inhibitors tested significantly enhanced the cytotoxic effect of GO in AML cell lines. We elucidated four mechanisms of enhancement: (1) increased expression of CD33, the target antigen of GO; (2) activation of a lysosomal function essential for hydrolysis of the GO linker; (3) reduced expression of MDR1 that eliminates calicheamicin, the payload of GO; and (4) reduced expression of the anti‐apoptotic factor Bcl‐2. A similar combination effect was observed against patient‐derived primary AML cells. Combining GO with GSK3 inhibitors may be efficacious in treating heterogeneous AML.

  Wiley, Dec. 2022, eJHaem, 4(1) (1), 153 - 164, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Data of programmed death-ligand 1 expression and VEGF: Nivolumab, bevacizumab and paclitaxel For HER2-negative metastatic breast cancer.

  Yukinori Ozaki, Junji Tsurutani, Toru Mukohara, Tsutomu Iwasa, Masato Takahashi, Yuko Tanabe, Hidetaka Kawabata, Norikazu Masuda, Manabu Futamura, Hironobu Minami, Koji Matsumoto, Kenichi Yoshimura, Shigehisa Kitano, Toshimi Takano

  The purpose was to explore potential biomarkers of the efficacy and toxicity of triple therapy of nivolumab, bevacizumab and paclitaxel in patients with HER2-negative metastatic breast cancer (MBC). Tumor tissues before treatment and blood samples at pretreatment, during and after treatment were collected. The serum samples were used to measure the concentrations of cytokines. Progression-free survival (PFS), overall survival (OS), and response were analyzed in association with the biomarker data using the Kaplan-Meier method and log-rank tests. Fifty patients were included in the biomarker analysis. Programmed death-ligand 1 (PD-L1) expression on tumor cells and immune cells were evaluated in tumor tissue samples using a Dako 28-8 immunohistochemistry assay and using a VENTANA SP142 immunohistochemistry assay. PD-L1 positive rates using anti-PD-L1 antibodies 28-8 (Combined positive score [CPS] ≥1) and SP142 (Immune cells [IC] ≥1) were 15% and 17%, respectively. The PFS and OS were not significantly different in the subgroups by PD-L1 expression. The median pretreatment vascular endothelial growth factor (VEGF)-A concentration was 116.1 pg/ml (range 0-740.23 pg/ml) on day 1 and decreased to <37 pg/ml on day 8 of cycle 1 in all patients. Subtypes (hormone receptor-positive HER2-negative or triple negative breast cancer), stage (recurrent or de novo stage IV) and liver metastasis (yes or no) were not significantly different between patients in VEGF-A high and VEGF-A low groups. PFS in the VEGF-A high group was similar to that in the VEGF-A low group.

  Dec. 2022, Data in brief, 45, 108558 - 108558, English, International magazine

  Scientific journal


• Global longitudinal strain is superior to ejection fraction for long‐term follow‐up after allogeneic hematopoietic stem cell transplantation

  Marika Watanabe, Kimikazu Yakushijin, Hidekazu Tanaka, Ruri Chijiki, Miki Saeki, Yuri Hirakawa, Hidetomo Takakura, Yutaro Usui, Hiroya Ichikawa, Rina Sakai, Sakuya Matsumoto, Shigeki Nagao, Yu Mizutani, Keiji Kurata, Akihito Kitao, Yoshiharu Miyata, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami

  Abstract Global longitudinal strain (GLS), a new cardiac parameter measured by the speckle‐tracking method, is reportedly more sensitive than ejection fraction (EF) in detecting slight cardiac dysfunction in heart failure patients. We validated the utility of GLS in allogeneic hematopoietic stem cell transplantation (HSCT) patients during a long‐term follow‐up. Medical records of patients who underwent allogeneic HSCT between 2013 and 2020 were reviewed retrospectively. We evaluated the last echocardiography performed before transplantation and those performed annually during the 5 years after transplantation. We also investigated newly diagnosed cardiac events, which developed after HSCT. Among 85 patients, 22 used cardioprotective drugs. The median follow‐up duration in surviving patients was 54.1 months (range, 2.9–92.6 months). GLS significantly decreased year by year, and patients taking cardioprotective agents tended to have a better GLS at 5 years than at 3 years, while EF did not change. Fifteen patients developed newly diagnosed cardiac events. Multivariate analysis revealed that low GLS and high serum ferritin levels at baseline were independently associated with the development of cardiac events. Therefore, we need a continuous follow‐up of cardiac function by GLS and prescription of cardioprotective drugs might be considered for HSCT patients with low GLS. Further research is warranted.

  Wiley, Nov. 2022, eJHaem, 4(1) (1), 192 - 198

  Scientific journal


• A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients

  Marika Watanabe, Kimikazu Yakushijin, Yohei Funakoshi, Goh Ohji, Hiroya Ichikawa, Hironori Sakai, Wataru Hojo, Miki Saeki, Yuri Hirakawa, Sakuya Matsumoto, Rina Sakai, Shigeki Nagao, Akihito Kitao, Yoshiharu Miyata, Taiji Koyama, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Tohru Murayama, Hiroshi Matsuoka, Hironobu Minami

  We previously reported that a second dose of BNT162b2 was safe and effective for allogeneic hematopoietic stem cell transplantation (HSCT) patients. Here, we investigated the safety and efficacy of a third dose of COVID-19 mRNA vaccine in allogeneic HSCT patients. Antibody titers against the S1 spike protein were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit. The previous study included 25 allogeneic HSCT patients who received two doses of BNT162b2. Following the exclusion of three patients because of the development of COVID-19 (n = 2) and loss to follow-up (n = 1), the study evaluated 22 allogeneic HSCT patients who received a third dose of COVID-19 mRNA vaccine (BNT162b2 [n = 15] and mRNA-1273 [n = 7]). Median age at the time of the first vaccination was 56 (range, 23–71) years. Five patients were receiving immunosuppressants at the third vaccination, namely calcineurin inhibitors (CI) alone (n = 1), steroids alone (n = 2), or CI combined with steroids (n = 2). Twenty-one patients (95%) seroconverted after the third dose. None of our patients had serious adverse events, new-onset graft-versus-host disease (GVHD), or GVHD exacerbation after vaccination. A third dose of the BNT162b2 and mRNA-1273 COVID-19 vaccines was safe and effective for allogeneic HSCT patients.

  MDPI AG, Oct. 2022, Vaccines, 10(11) (11), 1830 - 1830, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Real-World Outcomes of Systemic Therapy in Japanese Patients with Cancer (Tokushukai REAl-World Data Project: TREAD): Study Protocol for a Nationwide Cohort Study

  Rai Shimoyama, Yoshinori Imamura, Kiyoaki Uryu, Takahiro Mase, Yoshiaki Fujimura, Maki Hayashi, Megu Ohtaki, Keiko Ohtani, Nobuaki Shinozaki, Hironobu Minami

  Cohort studies using large-scale databases have become increasingly important in recent years. The Tokushukai Medical Group is a leading medical group in Japan that includes 71 general hospitals nationwide from Hokkaido to Okinawa, with a total of 18,000 beds, and a unified electronic medical record system. This retrospective cohort study aims to evaluate the real-world outcomes of systemic therapy for Japanese patients with cancer using this merit of scale. All adult patients with cancer who received systemic therapy using a centrally registered chemotherapy protocol system at 46 hospitals from April 2010 to March 2020 will be identified (~48,850 patients). Key exclusion criteria include active double cancer and inadequate data extraction. Data will be obtained through electronic medical records, diagnosis procedure combination data, medical prescription data, and the national cancer registration system that includes sociodemographic variables, diagnostic and laboratory tests, concomitant drug prescriptions, cost, and overall survival. Kaplan–Meier estimates will be calculated for time-to-event analyses. Stratified/conventional Cox proportional hazards regression analyses will be conducted to examine the relationships between overall survival and related factors. Our findings provide important insights for future research directions, policy initiatives, medical guidelines, and clinical decision-making.

  MDPI AG, Oct. 2022, Healthcare, 10(11) (11), 2146 - 2146

  Scientific journal


• Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

  Shinya Rai, Won Seog Kim, Kiyoshi Ando, Ilseung Choi, Koji Izutsu, Norifumi Tsukamoto, Masahiro Yokoyama, Kunihiro Tsukasaki, Junya Kuroda, Jun Ando, Michihiro Hidaka, Youngil Koh, Hirohiko Shibayama, Toshiki Uchida, Deok Hwan Yang, Kenji Ishitsuka, Kenichi Ishizawa, Jin Seok Kim, Hong Ghi Lee, Hironobu Minami, Hyeon Seok Eom, Mitsutoshi Kurosawa, Jae Hoon Lee, Jong Seok Lee, Won Sik Lee, Hirokazu Nagai, Takero Shindo, Dok Hyun Yoon, Shinichiro Yoshida, Mireille Gillings, Hiroshi Onogi, Kensei Tobinai

  Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDAC. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval : 30.9-61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were two CR and five partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AE) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥3 AE emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AE were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat could be a new therapeutic option in patients with R/R PTCL (clinicaltrials gov. Identifier: NCT02953652).

  Ferrata Storti Foundation (Haematologica), Oct. 2022, Haematologica, 108(3) (3), 811 - 821

  Scientific journal


• 切除不能進行/転移・再発固形癌に対するePROモニタリングの有用性を検証する比較試験

  平 成人, 南 博信, 岩田 広治, 弦間 昭彦, 室 圭, 市原 英基, 加藤 恭子, 木川 雄一郎, 清田 尚臣, 久保田 馨, 建石 良介, 中田 晃暢, 中村 圭一郎, 成田 有季哉, 堀田 勝幸

  (一社)日本癌治療学会, Oct. 2022, 日本癌治療学会学術集会抄録集, 60回, O48 - 3, English


• Safety and antitumor activity of copanlisib in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma: a phase Ib/II study

  Noriko Fukuhara, Dai Maruyama, Kiyohiko Hatake, Hirokazu Nagai, Shinichi Makita, Kenjiro Kamezaki, Toshiki Uchida, Shigeru Kusumoto, Junya Kuroda, Chisako Iriyama, Masamitsu Yanada, Norifumi Tsukamoto, Youko Suehiro, Hironobu Minami, Jose Garcia-Vargas, Barrett H. Childs, Masanobu Yasuda, Shigeo Masuda, Toshiaki Tsujino, Yui Terao, Kensei Tobinai

  Abstract The safety, efficacy, and pharmacokinetics of copanlisib were evaluated in this phase Ib/II study in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL). The primary endpoint was safety at the recommended dose; efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival. In phase Ib, patients received copanlisib 45 mg intravenously on days 1, 8, and 15 of a 28-day cycle, and when tolerated, consecutive patients received copanlisib 60 mg. As no dose-limiting toxicities occurred at the 45 mg (n = 3) or 60 mg (n = 7) dose in phase Ib, the recommended dose for Japanese patients was determined to be 60 mg, and this dose was used in phase II (n = 15). Although all patients experienced at least one treatment-emergent adverse event (TEAE), with hyperglycemia being the most common AE, no AE-related deaths were reported. The ORR was 68.0% (17/25 patients), median PFS was 302 (95% CI 231–484) days, and the duration of response was 330 (range 65–659) days. The pharmacokinetic properties of copanlisib were similar between Japanese and non-Japanese patients. Overall, copanlisib 60 mg had an acceptable safety profile and showed promising antitumor activity in Japanese patients with relapsed/refractory indolent NHL.

  Springer Science and Business Media LLC, Sep. 2022, International Journal of Hematology, 117(1) (1), 100 - 109

  Scientific journal


• Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B)

  Yukinori Ozaki, Junji Tsurutani, Toru Mukohara, Tsutomu Iwasa, Masato Takahashi, Yuko Tanabe, Hidetaka Kawabata, Norikazu Masuda, Manabu Futamura, Hironobu Minami, Koji Matsumoto, Kenichi Yoshimura, Shigehisa Kitano, Toshimi Takano

  BACKGROUND: Preclinical models revealed potential synergistic effects of programmed cell death-1 inhibitors and anti-vascular endothelial growth factor (VEGF) antibodies. Therefore, we investigated the use of nivolumab, bevacizumab, and paclitaxel triple therapy for metastatic breast cancer. METHODS: This phase 2, multicentre, single-arm study (NEWBEAT) investigated the safety and efficacy of first-line nivolumab, paclitaxel, and bevacizumab in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer, regardless of programmed cell death-ligand 1 expression. The primary end-point was objective response rate. Key secondary end-points included progression-free survival, overall survival, and toxicities. A biomarker study evaluated tumour programmed cell death-ligand 1 expression and serum VEGF-A levels. RESULTS: Between February 2018 and October 2018, 57 patients were enrolled. An objective response rate was seen in 39/56 patients (70%, 95% confidence interval [CI]: 55.9-81.2%), meeting the primary end-point. The objective response rate was 74% in patients with hormone receptor-positive breast cancer versus 59% in patients with triple-negative breast cancer. The median progression-free survival and overall survival were 14.0 (95% CI 11.0-16.3) and 32.5 (95% CI 26.0-not evaluable) months, respectively (median follow-up: 29.5 months). Grade 3/4 adverse drug reactions occurred in 33 of 57 patients (58%). There were no grade 5 adverse events. Immune-related adverse events occurred in 43 of 57 patients (75%), with grade 3/4 events in eight patients (14%). Biomarker analysis showed that tumour programmed cell death-ligand 1 expression was not correlated with the efficacy of triple therapy. Efficacy outcomes were similar between the serum VEGF-high and VEGF-low groups. CONCLUSIONS: First-line nivolumab, bevacizumab, and paclitaxel therapy showed promising efficacy and manageable toxicity in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer.

  Elsevier BV, Aug. 2022, European Journal of Cancer, 171, 193 - 202, English, International magazine

  Scientific journal


• Safety and Efficacy of Blinatumomab in Japanese Adult and Pediatric Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Final Results from an Expansion Cohort

  Hiroaki Goto, Chitose Ogawa, Hiroatsu Iida, Keizo Horibe, Iekuni Oh, Satoru Takada, Yoshinobu Maeda, Hironobu Minami, Yasuhiro Nakashima, Joan D. Morris, William Kormany, Yuqi Chen, Toshihiro Miyamoto

  <b><i>Introduction:</i></b> The safety and efficacy of blinatumomab, a CD19/CD3 bispecific T-cell engager (BiTE®) molecule, was evaluated in an expansion cohort of the phase 1b/2 study (NCT02412306) in Japanese adult (<i>n</i> = 14) and pediatric (<i>n</i> = 17) patients with relapsed/refractory Philadelphia-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). <b><i>Materials and methods:</i></b> Globally recommended blinatumomab doses were administered to adult (9–28 μg/day) and pediatric (5–15 μg/m²/day) patients. Primary endpoint was the incidence of treatment-emergent adverse events (TEAEs) and treatment-related AEs. <b><i>Results:</i></b> All adult and pediatric patients experienced ≥1 TEAE. Grade ≥3 TEAEs were observed in 11 (79%) adult and 15 (88%) pediatric patients. Blinatumomab was discontinued in 1 (6%) pediatric patient due to treatment-related grade 4 cytokine release syndrome. Fatal AEs such as disease progression and multiple-organ dysfunction syndrome, which were not treatment-related, were reported in 2 (12%) pediatric patients. Eleven (79%) adults achieved complete remission (CR)/CR with partial hematological recovery (CRh) within the first two blinatumomab cycles. Nine of 10 adult patients with CR/CRh and evaluable minimal residual disease (MRD) achieved MRD response. CR/CRh was achieved by 5 (29%) pediatric patients, of which two had MRD response. <b><i>Conclusion:</i></b> In conclusion, blinatumomab was safe and efficacious in Japanese patients with relapsed/refractory BCP ALL.

  S. Karger AG, Jul. 2022, Acta Haematologica, 145(6) (6), 592 - 602

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• Promising Efficacy of a Third Dose of mRNA SARS-CoV-2 Vaccination in Patients Treated with Anti-CD20 Antibody Who Failed 2-Dose Vaccination

  Yohei Funakoshi, Kimikazu Yakushijin, Goh Ohji, Wataru Hojo, Hironori Sakai, Marika Watanabe, Akihito Kitao, Yoshiharu Miyata, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Taiji Koyama, Yoshinori Imamura, Naomi Kiyota, Hiroshi Matsuoka, Yasuko Mori, Hironobu Minami

  Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells, but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for the S1 protein after a third vaccination in 22 patients treated with the anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving the seroconversion rate in patients treated with the anti-CD20 antibody who failed standard two-dose vaccination.

  MDPI AG, Jun. 2022, Vaccines, 10(6) (6), 965 - 965, English, International magazine

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• Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs

  Gérard Milano, Federico Innocenti, Hironobu Minami

  Abstract Irinotecan is a topoisomerase inhibitor, widely used in treatment of malignancies including pancreatic ductal adenocarcinoma (PDAC) as part of the FOLFIRINOX regimen prescribed as a first‐line treatment in several countries. However, irinotecan has not been successfully introduced as a second‐line treatment for pancreatic cancer and few randomized clinical studies have evaluated its added value. Efficacy of liposomal irinotecan (nal‐IRI) combined with 5‐fluorouracil and leucovorin (5‐FU/LV) was reported in the phase III NAPOLI‐1 trial in metastatic PDAC following failure of gemcitabine‐based therapy. Several features of nal‐IRI pharmacokinetics (PK) could result in better outcomes versus nonliposomal irinotecan. Irinotecan is a prodrug that is converted to active SN‐38 by carboxylesterase enzymes and inactivated by cytochrome P450 3A4/3A5. SN‐38 is inactivated by UGT1A1 enzymes. Individual variations in their expression and activity could influence enhanced localized irinotecan activity and toxicity. Liposomal irinotecan exploits the enhanced permeability and retention effect in cancer, accumulating in tumor tissues. Liposomal irinotecan also has a longer half‐life and higher area under the concentration‐time curve (0–∞) than nonliposomal irinotecan, as the liposomal formulation protects cargo from premature metabolism in the plasma. This results in irinotecan activation in tumor tissue, leading to enhanced cytotoxicity. Importantly, despite the longer exposure, overall toxicity for nal‐IRI is no worse than nonliposomal irinotecan. Liposomal irinotecan exemplifies how liposomal encapsulation of a chemotherapeutic agent can alter its PK properties, improving clinical outcomes for patients. Liposomal irinotecan is currently under investigation in other malignancies including biliary tract cancer (amongst other gastrointestinal cancers), brain tumors, and small‐cell lung cancer.

  Wiley, May 2022, Cancer Science, 113(7) (7), 2224 - 2231

  Scientific journal


• Transition of the PD‑1 occupancy of nivolumab on T cells after discontinuation and response of nivolumab re‑challenge

  Taku Nose, Yohei Funakoshi, Hirotaka Suto, Yoshiaki Nagatani, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Hironobu Minami

  Although nivolumab is administered every two or four weeks, high programmed cell death-1 (PD-1) binding of nivolumab on T cells lasting for several months has been reported. A relationship between the PD-1 occupancy rate on T-cells and the efficacy of nivolumab is not yet fully understood. The present study used flow cytometric analyses to determine the time-dependence of PD-1 occupancy in five patients who discontinued nivolumab. The relationship between PD-1 occupancy at relapse and the efficacy of re-challenge was also studied. Occupancies after discontinuation were measured at a total of 32 points. The data indicated that it took 32.4 and 48.9 weeks to decrease occupancy by 50 and 70%, respectively. Subsequently, two patients had recurrence and were re-challenged with nivolumab. At that time, one patient had 70.8% occupancy while the other had 6.6%. Treatment was effective only for the patient with lower occupancy. Overall, the present study suggests that re-challenge with nivolumab may be efficacious in patients with low occupancy at recurrence.

  Spandidos Publications, Apr. 2022, Molecular and Clinical Oncology, 16(5) (5), 104 - 104, English, International magazine

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• アルデヒド脱水素酵素応答性turn-on型蛍光プローブを用いるがん幹細胞の可視化

  三木 康嗣, 麻植 雅裕, 鈴木 叶瑛, 山中 大暉, 植田 誉志史, 森 泰生, 岡本 葵, 船越 洋平, 南 博信, 大江 浩一

  日本分子イメージング学会, Apr. 2022, JSMI Report, 15(2) (2), 77 - 77, Japanese


• アルデヒド脱水素酵素応答性turn-on型蛍光プローブを用いるがん幹細胞の可視化

  三木 康嗣, 麻植 雅裕, 鈴木 叶瑛, 山中 大暉, 植田 誉志史, 森 泰生, 岡本 葵, 船越 洋平, 南 博信, 大江 浩一

  日本分子イメージング学会, Apr. 2022, JSMI Report, 15(2) (2), 126 - 126, Japanese


• Safety and immunogenicity of the COVID-19 vaccine BNT162b2 in patients undergoing chemotherapy for solid cancer

  Yohei Funakoshi, Kimikazu Yakushijin, Goh Ohji, Wataru Hojo, Hironori Sakai, Ryo Takai, Taku Nose, Shinya Ohata, Yoshiaki Nagatani, Taiji Koyama, Akihito Kitao, Meiko Nishimura, Yoshinori Imamura, Naomi Kiyota, Kenichi Harada, Yugo Tanaka, Yasuko Mori, Hironobu Minami

  BACKGROUND: Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. METHODS: We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. RESULTS: Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. CONCLUSION: Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.

  Elsevier BV, Apr. 2022, Journal of Infection and Chemotherapy, 28(4) (4), 516 - 520, English, International magazine

  Scientific journal


• Identification of Breast Cancer Stem Cells Using a Newly Developed Long-acting Fluorescence Probe, C5S-A, Targeting ALDH1A1

  AOI OKAMOTO, YOHEI FUNAKOSHI, MASAHIRO OE, RYO TAKAI, HIROTAKA SUTO, YOSHIAKI NAGATANI, MEIKO NISHIMURA, YOSHINORI IMAMURA, TOMONARI KUNIHISA, NAOMI KIYOTA, KOJI MIKI, KOUICHI OHE, HIROKAZU TANINO, HIRONOBU MINAMI

  BACKGROUND/AIM: Aldehyde dehydrogenase (ALDH) 1A1 is a well-known marker for cancer stem cells (CSCs), characterized by self-renewal capacity and multidrug resistance in breast cancer. We developed a near-infrared turn-on fluorescence probe for ALDH1A1, C5S-A, which is suitable for observing and analyzing viable cells. Here, we demonstrated the utility of C5S-A in CSC research using breast cancer cell lines. MATERIALS AND METHODS: To evaluate concordance between C5S-A and conventional stem cell markers, breast cancer cells sorted for ALDEFLUOR-positive cells and for CD44+/CD24- cell populations were stained with C5S-A. Tumorigenicity of C5S-A-positive cells was examined by mammosphere formation assay and subcutaneous transplantation to immunodeficient mice. Additionally, to determine how long fluorescence from a single staining remained observable, we cultured breast cancer cells for 5 days after C5S-A staining. We then evaluated whether C5S-A-positive cells possessed resistance to cytotoxic drugs by chronological imaging. RESULTS: C5S-A staining showed good concordance with conventional breast CSC markers, and good utility for research into CSC characteristics in breast cancer cell lines, including tumorigenesis. Additionally, C5S-A was observable for more than 3 days with a single staining. Using this property, we then confirmed that C5S-A-positive cells possessed resistance to cytotoxic drugs, which is one of the characteristics of CSCs. CONCLUSION: We showed that C5S-A is suitable for CSC research using breast cancer cell lines, and confirmed its utility in observing cells over time.

  International Institute of Anticancer Research, Feb. 2022, Anticancer Research, 42(3) (3), 1199 - 1205, English, International magazine

  Scientific journal

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• Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary

  J. Tanizaki, K. Yonemori, K. Akiyoshi, H. Minami, H. Ueda, Y. Takiguchi, Y. Miura, Y. Segawa, S. Takahashi, Y. Iwamoto, Y. Kidera, K. Fukuoka, A. Ito, Y. Chiba, K. Sakai, K. Nishio, K. Nakagawa, H. Hayashi

  BACKGROUND: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP. PATIENTS AND METHODS: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1. RESULTS: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed. CONCLUSIONS: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.

  Elsevier BV, Feb. 2022, Annals of Oncology, 33(2) (2), 216 - 226, English, International magazine

  Scientific journal


• A phase I study of LCL161, a novel oral pan‐inhibitor of apoptosis protein (IAP) antagonist, in Japanese patients with advanced solid tumors

  Sachi Morita, Hironobu Minami, Ayako Mitsuma, Masanori Toyoda, Naomi Kiyota, Yuichi Ando

  Abstract Introduction LCL161 is a novel oral pan‐inhibitor of apoptosis protein (IAP) antagonist. LCL161 enhances paclitaxel activity in cell lines and xenograft models. A phase I study of LCL161 combined with paclitaxel for the treatment of Japanese patients with advanced solid tumors was conducted. Methods Each patient received oral LCL161 in a single weekly dose on days 1, 8, and 15 of a 21‐day treatment cycle. In the second cycle, patients received a combination treatment with weekly paclitaxel (80 mg/m²) whenever possible. A Bayesian logistic regression model by escalation with the overdose control principle was used. Results Nine patients were treated with LCL161 at a dose of 600 mg (five patients) or 1200 mg (four patients). Seven patients were treated with LCL161 plus paclitaxel, and two patients received only LCL161 monotherapy. Because this study was terminated early due to a change in the LCL161 development strategy, the maximum tolerated dose (MTD) was not determined. One patient treated with LCL161 monotherapy at a dose of 1200 mg experienced dose limitind toxicity (grade 3 maculopapular rash). Another patient died on day 86 of bacterial pneumonia, which was suspected to be related to the study treatment. The most common serious adverse events were infections and infestations (n = 3). Conclusion The present study suggests that the risk of infection may increase when LCL161 is combined with paclitaxel, but other conclusions about the MTD, pharmacokinetic profile, and preliminary activity of the combination of LCL161 plus paclitaxel were not drawn.

  Wiley, Jan. 2022, Asia-Pacific Journal of Clinical Oncology, 18(5) (5), e427-e434, English, International magazine

  Scientific journal


• Apixaban in Japanese patients with cancer-associated venous thromboembolism: a multi-center phase II trial

  Yoshinori Imamura, Kazunori Otsui, Kenta Mori, Koichi Kitagawa, Hideaki Okada, Akito Hata, Hidetoshi Hayashi, Taku Nose, Shinya Ohata, Yoshiharu Miyata, Yohei Funakoshi, Masanori Toyoda, Kimikazu Yakushijin, Naomi Kiyota, Hiroshi Matsuoka, Hironobu Minami

  BACKGROUND: Recent pivotal phase III trials involving direct oral anticoagulant (DOAC) versus low molecular weight heparin have demonstrated the utility of DOACs in Western patients with cancer-associated venous thromboembolism (VTE). However, these trials did not include Japanese patients. This phase II trial evaluated the safety and efficacy of apixaban in Japanese patients with cancer-associated VTE (UMIN000028447). METHOD AND RESULTS: Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. The primary endpoint was the incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. The study was terminated due to safety concerns after enrolling 27 patients. Median age was 71 years; median body weight was 51.3 kg; and major primary tumor sites were the gastrointestinal tract (26%) and lung (19%). During the median follow-up period of 5.4 months, major or CRNM bleeding occurred in in 26% of patients (major, n = 5; CRNM, n = 2; 95% confidence interval, 11-46%). No recurrent VTE or VTE-related death occurred. Estimated overall survival at 6 months was 68%. CONCLUSION: This study demonstrated the excessive bleeding risk of apixaban at the standard dose in Japanese patients with cancer-associated VTE.

  Springer Science and Business Media LLC, Jan. 2022, International Journal of Hematology, 115(4) (4), 499 - 507, English, Domestic magazine

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• The Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Japanese Patients after Allogeneic Stem Cell Transplantation

  Marika Watanabe, Kimikazu Yakushijin, Yohei Funakoshi, Goh Ohji, Wataru Hojo, Hironori Sakai, Miki Saeki, Yuri Hirakawa, Sakuya Matsumoto, Rina Sakai, Shigeki Nagao, Akihito Kitao, Yoshiharu Miyata, Taiji Koyama, Yasuyuki Saito, Shinichiro Kawamoto, Mitsuhiro Ito, Tohru Murayama, Hiroshi Matsuoka, Hironobu Minami

  Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of the COVID-19 vaccine in HSCT patients remain to be investigated. We prospectively evaluated the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) had seroconversion of anti-S1 IgG. The median optical density of antibody levels in HSCT patients with low IgG levels (<600 mg/dL), steroid treatment, or low lymphocytes (<1000/μL) was significantly lower than that in the other HSCT patients. There were no serious adverse events (>Grade 3) and no new development or exacerbation of graft-versus-host disease after vaccination. We concluded that the BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.

  MDPI AG, Jan. 2022, Vaccines, 10(2) (2), 158 - 158, English, International magazine

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• Marked recovery of cardiac function by chemotherapy and autologous stem cell transplantation of a patient with heart failure with preserved ejection fraction due to primary amyloid light-chain amyloidosis: a case report

  Hidekazu Tanaka, Akihito Kitao, Hironobu Minami, Ken-Ichi Hirata

  Abstract Background Cardiac involvement of amyloid light-chain (AL) amyloidosis is strongly associated with poor outcome, but the early detection of cardiac involvement of AL amyloidosis can be challenging. Case summary We present a case of 49-year-old-female with heart failure with preserved ejection fraction. Echocardiography revealed normal left ventricular (LV) ejection fraction of 63% and an enlarged left atrium with a left atrial volume index (LAVI) of 54 mL/m2. Mild LV hypertrophy with an interventricular septum of 12.3 mm and posterior wall thickness of 11.0 mm was observed, and Doppler-derived LV diastolic filling showed a restrictive filling pattern. The conventional echocardiographic findings did not unequivocally indicate typical cardiac amyloidosis, but global longitudinal strain (GLS) was as low as 14.2%, and an apical sparing pattern was observed with relative apical longitudinal strain of 1.11. Finally, the patient was diagnosed as primary AL amyloidosis including histological examination of the endomyocardial specimen. After treatment with a regime of bortezomib and dexamethasone followed by high-dose melphalan followed by autologous peripheral blood stem cell transplantation (auto-PBSCT), Doppler-derived LV diastolic filling improved to normal filling pattern, and left atrial size had also decreased with an LAVI of 31 mL/m2. Moreover, GLS improved to 19.8%, and the apical sparing pattern had disappeared with relative apical longitudinal strain of 0.62. The patient has been asymptomatic during 18-month follow-up after auto-PBSCT, and recovered LV function has been maintained. Discussion An earlier diagnosis of cardiac amyloidosis by using apical sparing may therefore allow for earlier treatment intervention for AL amyloidosis.

  Oxford University Press (OUP), Jan. 2022, European Heart Journal - Case Reports, 6(3) (3)

  Scientific journal


• Limited increase in antibody titers following mRNA SARS-CoV-2 vaccination for more than 3 years after final dose of anti-CD20 antibody

  Yohei Funakoshi, Kimikazu Yakushijin, Goh Ohji, Wataru Hojo, Hironori Sakai, Marika Watanabe, Miki Saeki, Yuri Hirakawa, Rina Sakai, Sakuya Matsumoto, Yu Mizutani, Akihito Kitao, Yoshiharu Miyata, Yasuyuki Saito, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Meiko Nishimura, Yoshinori Imamura, Naomi Kiyota, Hiroshi Matsuoka, Yasuko Mori, Hironobu Minami

  We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.

  Springer Science and Business Media LLC, Jan. 2022, International Journal of Hematology, 115(1) (1), 7 - 10, English, Domestic magazine

  Scientific journal


• Results from a First-in-Human Phase I Study of Siremadlin (HDM201) in Patients with Advanced Wild-Type TP53 Solid Tumors and Acute Leukemia

  Eytan M. Stein, Daniel J. DeAngelo, Jörg Chromik, Manik Chatterjee, Sebastian Bauer, Chia-Chi Lin, Cristina Suarez, Filip de Vos, Neeltje Steeghs, Philippe A. Cassier, David Tai, Jean-Jacques Kiladjian, Noboru Yamamoto, Rogier Mous, Jordi Esteve, Hironobu Minami, Stephane Ferretti, Nelson Guerreiro, Christophe Meille, Rajkumar Radhakrishnan, Bernard Pereira, Luisa Mariconti, Ensar Halilovic, Claire Fabre, Cecilia Carpio

  Abstract Purpose: This phase I, dose-escalation study investigated the recommended dose for expansion (RDE) of siremadlin, a p53–MDM2 inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers. Patients and Methods: Initial dosing regimens were: 1A (day 1; 21-day cycle; dose 12.5–350 mg) and 2A (days 1–14; 28-day cycle; dose 1–20 mg). Alternative regimens included 1B (days 1 and 8; 28-day cycle) and 2C (days 1–7; 28-day cycle). The primary endpoint was incidence of dose-limiting toxicities (DLT) during cycle 1. Results: Overall, 115 patients with solid tumors and 93 with hematologic malignancies received treatment. DLTs occurred in 8/92 patients with solid tumors and 10/53 patients with hematologic malignancies. In solid tumors, an RDE of 120 mg was defined in 1B. In hematologic tumors, RDEs were defined in 1A: 250 mg, 1B: 120 mg, and 2C: 45 mg. More patients with hematologic malignancies compared with solid tumors experienced grade 3/4 treatment-related adverse events (71% vs. 45%), most commonly resulting from myelosuppression. These were more frequent and severe in patients with hematologic malignancies; 22 patients exhibited tumor lysis syndrome. Overall response rates at the RDEs were 10.3% [95% confidence interval (CI), 2.2–27.4] in solid tumors and 4.2% (95% CI, 0.1–21.1), 20% (95% CI, 4.3–48.1), and 22.2% (95% CI, 8.6–42.3) in acute myeloid leukemia (AML) in 1B, 1A, and 2C, respectively. Conclusions: A common safety profile was identified and preliminary activity was noted, particularly in AML. Comprehensive investigation of dosing regimens yielded recommended doses/regimens for future combination studies.

  American Association for Cancer Research (AACR), Dec. 2021, Clinical Cancer Research, 28(5) (5), 870 - 881

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• Serum Cytokine Profiles of Rapid Recovery Patients with COVID-19: Series of 6 Cases.

  Goh Ohji, Yohei Funakoshi, Kei Ebisawa, Kimikazu Yakushijin, Yu Arakawa, Jun Saegusa, Shinichiro Kawamoto, Takamitsu Imanishi, Yasuko Mori, Kentaro Iwata, Hironobu Minami

  COVID-19 patients reveal various clinical manifestations; however, the specific mechanisms and factors contributing to rapid recovery remain unclear. We performed serum cytokine profiling using a bead-based immunoassay in six COVID-19 patients with mild symptoms who experienced rapid recovery. All patients had fever that resolved within 4 days. During the study, the interferon gamma-related protein 10 (IP-10) level rapidly increased initially, and then rapidly decreased in all six patients. Similarly, the interferon (IFN)-λ 2/3 levels rapidly increased initially, and then decreased in five of the six patients. IP-10 and IFN-λ2/3 may play a key role in the rapid recovery of mild COVID-19.

  Oct. 2021, The Kobe journal of medical sciences, 67(2) (2), E55-E60, English, Domestic magazine

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  Link to Kobe Univ. Repository (Kernel)


• Microsatellite instability-high colorectal cancer patient-derived xenograft models for cancer immunity research

  Hirotaka Suto, Yohei Funakoshi, Yoshiaki Nagatani, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Hisayuki Matsumoto, Shinwa Tanaka, Ryo Takai, Hiroshi Hasegawa, Kimihiro Yamashita, Takeru Matsuda, Yoshihiro Kakeji, Hironobu Minami

  Context: There is an increasing demand for appropriate preclinical mice models for evaluating the efficacy of cancer immunotherapies. Aims: Therefore, we established a humanized patient-derived xenograft (PDX) model using microsatellite instability-high (MSI-H) colorectal cancer (CRC) tissues and patient-derived peripheral blood mononuclear cells (PBMCs). Subjects and Methods: The CRC tissues of patients scheduled for surgery were tested for MSI status, and CRC tumors were transplanted into NOD/LtSz-scid/IL-2Rg-/-(NSG) mice to establish MSI-H PDX models. PDX tumors were compared to the original patient tumors in terms of histological and genetic characteristics. To humanize the immune system of MSI-H PDX models, patient PBMCs were injected through the tail vein. Results: PDX models were established from two patients with MSI-H CRC; one patient had a germline mutation in MLH1 (c.1990-2A > G), and the other patient had MLH1 promoter hypermethylation. PDX with the germline mutation was histologically similar to the patient tumor, and retained the genetic characteristics, including MSI-H, deficient mismatch repair (dMMR), and MLH1 mutation. In contrast, the histological features of the other PDX from a tumor with MLH1 promoter hypermethylation were clearly different from those of the original tumor, and MLH1 promoter hypermethylation and MSI-H/dMMR were lost in the PDX. When T cells from the same patient with MLH1 mutation were injected into the PDX through the tail vein, they were detected in the PDX tumor. Conclusions: The MSI-H tumor with an MMR mutation is suitable for MSI-H PDX model generation. The PBMC humanized MSI-H PDX has the potential to be used as an efficient model for cancer immunotherapy research.

  Medknow, Oct. 2021, Journal of Cancer Research and Therapeutics, 17(6) (6), 1358 - 1369, English, International magazine

  Scientific journal


• Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study

  Tomokazu Aoki, Naoki Kagawa, Kazuhiko Sugiyama, Toshihiko Wakabayashi, Yoshiki Arakawa, Shigeru Yamaguchi, Shota Tanaka, Eiichi Ishikawa, Yoshihiro Muragaki, Motoo Nagane, Mitsutoshi Nakada, Satoshi Suehiro, Nobuhiro Hata, Junichiro Kuroda, Yoshitaka Narita, Yukihiko Sonoda, Yasuo Iwadate, Manabu Natsumeda, Yoichi Nakazato, Hironobu Minami, Yuki Hirata, Shunsuke Hagihara, Ryo Nishikawa

  Abstract Background An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. Methods Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. Results Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27–66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4–17.7) and 1.5 (1.4–1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3–4 and 2.0% for Grade 5; most adverse events resolved and were manageable. Conclusions The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. Clinical Trial Registration JapicCTI-152967.

  Springer Science and Business Media LLC, Sep. 2021, International Journal of Clinical Oncology, 26(12) (12), 2205 - 2215

  Scientific journal


• Docetaxel plus cisplatin in recurrent and/or metastatic non-squamous-cell head and neck cancer: a multicenter phase II trial

  Yoshinori Imamura, Kaoru Tanaka, Naomi Kiyota, Hidetoshi Hayashi, Ichiro Ota, Akihito Arai, Shigemichi Iwae, Shujiro Minami, Katsunari Yane, Tomoko Yamazaki, Yoshiaki Nagatani, Masanori Toyoda, Takayuki Takahama, Kazuko Sakai, Kazuto Nishio, Naoki Otsuki, Ken-ichi Nibu, Hironobu Minami

  Springer Science and Business Media LLC, Sep. 2021, Medical Oncology, 38(11) (11)

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Cryptic insertion of CBFB into MYH11 leading to a type D fusion in acute myeloid leukemia with normal karyotype

  Katsuya Yamamoto, Keiji Kurata, Akihito Kitao, Rina Sakai, Sakuya Matsumoto, Hisayuki Matsumoto, Jun Saegusa, Kimikazu Yakushijin, Hironobu Minami

  Wiley, Sep. 2021, International Journal of Laboratory Hematology, 44(1) (1), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• GSK3阻害剤は、複数の薬剤耐性を1剤で克服し、初代AML細胞に対してゲムツズマブオゾガマイシンによる細胞死を増強する

  稲瀬 安希, 後藤 秀彰, 南 博信, 松岡 広

  (一社)日本癌学会, Sep. 2021, 日本癌学会総会記事, 80回, [J17 - 4], English


• NRAS c.38G>A変異により発症したRARAの相互転座を伴わない急性前骨髄球性白血病(Novel NRAS c.38G>A mutation causes RARA translocation negative acute promyelocytic-like leukemia)

  後藤 秀彰, 藥師神 公和, 足立 陽子, 松本 久幸, 山本 克也, 松本 咲耶, 東目 亜湖, 川口 晃司, 倉田 啓史, 松岡 広, 南 博信

  (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, PS - 7, English


• 新たなKMT2A/EPS15融合遺伝子発現とt(1;11)(p32;q23)転座を認めたFLT3変異陽性B細胞性急性リンパ性白血病(Expression of a novel KMT2A/EPS15 fusion gene in FLT3 mutation-positive B-ALL with t(1;11)(p32;q23))

  山本 克也, 藥師神 公和, 水谷 優, 渡部 まりか, 後藤 秀彰, 東目 亜湖, 宮田 吉晴, 北尾 章人, 松本 久幸, 三枝 淳, 松岡 広, 南 博信

  (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, PS - 2, English


• 慢性GVHDに対する肝移植後の一過性末梢血マクロキメリズム(Transient macrochimerism following a liver transplant for hepatic GVHD after an allo-PBSCT)

  渡部 まりか, 藥師神 公和, 蔵満 薫, 福本 巧, 林 宏樹, 安冨 栄一郎, 千々木 瑠里, 高倉 嗣丈, 坂井 里奈, 松本 咲耶, 長尾 茂輝, 水谷 優, 宮田 吉晴, 北尾 章人, 川本 晋一郎, 山本 克也, 松岡 広, 南 博信

  (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, PS - 6, English


• 自家造血幹細胞移植患者におけるsynbiotics投与の有効性についての臨床試験(Efficacy of synbiotics in auto-PBSCT patients: a prospective, double-blind, placebo-controlled trial)

  水谷 優, 川本 晋一郎, 丹田 雅明, 曽我 昭宏, 脇田 久美子, 田渕 聡子, 高橋 路子, 土井 久容, 千々木 瑠里, 高倉 嗣丈, 川口 晃司, 東目 亜湖, 渡部 まりか, 市川 大哉, 松本 咲耶, 坂井 里奈, 後藤 秀彰, 倉田 啓史, 垣内 誠司, 宮田 吉晴, 瓜生 恭章, 乾 由美子, 北尾 章人, 藥師神 公和, 松岡 広, 南 博信

  (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, OS2 - 4, English


• 同種移植におけるflash sensor-based glucose monitoringの安全性の検討(Safety and accuracy of flash sensor-based glucose monitoring devise in patients after Allo-HSCT)

  長尾 茂輝, 藥師神 公和, 東目 亜湖, 川口 晃司, 渡部 まりか, 坂井 里奈, 水谷 優, 垣内 誠司, 倉田 啓史, 北尾 章人, 宮田 吉晴, 今村 善宣, 廣田 勇士, 高橋 路子, 川本 晋一郎, 山本 克也, 松岡 広, 南 博信

  (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, OS3 - 5, English


• 【がんゲノム医療を検証する】がん遺伝子パネル検査の出口戦略

  南 博信, 西尾 和人, 吉田 輝彦, 中村 祐輔

  (株)メディカルレビュー社, Sep. 2021, がん分子標的治療, 19(1) (1), 65 - 71, Japanese


• Incidence of venous thromboembolism in patients with solid cancers in Japan: retrospective study of 2735 patients.

  Taku Nose, Yoshinori Imamura, Shinya Ohata, Shiro Kimbara, Yoshiharu Miyata, Yasuko Hyogo, Yoshimi Fujishima, Yohei Funakoshi, Masanori Toyoda, Naomi Kiyota, Hironobu Minami

  BACKGROUND: The incidence of cancer-associated venous thromboembolism (CA-VTE) in Japan has not been fully investigated. METHODS AND RESULTS: Clinicopathological information from patients with solid malignancies who first visited our department between November 2011 and March 2018 were retrospectively reviewed from medical records. The primary outcome was incidence of CA-VTE, defined as deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). On median follow-up of 187 days, 91 of 2735 patients (3.3%) developed CA-VTE during their clinical course, giving an incidence rate of 40.7 per 1000 person-years. Of the 91 patients, 75 (82%) were diagnosed with DVT alone, 6 (7%) with PE alone, and 10 (11%) with both DVT and PE. CA-VTE was most frequent in non-small cell lung cancer (10.8%), followed by cancer of unknown origin (5.8%). Forty-four patients (48%) had one or more symptoms at the initial diagnosis of VTE. Five patients (6%) had a normal D-dimer level (≤ 1.0 µg/mL); of these, 2 were asymptomatic. CONCLUSIONS: In this retrospective study, the incidence of CA-VTE in Japanese patients with cancer was equivalent to that in Western populations. Approximately half of CA-VTE patients were asymptomatic and 6% had normal D-dimer levels, indicating the need for closer attention to occult CA-VTE.

  Springer Science and Business Media LLC, Sep. 2021, International journal of hematology, 114(3) (3), 319 - 324, English, Domestic magazine

  Scientific journal


• Deep-Red/Near-Infrared Turn-On Fluorescence Probes for Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells

  Masahiro Oe, Koji Miki, Yoshifumi Ueda, Yasuo Mori, Aoi Okamoto, Yohei Funakoshi, Hironobu Minami, Kouichi Ohe

  Accumulating evidence supports that cancer stem cells (CSCs) are responsible for cancer proliferation, metastasis, and therapy resistance; therefore, an effective strategy to identify and isolate CSCs is required urgently. Because of their low invasiveness and high signal/noise ratio, "turn-on" fluorescence probes working in the deep-red/near-infrared (DR/NIR) region are one of the most attractive yet undeveloped tools for CSC detection. Herein, we report DR/NIR turn-on fluorescence probes, CS5-A and CS7-A, targeted to aldehyde dehydrogenase 1A1 as an intracellular CSC marker. In contrast to the conventional "always-on" green-fluorescent ALDEFLUOR, we succeeded in generating high-contrast (signal/noise ratio > 8.3) and wash-free in vitro CSC imaging with the DR probe C5S-A. This probe can facilitate CSC isolation with minimal contamination by autofluorescence from other tissues through fluorescence-activated cell sorting. Furthermore, the NIR absorbance/emission and turn-on properties of C7S-A allow simple and rapid CSC detection in vivo within 15 min.

  American Chemical Society (ACS), Aug. 2021, ACS Sensors, 6(9) (9), 3320 - 3329, English, International magazine

  Scientific journal


• Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan with Concomitant Ritonavir or Itraconazole in Patients with HER2-Expressing Advanced Solid Tumors

  Shunji Takahashi, Masato Karayama, Masato Takahashi, Junichiro Watanabe, Hironobu Minami, Noboru Yamamoto, Ichiro Kinoshita, Chia-Chi Lin, Young-Hyuck Im, Issei Achiwa, Emi Kamiyama, Yasuyuki Okuda, Caleb Lee, Yung-Jue Bang

  Abstract Purpose: To evaluate drug–drug interactions between the human epidermal growth factor receptor 2 (HER2)–targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd; DS-8201a) and the OATP1B/CYP3A inhibitor ritonavir or the strong CYP3A inhibitor itraconazole. Patients and Methods: Patients with HER2-expressing advanced solid tumors were enrolled in this phase I, open-label, single-sequence crossover study (NCT03383692) and received i.v. T-DXd 5.4 mg/kg every 3 weeks. Patients received ritonavir (cohort 1) or itraconazole (cohort 2) from day 17 of cycle 2 through the end of cycle 3. Primary endpoints were maximum serum concentration (Cmax) and partial area under the concentration-time curve from beginning of cycle through day 17 (AUC17d) for T-DXd and deruxtecan (DXd) with (cycle 3) and without (cycle 2) ritonavir or itraconazole treatment. Results: Forty patients were enrolled (cohort 1, n = 17; cohort 2, n = 23). T-DXd Cmax was similar whether combined with ritonavir [cohort 1, cycle 3/cycle 2; 90% confidence interval (CI): 1.05 (0.98–1.13)] or itraconazole [cohort 2, 1.03 (0.96–1.09)]. T-DXd AUC17d increased from cycle 2 to 3; however, the cycle 3/cycle 2 ratio upper CI bound remained at ≤1.25 for both cohorts. For DXd (cycle 3/cycle 2), Cmax ratio was 0.99 (90% CI, 0.85–1.14) for cohort 1 and 1.04 (0.92–1.18) for cohort 2; AUC17d ratio was 1.22 (1.08–1.37) and 1.18 (1.11–1.25), respectively. The safety profile of T-DXd plus ritonavir or itraconazole was consistent with previous studies of T-DXd monotherapy. T-DXd demonstrated promising antitumor activity across HER2-expressing solid-tumor types. Conclusions: T-DXd was safely combined with ritonavir or itraconazole without clinically meaningful impact on T-DXd or DXd pharmacokinetics.

  American Association for Cancer Research (AACR), Aug. 2021, Clinical Cancer Research, 27(21) (21), 5771 - 5780, English, International magazine

  Scientific journal


• Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction.

  Masahiro Mizuno, Behnoush Khaledian, Masao Maeda, Takanori Hayashi, Seiya Mizuno, Eiji Munetsuna, Takashi Watanabe, Seishi Kono, Seiji Okada, Motoshi Suzuki, Shintaro Takao, Hironobu Minami, Naoya Asai, Fumihiro Sugiyama, Satoru Takahashi, Yohei Shimono

  Adipose tissue is a component of the tumor microenvironment and is involved in tumor progression. We have previously shown that adipokine adipsin (CFD) functions as an enhancer of tumor proliferation and cancer stem cell (CSC) properties in breast cancers. We established the Cfd-knockout (KO) mice and the mammary adipose tissue-derived stem cells (mADSCs) from them. Cfd-KO in mADSCs significantly reduced their ability to enhance tumorsphere formation of breast cancer patient-derived xenograft (PDX) cells, which was restored by the addition of Cfd in the culture medium. Hepatocyte growth factor (HGF) was expressed and secreted from mADSCs in a Cfd-dependent manner. HGF rescued the reduced ability of Cfd-KO mADSCs to promote tumorsphere formation in vitro and tumor formation in vivo by breast cancer PDX cells. These results suggest that HGF is a downstream effector of Cfd in mADSCs that enhances the CSC properties in breast cancers.

  MDPI AG, Aug. 2021, Cancers, 13(16) (16), 4238 - 4238, English, International magazine

  Scientific journal


• Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19

  Yohei Funakoshi, Goh Ohji, Kimikazu Yakushijin, Kei Ebisawa, Yu Arakawa, Jun Saegusa, Hisayuki Matsumoto, Takamitsu Imanishi, Eriko Fukuda, Takaji Matsutani, Yasuko Mori, Kentaro Iwata, Hironobu Minami

  Background: Antibody production is one of the primary mechanisms for recovery from coronavirus disease 2019 (COVID-19). It is speculated that massive clonal expansion of B cells, which can produce clinically meaningful neutralizing antibodies, occurs in patients who recover on the timing of acquiring adaptive immunity. Methods: To evaluate fluctuations in clonal B cells and the size of the clones, we chronologically assessed the B-cell receptor (BCR) repertoire in three patients with COVID-19 who recovered around 10 days after symptom onset. Results: We focused on the three dominant clonotypes (top 3) in each individual. The percentage frequencies of the top 3 clonotypes increased rapidly and accounted for 27.8 % on day 9 in patient 1, 10.4 % on day 12 in patient 2, and 10.8 % on day 11 in patient 3, respectively. The frequencies of these top 3 clonotypes rapidly decreased as the patients' clinical symptoms improved. Furthermore, BCR network analysis revealed that accumulation of clusters composed of similar complementarity-determining region 3 (CDR3) sequences were rapidly formed, grew, and reached their maximum size around 10 days after symptom onset. Conclusions: BCR repertoire analysis revealed that a massive surge of some unique BCRs occurs during the acquisition of adaptive immunity and recovery. The peaks were more prominent than expected. These results provide insight into the important role of BCRs in the recovery from COVID-19 and raise the possibility of developing neutralizing antibodies as COVID-19 immunotherapy.

  Elsevier BV, Aug. 2021, Heliyon, 7(8) (8), e07748 - e07748, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Did the Randomized Phase III KEYNOTE-181 Study of Pembrolizumab for Esophageal Cancer Yield Negative or Positive Results?

  Hironobu Minami, Naomi Kiyota, Takashi Omori

  American Society of Clinical Oncology (ASCO), Jul. 2021, Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 39(20) (20), 2317 - 2318, English, International magazine

  Scientific journal


• Immunosuppressive effects and mechanisms of three myeloid-derived suppressor cells subsets including monocytic-myeloid-derived suppressor cells, granulocytic-myeloid-derived suppressor cells, and immature-myeloid-derived suppressor cells

  Yoshiaki Nagatani, Yohei Funakoshi, Hirotaka Suto, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Kimihiro Yamashita, Hironobu Minami

  Context: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immune cells of myeloid lineage. Recent reports have suggested that human MDSC are divided into three subsets: monocytic MDSC (M-MDSC), granulocytic MDSC (G-MDSC), and immature MDSC (I-MDSC). However, the characteristics of each human MDSC subset still remain unclear. Materials and Methods: To evaluate the immunosuppressive effects and mechanisms, we first performed a T-cell suppression assay using cells obtained from healthy donor peripheral blood samples. The levels of immune inhibitory molecules in the culture supernatant of each MDSC subset were measured to reveal the T-cell suppressive mechanisms. Then, we compared these results with the results from cells obtained from cancer patient blood samples. Finally, we investigated the difference in the frequency of each MDSC subset between the healthy donors and the cancer patients. Results: Although M-MDSC and G-MDSC suppressed T-cell activation, I-MDSC had no T-cell suppressive effect. We found that the culture supernatant of M-MDSC and G-MDSC contained high levels of interleukin-1 receptor antagonist (IL-1RA) and arginase, respectively, in both healthy donors and cancer patients. No inhibitory molecules were detected in the culture supernatant of I-MDSC. The population of functional MDSC (M-MDSC and G-MDSC) in the total MDSC was significantly increased in cancer patients compared with that in healthy donors. Conclusions: Although M-MDSC and G-MDSC, which released IL-1RA and arginase, respectively, suppressed T-cell activation, I-MDSC did not have an immunosuppressive effect. The population of functional MDSC was increased in cancer patients compared with that in healthy donors.

  Medknow, Jul. 2021, Journal of Cancer Research and Therapeutics, 17(4) (4), 1093 - 1100, English, International magazine

  Scientific journal


• Guidelines for clinical evaluation of anti-cancer drugs

  Hironobu Minami, Naomi Kiyota, Shiro Kimbara, Yuichi Ando, Tomoya Shimokata, Atsushi Ohtsu, Nozomu Fuse, Yasutoshi Kuboki, Toshio Shimizu, Noboru Yamamoto, Kazuto Nishio, Yutaka Kawakami, Shin ichi Nihira, Kazuhiro Sase, Takahiro Nonaka, Hideaki Takahashi, Yukiko Komori, Koshin Kiyohara

  Jul. 2021, Cancer Science, 112(7) (7), 2563 - 2577

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Guidelines for clinical evaluation of anti-cancer drugs.

  Hironobu Minami, Naomi Kiyota, Shiro Kimbara, Yuichi Ando, Tomoya Shimokata, Atsushi Ohtsu, Nozomu Fuse, Yasutoshi Kuboki, Toshio Shimizu, Noboru Yamamoto, Kazuto Nishio, Yutaka Kawakami, Shin-Ichi Nihira, Kazuhiro Sase, Takahiro Nonaka, Hideaki Takahashi, Yukiko Komori, Koshin Kiyohara

  Clinical studies intended for regulatory approval must demonstrate the clinical benefits of the drug in a target population. Clinical development of a drug proceeds by stepwise clinical studies; after safety and pharmacokinetics are evaluated and the recommended dosage and administration are determined, efficacy and safety are evaluated in an exploratory manner, and finally clinical benefits are compared with conventional standard therapies. Guidelines for the clinical evaluation of anti-cancer drugs in Japan were established in 1991 and amended in 2006 after molecular-targeted drugs were introduced. Recent progress in the development of drugs acting on the immune system and cancer genomic medicine targeting rare but important molecular subtypes have altered the strategy for development of anti-cancer drugs. It is often difficult to conduct a confirmatory randomized controlled study using overall survival as the primary endpoint in rare molecular subtypes, and the primary evaluation of the efficacy of some drugs and subsequent approval is based on the tumor response. As conducting clinical studies for rare subtypes solely within Japan is difficult, drug development needs to be conducted within a global study. However, this requires robust monitoring to detect possible ethnic differences in pharmacokinetics and drug efficacy. Development using the conditional approval system for drugs enforced in 2020 may be considered, when clinical utility is evaluated based on surrogate endpoints. Because of these changes, we have revised the guidelines for the clinical evaluation of anti-cancer drugs in Japan. To promote global development of anti-cancer drugs involving Japan, the guidelines have been translated into English.

  Wiley, Jul. 2021, Cancer science, 112(7) (7), 2563 - 2577, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Efficacy and safety of blinatumomab: Post hoc pooled analysis in Asian adults with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia

  Yukio Kobayashi, Iekuni Oh, Toshihiro Miyamoto, Won‐Sik Lee, Hiroatsu Iida, Hironobu Minami, Yoshinobu Maeda, Jun Ho Jang, Sung‐Soo Yoon, Su‐Peng Yeh, Qui Tran, Joan Morris, Janet Franklin, Hitoshi Kiyoi

  Wiley, Jun. 2021, Asia-Pacific Journal of Clinical Oncology, 18(3) (3), 311 - 318, English

  Scientific journal


• Expression of a novel type of KMT2A/EPS15 fusion transcript in FLT3 mutation-positive B-lymphoblastic leukemia with t(1;11)(p32;q23)

  Katsuya Yamamoto, Kimikazu Yakushijin, Yu Mizutani, Marika Okuni-Watanabe, Hideaki Goto, Ako Higashime, Yoshiharu Miyata, Akihito Kitao, Hisayuki Matsumoto, Jun Saegusa, Hiroshi Matsuoka, Hironobu Minami

  Elsevier BV, Jun. 2021, Cancer Genetics, 254-255, 92 - 97

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Device-related Mycobacterium mageritense Infection in a Patient Treated with Nivolumab for Metastatic Breast Cancer: A Case Report.

  Taiji Koyama, Yohei Funakoshi, Yoshinori Imamura, Sho Nishimura, Yoshimi Fujishima, Masanori Toyoda, Naomi Kiyota, Hirokazu Tanino, Hironobu Minami

  Treatment with anti-programmed cell death-1 (PD-1) antibodies improves the anti-cancer immune response and can provide a meaningful clinical benefit to cancer patients. However, this treatment can result in specific autoimmune toxicities, termed immune-related adverse events (irAEs). Although irAEs are well recognized, the development of infectious diseases due to this treatment is not often observed. Some recent reports have indicated that patients who receive anti-PD-1 antibodies are at a higher risk for tuberculosis than others. However, reports on nontuberculous mycobacterial infection during anti-PD-1 antibody treatment are still rare. We herein report the first case of Mycobacterium mageritense infection during anti-PD-1 antibody treatment.

  Japanese Society of Internal Medicine, May 2021, Internal medicine (Tokyo, Japan), 60(21) (21), 3485 - 3488, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Five-year survival with nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma.

  Hisashi Uhara, Yoshio Kiyohara, Jiro Uehara, Yasuhiro Fujisawa, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Satoshi Fukushima, Hironobu Minami, Masahiro Hatsumichi, Naoya Yamazaki

  We report the 5-year follow-up results from a single-arm, open-label, multicenter phase II study (ONO-4538-08) conducted in Japan. Twenty-four patients with treatment-naïve, recurrent, or unresectable stage III/IV malignant melanoma received 3 mg/kg nivolumab every 2 weeks until progressive disease or unacceptable toxicity occurred. The 5-year overall survival (OS) rate was 26.1%. Five years after the start of nivolumab treatment, there were six survivors. The 5-year OS rate was 66.7% for patients with a superficial spreading type, 14.3% for acral lentiginous type, and 16.7% for mucosal type. The 5-year progression-free survival rate was 17.2%. No new cases of partial response or complete response were observed after 3 years, and overall response and disease control rates were similar to those reported at 3 years. The treatment-related adverse events reported between the 3- and 5-year follow-up periods were anemia (grade 2), white blood cell count decrease (grade 2), and psoriasiform dermatitis (grade 2) in one patient each. No new grade 3 or higher treatment-related adverse events occurred in this period. In conclusion, first-line treatment with nivolumab in Japanese patients with unresectable or metastatic melanoma resulted in confirmed long-term survival. No new safety signals were reported in the studied population.

  Wiley, May 2021, The Journal of dermatology, 48(5) (5), 592 - 599, English, International magazine

  Scientific journal


• Surgical outcomes of metastatic bone tumors in the extremities (Surgical outcomes of bone metastases).

  Hitomi Hara, Yoshitada Sakai, Teruya Kawamoto, Naomasa Fukase, Yohei Kawakami, Toshiyuki Takemori, Shuichi Fujiwara, Kazumichi Kitayama, Shunsuke Yahiro, Tomohiro Miyamoto, Kenichiro Kakutani, Takahiro Niikura, Daisuke Miyawaki, Takuya Okada, Akihiro Sakashita, Yoshinori Imamura, Ryohei Sasaki, Yoshiyuki Kizawa, Hironobu Minami, Tomoyuki Matsumoto, Takehiko Matsushita, Ryosuke Kuroda, Toshihiro Akisue

  Background: Skeletal related events due to metastatic bone tumors markedly affect the activities of daily living (ADL) and quality of life (QOL) in cancer patients. We focused on multidisciplinary therapy for metastatic bone tumors. This study aimed to evaluate the outcomes of surgical treatment for metastatic bone tumors in the extremities. Methods: We retrospectively reviewed 114 patients who underwent surgical treatment for metastatic bone tumors of the extremities between 2008 and 2019 and 69 patients were reassessed for more than 6 months after surgery. The most common primary tumor was renal, followed by lung, thyroid, and breast cancers. We assessed 69 patients' performance status (PS), Barthel Index (BI) for ADL, EuroQol 5 Dimensions (EQ-5D) for QOL, and numerical rating scale (NRS) for pain and analyzed these postoperative values relative to preoperative values using Friedman's test. The postoperative overall survival and the prognostic factors were evaluated using the Kaplan-Meier method, the log-rank test and Cox proportional hazards analysis. Results: The 1-year overall survival rate was 59%, and the median survival time after surgery was 20 months. Primary tumor, visceral metastasis, and surgical procedure were risk factors correlated with overall survival. PS, BI, EQ-5D, and NRS improved at 3 months after surgery and these improvements were maintained for 6 months after surgery regardless of the surgical procedure. Conclusions: The significant factors affecting survival after surgical treatment for bone metastases included the primary tumor, presence of visceral metastases, and internal fixation without tumor resection or curettage. Surgical treatment for metastatic bone tumors effectively reduced pain and improved PS, ADL, and QOL postoperatively after 3 months.

  Elsevier BV, Apr. 2021, Journal of bone oncology, 27, 100352 - 100352, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Non-inverted Duplication of 11q, dup(11)(q11q24), in a Diffuse Large B Cell Lymphoma Without MYC Rearrangement: Case Report

  Katsuya Yamamoto, Keiji Kurata, Ako Higashime, Satoshi Sai, Kimikazu Yakushijin, Shinichiro Kawamoto, Kazuyoshi Kajimoto, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  Springer Science and Business Media LLC, Mar. 2021, SN Comprehensive Clinical Medicine, 3(6) (6), 1455 - 1462

  Scientific journal


• A phase I, dose-escalation study of oral PIM447 in Japanese patients with relapsed and/or refractory multiple myeloma

  Shinsuke Iida, Kazutaka Sunami, Hironobu Minami, Kiyohiko Hatake, Risa Sekiguchi, Kazuto Natsume, Norifumi Ishikawa, Mikael Rinne, Masafumi Taniwaki

  Springer Science and Business Media LLC, Feb. 2021, International Journal of Hematology, 113(6) (6), 797 - 806

  Scientific journal


• Secondary CIC‑rearranged sarcoma responsive to chemotherapy regimens for Ewing sarcoma: A case report

  Shiro Kimbara, Yoshinori Imamura, Naomi Kiyota, Hidetomo Takakura, Sakuya Matsumoto, Taiji Koyama, Yoshimi Fujishima, Yohei Funakoshi, Masanori Toyoda, Takanori Hirose, Maki Kanzawa, Teruya Kawamoto, Hitomi Hara, Hironobu Minami

  Capicua transcriptional repressor (CIC)-rearranged sarcoma is an Ewing-like sarcoma with an aggressive clinical course and poor prognosis. No standard treatment has been established. The present study describes a case of CIC-rearranged sarcoma with lung metastases developing in a 24-year-old woman as a therapy-associated malignancy following chemotherapy for anaplastic large cell lymphoma at nine years old. This was treated with palliative regimens used for Ewing sarcoma. The patient achieved disease control for one year. Of note, ifosfamide and etoposide (IE), which were used as a second line treatment lead to a partial response. The case described in the present study indicated that treatment with Ewing regimens is a reasonable option for patients with metastatic CIC-rearranged sarcoma, including those with a second malignant case.

  Spandidos Publications, Feb. 2021, Molecular and Clinical Oncology, 14(4) (4), 68 - 68, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Upregulation of S100A10 in metastasized breast cancer stem cells.

  Hisano Yanagi, Takashi Watanabe, Tatsunori Nishimura, Takanori Hayashi, Seiji Okada, Motoshi Suzuki, Hironobu Minami, Akira Suzuki, Kenji Kawada, Noriko Gotoh, Yohei Shimono

  Feb. 2021, CANCER SCIENCE, 112, 705 - 705, English

  Link to Kobe Univ. Repository (Kernel)


• Serum Soluble Interleukin-2 Receptor as a Potential Biomarker for Immune-related Adverse Events.

  Ryo Takai, Yohei Funakoshi, Hirotaka Suto, Yoshiaki Nagatani, Yoshinori Imamura, Masanori Toyoda, Kimikazu Yakushijin, Naomi Kiyota, Ken-Ichi Harada, Kimihiro Yamashita, Yoshihiro Kakeji, Hironobu Minami

  BACKGROUND/AIM: Biomarkers for immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) are required. We encountered a patient whose skin irAE fluctuated in parallel with serum soluble interleukin-2 receptor (sIL-2R). PATIENTS AND METHODS: We examined 15 patients with cancer who received ICIs. Serum sIL-2R levels before and during ICI treatment were measured. The sIL-2R levels of preserved serum samples from another five patients who developed grade 3 irAEs were measured. RESULTS: Twelve patients showed no significant changes in sIL-2R levels during ICI treatment. Baseline serum sIL-2R levels in three patients increased beyond the normal range before the second cycle. These three patients had grade ≥2 irAEs at the second cycle treatment visit, supporting our hypothesis. Furthermore, at diagnosis of irAEs, the sIL-2R levels of all preserved samples from patients with grade 3 irAEs were significantly elevated. CONCLUSION: Serum sIL-2R is a promising biomarker for the diagnosis of irAEs.

  International Institute of Anticancer Research, Feb. 2021, Anticancer research, 41(2) (2), 1021 - 1026, English, International magazine

  Scientific journal


• Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

  Hironobu Minami, Toshihiko Doi, Masanori Toyoda, Yoshinori Imamura, Naomi Kiyota, Ayako Mitsuma, Tomoya Shimokata, Yoichi Naito, Nobuaki Matsubara, Takeshi Tajima, Kota Tokushige, Kae Ishihara, Scott Cameron, Yuichi Ando

  Spartalizumab is a humanized IgG4/κ mAb directed against human programmed cell death-1 (PD-1). In this phase I study, we investigated safety, pharmacokinetics, preliminary antitumor activity, and toxicity of spartalizumab in patients with advanced malignancies. Patients (n = 18) with a range of tumor types received spartalizumab i.v. at doses of 1, 3, and 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or discontinuation at the discretion of the investigator or patient. Most patients (61%) had received five or more prior lines of therapy. No dose-limiting toxicities were reported and, hence, the maximum tolerated dose was 10 mg/kg or more. Pharmacokinetics in Japanese patients aligned with those reported in a global dose-escalation study. The safety profile was consistent with other approved anti-PD-1 mAbs; the most common drug-related adverse events were maculopapular rash (22%), followed by malaise and increased blood alkaline phosphatase (11% each). Partial responses were reported in two patients (11%), one with transitional cell carcinoma and the other with hepatocellular carcinoma. In conclusion, this study confirmed the safety of spartalizumab given at a dose of up to 10 mg/kg every 2 weeks in Japanese patients with cancers.

  Lead, Wiley, Feb. 2021, Cancer Science, 112(2) (2), 725 - 733, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Exploratory Analysis to Predict Optimal Tumor Burden for Starting Lenvatinib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer.

  Chiaki Suzuki, Naomi Kiyota, Yoshinori Imamura, Hideaki Goto, Hirotaka Suto, Naoko Chayahara, Masanori Toyoda, Yasuhiro Ito, Akihiro Miya, Akira Miyauchi, Masanori Teshima, Naoki Otsuki, Ken-Ichi Nibu, Hironobu Minami

  Background: We previously reported that a high tumor burden is a prognostic factor based on an analysis of 26 patients with radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) who were treated with lenvatinib. However, the optimal tumor burden for starting lenvatinib still remains to be defined. The aim of this retrospective study was to further explore in the same patient cohort the optimal timing for the start of lenvatinib by focusing on the pre- and post-treatment tumor burden. Methods: The 26 patients were treated with lenvatinib from 2012 to 2017. We explored the optimal timing for the start of lenvatinib by comparing the characteristics of long-term responders who were defined as patients with progression-free survival ≥ 30 months and non-long-term responders. Results: Long-term responders had a smaller post-treatment tumor burden at maximum shrinkage than non-long-term responders. Further, post-treatment tumor burden had a strong linear correlation with baseline tumor burden. We created an estimation formula for baseline tumor burden related to prognosis, using these regression lines. Patients with a sum of diameters of target lesions < 60 mm or maximum tumor diameter < 34 mm at baseline were estimated to have significantly better survival outcomes. Conclusions: We found a strong linear correlation between pre- and post-treatment tumor burden. Our results suggested a cut-off value for baseline tumor burden for long-term prognosis among patients treated with lenvatinib.

  Frontiers Media SA, 2021, Frontiers in oncology, 11, 638123 - 638123, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial).

  Satoshi Sai, Masanori Toyoda, Kazutoshi Tobimatsu, Hironaga Satake, Hisateru Yasui, Shiro Kimbara, Taiji Koyama, Yoshimi Fujishima, Yoshinori Imamura, Yohei Funakoshi, Naomi Kiyota, Hirochika Toyama, Yuzo Kodama, Hironobu Minami

  PURPOSE: We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer. METHODS: We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks. The starting dose was level 0 [gemcitabine 700 mg/m2, nab-paclitaxel 90 mg/m2, S-1 60/80/100 mg/day (< 1.25 m2/1.25-1.50 m2/ > 1.5 m2)]. Dose-limiting toxicities were determined during the first course, and a classical 3 + 3 dose finding design was planned. RESULTS: From March 2018 to October 2019, 20 patients were enrolled. At dose level 0, three of six patients experienced dose-limiting toxicities; one grade 3 skin rash on day 8, and two grade 3 or 4 neutropenia on day 8. At dose level-1 (gemcitabine 600 mg/m2, nab-paclitaxel 90 mg/m2, and S-1 50/70/80 mg/day), two of twelve patients experienced dose-limiting toxicities, all of which were grade 3 neutropenia on day 8. The most frequently observed toxicity during eight courses was neutropenia. Other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response. CONCLUSION: We defined the maximum tolerated dose and the recommended dose for combination therapy with gemcitabine/nab-paclitaxel/S-1 as dose level-1. Considering the observed response rate, further studies are warranted in order to determine the efficacy of this regimen (UMIN-CTR 000030007).

  Springer Science and Business Media LLC, Jan. 2021, Cancer chemotherapy and pharmacology, 87(1) (1), 65 - 71, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Relationship between PDGFR expression and the response to pazopanib in intimal sarcoma of the pulmonary artery: A case report.

  Satoshi Sai, Yoshinori Imamura, Naomi Kiyota, Naoe Jimbo, Masanori Toyoda, Yohei Funakoshi, Naoko Chayahara, Yasuko Hyogo, Kei Takenaka, Hirotaka Suto, Hironobu Minami

  Intimal sarcoma of the pulmonary artery (PAIS) is a rare disease with a poor prognosis. Pazopanib, which has been indicated in metastatic non-adipocytic soft-tissue sarcomas and is expected to be active in PAIS, is a multi-kinase inhibitor that targets the tyrosine kinase activity of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor. The present study reports findings related to two cases of PAIS with PDGF and VEGF expression following treatment with pazopanib. A case with a moderate to strong expression of PDGFR-α and -β presented a long-term stable disease when treated with pazopanib (progression-free survival, 5.8 months). In a second case with a weak expression of PDGFR-α and -β, the disease progressed rapidly on pazopanib (progression-free survival, 1.1 months). VEGFR-2 was not expressed in the tumors of both cases. The level of PDGFR expression in the tumor tissue may therefore be predictive of pazopanib efficacy.

  Spandidos Publications, Jan. 2021, Molecular and clinical oncology, 14(1) (1), 6 - 6, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy

  Kentaro Yamashita, Hidekazu Tanaka, Keiko Hatazawa, Yusuke Tanaka, Keiko Sumimoto, Ayu Shono, Makiko Suzuki, Shun Yokota, Makiko Suto, Jun Mukai, Hiroki Takada, Kensuke Matsumoto, Hironobu Minami, Ken-ichi Hirata

  Springer Science and Business Media LLC, Jan. 2021, The International Journal of Cardiovascular Imaging, 37(1) (1), 197 - 205

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Impact of hypertension on left ventricular function in patients after anthracycline chemotherapy for malignant lymphoma

  Yusuke Tanaka, Hidekazu Tanaka, Keiko Hatazawa, Kentaro Yamashita, Keiko Sumimoto, Ayu Shono, Makiko Suzuki, Shun Yokota, Makiko Suto, Jun Mukai, Hiroki Takada, Kensuke Matsumoto, Hironobu Minami, Ken-ichi Hirata

  Elsevier BV, Jan. 2021, International Journal of Cardiology, 323, 126 - 132

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Regorafenib‑induced exacerbation of chronic immune thrombocytopenic purpura in remission: A case report

  Shiro Kimbara, Yoshinori Imamura, Kimikazu Yakushijin, Ako Higashime, Taiji Koyama, Yoshimi Fujishima, Yohei Funakoshi, Masanori Toyoda, Naomi Kiyota, Hiroshi Matsuoka, Hironobu Minami

  Regorafenib is an oral multi-kinase inhibitor which targets tumor angiogenesis, the tumor microenvironment and oncogenesis. Based on this mode of action, regorafenib has a broad spectrum of toxicities. However, at present, few reports have focused on autoimmune adverse events. We report a first case of regorafenib-induced exacerbation of chronic immune thrombocytopenic purpura in remission during treatment for the patients with heavily treated advanced colorectal cancer. This case report highlights the need for caution with regard to regorafenib treatment in patients with cancer with concomitant immune thrombocytopenic purpura.

  Last, Spandidos Publications, Dec. 2020, Molecular and Clinical Oncology, 14(2) (2), 30 - 30, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Upregulation of S100A10 in metastasized breast cancer stem cells

  Hisano Yanagi, Takashi Watanabe, Tatsunori Nishimura, Takanori Hayashi, Seishi Kono, Hitomi Tsuchida, Munetsugu Hirata, Yuko Kijima, Shintaro Takao, Seiji Okada, Motoshi Suzuki, Kazuyoshi Imaizumi, Kenji Kawada, Hironobu Minami, Noriko Gotoh, Yohei Shimono

  Metastatic progression remains the major cause of death in human breast cancer. Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have previously established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 and its family proteins were much higher in the CD44+ cancer cells metastasized to the liver than those at the primary site. Knockdown of S100A10 in breast cancer cells suppressed and overexpression of S100A10 in breast cancer PDX cells enhanced their invasion abilities and 3D organoid formation capacities in vitro. Mechanistically, S100A10 regulated the matrix metalloproteinase activity and the expression levels of stem cell-related genes. Finally, constitutive knockdown of S100A10 significantly reduced their metastatic ability to the liver in vivo. These findings suggest that S100A10 functions as a metastasis promoter of breast CSCs by conferring both invasion ability and CSC properties in breast cancers.

  Wiley, Dec. 2020, Cancer Science, 111(12) (12), 4359 - 4370, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Lymphoplasmacytic lymphoma in a patient with Birt–Hogg–Dubé syndrome

  Keiji Kurata, Hisayuki Matsumoto, Naoe Jimbo, Kimikazu Yakushijin, Katsuya Yamamoto, Mitsuhiro Ito, Yuji Nakamachi, Hiroshi Matsuoka, Jun Saegusa, Kuniaki Seyama, Tomoo Itoh, Hironobu Minami

  Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disease characterized by benign skin hamartomas, pulmonary cysts leading to spontaneous pneumothorax, and an increased risk of renal cancer. BHD syndrome is caused by germline mutations in the folliculin (FLCN) gene, a putative tumor suppressor, which result in loss of function of the folliculin protein and may cause cancer predisposition. In a 45-year-old woman with anemia, lymphadenopathy, and a history of recurrent spontaneous pneumothorax, 18F-FDG PET/CT detected diffuse and slight 18F-FDG accumulation in the bone marrow, enlarged spleen, and systemic multiple enlarged lymph nodes. Genetic examination identified a germline nonsense mutation [c.998C > G (p.Ser333*)] on exon 9 of FLCN. Pathological examination of the lymph node revealed a diffuse neoplastic proliferation of plasmacytoid lymphocytes. The neoplastic lymphoid cells were positive for CD20, CD138, and light chain kappa as per immunohistochemistry and mRNA in situ hybridization, and a MYD88 gene mutation [c.755T > C (p.L252P)] was identified. Accordingly, she was diagnosed with lymphoplasmacytic lymphoma concomitant with BHD syndrome. To the best of our knowledge, this is the first report describing the development of hematological malignancy in a patient with BHD syndrome. The FLCN mutation might contribute lymphomagenesis as an additional mutation cooperating with the MYD88 mutation.

  Springer Science and Business Media LLC, Dec. 2020, International Journal of Hematology, 112(6) (6), 864 - 870, English, Domestic magazine

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  Link to Kobe Univ. Repository (Kernel)


• Site-Specific and Targeted Therapy Based on Molecular Profiling by Next-Generation Sequencing for Cancer of Unknown Primary Site

  Hidetoshi Hayashi, Yuichi Takiguchi, Hironobu Minami, Kohei Akiyoshi, Yoshihiko Segawa, Hiroki Ueda, Yasuo Iwamoto, Chihiro Kondoh, Koji Matsumoto, Shin Takahashi, Hisateru Yasui, Toshiyuki Sawa, Yusuke Onozawa, Yasutaka Chiba, Yosuke Togashi, Yoshihiko Fujita, Kazuko Sakai, Shuta Tomida, Kazuto Nishio, Kazuhiko Nakagawa

  Importance: Although profiling of gene expression and gene alterations by next-generation sequencing (NGS) to predict the primary tumor site and guide molecularly targeted therapy might be expected to improve clinical outcomes for cancer of unknown primary site (CUP), to our knowledge, no clinical trial has previously evaluated this approach. Objective: To assess the clinical use of site-specific treatment, including molecularly targeted therapy based on NGS results, for patients with CUP. Design, Setting, and Participants: This phase 2 clinical trial was conducted at 19 institutions in Japan and enrolled 111 previously untreated patients with the unfavorable subset of CUP between March 2015 and January 2018, with 97 patients being included in the efficacy analysis. Eligibility criteria included a diagnosis of unfavorable CUP after mandatory examinations, including pathological evaluation by immunohistochemistry, chest-abdomen-pelvis computed tomography scans, and a positron emission tomography scan. Interventions: RNA and DNA sequencing for selected genes was performed simultaneously to evaluate gene expression and gene alterations, respectively. A newly established algorithm was applied to predict tumor origin based on these data. Patients received site-specific therapy, including molecularly targeted therapy, according to the predicted site and detected gene alterations. Main Outcomes And Measures: The primary end point was 1-year survival probability. Secondary end points included progression-free survival (PFS), overall survival (OS), objective response rate, safety, efficacy according to predicted site, and frequency of gene alterations. Results: Of 97 participants, 49 (50.5%) were women and the median (range) age was 64 (21-81) years. The cancer types most commonly predicted were lung (21 [21%]), liver (15 [15%]), kidney (15 [15%]), and colorectal (12 [12%]) cancer. The most frequent gene alterations were in TP53 (45 [46.4%]), KRAS (19 [19.6%]), and CDKN2A (18 [18.6%]). The 1-year survival probability, median OS, and median PFS were 53.1% (95% CI, 42.6%-62.5%), 13.7 months (95% CI, 9.3-19.7 months), and 5.2 months (95% CI, 3.3-7.1 months), respectively. Targetable EGFR mutations in tumor specimens were detected in 5 patients with predicted non-small-cell lung cancer (5.2%), 4 of whom were treated with afatinib; 2 of these patients achieved a durable PFS of longer than 6 months. Conclusions and Relevance: This study's findings suggest that site-specific treatment, including molecularly targeted therapy based on profiling gene expression and gene alterations by NGS, can contribute to treating patients with the unfavorable subset of CUP. Trial Registration: UMIN Identifier: UMIN000016794.

  American Medical Association (AMA), Dec. 2020, JAMA Oncology, 6(12) (12), 1931 - 1931, English, International magazine

  Scientific journal


• Ibuprofen gargle for chemo- or Chemoradiotherapy-induced Oral Mucositis: a feasibility study

  Takeshi Ioroi, Naomi Kiyota, Yoshinori Imamura, Masaaki Tanda, Shiori Aoki, Mamoru Okuno, Kazuhiro Yamamoto, Ryohei Sasaki, Ken-ichi Nibu, Hironobu Minami, Midori Hirai, Ikuko Yano

  Background: Oral mucositis frequently occurs in cancer patients treated with chemotherapy and chemoradiotherapy (CRT). This study examined the safety and efficacy of ibuprofen gargle in healthy volunteers and patients with chemotherapy- and concomitant CRT-induced oral mucositis. Methods: We enrolled healthy volunteers and patients with chemotherapy- and CRT-induced oral mucositis. In cohort I, single and multiple doses of ibuprofen gargle (0.6% or 1.0%) were administered to healthy volunteers on day 1 and days 4-10. In cohort II, multiple doses of ibuprofen gargle (0.6%) were administered to patients with complicated grade 2-3 oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The primary endpoint of cohort I was the treatment-related adverse events (TRAEs) as defined by CTCAE version 4.0. The primary endpoint of cohort II was the change in the visual analogue scale (VAS) pain score from before to 15 min after gargle use on day 3. The incidence and severity of TRAEs were assessed based on the CTCAE version 4.0 and a subjective rating scale completed by healthy volunteers and patients. Results: In cohort I, 9 of 10 healthy volunteers were evaluable for safety. All 9 healthy volunteers reported the TRAE of oral irritation with single or multiple use of the gargle. In cohort II, 10 patients were enrolled and evaluable for safety and 7 of 10 patients were evaluable for efficacy. The mean change in the VAS pain score from before to 15 min after using the gargle on day 3 was - 1.28 (95% confidence interval: - 2.06, - 0.51), and all patients experienced some degree of pain relief (range: - 0.2 to - 2.5). All 10 patients reported the TRAE of oral irritation. No other TRAEs of ibuprofen gargle were observed in the healthy volunteers and patients. Conclusion: Despite oral irritation, the ibuprofen gargle appeared to be safe and effective for the pain related to chemo- or CRT-induced oral mucositis. However, ibuprofen-related oral irritation warrants further formulation improvement. Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000014433).

  Springer Science and Business Media LLC, Dec. 2020, Journal of Pharmaceutical Health Care and Sciences, 6(1) (1), 12 - 12, English, International magazine

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  Link to Kobe Univ. Repository (Kernel)


• Disseminated cryptococcosis resembling miliary tuberculosis in a patient with acute myeloid leukemia

  Keiji Kurata, Sho Nishimura, Ako Higashime, Koji Kawaguchi, Shigeki Nagao, Yoko Kozuki, Satoshi Sai, Kimikazu Yakushijin, Katsuya Yamamoto, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami

  Disseminated cryptococcosis, usually involving the lungs and central nervous system, carries a high risk of morbidity and mortality in immunocompromised hosts. In this report, we describe a case of miliary pulmonary cryptococcosis in a patient with acute myeloid leukemia, initially resembling miliary tuberculosis. The diagnosis of disseminated cryptococcosis was made based on transbronchial lung biopsy with subsequent detection of Cryptococcus neoformans in blood and cerebrospinal fluid. The patient was treated with liposomal amphotericin B as induction therapy, followed by fluconazole as consolidation and maintenance therapies thereafter. The infection was improved immediately, and he successfully underwent hematopoietic stem cell transplantation. The present case serves as a timely reminder that a radiological miliary pattern necessitates a thorough search for a definitive microbiological and histopathological diagnosis.

  Last, Elsevier BV, Nov. 2020, Journal of Infection and Chemotherapy, 26(11) (11), 1216 - 1219, English, International magazine

  Scientific journal


• Final analysis of a phase II study of nivolumab in combination with ipilimumab for unresectable chemotherapy‐naive advanced melanoma

  Kenjiro Namikawa, Yoshio Kiyohara, Tatsuya Takenouchi, Hisashi Uhara, Hiroshi Uchi, Shusuke Yoshikawa, Sumiko Takatsuka, Hiroshi Koga, Naoko Wada, Hironobu Minami, Masahiro Hatsumichi, Yoshinobu Namba, Naoya Yamazaki

  Nivolumab plus ipilimumab combination is currently one of the preferred regimens for advanced melanoma in recently updated clinical practice guidelines. However, the evidence on the efficacy of the combination for acral or mucosal subtypes remains less robust. This is the final analysis of a multicenter, open-label, uncontrolled phase II study that investigated the long-term efficacy and safety in treatment-naive Japanese patients with advanced melanoma, including acral or mucosal subtypes, and subsequent therapy after discontinuation of the investigational agents. Patients received four doses of nivolumab (1 mg/kg i.v.) in combination with ipilimumab (3 mg/kg i.v.) at 3-week intervals, followed by doses of nivolumab (3 mg/kg i.v.) at 2-week intervals. The median follow-up period was 20.8 months (range, 5.2-35.0). The centrally and locally assessed objective response rates were both 43.3% (13/30; 95% confidence interval [CI], 25.5-62.6). Median progression-free survival was not reached (95% CI, 3.02-not reached), and median overall survival was also not reached (95% CI, 19.52-not reached). The 30-month progression-free survival and overall survival rates were 50.3% and 54.2%, respectively. No new safety concerns were detected. After discontinuation of the investigational agents, 83.3% of patients received some form of subsequent therapy including 43.3% of patients who received nivolumab monotherapy and 26.7% of patients who received radiotherapy. Of the four patients who discontinued the investigational agents because of immune-related adverse events, two received subsequent therapy (nivolumab and ipilimumab, respectively) and the other two showed long-term treatment-free survival (659 and 590 days, respectively). Long-term survival with nivolumab plus ipilimumab was observed in Japanese patients with melanoma including acral and mucosal subtypes, which is consistent with the CheckMate 067 study. Many patients continued to receive some form of treatment safely after stopping treatment with nivolumab plus ipilimumab.

  Wiley, Nov. 2020, The Journal of Dermatology, 47(11) (11), 1257 - 1266, English, International magazine

  Scientific journal


• HER2陰性転移性乳癌患者に対する一次治療としてのニボルマブ+パクリタキセル+ベバシズマブ併用療法の有効性を評価する多施設第II相試験 WJOG9917B NEWBEAT試験(A multicenter Phase II study evaluating the efficacy of nivolumab plus paclitaxel plus bevacizumab triple-combination therapy as a first-line treatment in patients with HER2-negative metastatic breast cancer: WJOG9917B NEWBEAT trial)

  Ozaki Yukinori, Mukohara Toru, Tsurutani Junji, Takahashi Masato, Matsumoto Koji, Futamura Manabu, Masuda Norikazu, Kitano Shigehisa, Yoshimura Kenichi, Minami Hironobu, Takano Toshimi

  (一社)日本乳癌学会, Oct. 2020, 日本乳癌学会総会プログラム抄録集, 28回, 32 - 32, English


• 転移乳がん幹細胞におけるS100A10の発現上昇

  柳 久乃, 渡辺 崇, 西村 建徳, 林 孝典, 岡田 誠治, 鈴木 元, 南 博信, 鈴木 聡, 河田 健司, 後藤 典子, 下野 洋平

  (一社)日本癌学会, Oct. 2020, 日本癌学会総会記事, 79回, PJ11 - 1, English


• 転移乳がん幹細胞におけるS100A10の発現上昇

  柳 久乃, 渡辺 崇, 西村 建徳, 林 孝典, 岡田 誠治, 鈴木 元, 南 博信, 鈴木 聡, 河田 健司, 後藤 典子, 下野 洋平

  (一社)日本癌学会, Oct. 2020, 日本癌学会総会記事, 79回, PJ11 - 1, English


• Population pharmacokinetics and renal toxicity of cisplatin in cancer patients with renal dysfunction

  Tomoko Morita-Ogawa, Hiroki Sugita, Hironobu Minami, Takuhiro Yamaguchi, Kazuhiko Hanada

  PURPOSE: The pharmacokinetics (PKs) of cisplatin have not been investigated in patients with renal dysfunction, characterized by creatinine clearance (Ccr) < 60 mL/min. In this study, we performed a population pharmacokinetic (PPK) analysis of unchanged cisplatin in patients with renal dysfunction. We investigated the effects of renal dysfunction on the PKs and nephrotoxicity of unchanged cisplatin. METHODS: We enrolled 23 patients with moderate renal dysfunction (Ccr calculated to be 30-60 mL/min using the Cockcroft-Gault formula) treated with cisplatin. PPK analysis was performed by nonlinear mixed effect modeling using NONMEM (Version 7.2). We evaluated gender, age, body surface area (BSA), weight, baseline Ccr, baseline serum creatinine (Scr), and baseline urea nitrogen as potential covariates. The final model was evaluated using bootstrap analysis. Renal toxicity was evaluated using Common Terminology Criteria for Adverse Events ver. 4.0. The frequency of severe renal dysfunction (Grade 3/4 Scr elevation) was measured in the population. RESULTS: A one-compartment model adequately described the unchanged cisplatin data. The population mean values for clearance (CLtot) and volume of distribution (Vd) were 19.1 L/h [coefficient of variation (CV) 19.4%] and 13.8 L (CV 41.0%), respectively. The final model identified BSA as a significant covariate for CLtot. There were no significant covariates for Vd. No patients suffered from severe nephrotoxicity to the point that hemodialysis was required. CONCLUSION: Moderate renal dysfunction does not affect the PKs of unchanged cisplatin. The increased serum concentration of cisplatin may not lead to increased toxicity in patients with renal dysfunction. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: UMIN000007091 (January 17, 2012).

  Springer Science and Business Media LLC, Oct. 2020, Cancer Chemotherapy and Pharmacology, 86(4) (4), 559 - 566, English, International magazine

  Scientific journal


• Phase I Study of LFA102 in Patients With Advanced Breast Cancer or Castration-resistant Prostate Cancer

  HIRONOBU MINAMI, YUICHI ANDO, KENJI TAMURA, TAKESHI TAJIMA, RANDI ISAACS

  Lead, Anticancer Research USA Inc., Sep. 2020, Anticancer Research, 40(9) (9), 5229 - 5235

  Scientific journal


• Bleeding Events Associated with Anticoagulant Therapy; Apixaban in Japanese Patients with Cancer-associated Venous Thromboembolism: A Multicenter Phase II Trial(J-CAV)(和訳中)

  Mori Kenta, Otsui Kazunori, Imamura Yoshinori, Kitagawa Koichi, Okada Hideaki, Hata Akito, Hayashi Hidetoshi, Nose Taku, Ohata Shinya, Miyata Yoshiharu, Funakoshi Yohei, Toyoda Masanori, Kiyota Naomi, Yakushijin Kimikazu, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本循環器学会, Jul. 2020, 日本循環器学会学術集会抄録集, 84回, PE52 - 6, English


• 初期研修医の患者把握能力向上を目的としたTime-dependent Problem Listの有用性の更なる検討

  後藤 秀彰, 木村 真希, 坂井 里奈, 金原 史朗, 小山 泰司, 今村 善宣, 豊田 昌徳, 藥師神 公和, 河野 誠司, 南 博信

  (一社)日本医学教育学会, Jul. 2020, 医学教育, 51(Suppl.) (Suppl.), 105 - 105, Japanese


• Effect of tumor burden and growth rate on treatment outcomes of nivolumab in head and neck cancer

  C. Suzuki, N. Kiyota, Y. Imamura, J. Rikitake, S. Sai, T. Koyama, Y. Hyogo, Y. Nagatani, Y. Funakoshi, M. Toyoda, N. Otsuki, KI. Nibu, H. Minami

  BACKGROUND: Nivolumab improves overall survival (OS) in patients with platinum-refractory recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). In one study, however, Kaplan-Meier OS and progression-free survival (PFS) curves for the nivolumab and cytotoxic agent arms crossed at 3-6 months, suggesting that patients with initial resistance to immunotherapy might have better outcomes with cytotoxic treatment. Here, we explored the conditions and candidates which are predictive of nivolumab outcomes in R/M HNSCC. METHODS: We retrospectively reviewed the clinical records of 27 consecutive R/M HNSCC patients treated with nivolumab from 2014 to 2018. Tumor size was evaluated by RECIST ver.1.1. Tumor growth rate (Gr) was defined as 3log(D0/Dpre)/t, where D0 and Dpre are the sum of the diameters of the target lesions (SumTLs) at baseline and pre-baseline, and t is time, with 1t defined as 4 weeks. RESULTS: Twenty-five patients were enrolled. Survival was significantly worse in patients with disease progression within 3 months. Outcomes appeared poorer in patients with higher pre-treatment Gr and bigger SumTLs at baseline. We therefore explored the association between prognosis, Gr and SumTLs. Recursive partitioning analysis showed that the characteristics of patients with disease progression after 3 months were Gr < 0.76 and SumTLs < 31.0 mm. Further, Gr < 0.76 and SumTLs < 31.0 mm was associated with significantly longer PFS (p = 0.01) and OS (p < 0.01). CONCLUSIONS: These results suggest that Gr and SumTLs at baseline are significantly associated with OS and PFS in R/M HNSCC patients treated with nivolumab.

  Springer Science and Business Media LLC, Jul. 2020, International Journal of Clinical Oncology, 25(7) (7), 1270 - 1277, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Band 3 ectopic expression in colorectal cancer induces an increase in erythrocyte membrane-bound IgG and may cause immune-related anemia.

  Akihito Kitao, Shinichiro Kawamoto, Keiji Kurata, Ikuyo Hayakawa, Takashi Yamasaki, Hiroshi Matsuoka, Yasuo Sumi, Yoshihiro Kakeji, Toyomi Kamesaki, Hironobu Minami

  Autoimmune hemolytic anemia (AIHA) is a rare comorbidity in colorectal cancer (CRC) and has an unknown etiology. Previously, we described an AIHA case secondary to CRC with ectopic band 3 expression. Herein, we investigated ectopic band 3 expression and erythrocyte membrane-bound IgG in a CRC cohort. Between September 2016 and August 2018, 50 patients with CRC and 26 healthy controls were enrolled in the present study. The expression of band 3 and SLC4A1 mRNA was observed in 97% of CRC surgical specimens. Although clinical AIHA was not observed in any patient with CRC, a direct antiglobulin test was positive in 10 of the patients in the CRC group (p = 0.01). Flow cytometry revealed significantly increased erythrocyte membrane-bound IgG among patients with CRC compared to healthy controls (mean ± standard deviation; 38.8 ± 4.7 vs. 29.9 ± 15.6, p = 0.012). Normocytic anemia was observed, including in cases negative for fecal occult blood, suggesting a shortened erythrocyte life-span due to increased membrane-bound IgG. Immunoprecipitation revealed increased anti-band 3 autoantibodies in patients' sera. Mouse experiments recapitulated this phenomenon. We also confirmed that band 3 expression is controlled by 5'AMP-activated protein kinase under hypoxic conditions. These findings increase our understanding of the etiology of cancer-related anemia.

  Last, Springer Science and Business Media LLC, May 2020, International journal of hematology, 111(5) (5), 657 - 666, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• MYC amplification on double minute chromosomes in plasma cell leukemia with double IGH/CCND1 fusion genes

  Katsuya Yamamoto, Kimikazu Yakushijin, Mitsuhiro Ito, Hideaki Goto, Ako Higashime, Kazuyoshi Kajimoto, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  In multiple myeloma (MM), MYC rearrangements that result in increased MYC expression are associated with an aggressive form of MM and adverse outcome. However, the consequences of MYC amplification in MM remain unclear. Here, we describe an unusual case of plasma cell leukemia (PCL) harboring MYC amplification on double minute chromosomes (dmin). A 79-year-old woman was initially diagnosed as having BJP-κ type MM with bone lesions. After seven months, the disease progressed to secondary PCL: leukocytes 49.1 × 109/L with 77% plasma cells showing lymphoplasmacytic appearance. The bone marrow was infiltrated with 76% plasma cells immunophenotypically positive for CD38 and negative for CD45, CD19, CD20, and CD56. The karyotype by G-banding and spectral karyotyping was 48,XX,der(14)t(11;14)(q13;q32),+der(14)t(14;19)(q32;q13.1),+18,6~95dmin[15]/46,XX[5]. Fluorescence in situ hybridization detected multiple MYC signals on dmin and double IGH/CCND1 fusion signals on der(14)t(11;14) and der(14)t(14;19). Most plasma cells were diffusely and strongly positive for MYC and CCND1 by immunohistochemistry. The patient died of progressive disease after one week. MYC amplification led to high expression of MYC and rapid disease progression, indicating its clinical significance in the pathogenesis of MM/PCL. MYC amplification on dmin may be a very rare genetic event closely associated with the progression to PCL and coexistence of IGH/CCND1 fusions.

  Last, Elsevier BV, Apr. 2020, Cancer Genetics, 242, 35 - 40, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia

  Hitoshi Kiyoi, Joan D. Morris, Iekuni Oh, Yoshinobu Maeda, Hironobu Minami, Toshihiro Miyamoto, Toru Sakura, Hiroatsu Iida, Catherine A. Tuglus, Yuqi Chen, Cedric Dos Santos, James Kalabus, Abraham Anderson, Tomoko Hata, Yasuhiro Nakashima, Yukio Kobayashi

  Adult patients with relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) have a poor prognosis. Blinatumomab is a bispecific T-cell engager (BiTE) immuno-oncology therapy with dual specificity for CD19 and CD3 that redirects patients' CD3-positive cytotoxic T cells to lyse malignant and normal B cells. We conducted an open-label, phase 1b/2 study to determine the safety, pharmacokinetics, efficacy and recommended dose of blinatumomab in Japanese adults with R/R B-precursor ALL. Patients received 9 μg/day blinatumomab during week 1 and 28 μg/day during weeks 2-4, with a 2-week treatment-free interval (6-week cycle); patients received 28 μg/day blinatumomab in subsequent cycles. Primary endpoints were the incidence of dose-limiting toxicities (DLT) in phase 1b and complete remission (CR)/CR with partial hematologic recovery (CRh) within the first two cycles in phase 2. A total of 26 patients enrolled and 25 (96%) reported grade ≥3 adverse events (mostly cytopenias). There were no DLT. CR/CRh within two cycles was achieved by 4 of 5 patients (80%) in phase 1b and 8 of 21 patients (38%) in phase 2. Among patients with evaluable minimal residual disease, 4 (100%) in phase 1b and 3 (38%) in phase 2 had a complete MRD response. Median RFS for 8 patients who achieved CR/CRh in phase 2 was 5 (95% CI: 3.5-6.4) months; median OS was not estimable. There were no significant associations between maximum cytokine levels or percentage of specific cell types during cycle 1 and response. Consistent with global studies, blinatumomab appeared to be safe and efficacious in Japanese adults with R/R ALL.

  Wiley, Apr. 2020, Cancer Science, 111(4) (4), 1314 - 1323, English, International magazine

  Scientific journal


• がん免疫療法時代の再発・転移頭頸部扁平上皮癌における全身性炎症スコアの予後予測性

  今村 善宣, 清田 尚臣, 小山 泰司, 金原 史朗, 長谷 善明, 須藤 洋崇, 能勢 拓, 船越 洋平, 豊田 昌徳, 南 博信

  (一社)日本内科学会, Feb. 2020, 日本内科学会雑誌, 109(Suppl.) (Suppl.), 186 - 186, Japanese


• 2735人を対象とした悪性腫瘍関連静脈血栓塞栓症の合併率に関する後ろ向きコホート研究 甲状腺癌に対するチロシンキナーゼ阻害薬と血栓の関係

  能勢 拓, 今村 善宣, 清田 尚臣, 大幡 真也, 金原 史朗, 宮田 吉晴, 小山 泰司, 船越 洋平, 豊田 昌徳, 南 博信

  (一社)日本内科学会, Feb. 2020, 日本内科学会雑誌, 109(Suppl.) (Suppl.), 226 - 226, Japanese


• 当院における頭頸部がんに対する3-weekly高用量シスプラチン併用化学放射線療法の臨床的忍容性の検討

  高倉 嗣丈, 今村 善宣, 清田 尚臣, 金原 史朗, 小山 泰司, 藤島 佳未, 船越 洋平, 豊田 昌徳, 南 博信

  (一社)日本内科学会, Feb. 2020, 日本内科学会雑誌, 109(Suppl.) (Suppl.), 259 - 259, Japanese


• Detection of a novel CBFB-MYH11 fusion transcript in acute myeloid leukemia M1 with inv(16)(p13q22).

  Keiji Kurata, Katsuya Yamamoto, Yoko Okazaki, Yoriko Noguchi, Keiji Matsui, Hisayuki Matsumoto, Yumiko Inui, Kimikazu Yakushijin, Mitsuhiro Ito, Yuji Nakamachi, Hiroshi Matsuoka, Jun Saegusa, Hironobu Minami

  Acute myeloid leukemia (AML) with an inv(16)(p13q22) or t(16;16)(p13;q22) chromosomal abnormality represents one of the most common subtypes of de novo cases. These chromosomal rearrangements result in multiple CBFB-MYH11 fusion transcripts, with type-A being the most frequent. We here describe a unique case of de novo AML-M1, with inv(16)(p13q22), leading to an unusual CBFB-MYH11 fusion transcript, and der(7)t(7;11)(q31;q21). The fusion transcript involves a CBFB exon 5 with a breakpoint at nucleotide 754, an insertion of a 13-bp sequence of CBFB intron 5 at the fusion point, and the MYH11 exon 27 with a breakpoint at nucleotide 3464. To our knowledge, this CBFB-MYH11 fusion transcript has never been reported previously. The clinical characteristics of the present case are in line with previous reports suggesting that rare CBFB-MYH11 fusion transcripts lead to aberrant characteristics such as an atypical cytomorphology and additional cytogenetic abnormalities.

  Elsevier BV, Feb. 2020, Cancer genetics, 241, 72 - 76, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Amrubicin for Patients With Platinum-refractory Small-cell Prostate Cancer: Two Case Reports.

  Kotaro Suzuki, Tomoaki Terakawa, Shiro Kimbara, Masanori Toyoda, Naoe Jimbo, Yuzo Nakano, Hironobu Minami, Masato Fujisawa

  Jan. 2020, Clinical genitourinary cancer, English, International magazine

  [Refereed]

  Scientific journal


• Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure

  Timothy P. Hughes, Michael J. Mauro, Jorge E. Cortes, Hironobu Minami, Delphine Rea, Daniel J. DeAngelo, Massimo Breccia, Yeow-Tee Goh, Moshe Talpaz, Andreas Hochhaus, Philipp le Coutre, Oliver Ottmann, Michael C. Heinrich, Juan L. Steegmann, Michael W.N. Deininger, Jeroen J.W.M. Janssen, Francois-Xavier Mahon, Yosuke Minami, David Yeung, David M. Ross, Martin S. Tallman, Jae H. Park, Brian J. Druker, David Hynds, Yuyan Duan, Christophe Meille, Florence Hourcade-Potelleret, K. Gary Vanasse, Fabian Lang, Dong-Wook Kim

  Massachusetts Medical Society, Dec. 2019, New England Journal of Medicine, 381(24) (24), 2315 - 2326

  Scientific journal


• Tetrasomy 8 and isochromosome 7q in CD5-positive hepatosplenic T-cell lymphoma with leukemic presentation

  Katsuya Yamamoto, Kimikazu Yakushijin, Marika Okuni-Watanabe, Akiko Hashimoto, Hiroshi Matsuoka, Hironobu Minami

  Last, Springer Science and Business Media LLC, Nov. 2019, International Journal of Hematology, 110(5) (5), 521 - 523, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells

  Junko Mukohyama, Taichi Isobe, Qingjiang Hu, Takanori Hayashi, Takashi Watanabe, Masao Maeda, Hisano Yanagi, Xin Qian, Kimihiro Yamashita, Hironobu Minami, Koshi Mimori, Debashis Sahoo, Yoshihiro Kakeji, Akira Suzuki, Piero Dalerba, Yohei Shimono

  Abstract miRNAs are key players in the integrated regulation of cellular processes and shape many of the functional properties that define the “cancer stem cell” (CSC) phenotype. Little is known, however, about miRNAs that regulate such properties in human colorectal carcinoma. In this study, we compared the expression levels of 754 miRNAs between paired samples of EpCAM+/CD44+ cancer cells (enriched in CSCs) and EpCAM+/CD44neg cancer cells (with CSC depletion) sorted in parallel from human primary colorectal carcinomas and identified miR-221 as the miRNA that displayed the highest level of preferential expression in EpCAM+/CD44+ cancer cells. High levels of miR-221 expression were associated with Lgr5+ cells in mouse colon crypts and reduced survival in patients with colorectal carcinoma. Constitutive overexpression of miR-221 enhanced organoid-forming capacity of both conventional colorectal carcinoma cell lines and patient-derived xenografts (PDX) in vitro. Importantly, constitutive downregulation of miR-221 suppressed organoid-forming capacity in vitro and substantially reduced the tumorigenic capacity of CSC populations from PDX lines in vivo. Finally, the most abundant splicing isoform of the human Quaking (QKI) gene, QKI-5, was identified as a functional target of miR-221; overexpression of miR-221–reduced QKI-5 protein levels in human colorectal carcinoma cells. As expected, overexpression of QKI-5 suppressed organoid-forming capacity in vitro and tumorigenic capacity of colorectal carcinoma PDX cells in vivo. Our study reveals a mechanistic link between miR-221 and QKI and highlights their key role in regulating CSC properties in human colorectal cancer. Significance: These findings uncover molecular mechanisms underlying the maintenance of cancer stem cell properties in colon cancer.

  American Association for Cancer Research (AACR), Oct. 2019, Cancer Research, 79(20) (20), 5151 - 5158

  Scientific journal


• An mTORC1/2 dual inhibitor, AZD2014, acts as a lysosomal function activator and enhances gemtuzumab ozogamicin-induced apoptosis in primary human leukemia cells.

  Mizutani Y, Inase A, Maimaitili Y, Miyata Y, Kitao A, Matsumoto H, Kawaguchi K, Higashime A, Goto H, Kurata K, Yakushijin K, Minami H, Matsuoka H

  Gemtuzumab ozogamicin (GO), an anti-CD33 antibody linked to calicheamicin via an acid-labile linker, is the first antibody-drug conjugate (ADC). The acidic environment inside lysosomes of target cells is an important intracellular determinant of the cytocidal action of GO, as the linker is hydrolyzed under acidic conditions. However, lysosomal activity in acute myeloid leukemia (AML) blasts in GO therapy has been insufficiently evaluated. It has been suggested that lysosome activity is suppressed in AML due to hyperactivation of the phosphoinositide 3-kinase/Akt pathway. We therefore hypothesized that agents which activate lysosomal function would potentiate the cytotoxicity of GO. Here, we found that a clinically useful mTORC1/2 dual inhibitor, AZD2014, reduced pH in the acidic organelles, including lysosomes, as shown by increased LysoTracker fluorescent intensity, and synergistically enhanced the cytotoxic effect of GO in primary leukemia cells. GO-induced cytotoxicity appeared to be enhanced with the increase in lysosomal activity by AZD2014. These results indicate that AZD2014 activated lysosomal function in primary leukemia cells, which in turn enhanced the cytotoxicity of GO. Enhancement of lysosomal activity may represent a new therapeutic strategy in the treatment of GO and other ADCs, particularly in cases with low lysosomal activity.

  Springer Science and Business Media LLC, Oct. 2019, International journal of hematology, 110(4) (4), 490 - 499, English, Domestic magazine

  [Refereed]

  Scientific journal


• A Case of Multi-System Langerhans Cell Histiocytosis with Local Invasion of the Orbital Apex

  Hiroko Yamada, Takuji Kurimoto, Sotaro Mori, Mari Sakamoto, Kaori Ueda, Yuko Yamada-Nakanishi, Yoichi Uozumi, Hiroyasu Shose, Masaaki Taniguchi, Masanori Toyoda, Hironobu Minami, Makoto Nakamura

  Langerhans cell histiocytosis (LCH) is characterised by tissue destruction caused by the abnormal proliferation of pathogenic dendritic cells. We report a rare case of multi-system LCH with local invasion of the orbital apex.A 56-year-old woman suffered from a decrease of visual acuity in the left eye caused by central scotoma and the limitation of eye movement in all directions. Magnetic resonance imaging revealed an enhanced lesion in the left orbital apex, suggesting optic nerve compression. She had been diagnosed with eosinophilic granuloma 24 years previously. Two weeks after the current presentation, we admitted the patient for optic canal and orbital apex decompression and subtotal tumour resection. Histopathological analysis confirmed the diagnosis of LCH. Post-surgical treatment with low-dose cytarabine was initiated for the residual tumour. However, it was ceased because of myelosuppression-induced pyelonephritis. After surgery, the central scotoma disappeared on day 5 and eye movement palsy resolved by 6 months. After the cessation of cytarabine, she has received low-dose steroid therapy for 2 years with no recurrence. Early surgical intervention with low-dose steroid therapy can lead to recovery of visual acuity and resolve eye movement palsy in patients with lesions of the orbital apex caused by multi-system LCH.

  S. Karger AG, Sep. 2019, Case Reports in Ophthalmology, 10(3) (3), 319 - 326, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Pharmacokinetics of Oxaliplatin in a Hemodialysis Patient with Metastatic Colon Cancer

  Nagatani Yoshiaki, Imamura Yoshinori, Nakamura Tsutomu, Yamashita Kazuhiko, Okuno Mamoru, Yasui Hiroyuki, Hiraoka Jun, Niigata Riho, Kono Keiji, Hyogo Yasuko, Suto Hirotaka, Takenaka Kei, Funakoshi Yohei, Toyoda Masanori, Kiyota Naomi, Minami Hironobu

  {ClinMed} International Library, Sep. 2019, International Journal of Oncology Research, 2(2) (2)

  Scientific journal


• ヒト乳がん異種移植モデルの微小転移がん幹細胞で発現低下しているマイクロRNA-93の解析(Analyses of miR-93 that was downregulated in micrometastatic cancer stem cells in a human breast cancer xenograft model)

  渋谷 尚樹, 下野 洋平, 南 博信, 掛地 吉弘, 鈴木 聡

  (一社)日本癌学会, Sep. 2019, 日本癌学会総会記事, 78回, P - 2229, English


• Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open‐label phase 2 trial

  Kenji Tamura, Kosei Hasegawa, Noriyuki Katsumata, Koji Matsumoto, Hirofumi Mukai, Shunji Takahashi, Hiroyuki Nomura, Hironobu Minami

  Nivolumab is a human monoclonal antibody against the immune checkpoint receptor programmed death-1, inhibiting binding to programmed death-ligand 1 or 2 (PD-L1 or PD-L2). This phase 2 study evaluated the efficacy and safety of nivolumab in patients with advanced/recurrent uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma (STS). Patients received nivolumab 240 mg at 2-week intervals. Primary endpoint was objective response rate; secondary endpoints included overall survival, progression-free survival, and safety. PD-L1 expression and microsatellite-instability (MSI) status were analyzed as potential efficacy biomarkers. Objective response rate was 25%, 23%, and 0% in patients with cervical cancer (n = 20), corpus cancer (n = 22), and STS (n = 21), respectively. The lower 80% confidence intervals of objective response rates in patients with cervical or corpus cancer exceeded the threshold rate (5%); the primary endpoint was met in cervical and corpus cancer, but not in STS. Median progression-free survival was 5.6, 3.4, and 1.4 months, and 6-month overall survival was 84%, 73%, and 86% in cervical cancer, corpus cancer, and STS, respectively. The objective response rate was higher in patients with cervical cancer with PD-L1-positive (n = 5/15; 33%) versus PD-L1-negative (n = 0/5; 0%) tumors. The two patients with corpus cancer classified as MSI-high responded; the six patients classified as microsatellite stable did not respond. Overall, nivolumab showed acceptable toxicity in all cohorts, with evidence of clinical activity in uterine cervical or corpus cancer, but not in STS. PD-L1 expression in cervical cancer and MSI-high in corpus cancer may predict clinical activity of nivolumab in these cancers.

  Wiley, Sep. 2019, Cancer Science, 110(9) (9), 2894 - 2904, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Exploratory analysis of prognostic factors for lenvatinib in radioiodine-refractory differentiated thyroid cancer.

  Chiaki Suzuki, Naomi Kiyota, Yoshinori Imamura, Hideaki Goto, Hirotaka Suto, Naoko Chayahara, Masanori Toyoda, Yasuhiro Ito, Akihiro Miya, Akira Miyauchi, Naoki Otsuki, Ken-Ichi Nibu, Hironobu Minami

  BACKGROUND: Multitarget kinase inhibitors (m-TKI), including lenvatinib, are now available as treatment options for radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, the optimal timing of treatment initiation with m-TKI in these patients remains to be defined. METHODS: We retrospectively reviewed the clinical records of 30 consecutive patients with RR-DTC. The relationship between clinical characteristics was evaluated, including tumor growth parameters at pretreatment/post-treatment and efficacy of lenvatinib. RESULTS: A total of 26 patients with RR-DTC treated with lenvatinib were evaluable for response and eligible for analysis. From the results of multivariate analysis, baseline tumor size and tumor-related symptoms were independent negative prognostic factors for overall survival (OS) and progression-free survival (PFS). Pretreatment tumor growth parameters were not prognostic for either PFS or OS. CONCLUSIONS: Patients with RR-DTC with a high tumor burden and tumor-related symptoms had significantly worse prognosis. Greater tumor reduction after starting lenvatinib may lead to better prognosis, irrespective of pretreatment high tumor growth rate.

  Last, Wiley, Sep. 2019, Head & neck, 41(9) (9), 3023 - 3032, English, International magazine

  [Refereed]

  Scientific journal


• Phase I study of BGT226, a pan-PI3K and mTOR inhibitor, in Japanese patients with advanced solid cancers

  Hironobu Minami, Yutaka Fujiwara, Kei Muro, Masahiko Sato, Atsuko Moriya

  Springer Science and Business Media LLC, Aug. 2019, Cancer Chemotherapy and Pharmacology, 84(2) (2), 337 - 343

  Scientific journal


• Double-hit pancreatic B-lymphoblastic lymphoma with a variant translocation t(2;18)(p11;q21)

  Katsuya Yamamoto, Shinichiro Kawamoto, Akihito Kitao, Yu Mizutani, Yumiko Inui, Kimikazu Yakushijin, Kazuyoshi Kajimoto, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  Double-hit lymphoma is typically categorized as "high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements", but in infrequent cases in which terminal deoxynucleotidyl transferase (TdT) expression is positive, it is categorized as B-lymphoblastic lymphoma (B-LBL). BCL2 rearrangements are usually caused by t(14;18)(q32;q21); variant translocations are very rare. Here, we describe an unusual case of double-hit pancreatic B-LBL with a variant translocation t(2;18)(p11;q21). A 69-year-old man was admitted because of an abdominal mass. Computed tomography scans demonstrated a diffusely enlarged pancreas and massive ascites. Cell block preparations of ascites cells revealed marked proliferation of blastic lymphoid cells positive for CD19, CD10, CD79a, PAX5, and TdT, indicating a diagnosis of B-LBL. G-banding and spectral karyotyping showed 45,XY,+X,t(2;18)(p11;q21),-4,der(5)t(1;5)(q12;p15),der(6)t(6;21)(q21;q?),t(8;14)(q24;q32),-15. Fluorescence in situ hybridization detected split BCL2 and IGH/MYC fusion signals. Almost all ascites cells were diffusely and strongly positive for MYC and BCL2. The patient died of progressive disease 20 days after admission. To our knowledge, this is the first reported case of MYC and BCL2 double-hit B-LBL with t(2;18)(p11;q21). High coexpression of MYC by t(8;14) and BCL2 by t(2;18) may be implicated in the development of B-LBL. Furthermore, double-hit B-LBL may be associated with a less favorable outcome compared with typical B-LBL.

  Last, Springer Science and Business Media LLC, Jul. 2019, International Journal of Hematology, 110(1) (1), 107 - 114, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Adapalene Gel 0.1% Versus Placebo as Prophylaxis for Anti-Epidermal Growth Factor Receptor-Induced Acne-Like Rash: A Randomized Left-Right Comparative Evaluation (APPEARANCE).

  Naoko Chayahara, Toru Mukohara, Motoko Tachihara, Yoshimi Fujishima, Atsushi Fukunaga, Ken Washio, Masatsugu Yamamoto, Kyosuke Nakata, Kazuyuki Kobayashi, Kei Takenaka, Masanori Toyoda, Naomi Kiyota, Kazutoshi Tobimatsu, Hisayo Doi, Naomi Mizuta, Naho Marugami, Atsushi Kawaguchi, Chikako Nishigori, Yoshihiro Nishimura, Hironobu Minami

  LESSONS LEARNED: The results of the APPEARANCE trial indicate that adapalene does not prevent acne-like rash over placebo when added to topical moisturizer and oral minocycline but instead may have a detrimental effect. Therefore, adapalene is not recommended as prophylaxis against acne-like rash induced by anti-epidermal growth factor receptor therapies.Given that acne-like rash was completely controlled with placebo in approximately half of patients, predictive measures to identify patients needing intensive prophylaxis are required. BACKGROUND: Anti-epidermal growth factor receptor (EGFR) therapies are frequently associated with acne-like rash. To evaluate the prophylactic efficacy of adapalene, a topical retinoid used as first-line therapy for acne vulgaris, we conducted a randomized, placebo-controlled, evaluator-blinded, left-right comparative trial. METHODS: Patients with non-small cell lung, colorectal, or head and neck cancer scheduled to receive anti-EGFR therapies were randomly assigned to once-daily adapalene application on one side of the face, with placebo on the other side. All patients had topical moisturizer coapplied to both sides of the face, and received oral minocycline. The primary endpoint was the difference in total facial lesion count of acne-like rash at 4 weeks. Secondary endpoints included complete control rate (CCR) of acne-like rash (≤5 facial lesions) and global skin assessment (Investigator's Global Assessment [IGA] scale, grade 0-4) at 4 weeks. Two blinded dermatologists independently evaluated the endpoints from photographs. RESULTS: A total of 36 patients were enrolled, of whom 26 were evaluable. Adapalene treatment was associated with a greater lesion count than placebo at 4 weeks, although the difference was not statistically significant (mean, 12.6 vs. 9.8, p = .12). All four patients with a difference >10 in lesion count between face sides had a greater count on the adapalene-treated side. No significant differences were observed in CCR of acne-like rash (54% vs. 50%) or IGA scale (mean grade, 1.9 vs. 1.7) between the adapalene and placebo sides. CONCLUSION: Adapalene is not recommended as prophylaxis against acne-like rash induced by anti-EGFR therapies.

  Last, Oxford University Press (OUP), Jul. 2019, The oncologist, 24(7) (7), 885-e413 - e413, English, International magazine

  [Refereed]

  Scientific journal


• Corrigendum to "Phase 1/2 trial of glasdegib in patients with primary or secondary myelofibrosis previously treated with ruxolitinib" [Leukemia Res. 79 (2019) 38-44].

  Gerds AT, Tauchi T, Ritchie E, Deininger M, Jamieson C, Mesa R, Heaney M, Komatsu N, Minami H, Su Y, Shaik N, Zhang X, DiRienzo C, Zeremski M, Chan G, Talpaz M

  Jun. 2019, Leukemia research, 81, 105

  [Refereed]


• Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

  Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Yasuhiro Fujisawa, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Masahiro Hatsumichi, Hironobu Minami

  The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.

  Wiley, Jun. 2019, Cancer Science, 110(6) (6), 1995 - 2003, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

  Keiko Goto, Yutaka Fujiwara, Takeshi Isobe, Naoko Chayahara, Naomi Kiyota, Toru Mukohara, Yukari Tsubata, Takamasa Hotta, Kenji Tamura, Noboru Yamamoto, Hironobu Minami

  Although dose reduction of S-1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5-fluorouracil, 5-chloro-2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S-1 in patients with renal impairment. We classified patients receiving S-1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S-1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m2 ), 10 patients in cohort 2 (eGFR = 50-79 mL/min/1.73 m2 ), 10 patients in cohort 3 (eGFR = 30-49 mL/min/1.73 m2 ), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m2 ). Those in cohorts 3 and 4 treated with an adjusted dose of S-1 showed a similar area under the curve for 5-fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S-1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S-1 in patients with impaired renal function using eGFR is appropriate and safe.

  Wiley, Jun. 2019, Cancer Science, 110(6) (6), 1987 - 1994, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Phase 1/2 trial of glasdegib in patients with primary or secondary myelofibrosis previously treated with ruxolitinib

  Aaron T. Gerds, Tetsuzo Tauchi, Ellen Ritchie, Michael Deininger, Catriona Jamieson, Ruben Mesa, Mark Heaney, Norio Komatsu, Hironobu Minami, Yun Su, Naveed Shaik, Xiaoxi Zhang, Christine DiRienzo, Mirjana Zeremski, Geoffrey Chan, Moshe Talpaz

  Elsevier BV, Apr. 2019, Leukemia Research, 79, 38 - 44

  Scientific journal


• Successful Bridging Chemotherapy with Gemcitabine, Carboplatin, and Dexamethasone before Unrelated Stem Cell Transplantation for Hepatosplenic T-cell Lymphoma.

  Okuni M, Yakushijin Kimikazu, Uehara Keiichiro, Ichikawa H, Suto H, Hashimoto A, Tanaka Y, Shinzato I, Sakai R, Mizutani Y, Nagao S, Kurata K, Kakiuchi S, Miyata Y, Inui Y, Saito Y, Kawamoto Shinichiro, Yamamoto K, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu

  A 45-year-old woman was diagnosed with hepatosplenic T-cell lymphoma (HSTCL), a rare subtype of peripheral T-cell lymphoma. She received different types of chemotherapy, but disease progression was observed. To reduce the tumor burden before an unrelated bone marrow transplantation, combination chemotherapy consisting of the gemcitabine, carboplatin, and dexamethasone (GCD) was administered as bridging therapy, resulting in a reduction in the number of lymphoma cells. We were then able to perform bone marrow transplantation. Although she experienced some adverse events, she successfully achieved long-term remission. We herein report a successful case of HSTCL treated with unrelated stem cell transplantation following the GCD regimen as bridging chemotherapy.

  Last, Japanese Society of Internal Medicine, Mar. 2019, Intern Med., 58(5) (5), 707 - 712, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site

  Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, Matsumoto K, Onoue T, Mukai H, Matsubara N, Minami Hironobu, Toyota M, Onozawa Y, Ono A, Fujita Y, Sakai K, Koh Y, Takeuchi A, Nishio K, Nakagawa K

  Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types. Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.

  American Society of Clinical Oncology (ASCO), Mar. 2019, J Clin Oncol, 37(7) (7), 570 - 579, English

  [Refereed]

  Scientific journal


• A Phase II study of the safety and efficacy of lenvatinib in patients with advanced thyroid cancer.

  Shunji Takahashi, Naomi Kiyota, Tomoko Yamazaki, Naoko Chayahara, Kenji Nakano, Lina Inagaki, Kazuhisa Toda, Tomohiro Enokida, Hironobu Minami, Yoshinori Imamura, Naoki Fukuda, Tatsuya Sasaki, Takuya Suzuki, Hiroki Ikezawa, Corina E Dutcus, Makoto Tahara

  AIM: To investigate the safety and efficacy of lenvatinib in advanced thyroid cancer. PATIENTS/METHODS: In this Phase II study, 51 Japanese patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC), medullary thyroid cancer (MTC) or anaplastic thyroid cancer (ATC) received once-daily lenvatinib 24 mg. The primary end point was safety. RESULTS: All patients experienced ≥1 adverse event (AE); only one patient experienced an AE leading to discontinuation. The most common any-grade AEs were hypertension, decreased appetite, palmar-plantar erythrodysesthesia, fatigue and proteinuria. Response rates for RR-DTC: 68%; MTC: 22%; ATC: 24%. Median progression-free survival for RR-DTC: 25.8 months; MTC: 9.2 months; ATC: 7.4 months. CONCLUSION: Lenvatinib demonstrated a manageable safety profile, proven antitumor activity in RR-DTC and promising efficacy in MTC and ATC. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01728623.

  Informa UK Limited, Mar. 2019, Future oncology (London, England), 15(7) (7), 717 - 726, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 甲状腺癌に対するレンバチニブ治療中の観血的処置の安全性・予後への影響に関する遡及的検討

  金原 史朗, 清田 尚臣, 小山 泰司, 藤島 佳未, 今村 善宣, 船越 洋平, 豊田 昌徳, 南 博信

  (一社)日本内科学会, Feb. 2019, 日本内科学会雑誌, 108(Suppl.) (Suppl.), 284 - 284, Japanese

  [Refereed]


• Human herpesvirus 6 encephalitis in patients administered mycophenolate mofetil as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

  Inui Y, Yakushijin Kimikazu, Okamura A, Tanaka Y, Shinzato I, Nomura T, Ichikawa H, Mizutani Y, Kitao A, Kurata K, Kakiuchi S, Miyata Y, Sanada Y, Kitagawa K, Uryu K, Kawamoto Shinichiro, Yamamoto K, Matsuoka Hiroshi, Murayama T, Ito Mitsuhiro, Minami Hironobu

  BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. METHODS AND RESULTS: We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. CONCLUSIONS: Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

  Wiley, Feb. 2019, Transpl Infect Dis., 21(1) (1), e13024, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO–ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS

  K. Muro, F. Lordick, T. Tsushima, G. Pentheroudakis, E. Baba, Z. Lu, B.C. Cho, I.M. Nor, M. Ng, L -T Chen, K. Kato, J. Li, M -H Ryu, W I Wan Zamaniah, W -P Yong, K -H Yeh, T.E. Nakajima, K. Shitara, H. Kawakami, Y. Narita, T. Yoshino, E. Van Cutsem, E. Martinelli, E.C. Smyth, D. Arnold, H. Minami, J. Tabernero, J -Y Douillard

  Elsevier BV, Jan. 2019, Annals of Oncology, 30(1) (1), 34 - 43

  Scientific journal


• Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO–ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS

  K. Muro, E. Van Cutsem, Y. Narita, G. Pentheroudakis, E. Baba, J. Li, M -H Ryu, W I Wan Zamaniah, W -P Yong, K -H Yeh, K. Kato, Z. Lu, B.C. Cho, I.M. Nor, M. Ng, L -T Chen, T.E. Nakajima, K. Shitara, H. Kawakami, T. Tsushima, T. Yoshino, F. Lordick, E. Martinelli, E.C. Smyth, D. Arnold, H. Minami, J. Tabernero, J -Y Douillard

  Elsevier BV, Jan. 2019, Annals of Oncology, 30(1) (1), 19 - 33

  Scientific journal


• PET/MRI陰性だが頭部造影MRIにて中枢神経浸潤が明らかとなった精巣原発DLBCLの1例

  後藤秀彰, 東目亜湖, 坂井里奈, 川口晃司, 石川瑶子, 倉田啓史, 藥師神公和, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本血液学会-東京事務局, Jan. 2019, 臨床血液, 60(1号) (1号), 59 - 59, Japanese

  [Refereed]

  Research society


• Discontinuation of sorafenib can lead to the emergence of FLT3-ITD-positive acute myeloid leukemia

  Seiji Kakiuchi, Kimikazu Yakushijin, Rina Sakai, Koji Kawaguchi, Ako Higashime, Keiji Kurata, Hiroya Ichikawa, Shigeki Nagao, Junpei Rikitake, Naomi Kiyota, Hiroshi Matsuoka, Hironobu Minami

  A 69-year-old woman who had been diagnosed with unresectable papillary thyroid cancer was referred to our hospital. We initially treated her with sorafenib, but she subsequently developed erythema multiforme, which was suspected to be a drug rush due to sorafenib; therefore, sorafenib was discontinued. At the time of discontinuation, immature blast cells were detected in her peripheral blood. Approximately two weeks later, her skin rash improved substantially, but the proportion of blasts in the peripheral blood increased. We performed a bone marrow examination, and she was diagnosed with FLT3-ITD-positive acute myeloid leukemia. FLT3-ITD expression is found in 20–25% of AML and is a known independent poor prognostic factor. To overcome the poor prognosis associated with FLT3-ITD, molecular drugs targeting FLT3-ITD are attracting much attention. Sorafenib, a multi-kinase inhibitor, also has an effect on FLT3-ITD. Although primary disease flares after tyrosine kinase inhibitor discontinuation have been reported, this is the first report to describe discontinuation of sorafenib treatment as a potential trigger of FLT3-ITD-positive acute myeloid leukemia in papillary thyroid cancer.

  SAGE Publications, Dec. 2018, Journal of Oncology Pharmacy Practice, 25(8) (8), 2010 - 2015, English, International magazine

  [Refereed]

  Scientific journal


• Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria

  Hideaki Goto, Naomi Kiyota, Naoki Otsuki, Yoshinori Imamura, Naoko Chayahara, Hirotaka Suto, Yoshiaki Nagatani, Masanori Toyoda, Toru Mukohara, Ken-ichi Nibu, Toshihiko Kasahara, Yasuhiro Ito, Akihiro Miya, Mitsuyoshi Hirokawa, Akira Miyauchi, Hironobu Minami

  Elsevier BV, Dec. 2018, Auris Nasus Larynx, 45(6) (6), 1249 - 1252

  Scientific journal


• Analyses of miR-25 that was downregulated in micrometastatic cancer stem cells in a human breast cancer xenograft model

  Naoki Shibuya, Yohei Shimono, Hironobu Minami, Yoshihiro Kakeji, Akira Suzuki

  Dec. 2018, CANCER SCIENCE, 109, 447 - 447, English


• Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study

  Kenjiro Namikawa, Yoshio Kiyohara, Tatsuya Takenouchi, Hisashi Uhara, Hiroshi Uchi, Shusuke Yoshikawa, Sumiko Takatsuka, Hiroshi Koga, Naoko Wada, Hironobu Minami, Masahiro Hatsumichi, Suguru Asada, Yoshinobu Namba, Naoya Yamazaki

  AIM: The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naïve Japanese patients with advanced melanoma. METHODS: In this multicentre, single-arm study, treatment-naïve Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety. RESULTS: The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2-27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III-IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred. CONCLUSIONS: This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naïve Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade III-IV AEs were high but manageable with appropriate medical attention and treatment. TRIAL REGISTRATION: JapicCTI-152869.

  Elsevier BV, Dec. 2018, European Journal of Cancer, 105, 114 - 126, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Phase 2 Study of Blinatumomab in Japanese Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL)

  Kobayashi Yukio, Zimmerman Zachary F, Oh Iekuni, Maeda Yoshinobu, Minami Hironobu, Miyamoto Toshihiro, Sakura Toru, Iida Hiroatsu, Chen Yuqi, Kiyoi Hitoshi

  Nov. 2018, BLOOD, 132

  [Refereed]


• A phase I study of single-agent BEZ235 special delivery system sachet in Japanese patients with advanced solid tumors

  Masanori Toyoda, Koichiro Watanabe, Taro Amagasaki, Kazuto Natsume, Hiromi Takeuchi, Cornelia Quadt, Kuniaki Shirao, Hironobu Minami

  Springer Science and Business Media LLC, Nov. 2018, Cancer Chemotherapy and Pharmacology, 83(2) (2), 289 - 299, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Thrombotic Microangiopathy with Severe Proteinuria Induced by Lenvatinib for Radioactive Iodine-Refractory Papillary Thyroid Carcinoma

  Yasuko Hyogo, Naomi Kiyota, Naoki Otsuki, Shunsuke Goto, Yoshinori Imamura, Naoko Chayahara, Masanori Toyoda, Ken-ichi Nibu, Toshiki Hyodo, Shigeo Hara, Hiroo Masuoka, Toshihiko Kasahara, Yasuhiro Ito, Akihiro Miya, Mitsuyoshi Hirokawa, Akira Miyauchi, Hironobu Minami

  Nov. 2018, Case Reports in Oncology, 11(3) (3), 735 - 741, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• An mTORC1/2 kinase inhibitor enhances the cytotoxicity of gemtuzumab ozogamicin by activation of lysosomal function

  Yimamu Maimaitili, Aki Inase, Yoshiharu Miyata, Akihito Kitao, Yu Mizutani, Seiji Kakiuchi, Yohei Shimono, Yasuyuki Saito, Takashi Sonoki, Hironobu Minami, Hiroshi Matsuoka

  Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), has attracted the interest of hematologists because more than 90% of acute myeloid leukemia (AML) blasts express its target, CD33. Although GO and subsequently developed ADCs depend on lysosomes for activation, lysosome number and activity in tumor cells has not been well elucidated. In this study, we investigated whether an mTORC1/2 kinase inhibitor, PP242, which was reported to activate lysosomal function, potentiates the cytotoxicity of GO in AML cells. Eight AML cell lines (U937, THP-1, SKM-1, SKK-1, SKNO-1, HL-60, MARIMO and KO52) were treated with GO and PP242. The cytotoxic effect of GO was enhanced by concurrent treatment with a non-cytotoxic concentration (500 nM) of PP242 in most cell lines, except MARIMO and KO52 cells. We then used LysoTracker to label acidic lysosomes in U937, THP-1, SKM-1, MARIMO and KO52 cells. LysoTracker fluorescence was dramatically increased by treatment with PP242 in U937, THP-1 and SKM-1 cells, and the intensified fluorescence was retained with PP242 + GO. In contrast, PP242 did not induce a significant increase in fluorescence in MARIMO cells, consistent with the lack of combinatory cytotoxicity. LysoTracker fluorescence was also increased by PP242 in KO52 cells, which have been reported to strongly express multidrug resistance (MDR). Further, PP242 suppressed GO-induced Chk1 activation and G2/M cell cycle arrest, which in turn triggered cell cycle promotion and cell death. These results indicate that inhibition of mTORC1/2 kinase by PP242 enhanced the cytotoxicity of GO by increasing lysosomal compartments and promoting the cell cycle via suppression of GO-induced Chk1 activation. This combination may represent an attractive new therapeutic strategy for the treatment of leukemia.

  Elsevier BV, Nov. 2018, Leukemia Research, 74, 68 - 74, English, International magazine

  [Refereed]

  Scientific journal


• 甲状腺がんに対するレンバチニブ治療中の観血的処置の安全性に関する遡及的検討

  金原史朗, 清田尚臣, 今村善宣, 大月直樹, 丹生健一, 南川勉, Hara Hitomi, 角谷賢一朗, 佐々木良平, Minami Hironobu

  日本内分泌外科学会・日本甲状腺外科学会, Oct. 2018, 日本内分泌・甲状腺外科学会雑誌, 35(Suppl.2) (Suppl.2), S319 - S319, Japanese

  [Refereed]

  Research society


• EGFR阻害薬に伴うざ瘡様発疹へのアダパレンゲル予防投与のプラセボ対照左右ランダム化比較試験(APPEARANCE試験)

  鷲尾健, 福永淳, 茶屋原菜穂子, 向原徹, 豊田昌徳, 立原素子, 山本正嗣, 西村善博, 藤島佳未, 飛松和俊, 土井久容, 水田直美, 丸上菜穂, 川口淳, 錦織千佳子, Minami Hironobu

  (一社)日本皮膚免疫アレルギー学会, Oct. 2018, 日本皮膚免疫アレルギー学会雑誌, 2(1) (1), 178 - 178, Japanese

  [Refereed]

  Scientific journal


• Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin

  Hideaki Goto, Yohei Shimono, Yohei Funakoshi, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Seishi Kono, Shintaro Takao, Toru Mukohara, Hironobu Minami

  Tumor microenvironment plays a key role for tumor development and progression. Although adipose tissue is a predominant component of stroma in mammary tissues and secretes various cytokines, chemokines and growth factors, roles of adipocytes in breast cancers remain to be elucidated. In this study, we found that adipsin, an adipokine secreted from mammary adipose tissues, enhanced proliferation and cancer stem cell (CSC)-like properties of human breast cancer patient-derived xenograft (PDX) cells. Adipsin was predominantly expressed in both adipose tissues of the surgical specimens of breast cancer patients and adipose-derived stem cells (ADSCs) isolated from them, and its expression level was significantly higher in obese patients. ADSCs significantly enhanced the sphere-forming ability of breast cancer PDX cells derived from both estrogen receptor-positive and -negative breast cancer PDX cells. Suppression of adipsin-mediated signaling by a specific inhibitor or adipsin knockdown in ADSCs significantly decreased the sphere-forming ability and the expression of CSC markers in co-cultured breast cancer PDX cells. Growth of breast cancer PDX tumors was significantly enhanced by co-transplantation with ADSCs in vivo, and it was weakened when co-transplanted with the adipsin knocked-down ADSCs. These results suggest that adipsin is an important adipokine secreted from mammary adipose tissue that functions as a component of tumor microenvironment and a CSC niche in breast cancers.

  Springer Science and Business Media LLC, Sep. 2018, Oncogene, 38(6) (6), 767 - 779, English, International magazine

  [Refereed]

  Scientific journal


• sorafenib投薬を中断することで顕在化したFLT3-ITD陽性急性骨髄性白血病の一例(Discontinuation of sorafenib can lead to the emergence of FLT3-ITD-positive acute myeloid leukemia)

  垣内 誠司, 坂井 里奈, 川口 晃司, 東目 亜湖, 倉田 啓史, 市川 大哉, 長尾 茂輝, 力武 隼平, 清田 尚臣, 藥師神 公和, 松岡 広, 南 博信

  (一社)日本血液学会-東京事務局, Sep. 2018, 臨床血液, 59(9) (9), 1641 - 1641, English


• 本邦での大腸癌患者におけるマイクロサテライト不安定性検査の有用性についての検討(Universal screening with microsatellite instability testing in Japanese patients with colorectal cancer)(英語)

  須藤洋崇, 豊田昌徳, 後藤秀彰, 船越洋平, 山下公大, 鈴木知志, 掛地吉弘, Minami Hironobu

  Sep. 2018, 日本癌学会総会記事, (77回) (77回), 2402, Japanese

  [Refereed]

  Scientific journal


• 多発性筋炎様症状を呈したNK/T細胞リンパ腫(Extranodal NK/T-cell lymphoma mimicking polymyositis)(英語)

  長尾茂輝, 倉田啓史, 東目亜湖, 川口晃司, 市川大哉, 坂井里奈, 後藤秀彰, 水谷優, 垣内誠司, 宮田吉晴, 北尾章人, 藥師神公和, 山本克也, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本血液学会-東京事務局, Sep. 2018, 臨床血液, 59(9号) (9号), 1733 - 1733, Japanese

  [Refereed]

  Research society


• 新たなZMYND11/MBTD1融合遺伝子の発現とt(10;17)(p15;q21)転座を認めたCD7+CD56+急性骨髄性白血病(Expression of a novel ZMYND11/MBTD1 fusion transcript in CD7+CD56+ AML with t(10;17)(p15;q21))

  山本 克也, 藥師神 公和, 市川 大哉, 垣内 誠司, 川本 晋一郎, 松本 久幸, 中町 祐司, 三枝 淳, 松岡 広, 南 博信

  (一社)日本血液学会-東京事務局, Sep. 2018, 臨床血液, 59(9) (9), 1640 - 1640, English

  [Refereed]

  Research society


• 脂肪細胞は補体活性化経路を介して腫瘍増殖とがん幹細胞性を促進する(Adipocytes enhance tumor growth and cancer stem cell-like properties through the complement activation pathway)(英語)

  下野洋平, 後藤秀彰, 船越洋平, 豊田昌徳, 渋谷尚樹, 向原徹, Minami Hironobu

  (一社)日本癌学会, Sep. 2018, 日本癌学会総会記事, 77回(77回) (77回), 1910 - 1910, Japanese

  [Refereed]

  Scientific journal


• ヒト乳がん異種移植モデルの微小転移がん幹細胞で発現低下しているマイクロRNA-25の解析(Analyses of miR-25 that was downregulated in micrometastatic cancer stem cells in a human breast cancer xenograft model)(英語)

  渋谷尚樹, 下野洋平, Minami Hironobu, 掛地吉弘, 鈴木聡

  (一社)日本癌学会, Sep. 2018, 日本癌学会総会記事, 77回(77回) (77回), 664 - 664, Japanese

  [Refereed]

  Scientific journal


• シクロスポリン療法後の骨髄移植にて重症肝類洞閉塞症候群をきたした一例(Severe sinusoidal obstruction syndrome after cyclosporine treatment followed by transplantation)(英語)

  川口晃司, 坂井里奈, 垣内誠司, 東目亜湖, 倉田啓史, 長尾茂樹, 藥師神公和, 足立陽子, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本血液学会-東京事務局, Sep. 2018, 臨床血液, 59(9号) (9号), 1815 - 1815, Japanese

  [Refereed]

  Research society


• TLR9の一塩基多型により無症候性CMV感染症を呈した再生不良性貧血の一例(Aplastic anemia that developed asymptomatic CMV infection due to SNPs of TLR9)(英語)

  北尾章人, 川本晋一郎, 水谷優, 坂井里奈, 市川大哉, 須藤洋崇, 藥師神公和, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本血液学会-東京事務局, Sep. 2018, 臨床血液, 59(9号) (9号), 1756 - 1756, Japanese

  [Refereed]

  Research society


• 膀胱内病変が原因で両側水腎症による急性腎障害をきたした多発性骨髄腫の1例

  岡本光平, Kouno Kenji, Fujii Hideki, 清水真央, 神澤真紀, 福田輝雄, 垣内誠司, Minami Hironobu, Nishi Shinichi

  (一社)日本透析医学会, Aug. 2018, 日本透析医学会雑誌, 51(8号) (8号), 517 - 523, Japanese

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 用語解説 Precision Medicine

  金原史朗, Minami Hironobu

  Aug. 2018, Cancer Board of the Breast, 4(2号) (2号), 122, Japanese

  [Refereed]

  Scientific journal


• Invasive Scopulariopsis alboflavescens infection in patient with acute myeloid leukemia

  Keiji Kurata, Sho Nishimura, Hiroya Ichikawa, Rina Sakai, Yu Mizutani, Kei Takenaka, Seiji Kakiuchi, Yoshiharu Miyata, Akihito Kitao, Kimikazu Yakushijin, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Hiroshi Matsuoka, Issei Tokimatsu, Katsuhiko Kamei, Hironobu Minami

  Scopulariopsis alboflavescens is a soil saprophyte that is widely distributed in nature. Recently, there have been increasing number of reports of invasive infections with Scopulariopsis species in immunocompromised patients. In this report, we described an adult woman with acute myeloid leukemia and who developed S. alboflavescens pneumonia. Liposomal amphotericin B and voriconazole combination therapy was unsuccessful and the patient died because of pneumonia. Scopulariopsis is highly resistant to available antifungal agents and almost invariably fatal. This case report should alert clinicians to the importance of listing Scopulariopsis as a pathogenic fungus in immunocompromised patients.

  Springer Science and Business Media LLC, Jul. 2018, International Journal of Hematology, 108(6) (6), 658 - 664, English, Domestic magazine

  [Refereed]

  Scientific journal


• Adipsin enhanced clonogenicity and proliferation of human breast cancer patient-derived xenograft cells

  Hideaki Goto, Yohei Shimono, Toru Mukohara, Yohei Funakoshi, Yoshinori Imamura, Seishi Kono, Shintaro Takao, Akira Suzuki, Hironobu Minami

  Jul. 2018, CANCER RESEARCH, 78(13) (13), English


• Expression of a novelZMYND11/MBTD1fusion transcript in CD7⁺CD56⁺acute myeloid leukemia with t(10;17)(p15;q21)

  Katsuya Yamamoto, Kimikazu Yakushijin, Hiroya Ichikawa, Seiji Kakiuchi, Shinichiro Kawamoto, Hisayuki Matsumoto, Yuji Nakamachi, Jun Saegusa, Hiroshi Matsuoka, Hironobu Minami

  Last, Jun. 2018, Leukemia & Lymphoma, 59(11) (11), 2706 - 2710, English, International magazine

  [Refereed]

  Scientific journal


• 軟部肉腫の薬物療法 臨床試験から実地診療へ

  Minami Hironobu

  Jun. 2018, 日本整形外科学会雑誌, 92(6号) (6号), S1511, Japanese

  [Refereed]

  Scientific journal


• Expression of programmed death-1 in sentinel lymph nodes of breast cancer.

  Takashi Tatara, Toru Mukohara, Yohei Shimono, Takashi Yamasaki, Yoshinori Imamura, Yohei Funakoshi, Masanori Toyoda, Naomi Kiyota, Shintaro Takao, Seishi Kono, Yoshihiro Kakeji, Hironobu Minami

  BACKGROUND AND OBJECTIVES: To explore whether lymphocytes in sentinel lymph nodes (SLNs) are highly exposed to tumor neoantigens and thus express high level of programmed death 1 (PD-1), we examined PD-1 expression in SLNs and non-sentinel regional lymph nodes (non-SLNs) in breast cancer. METHODS: We performed PD-1 immunohistochemistry in two cohorts: 40 metastasis-negative SLNs including 10 patients for each subtype (luminal A-like, luminal B-like, HER2, and triple negative breast cancer [TNBC]); and 25 pairs of metastasis-positive SLNs and non-SLNs (10 luminal A-like, 10 luminal B-like, and 5 TNBC). RESULTS: Among 40 metastasis-negative SLNs, 34 and 6 samples were PD-1 intensity grade 1 (low) and 2 (high), respectively. PD-1 intensity correlated with PD-1-positive lymphocyte numbers (P = 0.005); TNBC had the highest PD-1 lymphocyte numbers among all subtypes. The median PD-1-positive lymphocyte number was higher in SLNs than non-SLNs. In most cases, more lymphocytes in SLNs expressed PD-1 than those in non-SLNs (P < 0.0001). CONCLUSIONS: TNBC had the greatest PD-1 expression among all subtypes, and metastasis-positive SLNs had more PD-1-positive lymphocytes than downstream non-SLNs. These data suggested that lymphocytes in SLNs are activated following exposure to tumor neoantigens and thus tumor specific, and could be utilized as a biomarker platform.

  May 2018, Journal of surgical oncology, 117(6) (6), 1131 - 1136, English, International magazine

  [Refereed]

  Scientific journal


• 再発・転移の頭頸部非扁平上皮癌に対するドセタキセル シスプラチン併用療法の第II相臨床試録

  今村善宣, 清田尚臣, 田中薫, 林秀俊, 太田一郎, 平野滋, 岩江信法, 南修司郎, 家根且有, 山崎知子, 長谷善明, 豊田昌徳, 大月直樹, 丹生健一, Minami Hironobu

  (一社)日本頭頸部癌学会, May 2018, 頭頸部癌, 44(2号) (2号), 126 - 126, Japanese

  [Refereed]

  Scientific journal


• Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging.

  Meiko Nishimura, Mitsuhiro Hayashi, Yu Mizutani, Kei Takenaka, Yoshinori Imamura, Naoko Chayahara, Masanori Toyoda, Naomi Kiyota, Toru Mukohara, Hiroaki Aikawa, Yasuhiro Fujiwara, Akinobu Hamada, Hironobu Minami

  Background: The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Results: Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm2; P = 0.009 in paired t-test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm3; P = 0.028 in paired t-test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, P < 0.0001). Conclusions: Focal distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin rashes was higher than that in the adjacent normal skin. Methods: We examined patients with advanced pancreatic cancer who developed skin rashes after treatment with erlotinib and gemcitabine. We biopsied both the rash and adjacent normal skin tissues, and visualized and compared the distribution of erlotinib within the skin using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The tissue concentration of erlotinib was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with laser microdissection.

  Apr. 2018, Oncotarget, 9(26) (26), 18540 - 18547, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Early lymphocyte recovery predicts clinical outcome after HSCT with mycophenolate mofetil prophylaxis in the Japanese population

  Keiji Kurata, Kimikazu Yakushijin, Ishikazu Mizuno, Hiroshi Gomyo, Atsuo Okamura, Hiroya Ichikawa, Rina Sakai, Yu Mizutani, Seiji Kakiuchi, Yoshiharu Miyata, Akihito Kitao, Yukinari Sanada, Yumiko Inui, Kiyoaki Uryu, Shinichiro Kawamoto, Takeshi Sugimoto, Katsuya Yamamoto, Mitsuhiro Ito, Hiroshi Matsuoka, Tohru Murayama, Hironobu Minami

  Springer Science and Business Media LLC, Mar. 2018, International Journal of Hematology, 108(1) (1), 58 - 65

  Scientific journal


• Pharmacokinetics of intravenous mycophenolate mofetil in allogeneic hematopoietic stem cell-transplanted Japanese patients

  Keiji Kurata, Kimikazu Yakushijin, Atsuo Okamura, Motohiro Yamamori, Hiroya Ichikawa, Rina Sakai, Yu Mizutani, Seiji Kakiuchi, Yoshiharu Miyata, Akihito Kitao, Shinichiro Kawamoto, Hiroshi Matsuoka, Tohru Murayama, Hironobu Minami

  Last, Springer Science and Business Media LLC, Mar. 2018, Cancer Chemotherapy and Pharmacology, 81(5) (5), 839 - 846

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 【新しい臨床試験のデザイン】 キナーゼ阻害薬か免疫チェックポイント阻害薬か、殺細胞性抗がん薬の生き残る道は?

  Minami Hironobu, 清原祥夫, 松原伸晃, 西尾誠人

  Mar. 2018, がん分子標的治療, 16(1号) (1号), 38 - 45, Japanese

  [Refereed]

  Scientific journal


• A Case of Classical Hodgkin Lymphoma with Total Lymph Node Infarction.

  Okuni M, Yakushijin Kimikazu, Sakai Y, Suto H, Ichikawa H, Sakai R, Kakiuchi S, Kurata K, Mizutani Y, Kitao A, Miyata Y, Saito Y, Kawamoto S, Yamamoto K, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu

  Lymph node infarction is very rare, and is frequently associated with neoplasms, such as malignant lymphoma and non-neoplastic disease, or interventions such as fine-needle aspiration (FNA). A 76-year-old-man presented with cervical lymph node swelling. Although FNA was performed, the findings were insufficient for a definitive diagnosis. Consequently, surgical biopsy of the cervical lymph node was performed, which revealed total infarction; a diagnosis of classical Hodgkin lymphoma was made later. Both lymphoma itself and FNA may cause total lymph node infarction, which makes diagnosis confusing. Therefore, it is important to repeat the biopsy rather than repeat FNA to correctly diagnose malignant lymphoma, including Hodgkin lymphoma.

  Mar. 2018, J Clin Exp Hematop., 58(1) (1), 24 - 26, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• MYC Amplification in the Form of Ring Chromosomes 8 in Acute Myeloid Leukemia with t(11;16)(q13;p11.2)

  Katsuya Yamamoto, Shinichiro Kawamoto, Keiji Kurata, Akihito Kitao, Yu Mizutani, Hiroya Ichikawa, Kimikazu Yakushijin, Kazuyoshi Kajimoto, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  S. Karger AG, Feb. 2018, Cytogenetic and Genome Research, 153(3) (3), 131 - 137, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 次世代シークエンサーを用いた唾液腺導管癌・腺癌NOSの新規治療標的遺伝子の同定

  今村善宣, 清田尚臣, 長谷善明, 鈴木千晶, 兵庫寧子, 崔諭司, 力武隼平, 船越洋平, 豊田昌徳, Minami Hironobu

  (一社)日本内科学会, Feb. 2018, 日本内科学会雑誌, 107(Suppl.) (Suppl.), 189 - 189, Japanese

  [Refereed]

  Scientific journal


• がんクリニカルシークエンスと遺伝性腫瘍の関係

  豊田昌徳, 味木徹夫, 今村善宣, 船越洋平, 清田尚臣, Minami Hironobu

  (一社)日本内科学会, Feb. 2018, 日本内科学会雑誌, 107(Suppl.) (Suppl.), 189 - 189, Japanese

  [Refereed]

  Scientific journal


• miR-221-QKI5 axis regulates tumorigenicity of human colorectal cancer stem cells

  Junko Mukohyama, Yohei Shimono, Taichi Isobe, Naoki Shibuya, Qingjiang Hu, Kimihiro Yamashita, Koshi Mimori, Hironobu Minami, Yoshihiro Kakeji, Akira Suzuki

  Jan. 2018, CANCER SCIENCE, 109, 469 - 469, English


• Discordance of MCM7 mRNA and its intronic microRNA levels under hypoxia

  Naoki Shibuya, Yohei Shimono, Hiroki Kondo, Junko Mukohyama, Yoshihiro Kakeji, Hironobu Minami, Akira Suzuki

  Jan. 2018, CANCER SCIENCE, 109, 602 - 602, English


• Identification of cancer-stem-cell-suppressor microRNAs through the analyses of human epithelial differentiation program

  Yohei Shimono, Shigeo Hisamori, Taichi Isobe, Junko Mukohyama, Naoki Shibuya, Yoshihiro Kakeji, Hironobu Minami, Akira Suzuki

  Jan. 2018, CANCER SCIENCE, 109, 86 - 86, English


• 【各臓器がんに対する免疫チェックポイント阻害薬】 免疫チェックポイント阻害薬の臨床試験デザイン

  Minami Hironobu, 藤原豊, 里内美弥子, 室圭

  Jan. 2018, がん分子標的治療, 15(4号) (4号), 400 - 407, Japanese

  [Refereed]

  Scientific journal


• Phase I study of panobinostat and 5-azacitidine in Japanese patients with myelodysplastic syndrome or chronic myelomonocytic leukemia

  Yukio Kobayashi, Wataru Munakata, Michinori Ogura, Toshiki Uchida, Masafumi Taniwaki, Tsutomu Kobayashi, Fumika Shimada, Masataka Yonemura, Fumiko Matsuoka, Takeshi Tajima, Kimikazu Yakushijin, Hironobu Minami

  Springer Tokyo, Jan. 2018, International Journal of Hematology, 107(1) (1), 83 - 91, English

  [Refereed]

  Scientific journal


• An mTORC1/2 Kinase Inhibitor Remarkably Enhances the Cytotoxicity of Gemtuzumab Ozogamicin By Activating Lysosomal Function and Cell Cycle Promotion in AML Cells

  Maimaitili Yimamu, Inase Aki, Minami Hironobu, Matsuoka Hiroshi

  Dec. 2017, BLOOD, 130

  [Refereed]


• ヒト大腸上皮の分化過程における腫瘍抑制的マイクロRNAの協調的発現上昇

  下野 洋平, 久森 重夫, Dalerba Piero, 磯部 大地, 向山 順子, 渋谷 尚樹, 掛地 吉弘, 南 博信, 鈴木 聡

  生命科学系学会合同年次大会運営事務局, Dec. 2017, 生命科学系学会合同年次大会, 2017年度, [1P - 0916], English


• 慢性C型肝炎治療後に発症したB細胞性前リンパ球性白血病の1例

  毛利華奈子, 坂井里奈, 須藤洋崇, 川本晋一郎, 藥師神公和, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本血液学会-東京事務局, Nov. 2017, 臨床血液, 58(11号) (11号), 2289 - 2289, Japanese

  [Refereed]

  Research society


• Roles of microRNAs and RNA-Binding Proteins in the Regulation of Colorectal Cancer Stem Cells

  Junko Mukohyama, Yohei Shimono, Hironobu Minami, Yoshihiro Kakeji, Akira Suzuki

  Colorectal cancer stem cells (CSCs) are responsible for the initiation, progression and metastasis of human colorectal cancers, and have been characterized by the expression of cell surface markers, such as CD44, CD133, CD166 and LGR5. MicroRNAs (miRNAs) are differentially expressed between CSCs and non-tumorigenic cancer cells, and play important roles in the maintenance and regulation of stem cell properties of CSCs. RNA binding proteins (RBPs) are emerging epigenetic regulators of various RNA processing events, such as splicing, localization, stabilization and translation, and can regulate various types of stem cells. In this review, we summarize current evidences on the roles of miRNA and RBPs in the regulation of colorectal CSCs. Understanding the epigenetic regulation of human colorectal CSCs will help to develop biomarkers for colorectal cancers and to identify targets for CSC-targeting therapies.

  MDPI AG, Oct. 2017, Cancers, 9(10) (10), 143 - 143

  Scientific journal


• Prospective Cohort Study of Performance Status and Activities of Daily Living After Surgery for Spinal Metastasis.

  Kenichiro Kakutani, Yoshitada Sakai, Koichiro Maeno, Toru Takada, Takashi Yurube, Takuto Kurakawa, Shingo Miyazaki, Yoshiki Terashima, Masaaki Ito, Hitomi Hara, Teruya Kawamoto, Yasuo Ejima, Akihiro Sakashita, Naomi Kiyota, Yoshiyuki Kizawa, Ryohei Sasaki, Toshihro Akisue, Hironobu Minami, Ryosuke Kuroda, Masahiro Kurosaka, Kotaro Nishida

  STUDY DESIGN: A prospective cohort study of performance status (PS) and activities of daily living (ADL) in patients with spinal metastasis. OBJECTIVE: To identify the effect of spinal surgery on PS and ADL in patients with spinal metastasis. SUMMARY OF BACKGROUND DATA: Spinal metastasis causes severe neurological deficits, resulting in drastic loss of patients' PS and ADL. However, the effect of spine surgery on PS and ADL is not well known. MATERIALS AND METHODS: Seventy patients with spinal metastasis were enrolled in this study. Forty-six patients desired and underwent spine surgery ("surgery" group) and 24 patients did not desire surgery ("nonsurgery" group). Both groups received optimal treatments, including radiation, chemotherapy, and palliative care services. Evaluation was performed at 1, 3, and 6 months after study enrollment using the Eastern Cooperative Oncology Group PS, the Barthel index (BI) for ADL, and Frankel classification for neurological status. RESULTS: There was no significant difference in baseline PS, the BI, or Frankel classification between the groups. The surgery group showed significant improvement in PS, maintaining grade 2 or less throughout the duration of the study, as well as in ADL, exceeding 70 points of the BI, compared with the nonsurgery group (P<0.05). Significantly improved neurological condition was also observed in the surgery group over the following 6 months. More than 95% of patients who underwent surgery improved their PS, the BI, and neurological status. Furthermore, >80% of these patients maintained improvement in PS, the BI, and neurological status for at least 6 months. In contrast, PS, the BI, and neurological status of patients in the "nonsurgery" group deteriorated throughout the study period. CONCLUSIONS: Spine surgery improves PS, ADL, and neurological status in patients with spinal metastasis for a minimum 6 months. This indicates that these patients can acquire an independent daily life.

  Oct. 2017, Clinical spine surgery, 30(8) (8), E1026-E1032, English, International magazine

  [Refereed]

  Scientific journal


• 臨床薬理学を化学療法の開発・個別化医療に如何にして生かすかを考える 抗がん薬の創薬・育薬における臨床薬理学研究

  Minami Hironobu

  Oct. 2017, 日本癌治療学会学術集会抄録集 55回, PD1 - 1, Japanese

  Research society


• Megakaryoblastic transformation of therapy-related myeloid neoplasms with concomitant MYC amplification on double minute chromosomes

  Katsuya Yamamoto, Kimikazu Yakushijin, Yumiko Inui, Shinichiro Kawamoto, Kazuyoshi Kajimoto, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  Springer Science and Business Media LLC, Sep. 2017, International Journal of Hematology, 106(6) (6), 729 - 731

  Scientific journal


• 低酸素環境におけるMCM7 mRNAとマイクロRNA発現レベルの乖離(英語)

  渋谷尚樹, 下野洋平, 近藤弘基, 向山順子, 掛地吉弘, Minami Hironobu, 鈴木聡

  (一社)日本癌学会, Sep. 2017, 日本癌学会総会記事, 76回(76回) (76回), P - 2064, Japanese

  Research society


• 悪性リンパ腫患者におけるコリンエステラーゼ値層別化による腫瘍崩壊症候群発症リスクの後方視的解析

  小嶋真理子, 坂井里奈, 川本晋一郎, 市川大哉, 水谷優, 倉田啓史, 垣内誠司, 宮田吉晴, 北尾章人, 藥師神公和, 山本克也, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本血液学会-東京事務局, Sep. 2017, 臨床血液, 58(9号) (9号), 1763 - 1763, Japanese

  [Refereed]

  Research society


• ヒト上皮分化プログラムの解析に基づく癌幹細胞抑制マイクロRNAの同定(英語)

  下野洋平, 久森重夫, 磯部大地, 向山順子, 渋谷尚樹, 掛地吉弘, Minami Hironobu, 鈴木聡

  (一社)日本癌学会, Sep. 2017, 日本癌学会総会記事, 76回(76回) (76回), E - 1013, Japanese

  Research society


• miR-221-QKI5経路による大腸癌幹細胞の制御機構の解明(英語)

  向山順子, 下野洋平, 磯部大地, 渋谷尚樹, 胡慶江, 山下公大, 三森功士, Minami Hironobu, 掛地吉弘, 鈴木聡

  (一社)日本癌学会, Sep. 2017, 日本癌学会総会記事, 76回(76回) (76回), J - 2014, Japanese

  Research society


• c-Kit遺伝子変異細胞株においてmicroRNA-7はRB1発現を抑制し染色体不安定性をもたらす(英語)

  倉田啓史, 川本晋一郎, 松岡宏, Minami Hironobu

  Sep. 2017, 日本癌学会総会記事, (76回) (76回), P - 2063, Japanese

  Research society


• 初期研修医の患者把握能力向上を目的としたTime-dependent Problem Listの有用性の検討

  後藤秀彰, 在間梓, 坂井里奈, 須藤洋崇, 今村善宣, 垣内誠司, 河野誠司, Minami Hironobu

  (一社)日本医学教育学会, Aug. 2017, 医学教育, 48(Suppl.) (Suppl.), 195 - 195, Japanese

  Research society


• 再発時にCD45発現が陰性化した急性骨髄性白血病

  山本克也, 薬師神公和, 倉田啓史, 水谷優, 乾由美子, 瓜生恭章, 川本晋一郎, 杉本健, Matsuoka Hiroshi, Minami Hironobu

  A 49-year-old female was initially diagnosed with acute myeloid leukemia (AML) M4 with a CD45＋CD13＋CD33＋CD34−HLA-DR＋ immunophenotype. She underwent allogeneic bone marrow transplantation, but the disease recurred. The bone marrow was infiltrated with 87.0% blasts negative for myeloperoxidase (MPO) staining. Immunophenotyping by flow cytometry identified the presence of a CD45-negative blast population. These blasts exhibited a CD13＋CD33＋CD19−CD10−CD34−HLA-DR− immunophenotype. The lack of CD45 expression is often observed in B-cell acute lymphoblastic leukemia, whereas CD45-negative AML is extremely rare; only one older male with AML-M0 has been reported. In the present case, the CD45-negative blasts had an MPO−CD13＋CD33＋ phenotype, which is similar to AML-M0.

  The Japanese Society of Hematology, Aug. 2017, 臨床血液, 58(8号) (8号), 938 - 941, Japanese

  [Refereed]

  Scientific journal


• Compatibility and Stability of Nab-Paclitaxel in Combination with Other Drugs

  Naomi Mizuta, Tsutomu Nakagawa, Kazuhiro Yamamoto, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Ikuko Yano, Hironobu Minami, Midori Hirai

  Jul. 2017, The Kobe journal of medical sciences, 63(1) (1), E9 - E16, English

  Scientific journal


• Compatibility and Stability of Nab-Paclitaxel in Combination with Other Drugs

  MizutaN, Nakagawa Tsutomu, YamamotoK, NishiokaT, KumeM, MakimotoH, Yano Ikuko, MinamiH, Hirai Midori

  Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases infusion time. We evaluated the comp

  神戸大学医学部, Jul. 2017, Kobe J Med Sci, 63(1) (1), E9 - E16, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Discordance of MCM7 mRNA and its Intronic MicroRNA Levels Under Hypoxia

  Hiroki Kondo, Yohei Shimono, Junko Mukohyama, Yasuteru Tanaka, Naoki Shibuya, Hironobu Minami, Yoshihiro Kakeji, Akira Suzuki

  Jul. 2017, ANTICANCER RESEARCH, 37(7) (7), 3885 - 3890, English

  [Refereed]

  Scientific journal


• Phase I study of glasdegib (PF‐04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies

  Yosuke Minami, Hironobu Minami, Toshihiro Miyamoto, Goichi Yoshimoto, Yukio Kobayashi, Wataru Munakata, Yasushi Onishi, Masahiro Kobayashi, Mari Ikuta, Geoffrey Chan, Adrian Woolfson, Chiho Ono, Mohammed Naveed Shaik, Yosuke Fujii, Xianxian Zheng, Tomoki Naoe

  The hedgehog signaling pathway regulates multiple morphogenetic processes during embryogenesis. Aberrant activation of the hedgehog pathway signal transduction in adult tissues is associated with the pathogenesis of hematologic malignancies and solid tumors. We report findings from an open‐label, multicenter phase I trial of the selective, small‐molecule hedgehog signaling inhibitor glasdegib (PF‐04449913) in Japanese patients with select advanced hematologic malignancies. Glasdegib was administered as once‐daily oral doses (25, 50 and 100 mg) in 28‐day cycles after a lead‐in dose on Day −5. The primary objectives were to determine first‐cycle dose‐limiting toxicities, safety, vital signs and laboratory test abnormalities. Secondary objectives included evaluation of pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity of glasdegib. No dose‐limiting toxicities were noted in the 13 patients in the present study. All patients experienced at least one treatment‐emergent, all‐causality adverse event. The most frequent treatment‐related adverse events (observed in ≥3 patients) were dysgeusia (n = 9), muscle spasms (n = 5), alopecia, decreased appetite (n = 4 each), and increased blood creatinine phosphokinase, constipation and diarrhea (n = 3 each). Two deaths occurred during the study and were deemed not to be treatment‐related due to disease progression. Glasdegib demonstrated dose‐proportional pharmacokinetics, marked downregulation of the glioma‐associated transcriptional regulator GLI1 expression in normal skin, and evidence of preliminary clinical activity, although data are limited. Glasdegib was safe and well tolerated across the dose levels tested. It is confirmed that the 100‐mg dose is safe and tolerable in Japanese patients, and this dose level will be examined in the future clinical trial.

  Wiley, Jun. 2017, Cancer Science, 108(8) (8), 1628 - 1633

  Scientific journal


• Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study

  Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami

  Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T‐cell activation through overexpression of the inhibitory receptor programmed death 1 (PD‐1) ligands. The PD‐1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single‐arm, open‐label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty‐four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee‐assessed overall response rate was 34.8% (90% confidence interval, 20.8–51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0–71.4). Treatment‐related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment‐related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI‐142533.)

  Wiley, Jun. 2017, Cancer Science, 108(6) (6), 1223 - 1230

  Scientific journal


• 大腸がん幹細胞におけるマイクロRNA-221の特異的発現

  渋谷尚樹, 向山順子, 磯部大地, 近藤弘基, 向原徹, 掛地吉弘, Minami Hironobu, 下野洋平, 鈴木聡

  (一社)日本サイトメトリー学会, Jun. 2017, Cytometry Research, 27(Suppl.) (Suppl.), 65 - 65, Japanese

  Research society


• Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study

  Shingo Miyazaki, Kenichiro Kakutani, Yoshitada Sakai, Yasuo Ejima, Koichiro Maeno, Toru Takada, Takashi Yurube, Yoshiki Terashima, Masaaki Ito, Yuji Kakiuchi, Yoshiki Takeoka, Hitomi Hara, Teruya Kawamoto, Akihiro Sakashita, Takuya Okada, Naomi Kiyota, Yoshiyuki Kizawa, Ryohei Sasaki, Toshihiro Akisue, Hironobu Minami, Ryosuke Kuroda, Kotaro Nishida

  Jun. 2017, INTERNATIONAL ORTHOPAEDICS, 41(6) (6), 1265 - 1271, English

  [Refereed]

  Scientific journal


• Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma

  Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Hajime Iizuka, Jiro Uehara, Fujio Otsuka, Yasuhiro Fujisawa, Tatsuya Takenouchi, Taiki Isei, Keiji Iwatsuki, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami, Hideaki Tahara

  Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death‐1 protein, were suggested in previous phase 1 studies. The present phase 2, single‐arm study (JAPIC‐CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3‐week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression‐free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1‐ and 2‐year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3–4 drug‐related adverse events were observed in 31.4% of patients. Pretreatment serum interferon‐γ, and interleukin‐6 and ‐10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy.

  Wiley, May 2017, Cancer Science, 108(5) (5), 1022 - 1031

  Scientific journal


• 骨転移診療の現状と各診療科の意識調査 整形外科医・腫瘍内科医・放射線治療医に対するアンケート

  秋末敏宏, 酒井良忠, 松原伸晃, 中村直樹, 角谷賢一朗, 原仁美, 河本旭哉, 深瀬直政, 黒田良祐, Kiyota Naomi, Minami Hironobu

  (公社)日本整形外科学会, Mar. 2017, 日本整形外科学会雑誌, 91(3) (3), S1058 - S1058, Japanese

  [Invited]

  Research society


• NANOG Expression as a Responsive Biomarker during Treatment with Hedgehog Signal Inhibitor in Acute Myeloid Leukemia

  Seiji Kakiuchi, Yosuke Minami, Yoshiharu Miyata, Yu Mizutani, Hideaki Goto, Shinichiro Kawamoto, Kimikazu Yakushijin, Keiji Kurata, Hiroshi Matsuoka, Hironobu Minami

  Aberrant activation of the Hedgehog (Hh) signaling pathway is involved in the maintenance of leukemic stem cell (LSCs) populations. PF-0444913 (PF-913) is a novel inhibitor that selectively targets Smoothened (SMO), which regulates the Hh pathway. Treatment with PF-913 has shown promising results in an early phase study of acute myeloid leukemia (AML). However, a detailed mode of action for PF-913 and relevant biomarkers remain to be elucidated. In this study, we examined bone marrow samples derived from AML patients under PF-913 monotherapy. Gene set enrichment analysis (GSEA) revealed that PF-913 treatment affected the self-renewal signature and cell-cycle regulation associated with LSC-like properties. We then focused on the expression of a pluripotency factor, NANOG, because previous reports showed that a downstream effector in the Hh pathway, GLI, directly binds to the NANOG promoter and that the GLI-NANOG axis promotes stemness and growth in several cancers. In this study, we found that a change in NANOG transcripts was closely associated with GLI-target genes and NANOG transcripts can be a responsive biomarker during PF-913 therapy. Additionally, the treatment of AML with PF-913 holds promise, possibly through inducing quiescent leukemia stem cells toward cell cycling.

  MDPI AG, Feb. 2017, International Journal of Molecular Sciences, 18(3) (3), 486 - 486

  Scientific journal


• Constitutional t(8;22)(q24;q11.2) that mimics the variant Burkitt-type translocation in Philadelphia chromosome-positive chronic myeloid leukemia

  Shinichiro Kawamoto, Katsuya Yamamoto, Masanori Toyoda, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  Feb. 2017, INTERNATIONAL JOURNAL OF HEMATOLOGY, 105(2) (2), 226 - 229, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Lenvatinib for Anaplastic Thyroid Cancer.

  Tahara M, Kiyota N, Yamazaki T, Chayahara N, Nakano K, Inagaki L, Toda K, Enokida T, Minami H, Imamura Y, Sasaki T, Suzuki T, Fujino K, Dutcus CE, Takahashi S

  BACKGROUND: Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need. PATIENTS AND METHODS: This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate. RESULTS: At data cutoff, 17 patients with ATC were enrolled. All experienced ≥1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7-12.9], the median OS was 10.6 months (95% CI: 3.8-19.8), and the objective response rate was 24%. CONCLUSION: In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC. CLINICALTRIALSGOV: NCT01728623.

  2017, Frontiers in oncology, 7, 25 - 25, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Randomized trial of standard pain control with or without gabapentin for pain related to radiation-induced mucositis in head and neck cancer.

  Tomoko Kataoka, Naomi Kiyota, Takanobu Shimada, Yohei Funakoshi, Naoko Chayahara, Masanori Toyoda, Yutaka Fujiwara, Ken-Ichi Nibu, Takahide Komori, Ryohei Sasaki, Toru Mukohara, Hironobu Minami

  OBJECTIVE: Radiation-induced mucositis (RIM) in chemoradiotherapy (CRT) for head and neck cancer (HNC) causes severe pain and worsens CRT compliance, QOL and outcome. Following retrospective reports, we conducted a randomized trial of the safety and efficacy of gabapentin for RIM-associated pain during CRT. METHODS: HNC patients (pts) receiving CRT were randomized to standard pain control (SPC) with acetaminophen and opioids, or SPC plus gabapentin (SPC+G). Gabapentin was maintained at 900mg/day for 4 weeks after CRT. Primary endpoint was maximum visual analogue scale (VAS) score during CRT, and secondary endpoints were total opioid dose, changes in QOL (EORTC QLQ-C30 and QLQ-HN 35) from baseline to 4 weeks after CRT, and adverse events. RESULTS: Twenty-two eligible Stage III or IV pts were randomly assigned to SPC or SPC+G (n=11 each). Twelve were treated in a locally advanced setting and 10 in a postoperative setting. Median maximum VAS scores, median total dose of opioids at maximum VAS and total dose of opioids at 4 weeks after CRT tended to be higher in the SPC+G arm (47 in SPC vs. 74 in SPC+G, p=0.517; 215mg vs. 745.3mg, p=0.880; and 1260mg vs. 1537.5mg, p=0.9438, respectively), without significance. QOL analysis showed significantly worse scores in the SPC+G arm for weight gain (p=0.005). Adverse events related to gabapentin were manageable. CONCLUSIONS: This pilot study is the first prospective randomized trial of gabapentin for RIM-related pain. Gabapentin had no apparent beneficial effect. Further research into agents for RIM-related pain is warranted.

  Dec. 2016, Auris, nasus, larynx, 43(6) (6), 677 - 84, English, International magazine

  [Refereed]

  Scientific journal


• 患者検体からのEBウイルスBamHI W領域の検出によるヒト腫瘍異種移植マウスのリンパ腫形成リスクの評価

  向山 順子, 向原 徹, 南 博信, 掛地 吉弘, 下野 洋平

  (一社)日本癌学会, Oct. 2016, 日本癌学会総会記事, 75回, J - 2001, English


• 選択的に発現上昇しているマイクロRNA-221がヒト大腸がん幹細胞のクローン原性を制御する

  渋谷 尚樹, 向山 順子, 磯部 大地, 近藤 弘基, 向原 徹, 掛地 吉弘, 南 博信, 鈴木 聡, 下野 洋平

  (一社)日本癌学会, Oct. 2016, 日本癌学会総会記事, 75回, P - 1130, English


• Safety and effectiveness of sorafenib in Japanese patients with hepatocellular carcinoma in daily medical practice: interim analysis of a prospective postmarketing all-patient surveillance study

  Shuichi Kaneko, Kenji Ikeda, Yasushi Matsuzaki, Junji Furuse, Hironobu Minami, Yutaka Okayama, Toshiyuki Sunaya, Yuichiro Ito, Lyo Inuyama, Kiwamu Okita

  Springer Tokyo, Oct. 2016, Journal of Gastroenterology, 51(10) (10), 1011 - 1021, English

  [Refereed]

  Scientific journal


• Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors

  Hironobu Minami, Yuichi Ando, Brigette Buig Yue Ma, Jih-Hsiang Lee, Hiroyuki Momota, Yutaka Fujiwara, Leung Li, Koichi Fukino, Koji Ito, Takeshi Tajima, Asuka Mori, Chia-Chi Lin

  Oct. 2016, CANCER SCIENCE, 107(10) (10), 1477 - 1483, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A prospective study of the antiemetic effect of palonosetron in malignant lymphoma patients treated with the CHOP regimen

  Yoshiharu Miyata, Kimikazu Yakushijin, Yumiko Inui, Yoshinori Imamura, Hideaki Goto, Yu Mizutani, Keiji Kurata, Seiji Kakiuchi, Yukinari Sanada, Yosuke Minami, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Ryo Tominaga, Hiroshi Gomyo, Ishikazu Mizuno, Tetsuhiko Nomura, Koichi Kitagawa, Takeshi Sugimoto, Tohru Murayama, Hiroshi Matsuoka, Hironobu Minami

  Springer Science and Business Media LLC, Sep. 2016, International Journal of Hematology, 104(6) (6), 682 - 691

  Scientific journal


• Mixed Phenotype Acute Leukemia with t(12;17)(p13;q21)/<b><i>TAF15-ZNF384</i></b> and Other Chromosome Abnormalities

  Katsuya Yamamoto, Shinichiro Kawamoto, Yu Mizutani, Kimikazu Yakushijin, Tomoe Yamashita, Yuji Nakamachi, Seiji Kawano, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  Sep. 2016, Cytogenetic and Genome Research, 149(3) (3), 165 - 170

  Scientific journal


• Prognostic Impact of Circulating Tumor Cell Detected Using a Novel Fluidic Cell Microarray Chip System in Patients with Breast Cancer

  Takeshi Sawada, Jungo Araki, Toshinari Yamashita, Manami Masubuchi, Tsuneko Chiyoda, Mayu Yunokawa, Kumiko Hoshi, Shoichi Tao, Shohei Yamamura, Shouki Yatsushiro, Kaori Abe, Masatoshi Kataoka, Tatsu Shimoyama, Yoshiharu Maeda, Katsumasa Kuroi, Kenji Tamura, Tsuneo Sawazumi, Hironobu Minami, Yoshihiko Suda, Fumiaki Koizumi

  Sep. 2016, EBIOMEDICINE, 11, 173 - 182, English

  [Refereed]

  Scientific journal


• Sea-blue histiocytes in acute myeloid leukemia with trisomy 9

  Katsuya Yamamoto, Yosuke Minami, Shinichiro Kawamoto, Kimikazu Yakushijin, Tomoe Kikuma, Jun Saegusa, Hiroshi Matsuoka, Hironobu Minami

  Springer Science and Business Media LLC, Aug. 2016, International Journal of Hematology, 104(5) (5), 531 - 533

  Scientific journal


• Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens

  Junko Mukohyama, Dai Iwakiri, Yoh Zen, Toru Mukohara, Hironobu Minami, Yoshihiro Kakeji, Yohei Shimono

  Aug. 2016, ONCOTARGET, 7(31) (31), 50150 - 50160, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Post-marketing surveillance of all patients treated with sorafenib for unresectable DTC in Japan: Interim report

  Makoto Tahara, Iwao Sugitani, Yasuhiro Ito, Yutaka Okayama, Yoshiko Kawakami, Toshiyuki Sunaya, Toshiaki Sakaguchi, Hironobu Minami, Tsuneo Imai

  Jul. 2016, ANNALS OF ONCOLOGY, 27, English

  [Refereed]


• Prognostic impact of CTC detected using a novel fluidic cell microarray chip CTC detection system in patients with breast cancer

  Takeshi Sawada, Jungo Araki, Toshinari Yamashita, Manami Masubuchi, Tsuneko Chiyoda, Mayu Yunokawa, Kumiko Hoshi, Shoichi Tao, Shohei Yamamura, Shouki Yatsushiro, Kaori Abe, Masatoshi Kataoka, Tatsu Shimoyama, Yoshiharu Maeda, Katsumasa Kuroi, Kenji Tamura, Tsuneo Sawazumi, Hironobu Minami, Yoshihiko Suda, Fumiaki Koizumi

  Jul. 2016, CANCER RESEARCH, 76, English

  [Refereed]


• Effect of Xenotransplantation Site on MicroRNA Expression of Human Colon Cancer Stem Cells.

  Junko Mukohyama, Yohei Shimono, Kimihiro Yamashita, Yasuo Sumi, Toru Mukohara, Hironobu Minami, Yoshihiro Kakeji

  BACKGROUND: Cancer stem cells (CSCs) have a high tumorigenic ability to form patient-derived tumor xenografts (PDXs). PDXs are an attractive pre-clinical model, but gene expression and biological behavior of cancer cells in the tumor will change during establishment and passage of PDXs. MATERIALS AND METHODS: Human colon cancer PDX was established and passaged either subcutaneously or orthotopically into the murine intestine. Histology and flow cytometric profile of the surgical specimen and the PDX were analyzed. CSCs were then isolated from the tumors and their microRNA (miRNA) expression was analyzed by semi-quantitative polymerase chain reaction. RESULTS: The surgical specimens and PDXs were histologically similar. The size of CSC population increased and expression of miRNAs in CSCs changed in the passaged PDXs. Expression of oncogenic miRNAs was highly up-regulated in the CSCs of the orthotopically passaged PDXs. CONCLUSION: The xenotransplantation site and the number of tumor passages affect the miRNA expression of human colon CSCs.

  Jul. 2016, Anticancer research, 36(7) (7), 3679 - 86, English, International magazine

  Scientific journal


• Phase 2 Trial of Bi-weekly Cetuximab for Recurrent or Metastatic Colorectal Cancer (BIC-K Trial)

  Naoko Chayahara, Naomi Kiyota, Masanori Toyoda, Toru Mukohara, Yoshimi Fujishima, Akihito Tsuji, Hironaga Satake, Sahchiko Kimura, Masahito Kotaka, Hironobu Minami

  Jul. 2016, ANNALS OF ONCOLOGY, 27, English

  [Refereed]


• 固形癌の分子・細胞特性の解明を目指して 臓器への潜在転移に関わるヒト乳がん幹細胞の解析

  下野洋平, 向山順子, 西村建徳, 磯部大地, 向原徹, 鈴木聡, 後藤典子, Minami Hironobu

  (一社)日本サイトメトリー学会, Jul. 2016, Cytometry Research, 26(Suppl.) (Suppl.), 38 - 38, Japanese

  Research society


• nab-paclitaxel(アブラキサン)の臨床

  Minami Hironobu

  Jun. 2016, 日本DDS学会学術集会プログラム予稿集 32回, 131, Japanese

  Research society


• The combination of HLA-B*15:01 and DRB1*15:01 is associated with gemcitabine plus erlotinib-induced interstitial lung disease in patients with advanced pancreatic cancer

  Meiko Nishimura, Masanori Toyoda, Kei Takenaka, Yoshinori Imamura, Naoko Chayahara, Naomi Kiyota, Toru Mukohara, Takeshi Kotake, Akihito Tsuji, Kosuke Saito, Yoshiro Saito, Hironobu Minami

  Springer Science and Business Media LLC, Apr. 2016, Cancer Chemotherapy and Pharmacology, 77(6) (6), 1165 - 1170

  Scientific journal


• 病院で起きている輸血副作用

  上田真弘, 早川郁代, 橋本誠, 南陽介, Minami Hironobu

  Apr. 2016, 日本輸血細胞治療学会誌, 62(2号) (2号), 339, Japanese

  Research society


• Sensitive cytometry based system for enumeration, capture and analysis of gene mutations of circulating tumor cells

  Takeshi Sawada, Masaru Watanabe, Yuu Fujimura, Shigehiro Yagishita, Tatsu Shimoyama, Yoshiharu Maeda, Shintaro Kanda, Mayu Yunokawa, Kenji Tamura, Tomohide Tamura, Hironobu Minami, Yasuhiro Koh, Fumiaki Koizumi

  Wiley, Feb. 2016, Cancer Science, 107(3) (3), 307 - 314, English

  [Refereed]

  Scientific journal


• 再発・転移頭頸部扁平上皮癌におけるプラチナ耐性獲得時の血液学的予後予測因子に関する検討

  今村善宣, 清田尚臣, 後藤秀彰, 竹中圭, 西村明子, 茶屋原菜穂子, Toyoda Masanori, 向原徹, 丹生健一, Minami Hironobu

  Feb. 2016, 日本内科学会雑誌, 105(Suppl.) (Suppl.), 232, Japanese

  Research society


• Validity of new methods to evaluate renal function in cancer patients treated with cisplatin

  Yohei Funakoshi, Yutaka Fujiwara, Naomi Kiyota, Toru Mukohara, Takanobu Shimada, Masanori Toyoda, Yoshinori Imamura, Naoko Chayahara, Hideo Tomioka, Michio Umezu, Naoki Otsuki, Ken-ichi Nibu, Hironobu Minami

  Jan. 2016, Cancer Chemotherapy and Pharmacology, 77(2) (2), 281 - 288, English

  [Refereed]

  Scientific journal


• Chemotherapy-induced Nausea and Vomiting in Patients with Hepatobiliary and Pancreatic Cancer Treated with Chemotherapy: A Prospective Observational Study by the CINV Study Group of Japan

  Nitta H, Baba H, Sugimori K, Furuse J, Ohkawa S, Yamamoto K, Minami H, Shimokawa M, Wakabayashi GO, Aiba K

  BACKGROUND: This study investigated the prevalence of chemotherapy-induced nausea and vomiting (CINV) in patients with hepatobiliary-pancreatic (HBP) cancer in a prospective nationwide survey. PATIENTS AND METHODS: One hundred patients with HBP cancer (biliary tract cancer; n=70, hepatocellular carcinoma; n=20, and pancreatic cancer; n=10) who received chemotherapy for the first time were analyzed. Medical personnel were surveyed to examine the accuracy of their predicted frequency of CINV. RESULTS: The compliance rate with the Japanese guideline with highly emetogenic chemotherapy was 36/89 (40%). Although the prevalence of CINV in patients with HBP cancer was significantly lower than that of the total 1,910 patients with cancer, the prevalence of delayed CINV in patients with HBP cancer was as high as 28%. The survey results suggested that the medical staff tended to overestimate the incidence of CINV. CONCLUSION: CINV appears to be controlled under management according to the guidelines, but delayed nausea remains prevalent and requires further investigation.

  2016, Anticancer Res, 36(4) (4), 1929 - 1935, English, International magazine

  Scientific journal


• Absolute Lymphocyte Count Recovery Predicts Clinical Outcome after Allogeneic Hematopoietic Stem Cell Transplantation in a Japanese Population

  Kurata K, Yakushijin K, Mizuno I, Inui Y, Gomyo H, Okamura A, Ichikawa H, Mizutani Y, Kakiuchi S, Miyata Y, Tominaga R, Kitao A, Sanada Y, Saito Y, Minami Y, Kawamoto S, Maeda A, Yamamoto K, Murayama T, Ito M, Matsuoka H, Minami H

  2016, Bone Marrow Transplantation, 51, S411

  [Refereed]


• Coexpression of NUP98/TOP1 and TOP1/NUP98 in de novo Acute Myeloid Leukemia with t(11;20)(p15;q12) and t(2;5)(q33;q31)

  Katsuya Yamamoto, Yosuke Minami, Kimikazu Yakushijin, Yu Mizutani, Yumiko Inui, Shinichiro Kawamoto, Keiji Matsui, Yuji Nakamachi, Seiji Kawano, Hiroshi Matsuoka, Hironobu Minami

  2016, Cytogenetic and Genome Research, 150(3-4) (3-4), 287 - 292

  Scientific journal


• トラスツズマブ投与中あるいは終了後早期に再発したHER2陽性乳癌に対して、トラスツズマブ+ペルツスマブ+ドセタキセル併用療法を行うべきか？行うべき vs 行うべきでない。

  Minami Hironobu

  メディカルレビュー社, 2016, Cancer Board of the Breast, 2(105) (105), 106 - 110, Japanese

  [Refereed]

  Scientific journal


• Mixed Phenotype Acute Leukemia with t(12;17)(p13;q21)/TAF15-ZNF384 and Other Chromosome Abnormalities

  Katsuya Yamamoto, Shinichiro Kawamoto, Yu Mizutani, Kinnikazu Yakushijin, Tonnoe Yamashita, Yuji Nakannachi, Seiji Kawano, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  2016, CYTOGENETIC AND GENOME RESEARCH, 149(3) (3), 165 - 170, English

  [Refereed]

  Scientific journal


• A prospective study on the efficacy of two-dose influenza vaccinations in cancer patients receiving chemotherapy

  Yukinari Sanada, Kimikazu Yakushijin, Tetsuhiko Nomura, Naoko Chayahara, Masanori Toyoda, Yosuke Minami, Naomi Kiyota, Toru Mukohara, Shinichiro Kawamoto, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami

  Oxford University Press, 2016, Japanese Journal of Clinical Oncology, 46(5) (5), 448 - 452, English

  [Refereed]

  Scientific journal


• Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101)

  Yutaka Fujiwara, Shogo Kobayashi, Hiroaki Nagano, Masashi Kanai, Etsuo Hatano, Masanori Toyoda, Tetsuo Ajiki, Yuki Takashima, Kenichi Yoshimura, Akinobu Hamada, Hironobu Minami, Tatsuya Ioka

  Dec. 2015, PLOS ONE, 10(12) (12), e0143072, English

  [Refereed]

  Scientific journal


• 30年来頸部腫瘤を有する患者より発症したDouble-hit lymphoma(DHL)の1例

  水谷 優, 川本 晋一郎, 後藤 秀彰, 倉田 啓史, 垣内 誠司, 眞田 幸尚, 宮田 吉晴, 山本 克也, 松岡 広, 南 博信, 伊藤 智雄

  (一社)日本血液学会-東京事務局, Nov. 2015, 臨床血液, 56(11) (11), 2377 - 2377, Japanese


• Erratum to: A new transcriptional variant and small azurophilic granules in an acute promyelocytic leukemia case with NPM1/RARA fusion gene.

  Tomoe Kikuma, Yuji Nakamachi, Yoriko Noguchi, Yoko Okazaki, Daiki Shimomura, Kimikazu Yakushijin, Katsuya Yamamoto, Hiroshi Matsuoka, Hironobu Minami, Tomoo Itoh, Seiji Kawano

  Nov. 2015, International journal of hematology, 102(5) (5), 643 - 643, English, Domestic magazine


• ヒト大腸直腸がん幹細胞のマイクロRNA発現に異種移植部位がおよぼす影響

  向山 順子, 下野 洋平, 船越 洋平, 向原 徹, 掛地 吉弘, 南 博信

  (一社)日本癌学会, Oct. 2015, 日本癌学会総会記事, 74回, P - 3067, English


• [Effect of Natural Killer Cell Infiltration on the Growth of Breast Cancer Patient-Derived Tumor Xenografts].

  Junko Mukohyama, Yohei Shimono, Yohei Funakoshi, Seishi Kono, Kimihiro Yamashita, Toru Mukohara, Shintaro Takao, Hironobu Minami, Yoshihiro Kakeji

  Natural killer (NK) cells, a component of the innate immunity, play important roles in tumor suppression. In this study, three human breast cancer patient-derived tumor xenografts (PDXs), established by the transplantation of surgical specimens, were passaged in immunodeficient NOD/SCID mice or NSG mice, that further lacks NK cell activity. The intensity of the relative growth suppression between NOD/SCID and NSG mice was clearly different depending on the PDX lines, and it was associated with the intensities of the CD49b-positive NK cell infiltration in the PDX tumor tissues. However, no obvious association was observed between the mRNA expression levels of the NK cell ligands in the PDX tumor cells and the intensity of NK cell infiltration into the PDX tumors. These results suggest that the suppressive effect of NK cells on the growth of breast cancer PDX is highly variable depending on the PDX lines. Further studies are needed to elucidate the molecular mechanism of NK cell infiltration in PDX tumors.

  Oct. 2015, Gan to kagaku ryoho. Cancer & chemotherapy, 42(10) (10), 1252 - 5, Japanese, Domestic magazine

  Scientific journal


• NK細胞浸潤がヒト乳がん異種移植マウスの腫瘍増殖に与える影響

  向山順子, Shimono Yohei, 船越洋平, Kono Seishi, Yamashita Kimihiro, 向原徹, 高尾信太郎, 南博信, Kakeji Yoshihiro

  (株)癌と化学療法社, Oct. 2015, 癌と化学療法, 42(10号) (10号), 1252 - 1255, Japanese

  [Refereed]

  Scientific journal


• A new transcriptional variant and small azurophilic granules in an acute promyelocytic leukemia case with NPM1/RARA fusion gene

  Tomoe Kikuma, Yuji Nakamachi, Yoriko Noguchi, Yoko Okazaki, Daisuke Shimomura, Kimikazu Yakushijin, Katsuya Yamamoto, Hiroshi Matsuoka, Hironobu Minami, Tomoo Itoh, Seiji Kawano

  Sep. 2015, International Journal of Hematology, 102(6) (6), 713 - 718, English

  [Refereed]


• Mediastinal Germ Cell Tumor Exhibiting a Discrepancy between Tumor Markers and Imaging: A Case Study

  Kei Takenaka, Toru Mukohara, Chihoko Hirai, Yohei Funakoshi, Yukiko Nakamura, Naoko Chayahara, Masanori Toyoda, Naomi Kiyota, Tomoo Itoh, Hiroshi Yokozaki, Hironobu Minami

  We report a mediastinal germ cell tumor (GCT) that exhibited a discrepancy between the time course of serum human chorionic gonadotropin (hCG) levels and clinical consequences. An otherwise healthy man, aged 34 years, was diagnosed with a nonseminomatous GCT, most likely embryonal carcinoma (EC), based on a mediastinal tumor biopsy. Standard chemotherapy resulted in an optimal decrease in serum hCG levels. However, multiple lesions in the liver continued to enlarge, which led to his death. Autopsy revealed few viable tumor cells in the liver, with the great majority of the tumor cells appearing to have undergone necrosis, suggesting that they responded to the chemotherapy. The residual tumor cells in the mediastinum and the liver were similar to syncytiotrophoblast cells, suggesting a choriocarcinoma (CC). On immunohistochemical analysis, the mediastinal tumor cells in the diagnostic biopsy specimen expressed both CD30 and hCG, whereas residual mediastinal and hepatic tumor cells in the autopsy specimen after chemotherapy also expressed hCG, but not CD30. These findings suggested that the patient suffered from a primary mixed GCT consisting of an EC and a CC. Both pre- and postchemotherapy tumors strongly expressed matrix metalloproteinase-2, supporting the aggressive and invasive features of the tumor phenotype. We speculate that the extremely invasive tumor destroyed normal liver structure, whereas chemotherapy and central necrosis reduced the number of viable cells themselves, causing a discordant decrease in serum hCG levels.

  S. Karger AG, Aug. 2015, Case Reports in Oncology, 8(2) (2), 323 - 331

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal

  Yumiko Inui, Hiroshi Matsuoka, Kimikazu Yakushijin, Atsuo Okamura, Takaki Shimada, Shingo Yano, Mai Takeuchi, Mitsuhiro Ito, Tohru Murayama, Katsuya Yamamoto, Tomoo Itoh, Keisuke Aiba, Hironobu Minami

  Informa UK Limited, May 2015, Leukemia & Lymphoma, 56(11) (11), 3045 - 3051

  Scientific journal


• 甲状腺がん 2015年の甲状腺がんの治療 甲状腺がんに対する分子標的療法(Thyroid Cancer: Treatment of Thyroid Cancer 2015 Molecular Targeted Treatment for Thyroid Cancer)

  Kiyota Naomi, Otsuki Naoki, Imamura Yoshinori, Sasaki Ryohei, Nibu Ken-ichi, Minami Hironobu

  (一社)日本頭頸部癌学会, May 2015, 頭頸部癌, 41(2) (2), 98 - 98, English


• Translocation t(11;19)(q23;q13.1) without <b><i>MLL </i></b>Rearrangement in Acute Myeloid Leukemia: Heterogeneity of the 11q23 Breakpoints

  Katsuya Yamamoto, Shinichiro Kawamoto, Seiji Kakiuchi, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  Apr. 2015, Acta Haematologica, 134(2) (2), 76 - 79, English

  [Refereed]

  Scientific journal


• Sterility Testing of Stem Cell Products by Broad-Range Bacterial 16S Ribosomal DNA Polymerase Chain Reaction

  Osamu Tokuno, Akira Hayakawa, Tomoko Yanai, Takeshi Mori, Kenichiro Ohnuma, Ayumi Tani, Hironobu Minami, Takeshi Sugimoto

  Oxford University Press (OUP), Feb. 2015, Laboratory Medicine, 46(1) (1), 34 - 41

  Scientific journal


• 再発・転移粘膜悪性黒色腫に対するダカルバジン単剤療法の後方視的検討

  西村 明子, 清田 尚臣, 豊田 昌徳, 茶屋原 菜穂子, 竹中 圭, 瓜生 恭章, 今村 善宣, 船越 洋平, 向原 徹, 南 博信

  (一社)日本内科学会, Feb. 2015, 日本内科学会雑誌, 104(臨増) (臨増), 282 - 282, Japanese


• 第1子新生児同種免疫性血小板減少症(NAIT)であった妊婦の第2子妊娠管理

  上田真弘, 早川郁代, 橋本誠, Minami Yosuke, 南博信

  Feb. 2015, 日本輸血細胞治療学会誌, 61(1号) (1号), 52 - 53, Japanese

  [Refereed]

  Scientific journal


• Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer

  YOSHINORI IMAMURA, TORU MUKOHARA, YOHEI SHIMONO, YOHEI FUNAKOSHI, NAOKO CHAYAHARA, MASANORI TOYODA, NAOMI KIYOTA, SHINTARO TAKAO, SEISHI KONO, TETSUYA NAKATSURA, HIRONOBU MINAMI

  It is becoming recognized that screening of oncology drugs on a platform using two-dimensionally (2D)-cultured cell lines is unable to precisely select clinically active drugs; therefore three-dimensional (3D)-culture systems are emerging and show potential for better simulating the in vivo tumor microenvironment. The purpose of this study was to reveal the differential effects of chemotherapeutic drugs between 2D- and 3D-cultures and to explore their underlying mechanisms. We evaluated differences between 2D- and 3D-cultured breast cancer cell lines by assessing drug sensitivity, oxygen status and expression of Ki-67 and caspases. Three cell lines (BT-549, BT-474 and T-47D) developed dense multicellular spheroids (MCSs) in 3D-culture, and showed greater resistance to paclitaxel and doxorubicin compared to the 2D-cultured cells. An additional three cell lines (MCF-7, HCC-1954, and MDA-MB‑231) developed only loose MCSs in 3D, and showed drug sensitivities similar to those found in the 2D-culture. Treatment with paclitaxel resulted in greater increases in cleaved-PARP expression in the 2D-culture compared with the 3D-culture, but only in cell lines forming dense 3D-MCSs, suggesting that MCS formation protected the cells from paclitaxel-induced apoptosis. Hypoxia was observed only in the dense 3D-MCSs. BT-549 had fewer cells positive for Ki-67 in 3D- than in 2D-culture, suggesting that the greater G0-dormant subpopulation was responsible for its drug resistance in the 3D-culture. BT-474 had a lower level of caspase-3 in the 3D- than in the 2D-culture, suggesting that the 3D-environment was anti-apoptotic. Finally, we compared staining for Ki-67 and caspases in the 2D- and 3D-primary‑cultured cells originating from a patient-derived xenograft (PDX), fresh PDX tumor, and the patient's original tumor; 2D-cultured cells showed greater proportions of Ki-67-positive and caspase-3-positive cells, in agreement with the view that 3D-primary culture better represents characteristics of tumors in vivo. In conclusion, 3D-cultured cells forming dense MCSs may be better than 2D-cultured cells in simulating important tumor characteristics in vivo, namely hypoxia, dormancy, anti-apoptotic features and their resulting drug resistance.

  Spandidos Publications, Jan. 2015, Oncology Reports, 33(4) (4), 1837 - 1843, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• An Evans Syndrome Case Expressing Anti-Jk&lt;sup&gt;a&lt;/sup&gt; Autoantibody under Condition of Primary IgA Immunodeficiency

  Takeshi Sugimoto, Ayumi Tani, Ikuyo Hayakawa, Makoto Hashimoto, Tomoko Yanai, Ikuko Kubokawa, Takeshi Mori, Takeshi Kato, Satoshi Hirase, Nobuyuki Yamamoto, Hironobu Minami, Akira Hayakawa

  Scientific Research Publishing, Inc., 2015, International Journal of Clinical Medicine, 06(07) (07), 496 - 499

  Scientific journal


• 抗がん薬の臨床薬理 オンコロジー領域におけるトピックス 分子標的薬アキシチニブのpharmacokinetics/pharmacodynamics

  Minami Hironobu

  Nov. 2014, 臨床薬理, 45(Suppl.) (Suppl.), S203, Japanese

  Research society


• Metabolomics Evaluation of Serum Markers for Cachexia and Their Intra-Day Variation in Patients with Advanced Pancreatic Cancer

  Yutaka Fujiwara, Takashi Kobayashi, Naoko Chayahara, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Toru Mukohara, Shin Nishiumi, Takeshi Azuma, Masaru Yoshida, Hironobu Minami, Antonio Gonzalez-Bulnes

  Public Library of Science ({PLoS}), Nov. 2014, PLoS ONE, 9(11) (11), e113259, English

  [Refereed]

  Scientific journal


• Transcriptional CCND1 expression as a predictor of poor response to neoadjuvant chemotherapy with trastuzumab in HER2-positive/ER-positive breast cancer

  M. Tanioka, K. Sakai, T. Sudo, T. Sakuma, K. Kajimoto, K. Hirokaga, S. Takao, S. Negoro, H. Minami, K. Nakagawa, K. Nishio

  Oct. 2014, BREAST CANCER RESEARCH AND TREATMENT, 147(3) (3), 513 - 525, English

  [Refereed]

  Scientific journal


• NK細胞浸潤がヒト乳がん異種移植マウスの腫瘍増殖に与える影響(Effect of natural killer cell infiltration on the growth of the mouse xenografts tumors of human breast cancers)

  向山 順子, 下野 洋平, 船越 洋平, 向原 徹, 松岡 広, 掛地 吉弘, 南 博信

  (一社)日本癌学会, Sep. 2014, 日本癌学会総会記事, 73回, P - 2060, English


• Phase Ii Study of Lenvatinib (Len), a Multi-Targeted Tyrosine Kinase Inhibitor, in Patients (Pts) with All Histologic Subtypes of Advanced Thyroid Cancer (Differentiated, Medullary and Anaplastic)

  S. Takahashi, M. Tahara, N. Kiyota, T. Yamazaki, N. Chayahara, K. Nakano, R. Inagaki, K. Toda, T. Enokida, H. Minami, Y. Imamura, T. Sasaki, T. Suzuki, K. Fujino, C. Dutcus

  Elsevier BV, Sep. 2014, Annals of Oncology, 25, iv343 - iv343

  Scientific journal


• 肺、大腸重複癌に合併した自己免疫性溶血性貧血における自己抗体の標的分子の同定

  Kawamoto Shinichiro, 宮田 吉晴, 桝谷 亮太, Matsuoka Hiroshi, 今北 正美, Minami Hironobu, 田窪 孝行, 玉置 俊治

  (一社)日本血液学会-東京事務局, Sep. 2014, 臨床血液, 55(9号) (9号), 1271 - 1271, Japanese

  Research society


• 進行甲状腺癌の治療戦略 進行性甲状腺癌(放射性ヨウ素治療抵抗性の分化癌、髄様癌、未分化癌)に対するレンバチニブの第2相試験

  Kiyota Naomi, 田原 信, 高橋 俊二, Chayahara Naoko, 山崎 知子, Minami Hironobu, 今村 善宣, 榎田 智弘, 仲野 兼司, 稲垣 里奈, 戸田 和寿, 佐々木 達哉, 鈴木 拓也, 藤野 克樹, Dutcus Corina E

  日本内分泌外科学会・日本甲状腺外科学会, Sep. 2014, 日本内分泌・甲状腺外科学会雑誌, 31(Suppl.2) (Suppl.2), S217 - S217, Japanese

  Research society


• Extramedullary T-lymphoid blast crisis of an ETV6/ABL1-positive myeloproliferative neoplasm with t(9;12)(q34;p13) and t(7;14)(p13;q11.2)

  Katsuya Yamamoto, Kimikazu Yakushijin, Yuji Nakamachi, Yoshiharu Miyata, Yukinari Sanada, Yasuhiro Tanaka, Atsuo Okamura, Seiji Kawano, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  Aug. 2014, ANNALS OF HEMATOLOGY, 93(8) (8), 1435 - 1438, English

  [Refereed]

  Scientific journal


• Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status

  Maki Tanioka, Masaoki Sasaki, Akihiko Shimomura, Makoto Fujishima, Mihoko Doi, Kazuo Matsuura, Toshiko Sakuma, Kenichi Yoshimura, Toshiaki Saeki, Masahiro Ohara, Junji Tsurutani, Masahiro Watatani, Toshimi Takano, Hidetaka Kawabata, Hirofumi Mukai, Yoichi Naito, Koichi Hirokaga, Shintaro Takao, Hironobu Minami

  Aug. 2014, BREAST, 23(4) (4), 466 - 472, English

  [Refereed]

  Scientific journal


• Left Ventricular Endocardial Dysfunction in Patients with Preserved Ejection Fraction after Receiving Anthracycline

  Tatsuya Miyoshi, Hidekazu Tanaka, Akihiro Kaneko, Kazuhiro Tatsumi, Kensuke Matsumoto, Hironobu Minami, Hiroya Kawai, Ken-ichi Hirata

  Aug. 2014, ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES, 31(7) (7), 848 - 857, English

  [Refereed]

  Scientific journal


• Effects of Aprepitant on the Pharmacokinetics of Controlled-Release Oral Oxycodone in Cancer Patients

  Yutaka Fujiwara, Masanori Toyoda, Naoko Chayahara, Naomi Kiyota, Takanobu Shimada, Yoshinori Imamura, Toru Mukohara, Hironobu Minami

  Aug. 2014, PLOS ONE, 9(8) (8), e104215, English

  [Refereed]

  Scientific journal


• TYRO3 as a Potential Therapeutic Target in Breast Cancer

  Roudy Chiminch Ekyalongo, Toru Mukohara, Yohei Funakoshi, Hideo Tomioka, Yu Kataoka, Yohei Shimono, Naoko Chayahara, Masanori Toyoda, Naomi Kiyota, Hironobu Minami

  Jul. 2014, ANTICANCER RESEARCH, 34(7) (7), 3337 - 3345, English

  [Refereed]

  Scientific journal


• Conversion from nuclear bilobation to indentation in BCR/ABL1-positive acute myeloid leukemia lacking CD34 and HLA-DR expression

  Katsuya Yamamoto, Kimikazu Yakushijin, Yukinari Sanada, Shinichiro Kawamoto, Yuji Nakamachi, Seiji Kawano, Hiroshi Matsuoka, Hironobu Minami

  Jun. 2014, Annals of Hematology, 94(1) (1), 177 - 179, English

  [Refereed]

  Scientific journal


• Rapid improvement of glucagonoma-related necrolytic migratory erythema with octreotide.

  Kimbara S, Fujiwara Y, Toyoda M, Chayahara N, Imamura Y, Kiyota N, Mukohara T, Fukunaga A, Oka M, Nishigori C, Minami H

  Necrolytic migratory erythema (NME) is a classical paraneoplastic symptom observed in patients with pancreatic glucagonoma. We report a 46-year-old Japanese woman with glucagonoma who presented with mucocutaneous manifestations 1 year prior to the diagnosis of the pancreatic neoplasm with multiple liver metastases. She was treated with octreotide long-acting release, a somatostatin analog, which resulted in a dramatic improvement of NME within 2 weeks after the start of treatment. Increased awareness of NME may avoid unnecessary delay in the diagnosis of pancreatic glucagonoma.

  Jun. 2014, Clinical journal of gastroenterology, 7(3) (3), 255 - 259, English, Domestic magazine

  [Refereed]

  Scientific journal


• 当院における『抗がん薬の安全な取り扱いと曝露対策に関するプロジェクト』の取り組み

  水田 直美, 和田 敦, 土井 久容, 黒川 敏子, 藤原 由佳, 藥師神 公和, 向原 徹, Minami Hironobu

  Jun. 2014, 日本癌治療学会誌, 49(3号) (3号), 2298, Japanese

  Research society


• 新しい抗癌剤治療の副作用対策

  Minami Hironobu

  Jun. 2014, 日本緩和医療学会学術大会プログラム・抄録集 19回, 118, Japanese

  Research society


• エストロゲン受容体関連遺伝子発現に基づいてHER2陽性乳癌に対して化学療法個別化治療を目指す基盤構築

  谷岡 真樹, 坂井 和子, 須藤 保, 佐久間 淑子, 根来 俊一, 広利 浩一, 高尾 信太郎, 南 博信, 中川 和彦, 西尾 和人

  (公財)大和証券ヘルス財団, Mar. 2014, 大和証券ヘルス財団研究業績集, (37) (37), 119 - 126, Japanese


• A mimicking "multiple liver metastasis" of breast cancer by recurrent B lymphoblastic leukemia

  Meiko Nishimura, Atsuo Okamura, Yumiko Inui, Yoshinori Imamura, Kimikazu Yakushijin, Hiroshi Matsuoka, Katsuya Yamamoto, Hironobu Minami

  Mar. 2014, ANNALS OF HEMATOLOGY, 93(3) (3), 499 - 500, English

  [Refereed]

  Scientific journal


• 当院における臨床的意義がない抗体の検出とその対応について

  上田 真弘, 早川 郁代, 橋本 誠, 杉本 健, 南 陽介, Minami Hironobu

  Feb. 2014, 日本輸血細胞治療学会誌, 60(1号) (1号), 65, Japanese

  Research society


• 当院における唾液腺導管癌15例の臨床病理学的検討

  今村 善宣, Kiyota Naomi, 大月 直樹, 平井 千浦子, Toyoda Masanori, Chayahara Naoko, 船越 洋平, 向原 徹, 丹生 健一, Minami Hironobu

  Feb. 2014, 日本内科学会雑誌, 103(Suppl.) (Suppl.), 253, Japanese

  Research society


• Tandem triplication of the BCL2 gene in CD5-positive intravascular large B cell lymphoma with bone marrow involvement

  Yamamoto K, Okamura A, Yakushijin Kimikazu, Hayashi Yoshitake, Matsuoka Hiroshi, Minami Hironobu

  Feb. 2014, Ann Hematol, 93(10) (10), 1791 - 3, English, International magazine

  [Refereed]

  Scientific journal


• Absence of primary cilia in cell cycle-arrested human breast cancer cells

  Kentaro Nobutani, Yohei Shimono, Midori Yoshida, Kiyohito Mizutani, Akihiro Minami, Seishi Kono, Toru Mukohara, Takashi Yamasaki, Tomoo Itoh, Shintaro Takao, Hironobu Minami, Takeshi Azuma, Yoshimi Takai

  Feb. 2014, GENES TO CELLS, 19(2) (2), 141 - 152, English

  [Refereed]

  Scientific journal


• Unbalanced Translocation der(7)t(7q;11q): A New Recurrent Aberration Leading to Partial Monosomy 7q and Trisomy 11q in Acute Myeloid Leukemia

  Katsuya Yamamoto, Kimikazu Yakushijin, Yoshiharu Miyata, Hiroshi Matsuoka, Hironobu Minami

  2014, ACTA HAEMATOLOGICA, 132(2) (2), 244 - 246, English

  [Refereed]

  Scientific journal


• Duplication of der(21) t(8;21)(q22;q22) in Acute Myeloid Leukemia

  Katsuya Yamamoto, Atsuo Okamura, Hiroshi Matsuoka, Hironobu Minami

  2014, INTERNAL MEDICINE, 53(1) (1), 73 - 74, English

  [Refereed]

  Scientific journal


• A new complex translocation t(8;11;21)(q22;q24;q22) in acute myeloid leukemia with RUNX1/RUNX1T1

  Yamamoto K, Yakushijin Kimikazu, Funakoshi Y, Sanada Y, Kawamoto Shinichiro, Matsuoka Hiroshi, Minami Hironobu

  2014, J Clin Exp Hematop, 54(2) (2), 167 - 70, English, Domestic magazine

  [Refereed]

  Scientific journal


• Barriers and Challenges to Global Clinical Cancer Research

  Bostjan Seruga, Aleksander Sadikov, Eduardo L. Cazap, Lucia Beatriz Delgado, Raghunadharao Digumarti, Natasha B. Leighl, Mohamed M. Meshref, Hironobu Minami, Eliezer Robinson, Nise Hitomi Yamaguchi, Doug Pyle, Tanja Cufer

  Jan. 2014, ONCOLOGIST, 19(1) (1), 61 - 67, English

  [Refereed]

  Scientific journal


• A phase I study of sorafenib in combination with S-1 plus cisplatin in patients with advanced gastric cancer

  Yasuhide Yamada, Naomi Kiyota, Nozomu Fuse, Ken Kato, Hironobu Minami, Kensei Hashizume, Yoshihiro Kuroki, Yuichiro Ito, Atsushi Ohtsu

  Jan. 2014, GASTRIC CANCER, 17(1) (1), 161 - 172, English

  [Refereed]

  Scientific journal


• Alterations in HbA1c resulting from the donation of autologous blood for elective surgery in patients with diabetes mellitus

  Takeshi Sugimoto, Makoto Hashimoto, Ikuyo Hayakawa, Osamu Tokuno, Tomoko Ogino, Mariko Okuno, Nobuhide Hayashi, Seiji Kawano, Daisuke Sugiyama, Hironobu Minami

  Jan. 2014, BLOOD TRANSFUSION, 12(Suppl 1) (Suppl 1), S209 - S213, English

  [Refereed]

  Scientific journal


• Guidance for peptide vaccines for the treatment of cancer

  Yoshiyuki Yamaguchi, Hiroki Yamaue, Takuji Okusaka, Kiyotaka Okuno, Hiroyuki Suzuki, Tomoaki Fujioka, Atsushi Otsu, Yasuo Ohashi, Rumiko Shimazawa, Kazuto Nishio, Junji Furuse, Hironobu Minami, Takuya Tsunoda, Yuzo Hayashi, Yusuke Nakamura

  Blackwell Publishing Ltd, 2014, Cancer Science, 105(7) (7), 924 - 931, English

  [Refereed]

  Scientific journal


• Moderate renal dysfunction may not require a cisplatin dose reduction: A retrospective study of cancer patients with renal impairment

  Tomoko Ogawa, Seiji Niho, Shunji Nagai, Takashi Kojima, Yoshiko Nishimura, Yuichiro Ohe, Naoki Kondo, Takuhiro Yamaguchi, Kazushi Endo, Keishiro Izumi, Hironobu Minami

  Dec. 2013, International Journal of Clinical Oncology, 18(6) (6), 977 - 982, English

  [Refereed]

  Scientific journal


• Marked thrombocytosis and dysmegakaryopoiesis in acute myeloid leukemia with t(2;3)(p22;q26.2) and EVI1 rearrangement

  Katsuya Yamamoto, Atsuo Okamura, Yukinari Sanada, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  Dec. 2013, Annals of Hematology, 92(12) (12), 1713 - 1715, English

  [Refereed]

  Scientific journal


• 乳癌における新規治療標的としてのTyro3(Tyro3 as a potential therapeutic target in breast cancer)

  エキャロンゴ・ルーディ・チミンチ, 向原 徹, 船越 洋平, 富岡 秀夫, 片岡 優, 豊田 昌徳, 清田 尚臣, 南 博信

  (一社)日本癌学会, Oct. 2013, 日本癌学会総会記事, 72回, 484 - 484, English


• Hypothyroidism in patients with colorectal carcinoma treated with fluoropyrimidines

  Yutaka Fujiwara, Naoko Chayahara, Toru Mukohara, Naomi Kiyota, Hideo Tomioka, Yohei Funakoshi, Hironobu Minami

  Oct. 2013, Oncology Reports, 30(4) (4), 1802 - 1806, English

  [Refereed]

  Scientific journal


• Excessive MET signaling causes acquired resistance and addiction to MET inhibitors in the MKN45 gastric cancer cell line

  Yohei Funakoshi, Toru Mukohara, Hideo Tomioka, Roudy Chiminch Ekyalongo, Yu Kataoka, Yumiko Inui, Yuriko Kawamori, Masanori Toyoda, Naomi Kiyota, Yutaka Fujiwara, Hironobu Minami

  Oct. 2013, INVESTIGATIONAL NEW DRUGS, 31(5) (5), 1158 - 1168, English

  [Refereed]

  Scientific journal


• Hyperdiploidy and duplication of der(11)ins(10;11)(p12;q23q14) in acute myeloid leukemia with MLL/MLLT10 fusion gene

  Katsuya Yamamoto, Kimikazu Yakushijin, Atsuo Okamura, Shinnosuke Ueda, Yuji Nakamachi, Seiji Kawano, Hiroshi Matsuoka, Hironobu Minami

  Sep. 2013, Leukemia and Lymphoma, 54(9) (9), 2055 - 2058, English

  [Refereed]

  Scientific journal


• A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy

  M. Tanioka, A. Kitao, K. Matsumoto, N. Shibata, S. Yamaguchi, K. Fujiwara, H. Minami, N. Katakami, S. Morita, S. Negoro

  Aug. 2013, British Journal of Cancer, 109(4) (4), 859 - 865, English

  [Refereed]

  Scientific journal


• Micronuclei-associated MYC amplification in the form of double minute chromosomes in acute myeloid leukemia

  Katsuya Yamamoto, Atsuo Okamura, Yukinari Sanada, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  Aug. 2013, American Journal of Hematology, 88(8) (8), 717 - 718, English

  [Refereed]

  Scientific journal


• L-Asparaginase-induced fulminating liver dysfunction

  Atsuo Okamura, Meiko Nishimura, Yukinari Sanada, Kimikazu Yakushijin, Hiroshi Matsuoka, Katsuya Yamamoto, Hironobu Minami

  Jul. 2013, INTERNATIONAL JOURNAL OF HEMATOLOGY, 98(1) (1), 6 - 7, English

  [Refereed]

  Scientific journal


• HER2陽性ホルモン受容体陽性(HR+)乳癌における術前化学療法後病理学的完全寛解(pCR)の臨床的意義

  谷岡 真樹, 佐々木 正興, 下村 昭彦, 藤島 成, 土井 美帆子, 松浦 一生, 広利 浩一, 内藤 陽一, 川端 英孝, 高尾 信太郎, 南 博信, 高野 利実, 菰池 佳史, 鶴谷 純司, 佐伯 俊昭, 大原 正裕, 向井 博文

  (一社)日本乳癌学会, Jun. 2013, 日本乳癌学会総会プログラム抄録集, 21回, 217 - 217, Japanese


• A Microarray-Based Gene Expression Analysis to Identify Diagnostic Biomarkers for Unknown Primary Cancer

  Issei Kurahashi, Yoshihiko Fujita, Tokuzo Arao, Takayasu Kurata, Yasuhiro Koh, Kazuko Sakai, Koji Matsumoto, Maki Tanioka, Koji Takeda, Yuichi Takiguchi, Nobuyuki Yamamoto, Asuka Tsuya, Nobuaki Matsubara, Hirofumi Mukai, Hironobu Minami, Naoko Chayahara, Yasuhiro Yamanaka, Keisuke Miwa, Shin Takahashi, Shunji Takahashi, Kazuhiko Nakagawa, Kazuto Nishio

  May 2013, PLOS ONE, 8(5) (5), e63249, English

  [Refereed]

  Scientific journal


• 骨髄原発B細胞リンパ腫において新規に見つかったMYCとBCL6の改変を伴った5ヶ所の転座 t(3;9;13;8;14)(q27;p13;q32;q24;q32)(A novel five-way translocation, t (3:9:13:8:14) (q27:p13:q32:q24:q32), with concurrent MYC and BCL6 rearrangements in primary bone marrow B-cell lymphoma)

  山本 克也, 松岡 広, 薬師神 公和, 船越 洋平, 岡村 篤夫, 林 祥剛, 南 博信

  (一社)日本リンパ網内系学会, Apr. 2013, 日本リンパ網内系学会会誌, 53, 109 - 109, English


• Mechanisms of acquired resistance to insulin-like growth factor 1 receptor inhibitor in MCF-7 breast cancer cell line

  Roudy Chiminch Ekyalongo, Toru Mukohara, Yu Kataoka, Yohei Funakoshi, Hideo Tomioka, Naomi Kiyota, Yutaka Fujiwara, Hironobu Minami

  Apr. 2013, INVESTIGATIONAL NEW DRUGS, 31(2) (2), 293 - 303, English

  [Refereed]

  Scientific journal


• A phase I study of tasisulam sodium using an albumin-tailored dose in Japanese patients with advanced solid tumors

  Yutaka Fujiwara, Yuichi Ando, Toru Mukohara, Naomi Kiyota, Naoko Chayahara, Ayako Mitsuma, Megumi Inada-Inoue, Masataka Sawaki, Robert Ilaria, P. Kellie Turner, Jumpei Funai, Kaijiro Maeda, Hironobu Minami

  Apr. 2013, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 71(4) (4), 991 - 998, English

  [Refereed]

  Scientific journal


• 外来がん化学療法を受ける患者の倦怠感の要因と生活行動に関する研究 : 決定木(decision tree)による解析

  FUKUDA ATSUKO, USAMI MAKOTO, SAKAMOTO NORIHIRO, TABUCHI HIROTO, TAKEMOTO NAOKO, SANO AYAKA, MINAMI HIRONOBU

  The purpose of this study is to clarify the factors consisting of the fatigue in outpatients receiving cancer chemotherapy and to provide the suitable information for nursing support for these patients.
  Decision tree analysis was performed to explore the relationship among the fatigue in cancer patients receiving chemotherapy, patients’ demographic and laboratory data, and da

  神戸大学大学院保健学研究科, Mar. 2013, 神戸大学大学院保健学研究科紀要, 28, 21 - 40, Japanese

  [Refereed]

  Scientific journal


• Prediction of Glomerular Filtration Rate in Cancer Patients by an Equation for Japanese Estimated Glomerular Filtration Rate

  Yohei Funakoshi, Yutaka Fujiwara, Naomi Kiyota, Toru Mukohara, Takanobu Shimada, Masanori Toyoda, Yoshinori Imamura, Naoko Chayahara, Michio Umezu, Naoki Otsuki, Ken-ichi Nibu, Hironobu Minami

  Mar. 2013, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 43(3) (3), 271 - 277, English

  [Refereed]

  Scientific journal


• Pericentric chromosome 8 inversion, inv(8)(p11.2q22), associated with RUNX1/RUNX1T1 rearrangement in acute myeloid leukemia

  Katsuya Yamamoto, Atsuo Okamura, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  Mar. 2013, ANNALS OF HEMATOLOGY, 92(3) (3), 403 - 405, English

  [Refereed]

  Scientific journal


• Tolvaptan as an alternative treatment for refractory fluid retention associated with sinusoidal obstruction syndrome after allogeneic stem cell transplantation

  Kimikazu Yakushijin, Katsuya Yamamoto, Keiji Kurata, Yoshiharu Miyata, Seiji Kakiuchi, Hideo Tomioka, Yuriko Kawamori-Iwamoto, Yumiko Inui, Yukinari Sanada, Atsuo Okamura, Tohru Murayama, Hiroshi Matsuoka, Hironobu Minami

  Feb. 2013, INTERNATIONAL JOURNAL OF HEMATOLOGY, 97(2) (2), 284 - 286, English

  [Refereed]

  Scientific journal


• Regulation of MET kinase inhibitor resistance by copy number of MET in gastric carcinoma cells

  Funakoshi Y, Mukohara Toru, Ekyalongo RC, Tomioka H, Kataoka Y, Shimono Yohei, Chayahara Naoko, Toyoda M, Kiyota N, Fujiwara Y, Minami H

  We previously established acquired resistant models for MET-tyrosine kinase inhibitors (TKIs) by continuously exposing the MET-amplified gastric cancer cell line MKN45 to MET-TKIs, PHA665752 (MKN45-PR), or GSK1363089 (MKN45-GR). We found resistant mechanisms caused by increased copy number of MET in both lines and Y1230H mutation in MKN45-PR. We also found that excessive MET signaling caused by these MET alterations resulted in intra-S-phase arrest in the absence of MET-TKIs, so that cells grew faster in the presence of MET-TKIs, a phenomenon referred to as "addiction." In this study, to investigate reversibility of the acquired resistance and "addiction" to MET-TKIs and their causative MET alterations, we sequentially cultured MKN45-PR and MKN45-GR in decreasing concentrations of MET-TKIs until they were able to grow in a drug-free condition. These "revertant" cell lines (designated MKN45-PR-RE and MKN45-GR-RE) were comparatively analyzed. Growth assay showed that both MKN45-PR-RE and MKN45-GR-RE partially lost the property of "addiction" to MET-TKIs. MKN45-GR-RE lost the property of resistance to GSK1363089, but MKN45-PR-RE retained resistance to PHA665752. Copy numbers and expression and phosphorylation of MET protein reduced in both MKN45-PR-RE and MKN45-GR-RE compared with MKN45-PR and MKN45-GR, respectively, but Y1230H mutation and biochemical resistance to PHA665752 remained in MKN45-PR-RE. The "addiction" to MET-TKIs appeared attributable to increased copy number, and the property and the MET alteration were reversible. The Y1230H mutation appeared enough in itself to keep cells resistant to MET-TKIs and was irreversible.

  2013, Oncol Res, 21(6) (6), 287 - 293, English, International magazine

  [Refereed]

  Scientific journal


• 薬物療法の用量調節の基本：治療目的と用量と治療間隔の調整など。

  西村 明子, Minami Hironobu

  2013, コンセンサス癌治療2013, (12) (12), 178 - 181, Japanese

  [Refereed]

  Scientific journal


• N0、センチネルリンパ節転移陽性乳癌に腋かリンパ節隔清は必要か？隔清は不要である vs 隔清は必要である。

  Minami Hironobu

  2013, Cancer Board乳癌, 54, Japanese

  [Refereed]

  Scientific journal


• Gain of 11q by an additional ring chromosome 11 and trisomy 18 in CD5-positive intravascular large B-cell lymphoma

  Yamamoto K, Yakushijin Kimikazu, Okamura A, Hayashi Yoshitake, Matsuoka Hiroshi, Minami Hironobu

  Chromosomal abnormalities of intravascular large B-cell lymphoma (IVLBCL), a rare form of extranodal diffuse large B-cell lymphoma, have been described in only a small number of cases. A 59-year-old female presented with pancytopenia and splenomegaly. Bone marrow was normocellular with 30.4% abnormal large lymphoid cells that were positive for CD5, CD19, CD20, HLA-DR and λ chain. Bone marrow biopsy showed intrasinusoidal infiltration of large lymphoid cells. G-banding and spectral karyotyping of the bone marrow cells demonstrated a complex karyotype as follows : 48,XX,-8,+r(11),+12,del(12)(p?) ×2,+18,der(19)(19?::p13 → qter),der(21)t(8;21)(q11.2;p11.2). Fluorescence in situ hybridization on interphase nuclei revealed three signals of CCND1 at 11q13, but two signals of BIRC3 at 11q22 and MLL at 11q23, indicating that r(11) contained CCND1. Together with other reported cases, our results indicate that the gain of 11q as well as trisomy 18 may be among the recurrent chromosomal aberrations in IVLBCL. Furthermore, an additional ring chromosome 11 could be a novel mechanism leading to the gain of 11q.

  2013, J Clin Exp Hematop, 53(2) (2), 161 - 5, English, Domestic magazine

  [Refereed]

  Scientific journal


• A novel TRB@/NOTCH1 fusion gene in T-cell lymphoblastic lymphoma with t(7;9)(q34;q34)

  Katsuya Yamamoto, Yuji Nakamachi, Kimikazu Yakushijin, Yoshiharu Miyata, Atsuo Okamura, Seiji Kawano, Hiroshi Matsuoka, Hironobu Minami

  Jan. 2013, EUROPEAN JOURNAL OF HAEMATOLOGY, 90(1) (1), 68 - 75, English

  [Refereed]

  Scientific journal


• Anovel serum metabolomics-based diagnostic approach to pancreatic cancer

  Kobayashi, T., Nishiumi, S., Ikeda, A., Yoshie, T., Sakai, A., Matsubara, A., Izumi, Y., Tsumura, H., Tsuda, M., Nishisaki, H., Hayashi, N., Kawano, S., Fujiwara, Y., Minami, H., Takenawa, T., Azuma, T., Yoshida, M.

  2013, Cancer Epidemiology Biomarkers and Prevention, 22(4) (4), 571 - 9, English

  [Refereed]

  Scientific journal


• 緩和ケアチーム介入によるがん患者QOLの変化についての検討

  新家 治子, Sakashita Akihiro, 石橋 有希, 大田垣 加奈子, 藤原 由佳, 五百蔵 武士, 田宮 裕子, Kotani Yoshikazu, Mukohara Toru, 南 博信, Nishimura Yoshihiro

  Purpose: We assessed the efficacy of a palliative care team (PCT) in improving quality of life (QOL) among Japanese cancer patients. Patients and methods: This prospective study involved adult patients treated in the Division of Respiratory Medicine and Medical Oncology/Hematology at Kobe University Hospital between November 1, 2009 and March 30, 2010. Every patient had requested intervention by the PCT. Patients were asked to complete the EORTC QLQ-C15-PAL questionnaire at baseline and 1 and 4 weeks after initiation of the PCT intervention. Result: Of the 35 patients enrolled, 26 patients and 15 patients completed the assessments at 1 and 4 weeks after starting the intervention, respectively. Pain subscale (PA) was improved at 1 week after starting the intervention (p<0.05). Dyspnea subscale (DY) and PA were improved at 4 weeks after starting the intervention (p<0.05). Conclusion: We prospectively showed that QOL of cancer patients was improved with the intervention of the PCT, using the Japanese version of the EORTC QLQ-C15-PAL. Even if the PCT can only provide short-term care for cancer patients, this intervention appears worthwhile to improve QOL of cancer patients.

  Japanese Society for Palliative Medicine, Dec. 2012, Palliative Care Research, 7(2号) (2号), 368 - 373, Japanese

  [Refereed]

  Scientific journal


• IGH@/BCL6 rearrangement on the der(3)t(3;14)(q27;q32) in primary mediastinal large B-cell lymphoma

  Katsuya Yamamoto, Atsuo Okamura, Yumiko Inui, Kimikazu Yakushijin, Fumi Kawakami, Tomoo Itoh, Hiroshi Matsuoka, Hironobu Minami

  Dec. 2012, LEUKEMIA RESEARCH, 36(12) (12), E218 - E221, English

  [Refereed]

  Scientific journal


• First clinical pharmacokinetic dose-escalation study of sagopilone, a novel, fully synthetic epothilone, in Japanese patients with refractory solid tumors

  Kazuhiro Araki, Koichi Kitagawa, Hirofumi Mukai, Toru Mukohara, Keiji Kodama, Yuichi Ando, Masaru Narabayashi, Hironobu Minami, Kiyomi Mera, Yasutsuna Sasaki

  Dec. 2012, INVESTIGATIONAL NEW DRUGS, 30(6) (6), 2327 - 2333, English

  [Refereed]

  Scientific journal


• Eribulin mesylate in patients with refractory cancers: a Phase I study

  Toru Mukohara, Shunji Nagai, Hirofumi Mukai, Masayuki Namiki, Hironobu Minami

  Oct. 2012, INVESTIGATIONAL NEW DRUGS, 30(5) (5), 1926 - 1933, English

  [Refereed]

  Scientific journal


• MCF-7乳癌細胞株におけるinsulin-like growth factor 1 receptor阻害薬に対する獲得耐性機構(Mechanisms of acquired resistance to insulin-like growth factor 1 receptor inhibitor in MCF-7 breast cancer cell line)

  エキャロンゴ・ルーディー・チミンチ, 向原 徹, 片岡 優, 船越 洋平, 富岡 秀夫, 清田 尚臣, 藤原 豊, 南 博信

  (一社)日本癌学会, Aug. 2012, 日本癌学会総会記事, 71回, 335 - 335, English


• Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks.

  Kataoka Y, Mukohara T, Tomioka H, Funakoshi Y, Kiyota N, Fujiwara Y, Yashiro M, Hirakawa K, Hirai M, Minami H

  To explore the mechanism of action of foretinib (GSK1363089), an oral multi-kinase inhibitor known to target MET, RON, AXL, and vascular endothelial growth factor receptors (VEGFRs), in gastric cancer, we evaluated the effects of the agent on cell growth and cell signaling in the following panel of gastric cancer cell lines: KATO-III, MKN-1, MKN-7, MKN-45, and MKN-74. Of these, only MKN-45 and KATO-III, which harbor MET and fibroblast growth factor receptor 2 (FGFR2) amplification, respectively, were highly sensitive to foretinib. In MKN-45, 1 μM of foretinib or PHA665752, another MET kinase inhibitor, inhibited phosphorylation of MET and downstream signaling molecules as expected. In KATO-III, however, PHA665752 inhibited phosphorylation of MET independently of downstream molecules. Further, 1 μM of foretinib or PD173074, a selective FGFR kinase inhibitor, inhibited phosphorylation of FGFR2 and downstream molecules, suggesting that foretinib targets FGFR2 in KATO-III. We confirmed this novel activity of foretinib against FGFR2 in OCUM-2M, another FGFR2-amplified gastric cancer cell line. Using a phospho-receptor tyrosine kinase array, we found that foretinib inhibits phosphorylation of epidermal growth factor receptor (EGFR), HER3 and FGFR3 via MET inhibition in MKN-45, and EGFR, HER3 and MET via FGFR2 inhibition in KATO-III. Knockdown of HER3 and FGFR3 in MKN-45 with siRNA resulted in the partial inhibition of cell signaling and cell growth. In conclusion, foretinib appears effective against gastric cancer cells harboring not only MET but also FGFR2 amplification, and exerts its inhibitory effects by blocking inter-RTK signaling networks with MET or FGFR2 at their core.

  Aug. 2012, Investigational new drugs, 30(4) (4), 1352 - 1360, English, International magazine

  [Refereed]

  Scientific journal


• 輸血後感染症検査通知システム導入による輸血後感染症検査実施率の変化について

  Takaoka Yutaka, Takaoka Yutaka, Maeda Eiichi, Maeda Eiichi, Kawano Seiji, Kawano Seiji, Saigo Katsuyasu, Saigo Katsuyasu, Sugiyama Daisuke, Sugiyama Daisuke, Sugimoto Takeshi, Sugimoto Takeshi, Minami Hironobu, Minami Hironobu

  Aug. 2012, 日本輸血細胞治療学会誌, 58(4) (4), 547 - 551, Japanese

  [Refereed]

  Scientific journal


• Inhibition of the mTOR/S6K signal is necessary to enhance fluorouracil-induced apoptosis in gastric cancer cells with HER2 amplification

  Hideo Tomioka, Toru Mukohara, Yu Kataoka, Roudy Chiminch Ekyalongo, Yohei Funakoshi, Yasuo Imai, Naomi Kiyota, Yutaka Fujiwara, Hironobu Minami

  Aug. 2012, INTERNATIONAL JOURNAL OF ONCOLOGY, 41(2) (2), 551 - 558, English

  [Refereed]

  Scientific journal


• Reed-Sternberg-like cells of ALK-positive anaplastic large cell lymphoma with near-tetraploidy

  Katsuya Yamamoto, Kimikazu Yakushijin, Yumiko Inui, Atsuo Okamura, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  Jun. 2012, EUROPEAN JOURNAL OF HAEMATOLOGY, 88(6) (6), 553 - 554, English

  [Refereed]

  Scientific journal


• Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients

  Yutaka Fujiwara, Naomi Kiyota, Naoko Chayahara, Akiyuki Suzuki, Yoshiko Umeyama, Toru Mukohara, Hironobu Minami

  Jun. 2012, INVESTIGATIONAL NEW DRUGS, 30(3) (3), 1055 - 1064, English

  [Refereed]

  Scientific journal


• 左室駆出率が保たれたアントラサイクリン系薬剤使用症例における左室心内膜機能障害

  Tanaka Hidekazu, Minami Hironobu, Hirata Kenichi

  Apr. 2012, 超音波医学, 39(Suppl.) (Suppl.), S366, Japanese

  [Refereed]

  Scientific journal


• A novel recurrent translocation t(7;17)(q22;p13) and a late-appearing t(2;3)(p13;q26.2) with dysmegakaryopoiesis in acute myeloid leukemia

  Katsuya Yamamoto, Atsuo Okamura, Yumiko Inui, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  Apr. 2012, LEUKEMIA RESEARCH, 36(4) (4), E84 - E86, English

  Scientific journal


• Expression of the novel NUP98/PSIP1 fusion transcripts in myelodysplastic syndrome with t(9;11)(p22;p15)

  Katsuya Yamamoto, Yuji Nakamachi, Kimikazu Yakushijin, Yohei Funakoshi, Atsuo Okamura, Seiji Kawano, Hiroshi Matsuoka, Hironobu Minami

  Mar. 2012, EUROPEAN JOURNAL OF HAEMATOLOGY, 88(3) (3), 244 - 248, English

  Scientific journal


• 当院が導入した輸血後感染症検査報告システム(Ver.2)

  Sugimoto Takeshi, Minami Hironobu

  Feb. 2012, 日本輸血細胞治療学会誌, 58(1号) (1号), 87, Japanese

  Research society


• 抗がん薬投与におけるeGFRの有用性の検討

  Fujiwara Yutaka, Toyoda Masanori, Chayahara Naoko, Kiyota Naomi, Umezu Michio, Mukohara Toru, Minami Hironobu

  Feb. 2012, 日本内科学会雑誌, 101(Suppl.) (Suppl.), 192, Japanese

  [Refereed]

  Research society


• Evaluation with the BacT/ALERT microbial detection system of bacterial contamination in autologous blood donation and transfusion

  O. Tokuno, I. Hayakawa, M. Hashimoto, M. Nakamura, T. Sugimoto, H. Minami

  Feb. 2012, TRANSFUSION MEDICINE, 22(1) (1), 73 - 74, English

  [Refereed]

  Scientific journal


• SMILE療法及び同種骨髄移植によって良好な経過が得られた再発・難治性NK/T細胞リンパ腫の1例

  垣内 誠司, 船越 洋平, 薬師神 公和, 乾 由美子, 川森 有里子, 岡村 篤夫, 松岡 広, 南 博信

  (一社)日本血液学会-東京事務局, Jan. 2012, 臨床血液, 53(1) (1), 118 - 119, Japanese


• Isolated Isochromosome 17q in Myelodysplastic Syndromes with Pure Red Cell Aplasia and Basophilia

  Yumiko Inui, Katsuya Yamamoto, Atsuo Okamura, Kimikazu Yakushijin, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  2012, INTERNAL MEDICINE, 51(12) (12), 1579 - 1584, English

  [Refereed]

  Scientific journal


• THE ALERT SYSTEM FOR TESTING TRANSFUSION-RELATED VIRAL INFECTION ON THE ELECTRIC MEDICAL RECORD

  T. Sugimoto, Hayakawa, I, O. Tokuno, M. Hashimoto, H. Minami

  Dec. 2011, VOX SANGUINIS, 101, 88 - 88, English

  [Refereed]

  Scientific journal


• Biallelic ETV6 rearrangements by recurrent translocations t(7;12)(p15;p13) and t(3;12)(q26.2;p13) in acute myeloid leukemia

  Katsuya Yamamoto, Kimikazu Yakushijin, Yohei Funakoshi, Yumiko Inui, Atsuo Okamura, Hiroshi Matsuoka, Hironobu Minami

  Nov. 2011, LEUKEMIA RESEARCH, 35(11) (11), E212 - E214, English

  Scientific journal


• ゲノム薬理学研究の臨床的妥当性・有用性 ゲノム薬理学研究によるがん薬物療法の個別化

  Minami Hironobu

  Oct. 2011, 臨床薬理, 42巻, Suppl., pp. S140-S140, Japanese

  International conference proceedings


• Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer

  M. Tahara, H. Minami, Y. Hasegawa, K. Tomita, A. Watanabe, K. Nibu, M. Fujii, Y. Onozawa, Y. Kurono, D. Sagae, T. Seriu, M. Tsukuda

  Sep. 2011, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 68(3) (3), 769 - 776, English

  [Refereed]

  Scientific journal


• A novel five-way translocation, t(3;9;13;8;14)(q27;p13;q32;q24;q32), with concurrent MYC and BCL6 rearrangements in a primary bone marrow B-cell lymphoma

  Katsuya Yamamoto, Hiroshi Matsuoka, Kimikazu Yakushijin, Yohei Funakoshi, Atsuo Okamura, Yoshitake Hayashi, Hironobu Minami

  Sep. 2011, CANCER GENETICS, 204(9) (9), 501 - 506, English

  [Refereed]

  Scientific journal


• Effects of surgery and chronic disease states on the concentrations and phenotype distribution of α1-acid glycoprotein: studies in patients with breast cancer and patients with chronic inflammatory disease

  K. Hanada, E. Yamanaka, N. Yamamoto, H. Minami, S. Kawai, Y. Sasaki, H. Ogata

  Dustri-Verlgag Dr. Karl Feistle, Jul. 2011, Int. Journal of Clinical Pharmacology and Therapeutics, 49(07) (07), 415 - 421

  Scientific journal


• A novel dicentric chromosome, dic(9;9)(p12;q34), leading to trisomy 9 in follicular lymphoma without t(14;18)

  Katsuya Yamamoto, Hiroshi Matsuoka, Yohei Funakoshi, Kimikazu Yakushijin, Atsuo Okamura, Tomoo Itoh, Hironobu Minami

  Jul. 2011, LEUKEMIA RESEARCH, 35(7) (7), E100 - E103, English

  [Refereed]

  Scientific journal


• 当院における貯血式自己血輸血の細菌培養検査について

  Minami Hironobu

  Jun. 2011, 日本輸血細胞治療学会誌, 57巻, 3号, pp. 231-231, Japanese

  International conference proceedings


• 悪性腫瘍患者における緩和ケアニーズと緩和ケアチーム介入希望に関する検討 EORTC QLQ-C15-PALを用いた探索研究

  Sakashita Akihiro, Minami Hironobu

  Jun. 2011, 日本緩和医療学会学術大会プログラム・抄録集16回, 巻, , pp. 282-282, Japanese

  International conference proceedings


• Successful neutrophil engraftment by reduced use of granulocyte colony-stimulating factor after allogeneic hematopoietic stem cell transplantation with mycophenolate mofetil for graft-versus-host disease prophylaxis

  Atsuo Okamura, Kimikazu Yakushijin, Yumiko Inui, Yohei Funakoshi, Yuriko Kawamori, Takanobu Shimada, Masanori Toyoda, Naoko Chayahara, Naomi Kiyota, Yutaka Fujiwara, Toru Mukohara, Hiroshi Matsuoka, Katsuya Yamamoto, Hironobu Minami

  Jun. 2011, INTERNATIONAL JOURNAL OF HEMATOLOGY, 93(6) (6), 765 - 770, English

  [Refereed]

  Scientific journal


• NPM/RARαキメラ遺伝子を認めた急性前骨髄性白血病の一例

  Kawano Seiji, Yakushijin Kimikazu, Minami Hironobu

  Jun. 2011, 日本検査血液学会雑誌, 12巻, 学術集会, pp. S79-S79, Japanese

  International conference proceedings


• 遺伝性乳がん卵巣がんの臨床 BRCA1/2遺伝子検査と薬物療法 PARP阻害薬の臨床開発

  Minami Hironobu

  May 2011, 日本遺伝カウンセリング学会誌, 32巻, 2号, pp. 26-26, Japanese

  International conference proceedings


• 遺伝性乳がん卵巣がんの臨床 BRCA1/2遺伝子検査と薬物療法 PARP阻害薬の臨床開発

  Minami Hironobu

  May 2011, 家族性腫瘍, 11巻, 2号, pp. A26-A26, Japanese

  International conference proceedings


• 当院が導入した輸血後感染症検査報告システム

  Sugiyama Daisuke, Minami Hironobu

  Mar. 2011, 日本輸血細胞治療学会誌, 57巻, 2号, pp. 323-323, Japanese

  International conference proceedings


• Sorafenib-associated hand-foot syndrome in Japanese patients

  Masafumi Iijima, Koichi Fukino, Masatoshi Adachi, Taiji Tsukamoto, Masaru Murai, Seiji Naito, Hironobu Minami, Junji Furuse, Hideyuki Akaza

  Mar. 2011, JOURNAL OF DERMATOLOGY, 38(3) (3), 261 - 266, English

  [Refereed]

  Scientific journal


• Phase I trial of chemoradiotherapy with the combination of S-1 plus cisplatin for patients with unresectable locally advanced squamous cell carcinoma of the head and neck

  Makoto Tahara, Hironobu Minami, Mitsuhiko Kawashima, Kenji Kawada, Hirofumi Mukai, Minoru Sakuraba, Kazuto Matsuura, Takashi Ogino, Ryuichi Hayashi, Atsushi Ohtsu

  Feb. 2011, CANCER SCIENCE, 102(2) (2), 419 - 424, English

  [Refereed]

  Scientific journal


• Phase I trial of combination chemotherapy with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer

  M. Tahara, K. Araki, S. Okano, N. Kiyota, N. Fuse, K. Minashi, T. Yoshino, T. Doi, S. Zenda, M. Kawashima, T. Ogino, R. Hayashi, H. Minami, A. Ohtsu

  Jan. 2011, ANNALS OF ONCOLOGY, 22(1) (1), 175 - 180, English

  [Refereed]

  Scientific journal


• Therapy-Related Pure Erythroid Leukemia with Hepatic Infiltration and Hemophagocytic Syndrome

  Yohei Funakoshi, Hiroshi Matsuoka, Katsuya Yamamoto, Kimikazu Yakushijin, Yumiko Inui, Atsuo Okamura, Mai Takeuchi, Hiroshi Yokozaki, Hironobu Minami

  2011, INTERNAL MEDICINE, 50(24) (24), 3031 - 3035, English

  [Refereed]

  Scientific journal


• Fungal Endophthalmitis Successfully Treated with Intravitreal Voriconazole Injection

  Yohei Funakoshi, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami

  2011, INTERNAL MEDICINE, 50(8) (8), 941 - 941, English

  [Refereed]

  Scientific journal


• Genome-Wide Association Study on Overall Survival of Advanced Non-small Cell Lung Cancer Patients Treated with Carboplatin and Paclitaxel

  Yasunori Sato, Noboru Yamamoto, Hideo Kunitoh, Yuichiro Ohe, Hironobu Minami, Nan M. Laird, Noriko Katori, Yoshiro Saito, Sumiko Ohnami, Hiromi Sakamoto, Jun-ichi Sawada, Nagahiro Saijo, Teruhiko Yoshida, Tomohide Tamura

  Jan. 2011, JOURNAL OF THORACIC ONCOLOGY, 6(1) (1), 132 - 138, English

  [Refereed]

  Scientific journal


• PHASE I TRIAL OF COMBINATION CHEMOTHERAPY WITH DOCETAXEL, CISPLATIN AND S-1 IN PATIENTS WITH HEAD AND NECK CANCER

  Makoto Tahara, Kazuhiro Araki, Susumu Okano, Naomi Kiyota, Nozomu Fuse, Keiko Minashi, Takayuki Yoshino, Toshihiko Doi, Sadamoto Zenda, Mitushiko Kawashima, Takashi Ogino, Ryuichi Hayashi, Hironobu Minami, Atsushi Ohstu

  Nov. 2010, ANNALS OF ONCOLOGY, 21, 34 - 34, English

  [Refereed]


• がん分子標的薬の臨床薬理

  Minami Hironobu

  Nov. 2010, 臨床薬理, 41巻, Suppl., pp. S101-S101, Japanese

  International conference proceedings


• Phase I dose escalation and pharmacokinetic study of oral enzastaurin (LY317615) in advanced solid tumors

  Toru Mukohara, Shunji Nagai, Minori Koshiji, Kenichi Yoshizawa, Hironobu Minami

  Oct. 2010, CANCER SCIENCE, 101(10) (10), 2193 - 2199, English

  [Refereed]

  Scientific journal


• Sagopiloneの第1相臨床薬理試験(Phase I clinical and pharmacokinetic study of Sagopilone in patients with refractory solid tumors)

  荒木 和浩, 南 博信, 喜多川 浩一, 向原 徹, 向井 博文, 児玉 圭司, 安藤 雄一, 奈良林 至, 佐々木 康綱

  日本癌学会, Aug. 2010, 日本癌学会総会記事, 69回, 197 - 197, English

  [Refereed]


• Association of carboxylesterase 1A genotypes with irinotecan pharmacokinetics in Japanese cancer patients

  Kimie Sai, Yoshiro Saito, Naoko Tatewaki, Masakiyo Hosokawa, Nahoko Kaniwa, Tomoko Nishimaki-Mogami, Mikihiko Naito, Jun-ichi Sawada, Kuniaki Shirao, Tetsuya Hamaguchi, Noboru Yamamoto, Hideo Kunitoh, Tomohide Tamura, Yasuhide Yamada, Yuichiro Ohe, Teruhiko Yoshida, Hironobu Minami, Atsushi Ohtsu, Yasuhiro Matsumura, Nagahiro Saijo, Haruhiro Okuda

  Aug. 2010, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 70(2) (2), 222 - 233, English

  [Refereed]

  Scientific journal


• Drug Lag, Molecular Targeting Agents, Predicted Side Effects and Countermeasures.

  Eguchi Kenji, Sugiyama Yukihiko, Minami Hironobu, Niki Yoshihito

  The Japanese Society of Internal Medicine, Jul. 2010, Nihon Naika Gakkai Kaishi, 99(7) (7), 1628 - 1641, Japanese


• 悪性腫瘍患者における緩和ケアニーズのスクリーニングに関する検討

  Kotani Yoshikazu, Minami Hironobu

  Jun. 2010, 日本緩和医療学会学術大会プログラム・抄録集15回, 巻, , pp. 165-165, Japanese

  International conference proceedings


• Phase I and Pharmacokinetic Study of ABI-007, Albumin-bound Paclitaxel, Administered Every 3 Weeks in Japanese Patients with Solid Tumors

  Kazuhiko Yamada, Noboru Yamamoto, Yasuhide Yamada, Toru Mukohara, Hironobu Minami, Tomohide Tamura

  May 2010, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 40(5) (5), 404 - 411, English

  [Refereed]

  Scientific journal


• Additive effects of drug transporter genetic polymorphisms on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients

  Kimie Sai, Yoshiro Saito, Keiko Maekawa, Su-Ryang Kim, Nahoko Kaniwa, Tomoko Nishimaki-Mogami, Jun-ichi Sawada, Kuniaki Shirao, Tetsuya Hamaguchi, Noboru Yamamoto, Hideo Kunitoh, Yuichiro Ohe, Yasuhide Yamada, Tomohide Tamura, Teruhiko Yoshida, Yasuhiro Matsumura, Atsushi Ohtsu, Nagahiro Saijo, Hironobu Minami

  May 2010, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 66(1) (1), 95 - 105, English

  [Refereed]

  Scientific journal


• Effect of axitinib (AG-013736) on fatigue, thyroid-stimulating hormone, and biomarkers: A phase I study in Japanese patients

  Toru Mukohara, Hikaru Nakajima, Hirofumi Mukai, Shunji Nagai, Kuniaki Itoh, Yoshiko Umeyama, Junichi Hashimoto, Hironobu Minami

  Apr. 2010, CANCER SCIENCE, 101(4) (4), 963 - 968, English

  [Refereed]

  Scientific journal


• 結腸直腸がんに対するmFOLFOX6/FOLFIRI±Bevacizumab療法における甲状腺機能の評価

  Minami Hironobu

  Feb. 2010, 日本内科学会雑誌, 99巻, Suppl., pp. 162-162, Japanese

  International conference proceedings


• Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines

  Y. Kataoka, T. Mukohara, H. Shimada, N. Saijo, M. Hirai, H. Minami

  Feb. 2010, ANNALS OF ONCOLOGY, 21(2) (2), 255 - 262, English

  [Refereed]

  Scientific journal


• Left atrial extension of metastatic lung tumor via pulmonary vein: Report on the first case of Ewing sarcoma

  Yohei Funakoshi, Toru Mukohara, Tomoko Kataoka, Hideo Tomioka, Naoko Chayahara, Yutaka Fujiwara, Naomi Kiyota, Tomonori Shirasaka, Takanori Oka, Kenji Okada, Yutaka Okita, Shigeo Hara, Tomoo Itoh, Soichi Fumita, Kazuhiko Nakagawa, Hironobu Minami

  2010, Rare Tumors, 2(3) (3), 151 - 153, English

  [Refereed]

  Scientific journal


• A phase I study of sorafenib (BAY 43-9006) in combination with S-1 plus cisplatin in patients with advanced gastric cancer

  Yasuhide Yamada, Hironobu Minami, Nozomu Fuse, Atsushi Ohtsu, Ken Kato, Naomi Kiyota, Yasushiro Shimada, Toshihiko Doi, Takako Nakajima, Tetsuya Hamaguchi, Yutaka Fujiwara, Yuichiro Ito, Kiyomi Mera

  Dec. 2009, MOLECULAR CANCER THERAPEUTICS, 8(12) (12), English

  [Refereed]


• Phase I study of larotaxel administered as a 1-h intravenous infusion every 3 weeks to Japanese patients with advanced solid tumours

  Nobuyuki Yamamoto, Narikazu Boku, Hironobu Minami

  Dec. 2009, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 65(1) (1), 129 - 136, English

  [Refereed]

  Scientific journal


• Association of carboxylesterase 1A genotypes with irinotecan pharmacokinetics in japanese cancer patients

  Kimie Sai, Yoshiro Saito, Naoko Tatewaki, Masakiyo Hosokawa, Nahoko Kaniwa, Tomoko Nishimaki-Mogami, Mikihiko Naito, Jun-ichi Sawada, Kuniaki Shirao, Tetsuya Hamaguchi, Noboru Yamamoto, Hideo Kunitoh, Yuichiro Ohe, Tomohide Tamura, Yasuhide Yamada, Teruhiko Yoshida, Hironobu Minami, Atsushi Ohtsu, Yasuhiro Matsumura, Nagahiro Saijo, Haruhiro Okuda

  Oct. 2009, DRUG METABOLISM REVIEWS, 41, 155 - 156, English

  [Refereed]


• Sensitivity of breast cancer cell lines to the novel insulin-like growth factor-1 receptor (IGF-1R) inhibitor NVP-AEW541 is dependent on the level of IRS-1 expression

  Toru Mukohara, Hiroyuki Shimada, Naomi Ogasawara, Ryoko Wanikawa, Manami Shimomura, Tetsuya Nakatsura, Genichiro Ishii, Joon Oh Park, Pasi A. Jaenne, Nagahiro Saijo, Hironobu Minami

  Sep. 2009, CANCER LETTERS, 282(1) (1), 14 - 24, English

  [Refereed]

  Scientific journal


• Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802)

  N. Katsumata, T. Watanabe, H. Minami, K. Aogi, T. Tabei, M. Sano, N. Masuda, J. Andoh, T. Ikeda, T. Shibata, S. Takashima

  Jul. 2009, ANNALS OF ONCOLOGY, 20(7) (7), 1210 - 1215, English

  [Refereed]

  Scientific journal


• Clinical Trial Simulations for Dosage Optimization of Docetaxel in Patients with Liver Dysfunction, Based on a Log-binominal Regression for Febrile Neutropenia

  Kazuhiro Ozawa, Hironobu Minami, Hitoshi Sato

  Jun. 2009, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 129(6) (6), 749 - 757, Japanese

  [Refereed]

  Scientific journal


• Pharmacokinetics of ABI-007, cremophor-free nanoparticle formulation of paclitaxel, in Japanese and Chinese patients with malignancies

  Koji Furushiro, Tomohide Tamura, Hironobu Minami, Toru Mukohara, Yasuhiro Fujiwara, Noboru Yamamoto, Kazuhiko Yamada, Yasuhide Yamada, Hikaru Nakajima, Shunji Nagai, Masashi Ando, Kan Yonemori, Eriko Nakano, Mayu Yunokawa, Tsutomu Kouno, Chikako Shimizu, Kenji Tamura, Noriyuki Katsumata, Guan Zhongzhen, Hidetoshi Yamaya, Neil Desai, Vuong Trieu

  May 2009, CANCER RESEARCH, 69, English

  [Refereed]


• Systemic Chemotherapy with Cisplatin Plus 5-FU (PF) for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN): Efficacy and Safety of a Lower Dose of PF (80/800) at a Single Institution in Japan

  Naomi Kiyota, Makoto Tahara, Shigenori Kadowaki, Nozomu Fuse, Toshihiko Doi, Hironobu Minami, Atsushi Ohtsu

  Apr. 2009, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 39(4) (4), 225 - 230, English

  [Refereed]

  Scientific journal


• Phase I Dose-escalation and Pharmacokinetic Trial of Lapatinib (GW572016), a Selective Oral Dual Inhibitor of ErbB-1 and-2 Tyrosine Kinases, in Japanese Patients with Solid Tumors

  Kazuhiko Nakagawa, Hironobu Minami, Masayuki Kanezaki, Akihira Mukaiyama, Yoshiyuki Minamide, Hisao Uejima, Takayasu Kurata, Toshiji Nogami, Kenji Kawada, Hirofumi Mukai, Yasutsuna Sasaki, Masahiro Fukuoka

  Feb. 2009, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 39(2) (2), 116 - 123, English

  [Refereed]

  Scientific journal


• Close Association of UGT1A9 IVS1+399C > T with UGT1A1*28, *6, or*60 Haplotype and Its Apparent Influence on 7-Ethyl-10-hydroxycamptothecin (SN-38) Glucuronidation in Japanese

  Yoshiro Saito, Kimie Sai, Keiko Maekawa, Nahoko Kaniwa, Kuniaki Shirao, Tetsuya Hamaguchi, Noboru Yamamoto, Hideo Kunitoh, Yuichiro Ohe, Yasuhide Yamada, Tomohide Tamura, Teruhiko Yoshida, Hironobu Minami, Atsushi Ohtsu, Yasuhiro Matsumura, Nagahiro Saijo, Jun-ichi Sawada

  Feb. 2009, DRUG METABOLISM AND DISPOSITION, 37(2) (2), 272 - 276, English

  [Refereed]

  Scientific journal


• Population pharmacokinetics of docetaxel in patients with hepatic dysfunction treated in an oncology practice

  Hironobu Minami, Kenji Kawada, Yasutsuna Sasaki, Makoto Tahara, Tadahiko Igarashi, Kuniaki Itoh, Hirofumi Fujii, Toshiaki Saeki, Kazuhiro Ozawa, Hitoshi Sato

  Lead, Jan. 2009, CANCER SCIENCE, 100(1) (1), 144 - 149, English

  [Refereed]

  Scientific journal


• がん臨床試験の準備と実践 臨床薬理学的解析(PK、PD)

  Minami Hironobu

  日本癌治療学会, Oct. 2008, 日本癌治療学会誌, 43巻, 3号, pp. 1205-1208(3) (3), 1205 - 1208, Japanese

  International conference proceedings


• A phase I study of eribulin mesylate (E7389) in patients with refractory cancers

  H. Minami, T. Mukohara, S. Nagai, H. Mukai, M. Namiki

  Oct. 2008, EJC SUPPLEMENTS, 6(12) (12), 140 - 140, English

  International conference proceedings


• 乳がん研究の新展開 基礎と臨床 Triple negative breast cancerの治療。Molecular profilingによる個別化は必要か?(New Perspectives of Basic and Clinical Research in Breast Cancer Drug therapy for triple negative breast cancer: Do we need to individualize therapy by molecular profiling of

  Minami Hironobu

  Sep. 2008, 日本癌学会総会記事, 巻, 67回, pp. 40-40, Japanese

  International conference proceedings


• VEGFR阻害薬Axitinib(AG-013736)の日本人進行固形癌患者を対象とした第I相試験(A Phase I study of axitinib (AG-013736), an inhibitor of VEGFRs, in Japanese patients with advanced solid tumors)(英語)

  Minami Hironobu

  Sep. 2008, 日本癌学会総会記事, 巻, 67回, pp. 306-306, Japanese

  International conference proceedings


• EFFECT OF AXITINIB (AG-013736) ON FATIGUE, THYROID STIMULATING HORMONE (TSH), AND BIOMARKERS: RESULT FROM A PHASE I STUDY IN JAPANESE PATIENTS

  H. Minami, T. Mukohara, H. Nakajima, H. Mukai, S. Nagai, Y. Umeyama, J. Hashimoto, K. Itoh

  Sep. 2008, ANNALS OF ONCOLOGY, 19, 154 - 155, English

  International conference proceedings


• Impact of CYP3A4 haplotypes on irinotecan pharmacokinetics in Japanese cancer patients

  Kimie Sai, Yoshiro Saito, Hiromi Fukushima-Uesaka, Koichi Kurose, Nahoko Kaniwa, Naoyuki Kamatani, Kuniaki Shirao, Noboru Yamamoto, Tetsuya Hamaguchi, Hideo Kunitoh, Yuichiro Ohe, Tomohide Tamura, Yasuhide Yamada, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Jun-ichi Sawada

  Aug. 2008, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 62(3) (3), 529 - 537, English

  [Refereed]

  Scientific journal


• Logistic regression analysis for febrile neutropenia (FN) induced by docetaxel in Japanese cancer patients

  Kazuhiro Ozawa, Hironobu Minami, Hitoshi Sato

  Aug. 2008, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 62(3) (3), 551 - 557, English

  [Refereed]

  Scientific journal


• Phase I and pharmacokinetic study of sorafenib, an oral multikinase inhibitor, in Japanese patients with advanced refractory solid tumors

  Hironobu Minami, Kenji Kawada, Hiromichi Ebi, Koichi Kitagawa, Yon-il Kim, Kazuhiro Araki, Hirofumi Mukai, Makoto Tahara, Hikaru Nakajima, Keiko Nakajima

  Jul. 2008, CANCER SCIENCE, 99(7) (7), 1492 - 1498, English

  [Refereed]

  Scientific journal


• Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer-related bone metastases

  Kan Yonemori, Yasuhiro Fujiwara, Hironobu Minami, Koichi Kitagawa, Hirofumi Fujii, Tatsuhiro Arai, Winnie Sohn, Masayuki Ohkura, Tomoko Ohtsu

  Jun. 2008, CANCER SCIENCE, 99(6) (6), 1237 - 1242, English

  [Refereed]

  Scientific journal


• Irinotecan pharmacogenetics in Japanese cancer patients: Roles of UGT1A1*6 and*28

  Kirnie Sai, Jun-Ichi Sawada, Hironobu Minami

  Apr. 2008, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 128(4) (4), 575 - 584, Japanese

  [Refereed]


• Weekly epoetin beta maintains haemoglobin levels and improves quality of life in patients with non-myeloid malignancies receiving chemotherapy

  Yasuhiro Suzuki, Yutaka Tokuda, Yasuhiro Fujiwara, Hironobu Minami, Yasuo Ohashi, Nagahiro Saijo

  Mar. 2008, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 38(3) (3), 214 - 221, English

  [Refereed]

  Scientific journal


• Nonplatinum-based chemotherapy with irinotecan plus docetaxel for advanced or metastatic olfactory neuroblastoma - A retrospective analysis of 12 cases

  Naomi Kiyota, Makoto Tahara, Satoshi Fujii, Mitsuhiko Kawashima, Takashi Ogino, Hironobu Minami, Ryuichi Hayashi, Atsushi Ohtsu

  Feb. 2008, CANCER, 112(4) (4), 885 - 891, English

  [Refereed]

  Scientific journal


• Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells

  Naoki Ishiguro, Masanobu Oyabu, Toshihiro Sato, Tomoji Maeda, Hironobu Minami, Ikumi Tamai

  Feb. 2008, PHARMACEUTICAL RESEARCH, 25(2) (2), 417 - 427, English

  [Refereed]

  Scientific journal


• Genetic Variations and Haplotypes of ABCC2 Encoding MRP2 in a Japanese Population

  Kimie Sai, Yoshiro Saito, Masaya Itoda, Hiromi Fukushima-Uesaka, Tomoko Nishimaki-Mogami, Shogo Ozawa, Keiko Maekawa, Kouichi Kurose, Nahoko Kaniwa, Manabu Kawamoto, Naoyuki Kamatani, Kuniaki Shirao, Tetsuya Hamaguchi, Noboru Yamamoto, Hideo Kunitoh, Yuichiro Ohe, Yasuhide Yamada, Tomohide Tamura, Teruhiko Yoshida, Hironobu Minami, Yasuhiro Matsumura, Atsushi Ohtsu, Nagahiro Saijo, Jun-ichi Sawada

  2008, Drug Metabolism and Pharmacokinetics, 23(2) (2), 139 - 147, English

  [Refereed]

  Scientific journal


• Phase I and II pharmacokinetic and pharmacodynamic study of the proteasome inhibitor bortezomib in Japanese patients with relapsed or refractory multiple myeloma

  Yoshiaki Ogawa, Kensei Tobinai, Michinori Ogura, Kiyoshi Ando, Takahide Tsuchiya, Yukio Kobayashi, Takashi Watanabe, Dai Maruyama, Yasuo Morishima, Yoshitoyo Kagami, Hirofumi Taji, Hironobu Minami, Kuniaki Itoh, Masanobu Nakata, Tomomitsu Hotta

  Jan. 2008, CANCER SCIENCE, 99(1) (1), 140 - 144, English

  [Refereed]

  Scientific journal


• Phase I and pharmacokinetic study of ABI-007, a Cremophor((R))-free nanoparticle formulation of paclitaxel, administered once every 3 weeks in Japanese patients with solid tumors.

  Toru Mukohara, Hikaru Nakajima, Shunji Nagai, Hironobu Minami, Noboru Yamamoto, Kazuhiko Yamada, Yasuhide Yamada, Tomohide Tamura

  Dec. 2007, MOLECULAR CANCER THERAPEUTICS, 6(12) (12), 3456S - 3456S, English

  [Refereed]


• Population pharmacokinetic and pharmacodynamic analysis for time courses of docetaxel-induced neutropenia in Japanese cancer patients

  Kazuhiro Ozawa, Hironobu Minami, Hitoshi Sato

  Dec. 2007, CANCER SCIENCE, 98(12) (12), 1985 - 1992, English

  [Refereed]

  Scientific journal


• Impact of CYP2A6 genotype on pharmacokinetics, safety and efficacy of letrozole treatment in Japanese postmenopausal women with metastatic breast cancer

  H. Minami, S. Ohsumi, S. Nakamura, H. Inaji, S. Takenoshita, Y. Fujiwara, Y. Lino, M. Woo, H. Tami, T. Tominaga, S. Takashima

  Dec. 2007, BREAST CANCER RESEARCH AND TREATMENT, 106, S113 - S113, English

  International conference proceedings


• Haplotypes and a novel defective allele of CES2 found in a Japanese population

  Su-Ryang Kim, Kimie Sai, Toshiko Tanaka-Kagawa, Hideto Jinno, Shogo Ozawa, Nahoko Kaniwa, Yoshiro Saito, Akira Akasawa, Kenji Matsumoto, Hirohisa Saito, Naoyuki Kamatani, Kuniaki Shirao, Noboru Yamamoto, Teruhiko Yoshida, Hironobu Minami, Atsushi Ohtsu, Nagahiro Saijo, Jun-ichi Sawada

  Oct. 2007, DRUG METABOLISM AND DISPOSITION, 35(10) (10), 1865 - 1872, English

  [Refereed]

  Scientific journal


• Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and*28

  Hironobu Minami, Kimie Sai, Mayumi Saeki, Yoshiro Saito, Shogo Ozawa, Kazuhiro Suzuki, Nahoko Kaniwa, Jun-ichi Sawada, Tetsuya Hamaguchi, Noboru Yamamoto, Kuniaki Shirao, Yasuhide Yamada, Hironobu Ohmatsu, Kaoru Kubota, Teruhiko Yoshida, Atsushi Ohtsu, Nagahiro Saijo

  Jul. 2007, PHARMACOGENETICS AND GENOMICS, 17(7) (7), 497 - 504, English

  [Refereed]

  Scientific journal


• CYP2C8 haplotype structures and their influence on pharmacokinetics of paclitaxel in a Japanese population

  Yoshiro Saito, Noriko Katori, Akiko Soyama, Yukiko Nakajima, Takashi Yoshitani, Su-Ryang Kim, Hiromi Fukushima-Uesaka, Kouichi Kurose, Nahoko Kaniwa, Shogo Ozawa, Naoyuki Kamatani, Kazuo Komamura, Shiro Kamakura, Masafumi Kitakaze, Hitonobu Tomoike, Kenji Sugai, Narihiro Minami, Hideo Kimura, Yu-ichi Goto, Hironobu Minami, Teruhiko Yoshida, Hideo Kunitoh, Yuichiro Ohe, Noboru Yamamoto, Tomohide Tamura, Nagahiro Saijo, Jun-Ichi Sawada

  Jul. 2007, PHARMACOGENETICS AND GENOMICS, 17(7) (7), 461 - 471, English

  [Refereed]

  Scientific journal


• Multifaceted psychosocial intervention program for breast cancer patients after first recurrence: Feasibility study

  Tatsuo Akechi, Koji Taniguchi, Shimako Suzuki, Masako Okamura, Hironobu Minami, Toru Okuyama, Toshiaki A. Furukawa, Yosuke Uchitomi

  Jun. 2007, PSYCHO-ONCOLOGY, 16(6) (6), 517 - 524, English

  [Refereed]

  Scientific journal


• Genetic polymorphisms of CYP2B6 affect the pharmacokinetics/pharmacodynamics of cyclophosphamide in Japanese cancer patients

  Miki Nakajima, Sayaka Komagata, Yuto Fujiki, Yoshihiro Kanada, Hiromichi Ebi, Kuniaki Itoh, Hirofumi Mukai, Tsuyoshi Yokoi, Hironobu Minami

  Jun. 2007, PHARMACOGENETICS AND GENOMICS, 17(6) (6), 431 - 445, English

  [Refereed]

  Scientific journal


• Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer

  Toshiaki Saeki, Tadashi Nomizu, Masakazu Toi, Yoshinori Ito, Shinzaburo Noguchi, Tadashi Kobayashi, Taro Asaga, Hironobu Minami, Naohito Yamamoto, Kenjiro Aogi, Tadashi Ikeda, Yasuo Ohashi, Wakao Sato, Takashi Tsuruo

  Feb. 2007, JOURNAL OF CLINICAL ONCOLOGY, 25(4) (4), 411 - 417, English

  [Refereed]

  Scientific journal


• Phase I and pharmacokinetic study of ABI-007, a Cremophor-free nanoparticle formulation of paclitaxel, administered once every 3 weeks in patients with non-hematological cancers

  Minami Hironobu

  2007, Clinical cancer research, Vol. 13, No. , pp. -, English

  International conference proceedings


• DRUG-INDUCED LUNG TOXICITY CAUSED BY THE INHIBITION OF CHOLINE UPTAKE TRANSPORTER IN HUMAN LUNG ADENOCARCINOMA A549 CELLS AND RAT ALVEOLAR TYPE II CELLS

  Naoki Ishiguro, Toshihiro Sato, Masanobu Oyabu, Tomoji Maeda, Hironobu Minami, Ikumi Tamai

  2007, DRUG METABOLISM REVIEWS, 39, 147 - 147, English

  International conference proceedings


• Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors

  Kenji Kawada, Koji Murakami, Takashi Sato, Yoshiki Kojima, Hiromichi Ebi, Hirofumi Mukai, Makoto Tahara, Kaoru Shimokata, Hironobu Minami

  Jan. 2007, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 37(1) (1), 44 - 48, English

  [Refereed]

  Scientific journal


• Genetic variations and frequencies of major Haplotypes in SLCO1B1 encoding the transporter OATP1B1 in Japanese subjects: SLCO1B1*17 is more prevalent than*15

  Su-Ryang Kim, Yoshiro Saito, Kimie Sai, Kouichi Kurose, Keiko Maekawa, Nahoko Kaniwa, Shogo Ozawa, Naoyuki Kamatani, Kuniaki Shirao, Noboru Yamamoto, Tetsuya Hamaguchi, Hideo Kunitoh, Yuichiro Ohe, Yasuhide Yamada, Tomohide Tamura, Teruhiko Yoshida, Hironobu Minami, Atsushi Ohtsu, Nagahiro Saijo, Jun-ichi Sawada

  2007, DRUG METABOLISM AND PHARMACOKINETICS, 22(6) (6), 456 - 461, English

  [Refereed]

  Scientific journal


• IMPACT OF CYP3A4 HAPLOTYPES ON IRINOTECAN PHARMACOKINETICS IN JAPANESE CANCER PATIENTS

  Kimie Sai, Yoshiro Saito, Hiromi Fukushima-Uesaka, Nahoko Kaniwa, Kuniaki Shirao, Noboru Yamamoto, Tetsuya Hamaguchi, Hideo Kunitoh, Yuichiro Ohe, Tomohide Tamura, Yasuhide Yamada, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Jun-ichi Sawada

  2007, DRUG METABOLISM REVIEWS, 39, 157 - 158, English

  [Refereed]

  Scientific journal


• Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

  Kiyotaka Yoh, Makoto Tahara, Kenji Kawada, Hirofumi Mukai, Masanobu Nakata, Kuniaki Itoh, Mitsuhiko Kawashima, Hideki Nishimura, Ryuichi Hayashi, Takashi Ogino, Hironobu Minami

  Dec. 2006, Asia-Pacific Journal of Clinical Oncology, 2(4) (4), 180 - 184, English

  [Refereed]

  Scientific journal


• A phase I dose-escalation study of ZD6474 in Japanese patients with solid, malignant tumors

  Tomohide Tamura, Hironobu Minami, Yasuhide Yamada, Noboru Yamamoto, Tatsu Shimoyama, Haruyasu Murakami, Atsushi Horiike, Yasuhito Fujisaka, Tetsu Shinkai, Makoto Tahara, Kenji Kawada, Hiromichi Ebi, Yasutsuna Sasaki, Haiyi Jiang, Nagahiro Saijo

  Nov. 2006, Journal of Thoracic Oncology, 1(9) (9), 1002 - 1009

  Scientific journal


• Once-Weekly Epoetin-Beta Improves Hemoglobin Levels in Cancer Patients with Chemotherapy-Induced Anemia: A Randomized, Double-Blind, Dose-Finding Study

  Yasuo Morishima, Michinori Ogura, Shuichi Yoneda, Hiroshi Sakai, Kensei Tobinai, Yutaka Nishiwaki, Hironobu Minami, Tomomitsu Hotta, Kohji Ezaki, Yuichiro Ohe, Akira Yokoyama, Masahiro Tsuboi, Kiyoshi Mori, Koshiro Watanabe, Yasuo Ohashi, Kunitake Hirashima, Nagahiro Saijo

  Oxford University Press (OUP), Sep. 2006, Japanese Journal of Clinical Oncology, 36(10) (10), 655 - 661

  Scientific journal


• Impact of the haplotype CYP3A4*16B harboring the Thr185Ser substitution on paclitaxel metabolism in Japanese patients with cancer

  Yukiko Nakajima, Takashi Yoshitani, Hiromi Fukushima-Uesaka, Yoshiro Saito, Nahoko Kaniwa, Kouichi Kurose, Shogo Ozawa, Nobuo Aoyagi, Naoyuki Kamatani, Noboru Yamamoto, Hideo Kunitoh, Yuichiro Ohe, Tomohide Tamura, Teruhiko Yoshida, Hironobu Minami, Nagahiro Saijo, Noriko Katori, Jun ichi Sawada

  Aug. 2006, Clinical Pharmacology and Therapeutics, 80(2) (2), 179 - 191

  Scientific journal


• Thirty novel genetic variations in the SLC29A1 gene encoding human equilibrative nucleoside transporter 1 (hENT1).

  Su Ryang Kim, Yoshiro Saito, Keiko Maekawa, Emiko Sugiyama, Nahoko Kaniwa, Hideki Ueno, Takuji Okusaka, Chigusa Morizane, Noboru Yamamoto, Masafumi Ikeda, Teruhiko Yoshida, Hironobu Minami, Junji Furuse, Hiroshi Ishii, Nagahiro Saijo, Naoyuki Kamatani, Shogo Ozawa, Jun ichi Sawada

  Jun. 2006, Drug metabolism and pharmacokinetics, 21(3) (3), 248 - 256

  Scientific journal


• Genetic Variations and Haplotype Structures of the ABCB1 Gene in a Japanese Population: An Expanded Haplotype Block Covering the Distal Promoter Region, and Associated Ethnic Differences

  K. Sai, M. Itoda, Y. Saito, K. Kurose, N. Katori, N. Kaniwa, K. Komamura, T. Kotake, H. Morishita, H. Tomoike, S. Kamakura, M. Kitakaze, T. Tamura, N. Yamamoto, H. Kunitoh, Y. Yamada, Y. Ohe, Y. Shimada, K. Shirao, H. Minami, A. Ohtsu, T. Yoshida, N. Saijo, N. Kamatani, S. Ozawa, J. Sawada

  Summary As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks −1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms −1789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re‐assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally‐important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease‐association studies carried out using Asian subjects.

  Wiley, Apr. 2006, Annals of Human Genetics, 70(5) (5), 605 - 622

  Scientific journal


• Genetic variation and haplotype structure of the ABC transporter gene ABCG2 in a Japanese population.

  Keiko Maekawa, Masaya Itoda, Kimie Sai, Yoshiro Saito, Nahoko Kaniwa, Kuniaki Shirao, Tetsuya Hamaguchi, Hideo Kunitoh, Noboru Yamamoto, Tomohide Tamura, Hironobu Minami, Kaoru Kubota, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Naoyuki Kamatani, Shogo Ozawa, Jun ichi Sawada

  Apr. 2006, Drug metabolism and pharmacokinetics, 21(2) (2), 109 - 121

  Scientific journal


• The forefront of genome clinical pharmacology. The result that the millennium project brought about. 5. Polymorphism of drug response-related gene and application to tailor-made dosing. Focusing on the case of irinotecan.

  佐井 君江, 斎藤 嘉朗, 澤田 純一, 白尾 国昭, 南 博信, 西條 長宏

  The Japanese Society of Clinical Pharmacology and Therapeutics, Mar. 2006, Jpn. J. Clin. Pharmacol. Ther., 37(2) (2), 11S - 12S, Japanese


• Inhibition of bone‐derived insulin‐like growth factors by a ligand‐specific antibody suppresses the growth of human multiple myeloma in the human adult bone explanted in NOD/SCID mouse

  Kazuhiro Araki, Takafumi Sangai, Shin'ichi Miyamoto, Hiroyuki Maeda, Shi‐Chuan Zhang, Michio Nakamura, Genichiro Ishii, Takahiro Hasebe, Hideaki Kusaka, Tadakazu Akiyama, Yoshimi Tokuda, Kanji Nagai, Hironobu Minami, Atsushi Ochiai

  Abstract Multiple myeloma (MM) is a fatal disease that affects plasma cells. Patients with MM have 1 or more osteolytic lesions in their bone tissues, where insulin‐like growth factors (IGFs; IGF‐I and IGF‐II) are mainly stored. The role of bone‐derived IGFs in the development of MM has not been extensively studied because reliable animal models are lacking. We established an animal model using a human MM cell line, RPMI8226, in nonobese diabetic/severe‐combined immunodeficient (NOD/SCID) mice implanted with human adult bone (HAB) fragments. Treatment with an anti‐human IGF‐neutralizing monoclonal antibody, KM1468, inhibited the IGF‐I‐stimulated phosphorylation of type‐I IGF receptors (IGF‐IR) in RPMI8226 cells and the activation of the downstream PI3‐K/Akt signaling pathway in vitro. KM1468 inhibited IGF‐I‐mediated RPMI8226 cell growth in a dose‐dependent manner. In the NOD/SCID‐HAB model, treatment with KM1468 significantly inhibited the growth of RPMI8226 cells (p < 0.02). These results indicated that the growth of MM cells was predominantly stimulated not by serum‐derived IGFs, but by bone‐derived IGFs. Furthermore, the targeting of bone‐derived IGFs, using a neutralizing antibody, may offer a new therapeutic strategy for MM. © 2005 Wiley‐Liss, Inc.

  Wiley, Feb. 2006, International Journal of Cancer, 118(10) (10), 2602 - 2608

  Scientific journal


• Phase I and pharmacokinetic study of oral fludarabine phosphate in relapsed indolent B-cell non-Hodgkin's lymphoma

  Y. Ogawa, T. Hotta, K. Tobinai, T. Watanabe, Y. Sasaki, H. Minami, Y. Morishima, M. Ogura, T. Seriu

  Elsevier BV, Feb. 2006, Annals of Oncology, 17(2) (2), 330 - 333

  Scientific journal


• Phase II Study of Oral Fludarabine Phosphate in Relapsed Indolent B-Cell Non-Hodgkin's Lymphoma

  Kensei Tobinai, Takashi Watanabe, Michinori Ogura, Yasuo Morishima, Yoshiaki Ogawa, Ken-ichi Ishizawa, Hironobu Minami, Atae Utsunomiya, Masafumi Taniwaki, Takashi Terauchi, Shigeru Nawano, Masaki Matsusako, Yoshihiro Matsuno, Shigeo Nakamura, Shigeo Mori, Yasuo Ohashi, Masaki Hayashi, Taku Seriu, Tomomitsu Hotta

  Purpose Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkin's lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. Patients and Methods Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). Results Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. Conclusion Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

  American Society of Clinical Oncology (ASCO), Jan. 2006, Journal of Clinical Oncology, 24(1) (1), 174 - 180

  Scientific journal


• Haplotype structures of the UGT1A gene complex in a Japanese population

  M Saeki, Y Saito, H Jinno, K Sai, S Ozawa, K Kurose, N Kaniwa, K Komamura, T Kotake, H Morishita, S Kamakura, M Kitakaze, H Tomoike, K Shirao, T Tamura, N Yamamoto, H Kunitoh, T Hamaguchi, T Yoshida, K Kubota, A Ohtsu, M Muto, H Minami, N Saijo, N Kamatani, J-i Sawada

  Springer Science and Business Media LLC, Nov. 2005, The Pharmacogenomics Journal, 6(1) (1), 63 - 75

  Scientific journal


• Functional characterization of three naturally occurring single nucleotide polymorphisms in the CES2 gene encoding carboxylesterase 2 (HCE-2)

  Takashi Kubo, Su Ryang Kim, Kimie Sai, Yoshiro Saito, Toshiharu Nakajima, Kenji Matsumoto, Hirohisa Saito, Kuniaki Shirao, Noboru Yamamoto, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Yasuo Ohno, Shogo Ozawa, Jun Ichi Sawada

  Oct. 2005, Drug Metabolism and Disposition, 33(10) (10), 1482 - 1487

  Scientific journal


• Functional analysis of four naturally occurring variants of human constitutive androstane receptor

  Shinobu Ikeda, Kouichi Kurose, Hideto Jinno, Kimie Sai, Shogo Ozawa, Ryuichi Hasegawa, Kazuo Komamura, Takeshi Kotake, Hideki Morishita, Shiro Kamakura, Masafumi Kitakaze, Hitonobu Tomoike, Tomohide Tamura, Noboru Yamamoto, Hideo Kunitoh, Yasuhide Yamada, Yuichiro Ohe, Yasuhiro Shimada, Kuniaki Shirao, Kaoru Kubota, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Yoshiro Saito, Jun Ichi Sawada

  Sep. 2005, Molecular Genetics and Metabolism, 86(1-2) (1-2), 314 - 319

  Scientific journal


• Pharmacokinetic and pharmacodynamic comparison of fluoropyrimidine derivatives, capecitabine and 5 '-deoxy-5-fluorouridine (5 '-DFUR)

  H Ebi, Y Sigeoka, T Saeki, K Kawada, T Igarashi, N Usubuchi, R Ueda, Y Sasaki, H Minami

  Aug. 2005, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 56(2) (2), 205 - 211, English

  [Refereed]

  Scientific journal


• Functional analysis of six human aryl hydrocarbon receptor variants in a Japanese population

  Satoru Koyano, Yoshiro Saito, Hiromi Fukushima-Uesaka, Seiichi Ishida, Shogo Ozawa, Naoyuki Kamatani, Hironobu Minami, Atsushi Ohtsu, Tetsuya Hamaguchi, Kuniaki Shirao, Teruhiko Yoshida, Nagahiro Saijo, Hideto Jinno, Jun Ichi Sawada

  Aug. 2005, Drug Metabolism and Disposition, 33(8) (8), 1254 - 1260

  Scientific journal


• Sequence effect of docetaxel and carboplatin on toxicity, tumor response and pharmacokinetics in non-small-cell lung cancer patients: a phase I study of two sequences.

  Maki Ando, Hideo Saka, Yuichi Ando, Hironobu Minami, Takafumi Kuzuya, Masashi Yamamoto, Atsushi Watanabe, Shuzo Sakai, Kaoru Shimokata, Yoshinori Hasegawa

  PURPOSE: To investigate sequence effects on toxicity, tumor response and pharmacokinetics of docetaxel and carboplatin, together with a determination of the maximum-tolerated dose (MTD) and recommended dose for each schedule. PATIENTS AND METHODS: A total of 46 chemotherapy-naive patients with advanced non-small-cell lung cancer were randomized to receive docetaxel before (schedule A) or after (schedule B) carboplatin. The dose levels studied were [docetaxel (mg/m(2))/carboplatin (mg x min/ml)] 50/5, 60/5, 60/6, 60/7, and 70/6. Treatment cycles were repeated every 3 or 4 weeks unless disease progression or undue toxicity occurred. RESULTS: Of the 46 patients, 44 were assessable for toxicity and received a total of 84 cycles. The major dose-limiting toxicity was neutropenia. When the docetaxel dose was 60 mg/m(2), the carboplatin MTD was deemed to be AUC 7 in both schedules. When the docetaxel dose was escalated to 70 mg/m(2), the carboplatin MTD was reached in schedule A, and the dose-limiting toxicity was not observed in schedule B. Tumor response was observed in 4 of 22 patients (18%) with schedule A and 8 of 19 (42%) with schedule B. Clearances of both drugs were not affected by sequence: 111.2+/-26.8 ml/min and 107.8+/-29.0 ml/min for carboplatin (P=0.69), and 26.7+/-8.3 l/h and 22.8+/-7.0 l/h for docetaxel (P=0.19) in schedules A and B, respectively. CONCLUSIONS: Carboplatin AUC 6 followed by docetaxel 70 mg/m(2) was a favorable regimen for phase II study because of likely lower toxicity and a potentially higher response rate than the reverse sequence schedule. The mechanism of the sequence effects on toxicity and tumor response could not be explained by the pharmacokinetic interactions.

  Jun. 2005, Cancer chemotherapy and pharmacology, 55(6) (6), 552 - 8, English, International magazine

  Scientific journal


• Zoledronic Acid Significantly Reduces Skeletal Complications Compared With Placebo in Japanese Women With Bone Metastases From Breast Cancer: A Randomized, Placebo-Controlled Trial

  Norio Kohno, Kenjiro Aogi, Hironobu Minami, Seigo Nakamura, Taro Asaga, Yuichi Iino, Toru Watanabe, Carsten Goessl, Yasuo Ohashi, Shigemitsu Takashima

  Purpose To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer. Patients and Methods Women with bone metastases (N = 228) were randomly assigned to receive 4 mg zoledronic acid (n = 114) or placebo (n = 114) via 15-minute infusions every 4 weeks for 1 year. The primary efficacy end point was the skeletal-related event (SRE) rate ratio between treatment groups. An SRE was defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Secondary end points included percentage of patients with at least one SRE, time-to-first SRE, and Andersen-Gill multiple-event analysis. Results The SRE rate ratio at 1 year (excluding HCM and adjusted for prior fracture) was 0.61 (permutation test; P = .027), indicating that zoledronic acid reduced the rate of SRE by 39% compared with placebo. The percentage of patients with at least one SRE (excluding HCM) was significantly reduced by 20% by zoledronic acid (29.8% v 49.6% for placebo; P = .003). Zoledronic acid significantly delayed time-to-first SRE (median not reached v 364 days; Cox regression; P = .007) and reduced the risk of SREs by 41% in multiple event analysis (risk ratio = 0.59; P = .019) compared with placebo. Zoledronic acid was well tolerated with a safety profile similar to placebo. No patient treated with zoledronic acid had grade 3 or 4 serum creatinine increase. Conclusion Zoledronic acid significantly reduced skeletal complications compared with placebo across multiple end points in Japanese women with bone metastases from breast cancer.

  American Society of Clinical Oncology (ASCO), May 2005, Journal of Clinical Oncology, 23(15) (15), 3314 - 3321

  Scientific journal


• 根治切除不能局所進行頭頸部扁平上皮癌に対する化学放射線療法 当院における長期成績

  田原 信, 藤井 博文, 河島 光彦, 山崎 光男, 宮崎 眞和, 鵜久森 徹, 林 隆一, 荻野 尚, 南 博信, 佐々木 康綱, 海老原 敏

  (一社)日本頭頸部癌学会, May 2005, 頭頸部癌, 31(2) (2), 233 - 233, Japanese


• Functional characterization of five novel CYP2C8 variants, G171S, R186X, R186G, K247R, and K383N, found in a Japanese population

  Hiroyuki Hichiya, Toshiko Tanaka-Kagawa, Akiko Soyama, Hideto Jinno, Satoru Koyano, Noriko Katori, Erika Matsushima, Shigehisa Uchiyama, Hiroshi Tokunaga, Hideo Kimura, Narihiro Minami, Masaaki Katoh, Kenji Sugai, Yu Ichi Goto, Tomohide Tamura, Noboru Yamamoto, Yuichiro Ohe, Hideo Kunitoh, Hiroshi Nokihara, Teruhiko Yoshida, Hironobu Minami, Nagahiro Saijo, Masanori Ando, Shogo Ozawa, Yoshiro Saito, Jun Ichi Sawada

  May 2005, Drug Metabolism and Disposition, 33(5) (5), 630 - 636

  Scientific journal


• Genetic variations and haplotypes of UGT1A4 in a Japanese population.

  Mayumi Saeki, Yoshiro Saito, Hideto Jinno, Kimie Sai, Akiko Hachisuka, Nahoko Kaniwa, Shogo Ozawa, Manabu Kawamoto, Naoyuki Kamatani, Kuniaki Shirao, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Kazuo Komamura, Takeshi Kotake, Hideki Morishita, Shiro Kamakura, Masafumi Kitakaze, Hitonobu Tomoike, Jun-ichi Sawada

  Nineteen genetic variations, including 11 novel ones, were found in exon 1 and its flanking region of the UDP-glucuronosyltransferase (UGT) 1A4 gene from 256 Japanese subjects, consisting of 60 healthy volunteers, 88 cancer patients and 108 arrhythmic patients. These variations include -217T>G and -36G>A in the 5'-flanking region, 30G>A (P10P), 127delA (43fsX22; frame-shift from codon 43 resulting in the termination at the 22nd codon, codon 65), 175delG (59fsX6), 271C>T (R91C), 325A>G (R109G), and 357T>C (N119N) in exon 1, and IVS1+1G>T, IVS1+98A>G and IVS1+101G>T in the following intron. Among them, 127delA and 175delG can confer early termination of translation, resulting in an immature protein that probably lacks enzymatic activity. Variation IVS1+1G>T is located at a splice donor site and thus may lead to aberrant splicing. Since we did not find any significant differences in the frequencies of all the variations among the three subject groups, the data were analyzed as one group. The allele frequencies of the novel variations were 0.006 for IVS1+101G>T, 0.004 for 30G>A (P10P) and 357T>C (N119N), and 0.002 for the 8 other variations. In addition, the two known nonsynonymous single nucleotide polymorphisms (SNPs), 31C>T (R11W) and 142T>G (L48V), were found at 0.012 and 0.129 frequencies, respectively. The SNP 70C>A (P24T), mostly linked with 142T>G (L48V) in German Caucasians, was not detected in this study. Sixteen haplotypes were identified or inferred, and some haplotypes were confirmed by cloning and sequencing. It was shown that most of 142T>G (L48V) was linked with -219C>T, -163G>A, 448T>C (L150L), 804G>A (P268P), and IVS1+43C>T, comprising haplotype *3a; haplotype *4a harbors 31C>T (R11W); 127delA (43fsX22) and 142T>G (L48V) were linked (haplotype *5a); 175delG (59fsX6) was linked with 325A>G (R109G) (*6a haplotype); and -219C>T, -163G>A, 142T>G (L48V), 271C>T (R91C), 448T>C (L150L), 804G>A (P268P), and IVS1+43C>T comprised haplotype *7a. Our results provide fundamental and useful information for genotyping UGT1A4 in the Japanese and probably Asian populations.

  Apr. 2005, Drug metabolism and pharmacokinetics, 20(2) (2), 144 - 51, English, International magazine

  Scientific journal


• Novel genetic polymorphisms in the NR3C1 (glucocorticoid receptor) gene in a Japanese population.

  Koyano S, Saito Y, Sai K, Kurose K, Ozawa S, Nakajima T, Matsumoto K, Saito H, Shirao K, Yoshida T, Minami H, Ohtsu A, Saijo N, Sawada J

  Feb. 2005, Drug metabolism and pharmacokinetics, 20(1) (1), 79 - 84

  [Refereed]


• Genetic polymorphisms of UGT1A6 in a Japanese population.

  Mayumi Saeki, Yoshiro Saito, Hideto Jinno, Kimie Sai, Nahoko Kaniwa, Shogo Ozawa, Kazuo Komamura, Takeshi Kotake, Hideki Morishita, Shiro Kamakura, Masafumi Kitakaze, Hitonobu Tomoike, Kuniaki Shirao, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Naoyuki Kamatani, Jun-ichi Sawada

  Thirteen single nucleotide polymorphisms (SNPs), including 6 novel ones, were found in exon 1 and its flanking region of UDP-glucuronosyltransferase (UGT) 1A6 from 195 Japanese subjects. Several novel SNPs were identified, including 269G>A (R90H), 279A>G (S93S), and 308C>A (S103X) in exon 1, and IVS1+109C>T, IVS1+120A>G, and IVS1+142C>T in the intron downstream of exon 1. Among these SNPs, 308C>A confers termination of translation at codon 103, resulting in the production of an immature protein that probably lacks enzymatic activity. The allele frequencies were 0.003 for all the 6 SNPs. In addition, the 3 known nonsynonymous SNPs were detected: 19T>G (S7A), 541A>G (T181A), and 552A>C (R184S) with frequencies of 0.226, 0.218, and 0.226, respectively. High linkage disequilibrium was observed among 19T>G (S7A), 315A>G (L105L), 541A>G (T181A), 552A>C (R184S), and IVS1+130G>T, as reported in Caucasian and African-American populations. Then, 11 haplotypes in UGT1A6 were estimated. The novel nonsynonymous variant, 269A or 308A, was shown to be located on the same DNA strand together with 19G, 315G, 541G, 552C, and IVS1+130T. Our results provide fundamental and useful information for genotyping UGT1A6 in the Japanese, and probably Asian populations.

  Feb. 2005, Drug metabolism and pharmacokinetics, 20(1) (1), 85 - 90, English, International magazine

  Scientific journal


• A Point, a Line, or an Area? Which Is the Most Important in the Pharmacological Analysis of Cancer Chemotherapy?

  Hironobu Minami

  American Society of Clinical Oncology (ASCO), Jan. 2005, Journal of Clinical Oncology, 23(3) (3), 405 - 406

  Scientific journal


• A Multicenter and Open Label Clinical Trial of Zoledronic Acid 4 mg in Patients with Hypercalcemia of Malignancy

  K. Kawada

  Oxford University Press (OUP), Jan. 2005, Japanese Journal of Clinical Oncology, 35(1) (1), 28 - 33

  Scientific journal


• ROLE OF ORGANIC ANION TRANSPORTER OATP1B1 (OATP-C) IN HEPATIC UPTAKE OF IRINOTECAN AND ITS ACTIVE METABOLITE, 7-ETHYL-10-HYDROXYCAMPTOTHECIN: IN VITRO EVIDENCE AND EFFECT OF SINGLE NUCLEOTIDE POLYMORPHISMS

  Takashi Nozawa, Hironobu Minami, Shigeki Sugiura, Akira Tsuji, Ikumi Tamai

  Elsevier BV, Dec. 2004, Drug Metabolism and Disposition, 33(3) (3), 434 - 439

  Scientific journal


• ZD6474の第I相臨床試験における血清中VEGF濃度の検討

  河田 健司, 田原 信, 南 博信, 佐々木 康綱, 村上 晴康, 下山 達, 山本 昇, 山田 康秀, 田村 友秀, 西條 長宏

  (NPO)日本肺癌学会, Oct. 2004, 肺癌, 44(5) (5), 645 - 645, Japanese


• 頭頸部癌に対する治療の新展開 頭頸部腫瘍に対する放射線化学療法前の内視鏡下胃瘻造設の有用性

  田原 信, 武藤 学, 矢野 友規, 服部 三太, 山下 啓史, 堅田 親利, 安永 真, 岩崎 順子, 目良 清美, 河田 健司, 向井 博文, 南 博信, 大津 敦

  (一社)日本癌治療学会, Sep. 2004, 日本癌治療学会誌, 39(2) (2), 392 - 392, Japanese


• Comparison of pharmacokinetics and pharmacodynamics of docetaxel and Cisplatin in elderly and non-elderly patients: why is toxicity increased in elderly patients?

  Hironobu Minami, Yuichi Ohe, Seiji Niho, Koichi Goto, Hironobu Ohmatsu, Kaoru Kubota, Ryutaro Kakinuma, Yutaka Nishiwaki, Hiroshi Nokihara, Ikuo Sekine, Nagahiro Saijo, Kazuhiko Hanada, Hiroyasu Ogata

  PURPOSE: Following phase I studies of docetaxel and cisplatin in patients with non-small-cell lung cancer, the recommended doses of docetaxel were different for elderly (> or = 75 years) and non-elderly (< 75 years) patients. To elucidate the mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were investigated in two phase II studies separately conducted in elderly and non-elderly patients. PATIENTS AND METHODS: Twenty-seven elderly and 25 non-elderly patients were treated with three weekly administrations of docetaxel and cisplatin every 4 weeks. Doses of docetaxel were 20 and 35 mg/m(2) for elderly and non-elderly patients, respectively. All patients received 25 mg/m(2) of cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin were compared in elderly and non-elderly patients. RESULTS: There were no differences in pharmacokinetics of docetaxel or cisplatin between elderly versus non-elderly patients with regard to clearance and volume of distribution. In the pharmacodynamic analysis, neutropenia was positively correlated with the area under the concentration-time curve for docetaxel but not for cisplatin. In evaluating the relationship between neutropenia and the area under the concentration-time curve of docetaxel, elderly patients experienced greater neutropenia than those predicted by a pharmacodynamic model developed in non-elderly patients; the residual for prediction of the percent change in neutrophil count was -11.2% (95% CI, -21.8 to -0.5%). CONCLUSION: The pharmacokinetics of docetaxel and unchanged cisplatin were not different between elderly and non-elderly patients. The elderly patients were more sensitive to docetaxel exposure than the non-elderly patients, resulting in the different recommended doses for the phase II studies.

  Jul. 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 22(14) (14), 2901 - 8, English, International magazine

  Scientific journal


• UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer.

  Kimie Sai, Mayumi Saeki, Yoshiro Saito, Shogo Ozawa, Noriko Katori, Hideto Jinno, Ryuichi Hasegawa, Nahoko Kaniwa, Jun-ichi Sawada, Kazuo Komamura, Kazuyuki Ueno, Shiro Kamakura, Masafumi Kitakaze, Yutaka Kitamura, Naoyuki Kamatani, Hironobu Minami, Atsushi Ohtsu, Kuniaki Shirao, Teruhiko Yoshida, Nagahiro Saijo

  PURPOSE: A comprehensive haplotype analysis of UGT1A1 in the Japanese population was conducted, and the effects of these haplotypes were investigated with respect to UGT1A1-related phenotypic parameters in patients with cancer who received irinotecan. METHODS: The UGT1A1 gene, including the enhancer, the promoter, and all 5 exons and their flanking regions, was sequenced from 195 Japanese subjects. The gene was divided into 2 blocks, and the haplotypes of each block were assigned. The association of these haplotypes with area under the concentration-time curve (AUC) ratios (7-ethyl-10-hydroxycamptothecin glucuronide [SN-38G]/7-ethyl-10-hydroxycamptothecin [SN-38]) and pretreatment levels of serum total bilirubin was investigated in 85 cancer patients who received irinotecan. RESULTS: Four haplotype groups (*1, *60, *28, and *6) were assigned in block 1, and 2 haplotype groups (*IA and *IB) were in block 2. The majority of the *IB haplotypes in block 2 were linked to either the *1 or the *60 haplotype but not to *28 in block 1. Highly significant associations were obtained between the *28 haplotypes and both a reduced AUC ratio (P =.0014, Jonckheere-Terpstra [JT] test) and an increased total bilirubin level (P =.0007, JT test). Increased total bilirubin levels in the *60 (P =.0048, JT test) and *IB groups (P =.0224, JT test) were also observed. The reduction in the AUC ratio by the *6 group was moderate (P =.0372, JT test) but was remarkable in combination with *60 (*6/*60) or *28 (*6/*28) as compared with the *1 group (*1/*1) (P =.049 and P =.0071, respectively; nonparametric Dunnett test). CONCLUSION: This study identified several UGT1A1 haplotypes significantly associated with the reduced AUC ratio (*28 and *6) and with the increased total bilirubin level (*28, *60, and *IB) and suggested that the novel haplotype *IB might be functionally important. These findings will be useful for further pharmacogenetic studies on adverse reactions to irinotecan.

  Jun. 2004, Clinical pharmacology and therapeutics, 75(6) (6), 501 - 15, English, International magazine

  Scientific journal


• Genetic variations of the AHR gene encoding aryl hydrocarbon receptor in a Japanese population.

  Hiromi Fukushima-Uesaka, Kimie Sai, Keiko Maekawa, Satoru Koyano, Nahoko Kaniwa, Shogo Ozawa, Manabu Kawamoto, Naoyuki Kamatani, Kazuo Komamura, Shiro Kamakura, Masafumi Kitakaze, Hitonobu Tomoike, Kazuyuki Ueno, Hironobu Minami, Atsushi Ohtsu, Kuniaki Shirao, Teruhiko Yoshida, Nagahiro Saijo, Yoshiro Saito, Jun-ichi Sawada

  2004, Drug metabolism and pharmacokinetics, 19(4) (4), 320 - 326, English

  Scientific journal


• Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population.

  Hiromi Fukushima-Uesaka, Yoshiro Saito, Hidemi Watanabe, Kisho Shiseki, Mayumi Saeki, Takahiro Nakamura, Kouichi Kurose, Kimie Sai, Kazuo Komamura, Kazuyuki Ueno, Shiro Kamakura, Masafumi Kitakaze, Sotaro Hanai, Toshiharu Nakajima, Kenji Matsumoto, Hirohisa Saito, Yu-ichi Goto, Hideo Kimura, Masaaki Katoh, Kenji Sugai, Narihiro Minami, Kuniaki Shirao, Tomohide Tamura, Noboru Yamamoto, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Yutaka Kitamura, Naoyuki Kamatani, Shogo Ozawa, Jun-ichi Sawada

  In order to identify single nucleotide polymorphisms (SNPs) and haplotype frequencies of CYP3A4 in a Japanese population, the distal enhancer and proximal promoter regions, all exons, and the surrounding introns were sequenced from genomic DNA of 416 Japanese subjects. We found 24 SNPs, including 17 novel ones: two in the distal enhancer, four in the proximal promoter, one in the 5'-untranslated region (UTR), seven in the introns, and three in the 3'-UTR. The most common SNP was c.1026+12G>A (IVS10+12G>A), with a 0.249 frequency. Four non-synonymous SNPs, c.554C>G (p.T185S, CYP3A4(*)16), c.830_831insA (p.E277fsX8, (*)6), c.878T>C (p.L293P, (*)18), and c.1088 C>T (p.T363M, (*)11) were found with frequencies of 0.014, 0.001, 0.028, and 0.002, respectively. No SNP was found in the known nuclear transcriptional factor-binding sites in the enhancer and promoter regions. Using these 24 SNPs, 16 haplotypes were unambiguously identified, and nine haplotypes were inferred by aid of an expectation-maximization-based program. In addition, using data from 186 subjects enabled a close linkage to be found between CYP3A4 and CYP3A5 SNPs, especially among the SNPs at c.1026+12 in CYP3A4 and c.219-237 (IVS3-237, a key SNP site for CYP3A5(*)3), c.865+77 (IVS9+77) and c.1523 in CYP3A5. This result suggested that CYP3A4 and CYP3A5 are within the same gene block. Haplotype analysis between CYP3A4 and CYP3A5 revealed several major haplotype combinations in the CYP3A4-CYP3A5 block. Our findings provide fundamental and useful information for genotyping CYP3A4 (and CYP3A5) in the Japanese, and probably Asian populations.

  Jan. 2004, Human mutation, 23(1) (1), 100 - 100, English, International magazine

  Scientific journal


• 【がんの化学療法 知っておきたい標準的治療法】推薦処方とその解説 頭頸部がん

  田原 信, 南 博信

  (株)総合医学社, Jan. 2004, 今月の治療, 12(2) (2), 211 - 214, Japanese


• Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype-dependent renal clearance of irinotecan

  Kimie Sai, Nahoko Kaniwa, Masaya Itoda, Yoshiro Saito, Ryuichi Hasegawa, Kazuo Komamura, Kazuyuki Ueno, Shiro Kamakura, Masafumi Kitakaze, Kuniaki Shirao, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Yutaka Kitamura, Naoyuki Kamatani, Shogo Ozawa, Jun-ichi Sawada

  Ovid Technologies (Wolters Kluwer Health), Dec. 2003, Pharmacogenetics, 13(12) (12), 741 - 757

  Scientific journal


• Extragonadal germ cell tumors in Japan

  H Ebi, M Nakata, M Tahara, T Igarashi, K Kawada, K Itoh, R Ueda, H Minami

  Dec. 2003, CANCER SCIENCE, 94(12) (12), 1107 - 1111, English

  [Refereed]

  Scientific journal


• 原発乳癌に対するFEC100術前化学療法の有効性と安全性

  向井 博文, 南 博信, 和田 徳昭, 井本 滋

  (一社)日本癌治療学会, Sep. 2003, 日本癌治療学会誌, 38(2) (2), 258 - 258, Japanese


• 嗅神経芽細胞腫における化学療法

  葉 清隆, 田原 信, 河田 健司, 向井 博文, 中田 匡信, 五十嵐 忠彦, 伊藤 國明, 南 博信

  (一社)日本癌治療学会, Sep. 2003, 日本癌治療学会誌, 38(2) (2), 547 - 547, Japanese


• 進行固形癌に対するドセタキセル(DOC)と塩酸イリノテカン(IRN)併用毎週投与の第1相試験と薬物動態

  河田 健司, 佐々木 康綱, 田原 信, 松澤 かおり, 衣斐 寛倫, 臼渕 規子, 向井 博文, 中田 匡信, 五十嵐 忠彦, 伊藤 國明, 南 博信

  (一社)日本癌治療学会, Sep. 2003, 日本癌治療学会誌, 38(2) (2), 636 - 636, Japanese


• 外来化学療法における時間外電話対応の実態調査

  五十嵐 忠彦, 伊藤 国明, 田原 信, 向井 博文, 中田 匡信, 河田 健司, 南 博信

  (一社)日本癌治療学会, Sep. 2003, 日本癌治療学会誌, 38(2) (2), 666 - 666, Japanese


• Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients.

  Hideto Jinno, Mayumi Saeki, Yoshiro Saito, Toshiko Tanaka-Kagawa, Nobumitsu Hanioka, Kimie Sai, Nahoko Kaniwa, Masanori Ando, Kuniaki Shirao, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Shogo Ozawa, Jun-ichi Sawada

  SN-38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of the antitumor prodrug irinotecan, is conjugated and detoxified to SN-38 10-O-beta-d-glucuronide by hepatic UDP-glucuronosyltransferase (UGT) 1A1. Recent studies have revealed that other UGT1A isoforms, UGT1A7 and UGT1A9, also participate in SN-38 glucuronidation. Although several genetic polymorphisms are reported for UGT1A1 and UGT1A7 that affect the SN-38 glucuronidation activities, no such polymorphisms have been identified for UGT1A9. In the present study, UGT1A9 exon 1 and its flanking regions were sequenced from 61 Japanese cancer patients who were all treated with irinotecan. A novel nonsynonymous single nucleotide polymorphism was identified in UGT1A9 exon 1, heterozygous 766G>A resulting in the amino acid substitution of D256N. The wild-type and D256N UGT1A9s were transiently expressed at similar protein levels in COS-1 cells, and their membrane fractions were characterized in vitro for the glucuronidation activities toward SN-38. The apparent Km values were 19.3 and 44.4 microM, and the Vmax values were 2.94 and 0.24 pmol/min/mg of membrane protein for the wild-type and D256N variant, respectively. The SN-38 glucuronidation efficiency (normalized Vmax/Km) of D256N was less than 5% that of wild-type UGT1A9. These results clearly indicate that the D256N variant is essentially nonfunctional with regard to SN-38 glucuronidation. These findings highlight the importance of further studies into the potential influence of UGT1A9 D256N variant to irinotecan metabolism in vivo.

  Aug. 2003, The Journal of pharmacology and experimental therapeutics, 306(2) (2), 688 - 93, English, International magazine

  Scientific journal


• Functional characterization of wild-type and variant (T202I and M59I) human UDP-glucuronosyltransferase 1A10.

  Hideto Jinno, Mayumi Saeki, Toshiko Tanaka-Kagawa, Nobumitsu Hanioka, Yoshiro Saito, Shogo Ozawa, Masanori Ando, Kuniaki Shirao, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Jun-Ichi Sawada

  UDP-glucuronosyltransferase (UGT) 1A10 is an isoform of UGT1A, which is expressed in extrahepatic, biliary and aerodigestive/gastrointestinal tissues. We have previously reported two nonsynonymous single nucleotide polymorphisms in exon 1 of human UGT1A10 gene; 177G>A and 605C>T resulting in amino acid alterations, M59I and T202I, respectively. In the present study, wild-type (WT) and these variant UGT1A10 cDNAs were transiently expressed in COS-1 cells for functional characterization. Glucuronidation activities in these COS-1 membrane fractions were assayed using 7-hydroxy-4-trifluoromethylcoumarin (HTFMC) and 17 beta-estradiol (E2) as substrates. WT and variant UGT1A10s catalyzed HTFMC glucuronidation with similar apparent K(m) values of approximately 5 microM, whereas the V(max) value of T202I normalized by the expressed UGT1A10 protein levels was nearly half of those of WT and M59I. High-performance liquid chromatography analysis of E2 glucuronide revealed that UGT1A10 catalyzed E2 3-O-glucuronidation but not 17-O-glucuronidation. Similarly, the three UGT1A10s catalyzed E2 3-O-glucuronidation with comparable apparent K(m) values (approximately 2 microM), whereas the normalized V(max) value of T202I was almost half that of WT and M59I. These results suggest that the lowered glucuronidation activity of T202I affects the gastrointestinal glucuronidation of orally administrated chemicals and the enterohepatic circulation of biliary excreted metabolites.

  May 2003, Drug metabolism and disposition: the biological fate of chemicals, 31(5) (5), 528 - 32, English, International magazine

  Scientific journal


• Twenty­six Novel Single Nucleotide Polymorphisms and their Frequencies of the NR1I3(CAR) Gene in a Japanese Population

  Shinobu Ikeda, Kouichi Kurose, Shogo Ozawa, Kimie Sai, Ryuichi Hasegawa, Kazuo Komamura, Kazuyuki Ueno, Shiro Kamakura, Masafumi Kitakaze, Hitonobu Tomoike, Toshiharu Nakajima, Kenji Matsumoto, Hirohisa Saito, Yu­ichi Goto, Hideo Kimura, Masaaki Katoh, Kenji Sugai, Narihiro Minami, Kuniaki Shirao, Tomohide Tamura, Noboru Yamamoto, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Yoshiro Saito, Jun­ichi Sawada

  Japanese Society for the Study of Xenobiotics, 2003, Drug Metabolism and Pharmacokinetics, 18(6) (6), 413 - 418

  Scientific journal


• 薬物動態関連遺伝子の発現制御に関わる転写因子CARの遺伝子多型

  池田 仁子, 黒瀬 光一, 小澤 正吾, 斎藤 嘉朗, 澤田 純一, 田村 友秀, 白尾 国昭, 西條 長宏, 南 博信, 南 成祐, 後藤 雄一, 中島 敏治, 斎藤 博久, 駒村 和雄, 北風 政史

  [目的] CAR (Constitutive Androstane Receptor)は、薬物動態関連分子の遺伝子(CYP2B6、CYP3A4、CYP2C9、UGT1A1、ABCC2、ABCC3等)の転写活性に関与する核内レセプターの１つであり、CARの遺伝子多型の解析及び機能解析は、薬物応答性の個人差発現の原因解明につながると考えられる。今回、我々は抗がん剤、抗不整脈薬、抗喘息薬、抗てんかん薬を投与された患者約250例より得られたDNAを用いて、ヒトCAR遺伝子(NR1I3)の9つのエクソン領域及びイントロン領域における一塩基多型(SNP)解析を行った。
  [方法] NR1I3の塩基配列を決定するため、NCBI( National Center for Biotechnology Information)データベースに報告されているNR1I3DNA配列（NT_004668.15)をリファレンス配列として鋳型増幅用プライマーを設計した。全長約8.5kbをZ-Taq (1st PCR)により増幅し、次いで各エクソン領域をEx-Taq (2nd PCR)により増幅した。各エクソン領域ごとに設計した2方向の塩基配列決定用プライマーを用いるDNAシークエンシングにより、SNP検出を行った。
  [結果・考察] 検体DNAで見つかったSNPsは19種類であった。うち新規SNPsは16種類で、エクソン領域に位置するアミノ酸置換SNPは1種類であった。今回の結果から、アミノ酸置換を起こすSNPが非常に少ないことが明らかにされたが、構成的に発現する遺伝子の転写調節にCARが重要な役割を担っているためと推測された。次いで、得られたSNPを利用して、ハプロタイプの決定を行った。今後は、CYP3A4やUGT1A1により代謝を受ける薬物に関して、代謝物生成とハプロタイプの間の相関を検討する予定である。

  一般社団法人 日本薬物動態学会, 2003, 日本薬物動態学会年会講演要旨集, 18, 212 - 212, Japanese


• Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese cancer patients administered irinotacan.

  Masaya Itoda, Yoshiro Saito, Kuniaki Shirao, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Hiroshi Suzuki, Yuichi Sugiyama, Shogo Ozawa, Jun-ichi Sawada

  Eight novel single nucleotide polymorphisms (SNPs) were found in the gene encoding the ATP-binding cassette transporter, ABCG2/BCRP, from 60 Japanese individuals administered the anti-cancer drug irinotecan. The detected SNPs were as follows: 1) SNP, MPJ6_AG2005 (IVS2-93T>C); Gene Name, ABCG2; Accession Number, NT_006204; 2) SNP, MPJ6_AG2007 (IVS3+71_72 insT); Gene Name, ABCG2; Accession Number, NT_006204; 3) SNP, MPJ6_AG2012 (IVS6-204C>T); Gene Name, ABCG2; Accession Number, NT_006204; 4) SNP, MPJ6_AG2015 (at nucleotide 1098G>A (exon 9) from the A of the translation initiation codon); Gene Name, ABCG2; Accession Number, NT_006204; 5) SNP, MPJ6_AG2017 (1291T>C (exon 11)); Gene Name, ABCG2; Accession Number, NT_006204; 6) SNP, MPJ6_AG2019 (IVS11-135G>A); Gene Name, ABCG2; Accession Number, NT_006204; 7) SNP, MPJ6_AG2020 (1465T>C (exon 12)); Gene Name, ABCG2; Accession Number, NT_006204; 8) SNP, MPJ6_AG2023 (IVS13+65T>G); Gene Name, ABCG2; Accession Number, NT_006204.MPJ6_AG2015 was a synonymous SNP (E366E). MPJ6_AG2017 and MPJ6_AG2020 resulted in amino acid alterations, F431L and F489L, respectively.

  2003, Drug metabolism and pharmacokinetics, 18(3) (3), 212 - 7, English, International magazine

  [Refereed]


• Twelve Novel Single Nucleotide Polymorphisms in the CES2 Gene Encoding Human Carboxylesterase 2 (hCE-2)

  Su-Ryang Kim, Takahiro Nakamura, Yoshiro Saito, Kimie Sai, Shogo Ozawa, Jun-Ichi Sawada, Toshiharu Nakajima, Hirohisa Saito, Kuniaki Shirao, Nagahiro Saijo, Teruhiko Yoshida, Hironobu Minami

  2003, Drug Metabolism and Pharmacokinetics, 18(5) (5), 327 - 332, English

  [Refereed]

  Scientific journal


• Three novel single nucleotide polymorphisms in UGT1A9.

  Mayumi Saeki, Yoshiro Saito, Hideto Jinno, Kimie Sai, Kazuo Komamura, Kazuyuki Ueno, Shiro Kamakura, Masafumi Kitakaze, Kuniaki Shirao, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Shogo Ozawa, Jun-ichi Sawada

  Three novel single nucleotide polymorphisms (SNPs) were found in the UDP-glucuronosyltransferase (UGT) 1A9 gene from 97 Japanese subjects (47 cancer patients and 50 cardiovascular disease patients). The detected SNPs were as follows: 1) SNP, MPJ6_U1A006; GENE NAME, UGT1A9; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-AATTCTCTTAGGG/TTTCTCAGATGCC-3'. 2) SNP, MPJ6_U1A007; GENE NAME, UGT1A9; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-TGTTACGGAGTAT/GGATCTCTACAGC-3'. 3) SNP, MPJ6_U1A031; GENE NAME, UGT1A9; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-ACTCATTCTCAGG/AGGGCATGAGGTG-3'. All three SNPs were located in exon 1 with frequencies of 0.036 for MPJ6_U1A006, and 0.005 for MPJ6_U1A007 and MPJ6_U1A031. SNP MPJ6_U1A007 (726T>G) results in formation of a termination codon TAG (Y242X). The other two SNPs, MPJ6_U1A006 (588G>T) and MPJ6_U1A031 (153G>A), result in synonymous changes (G196G and R51R, respectively).

  2003, Drug metabolism and pharmacokinetics, 18(2) (2), 146 - 9, English, International magazine

  Scientific journal


• 頭頸部扁平上皮癌に対する放射線化学同時併用療法の有用性について

  田原 信, 藤井 博文, 河島 光彦, 朝蔭 孝宏, 鬼塚 哲郎, 羽田 達正, 小室 哲, 林 隆一, 南 博信, 佐々木 康綱, 海老原 敏

  (一社)日本癌治療学会, Sep. 2002, 日本癌治療学会誌, 37(2) (2), 282 - 282, Japanese


• Three novel single nucleotide polymorphisms in UGT1A10.

  Mayumi Saeki, Shogo Ozawa, Yoshiro Saito, Hideto Jinno, Tetsuya Hamaguchi, Hiroshi Nokihara, Yasuhiro Shimada, Hideo Kunitoh, Noboru Yamamoto, Yuichiro Ohe, Yasuhide Yamada, Kuniaki Shirao, Manabu Muto, Kiyomi Mera, Koichi Goto, Hironobu Ohmatsu, Kaoru Kubota, Seiji Niho, Ryutaro Kakinuma, Hironobu Minami, Atsushi Ohtsu, Teruhiko Yoshida, Nagahiro Saijo, Jun-ichi Sawada

  Three novel single nucleotide polymorphisms (SNPs) were found in the UDP-glucuronosyltransferase (UGT) 1A10 gene from 24 Japanese patients with various cancers who were administered the anti-tumor drug, irinotecan (CPT-11). The detected SNPs were as follows: 1) SNP, MPJ6_U1A003; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CAGATGCCATGAC/TTTTCAAGGAGAG-3'. 2) SNP, MPJ6_U1A004; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CCTAGAAATAGCC/TTCTGAAATTCTC-3'. 3) SNP, MPJ6_U1A030; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-GGTTGTAGTCATG/ACCAGAGGTGAGT-3' All the three SNPs were located in exon 1 and their frequencies were all 0.021. Among these SNPs, MPJ6_U1A003 and U1A030 resulted in amino acid alterations, T202I and M59I, respectively. The third SNP, MPJ6_U1A004, introduced a synonymous amino acid change (A231A).

  2002, Drug metabolism and pharmacokinetics, 17(5) (5), 488 - 90, English, International magazine

  [Refereed]

  Scientific journal


• 癌化学療法に伴う血液毒性の検討

  臼渕 規子, 石澤 賢一, 五十嵐 忠彦, 伊藤 國明, 田原 信, 南 博信, 佐々木 康綱

  (一社)日本輸血・細胞治療学会, Jan. 2002, 日本輸血学会雑誌, 47(6) (6), 860 - 861, Japanese


• Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer

  Mitsuo Sato, Masahiko Ando, Hironobu Minami, Yuichi Ando, Maki Ando, Masashi Yamamoto, Shuzo Sakai, Atsushi Watanabe, Takuya Ikeda, Yoshitaka Sekido, Hideo Saka, Kaoru Shimokata, Yoshinori Hasegawa

  Springer Science and Business Media LLC, Dec. 2001, Cancer Chemotherapy and Pharmacology, 48(6) (6), 481 - 487

  Scientific journal


• Prognostic value of performance status assessed by patients themselves, nurses and oncologists in advanced non-small cell lung cancer

  M Ando, Y Ando, Y Hasegawa, K Shimokata, H Minami, K Wakai, Y Ohno, S Sakai

  Springer Science and Business Media LLC, Nov. 2001, British Journal of Cancer, 85(11) (11), 1634 - 1639

  Scientific journal


• Phase I and pharmacological study of a new camptothecin derivative, exatecan mesylate (DX-8951f), infused over 30 minutes every 3 weeks

  Minami H., Fujii H., Igarashi T., Itoh K., Tamanoi K., Oguma T., Sasaki Y.

  Lead, Oct. 2001, Clinical Cancer Research, 7(10) (10), 3056 - 3064


• B細胞性リンパ腫の表面マーカーの解析

  石澤 賢一, 一迫 玲, 田丸 淳一, 臼渕 規子, 衣斐 寛倫, 河田 健司, 田原 信, 南 博信, 五十嵐 忠彦, 伊藤 国明

  (一社)日本血液学会-東京事務局, Oct. 2001, 臨床血液, 42(10) (10), 1007 - 1007, Japanese


• Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes

  C. Senda, Y. Yamaura, K. Kobayashi, H. Fujii, H. Minami, Y. Sasaki, T. Igarashi, K. Chiba

  Aims  To study the influence of CYP2D6*10 on the formation of p‐hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM) using microsomes from human liver of known genotypes. Methods  Microsomes from human livers of genotype CYP2D6*1/*1 (n = 5), *1/*10 (n = 6) and *10/*10 (n = 6) were used in this study. The formation of PHM and HMM was determined by high‐performance liquid chromatography. Results  The formation rates of PHM and HMM were decreased by more than 50% and 85% in CYP2D6*1/*10 and *10/*10 microsomes, respectively, compared with *1/*1 microsomes. Conclusions  The metabolism of mexiletine to form PHM and HMM appears to be impaired to a significant extent in human liver microsomes from hetero‐ and homozygotes of CYP2D6*10.

  Wiley, Jul. 2001, British Journal of Clinical Pharmacology, 52(1) (1), 100 - 103

  Scientific journal


• Treatable Subsets in Cancer of Unknown Primary Origin

  Hajime Sumi, Kuniaki Itoh, Yusuke Onozawa, Yasushi Shigeoka, Keiji Kodama, Kenichi Ishizawa, Hirofumi Fujii, Hironobu Minami, Tadahiko Igarashi, Yasutsuna Sasaki

  The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum‐based in 31, non‐platinum‐based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1–50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom p‐subunit of human chorionic gonadotropin (β‐HCG) was elevated more than 10 mlU/ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum‐based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum‐based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of β‐HCG in patients with poorly differentiated carcinoma might predict a better response to platinum‐based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.

  Wiley, Jun. 2001, Japanese Journal of Cancer Research, 92(6) (6), 704 - 709

  Scientific journal


• Factors Affecting the Pharmacokinetics of CPT-11: The Body Mass Index, Age and Sex are Independent Predictors of Pharmacokinetic Parameters of CPT-11

  Toshimichi Miya, Tomoyuki Goya, Hirofumi Fujii, Tomoko Ohtsu, Kuniaki Itoh, Tadahiko Igarashi, Hironobu Minami, Yasutsuna Sasaki

  Springer Science and Business Media LLC, Feb. 2001, Investigational New Drugs, 19(1) (1), 61 - 67

  Scientific journal


• Pharmacodynamic Modeling of the Entire Time Course of Leukopenia after a 3‐Hour Infusion of Paclitaxel

  Hironobu Minami, Yasutsuna Sasaki, Torn Watanabe, Makoto Ogawa

  The entire time course of leukopenia after anticancer treatment is clinically more relevant than a singly measured nadir count. In order to identify factors associated with neutropenic fever, a mechanistic pharmacodynamic model with two compartments corresponding to leukocytes in bone marrow and peripheral blood was applied to describe the time course of leukopenia. Seventeen patients with breast cancer were treated with 210 mg/m² of paclitaxel infused over 3 h as a single agent in a phase II study. Adequate fitting of the time course of leukopenia was achieved in all patients, and time‐dependent parameters, including the tune period during which leukocyte counts remained below 2000/μl and the area between the curve for time versus leukocyte counts and the line of a leukocyte count of 2000/μl (A <2000), were calculated in each patient. Leukopenia was not significantly correlated with pharmacokinetic parameters, including time above a threshold concentration or the area under the tune‐concentration curve. A negative correlation between age and the sensitivity parameter of the pharmacodynamic model was observed (r²=0.21, P=0.07). Patients who experienced neutropenic fever had a larger A<2000 than patients who did not experience fever (4512 vs. 6 days/μl, P=0.05), but fever was not significantly related to any pharmacokinetic parameter or the leukocyte nadir count. Febrile episodes were better associated with the time course of leukopenia than the singly measured nadir count, and the pharmacodynamic model presents a novel platform to analyze the entire tune course of leukopenia.

  Lead, Wiley, Feb. 2001, Japanese Journal of Cancer Research, 92(2) (2), 231 - 238

  Scientific journal


• Phase I Study of Intravenous PSC‐833 and Doxorubicin: Reversal of Multidrug Resistance

  Hironobu Minami, Tomoko Ohtsu, Hirofumi Fujii, Tadahiko Igarashi, Kuniaki Itoh, Noriko Uchiyama‐Kokubu, Tetsushi Aizawa, Torn Watanabe, Yoshinori Uda, Yusuke Tanigawara, Yasutsuna Sasaki

  PSC‐833 reverses multidrug resistance by P‐glycoprotein at concentrations <1000 ng/ml. A phase I study of PSC‐833 and doxorubicin was conducted to determine the maximum tolerated dose and to investigate pharmacokinetics. PSC‐833 was intravenously infused as a 2‐h loading dose (LD) and a subsequent 24‐h continuous dose (CD). Doxorubicin was infused over 5 min, 1 h after the LD. The starting dose was 1 mg/kg for both LD and CD with 30 mg/m² doxorubicin; these dosages were increased to 2 and 10 mg/kg and 50 mg/m², respectively. Thirty‐one patients were treated. Nausea/ vomiting was controllable with granisetron and dexamethasone. Neutropenia and ataxia were dose limiting. Steady‐state concentrations of PSC‐833 >1000 ng/ml were achieved at a 2 mg/kg LD and a 10 mg/kg CD. Ex‐vivo bioassay revealed that activity in serum for reversing multidrug resistance was achieved in all patients; IC₅₀ of P‐glycoprotein expressing 8226/Dox₆; in patients’ serum was decreased from 5.9 to 1.3 μg/ml (P<0.0001) by PSC‐833 administration. Doxorubicin clearance was 24.3±13.7 (mean±SD) liter/h/m², which was lower than the 49.0±16.9 liter/h/m² without PSC‐833 (P<0.0001). The relationship between doxorubicin exposure and neutropenia did not differ between patients treated and not treated with PSC‐833. The recommended phase II dose of PSC‐833 was 2 and 10 mg/kg for LD and CD, respectively, which achieved a sufficient concentration in serum to reverse drug resistance, as confirmed by bioassay. The dose of doxorubicin should be reduced to 40 mg/m², not because of the pharmacodynamic interaction between PSC‐833 and doxorubicin affecting hematopoiesis, but because of pharmacokinetic interaction.

  Wiley, Feb. 2001, Japanese Journal of Cancer Research, 92(2) (2), 220 - 230

  Scientific journal


• Clinical effect of irinotecan in advanced and metastatic breast cancer patients previously treated with doxorubicin- and docetaxel-containing regimens

  Yasushi Shigeoka, Kuniaki Itoh, Tadahiko Igarashi, Kenichi Ishizawa, Toshiaki Saeki, Hirofumi Fujii, Hironobu Minami, Shigeru Imoto, Yasutsuna Sasaki

  2001, Japanese Journal of Clinical Oncology, 31(8) (8), 370 - 374, English

  [Refereed]

  Scientific journal


• 1. EtoposideのPK/PD相関とIndividualization

  南 博信

  The Japanese Society of Clinical Pharmacology and Therapeutics, 2001, 臨床薬理, 32(3) (3), 473S - 473S, Japanese


• Multi-institutional validation study of carboplatin dosing formula using adjusted serum creatinine level

  Ando M., Minami H., Ando Y., Saka H., Sakai S., Yamamoto M., Sasaki Y., Shimokata K., Hasegawa Y.

  Dec. 2000, Clinical Cancer Research, 6(12) (12), 4733 - 4738


• Dose-escalation study of CHOP with or without prophylactic G-CSF in aggressive non-Hodgkin's lymphoma

  K. Itoh, T. Ohtsu, H. Wakita, T. Igarashi, K. Ishizawa, Y. Onozawa, H. Fujii, H. Minami, Y. Sasaki

  Elsevier BV, Oct. 2000, Annals of Oncology, 11(10) (10), 1241 - 1248

  Scientific journal


• Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate

  Kobayashi K., Mimura N., Fujii H., Minami H., Sasaki Y., Shimada N., Chiba K.

  Aug. 2000, Clin Cancer Res, 6(8) (8), 3297 - 3303


• Study of dose escalation and sequence switching of administration of the combination of docetaxel and doxorubicin in advanced breast cancer

  Itoh K., Sasaki Y., Fujii H., Minami H., Ohtsu T., Wakita H., Igarashi T., Watanabe Y., Onozawa Y., Kashimura N., Ohashi Y.

  2000, Clin Cancer Res, 6(10) (10), 4082 - 4090


• Pharmacological analysis of etoposide in elderly patients with lung cancer.

  M Ando, H Minami, Y Ando, S Sakai, Y Shimono, S Sugiura, H Saka, K Shimokata, Y Hasegawa

  To analyze the pharmacological characteristics of etoposide in elderly patients, we conducted a Phase I trial of a 14-day administration of oral etoposide on 12 chemotherapy-naive patients, ages 75 years or older, with lung cancer. The pharmacological profiles of etoposide in elderly patients were compared with those of younger patients in our previous studies (H. Minami et al., J. Clin. Oncol., 11: 1602-1608, 1993; H. Minami et al., J. Clin. Oncol., 13: 191-199, 1995; Y. Ando et al., Jpn. J. Cancer Res., 87: 200-205, 1996). The sigmoid Emax model and logistic regression model were used for pharmacodynamic analysis. The maximum tolerated dose for elderly patients was 75 mg/body/day. The apparent oral clearance in elderly patients was 37+/-10 (mean +/- SD) ml/min, which was not different from that in younger patients (44+/-12 ml/min). The area under the concentration-versus-time curve of etoposide over the treatment period (total AUC) that produced a 50% decrease in absolute neutrophil counts was significantly different between elderly and younger patients, 14.3+/-2.5 and 21.6+/-2.7 mg x min/ml, respectively (P = 0.048). The incidence of grade 3 or 4 neutropenia at total AUC of 30 mg x min/ml (corresponding to a plasma concentration of 1.5 microg/ml for 14 days) was 81% in elderly patients but only 48% in younger patients. Although there was no pharmacokinetic difference between elderly and younger patients, equivalent exposure to etoposide resulted in severer myelosuppression in elderly patients. These findings suggest that prolonged etoposide administration with plasma concentration maintained at 1-2 microg/ml may cause severe myelotoxicity in elderly patients.

  Jul. 1999, Clinical cancer research : an official journal of the American Association for Cancer Research, 5(7) (7), 1690 - 5, English, International magazine

  Scientific journal


• Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue in the lung: a report of a case with pleural dissemination

  Keiji Kodama, Tomoyuki Yokose, Kenro Takahashi, Hironobu Minami, Kanji Nagai, Yoshihiro Matsuno, Yutaka Nishiwaki, Atsushi Ochiai

  Elsevier BV, Jun. 1999, Lung Cancer, 24(3) (3), 175 - 178

  Scientific journal


• Pharmacokinetics and pharmacodynamics of 9-aminocamptothecin infused over 72 hours in phase II studies

  Minami H., Lad TE, Nicholas MK, Vokes EE, Ratain MJ

  Lead, Jun. 1999, Clin Cancer Res, 5(6) (6), 1325 - 1330

  [Refereed]


• Prognostic Factors for Short‐term Survival in Patients with Stage IV Non‐small Cell Lung Cancer

  Masahiko Ando, Yuichi Ando, Seiji Sugiura, Hironobu Minami, Hideo Saka, Shuzo Sakai, Kaoru Shimokata, Yoshinori Hasegawa

  Prognostic factors which can forecast short‐term survival in patients with stage IV non‐small cell lung cancer have not been well evaluated. Characteristics of such factors may be different from those for overall survival, and would be an important eligibility criterion for clinical trials of chemotherapy. We retrospectively analyzed the data of 158 patients with stage IV non‐small cell lung cancer whose performance status was 0, 1 or 2. Univariate and multivariate logistic regression models revealed demographic variables which significantly correlated with the survival at 8 or 12 weeks. The univariate model showed the following significant variables: T factor, N factor, number of organs with metastases, grade of performance status, weight loss within 6 months, evidence of metastasis either at bone or lymph node, and lactate dehydrogenase level. The subsequent multivariate model demonstrated that both grade of performance status under 2 and number of metastasized organs less than 3 are important factors for 8‐ or 12‐week survival. The survival rate in patients meeting the two criteria (grade of performance status under 2 and number of metastasized organs less than 3) and in those meeting only one of them was 93% versus 80% at 8 weeks (P=0.030) and 88% versus 62% at 12 weeks (P<0.001), respectively. Grade of performance status and number of organs with metastases appear to be important prognostic factors for short‐term survival in patients with stage IV non‐small cell lung cancer.

  Wiley, Feb. 1999, Japanese Journal of Cancer Research, 90(2) (2), 249 - 253

  Scientific journal


• Indirect-response model for the time course of leukopenia with anticancer drugs*

  Hironobu Minami, Yasutsuna Sasaki, Nagahiro Saijo, Tomoko Ohtsu, Hirofumi Fujii, Tadahiko Igarashi, Kuniaki Itoh

  Wiley, Nov. 1998, Clinical Pharmacology & Therapeutics, 64(5) (5), 511 - 521

  Scientific journal


• Acute Myelogenous Leukemia with Monosomy 7, inv(3) (q21q26), Involving Activated EVI 1 Gene Occurring after a Complete Remission of Lymphoblastic Lymphoma: A Case Report

  T. Igarashi, S. Shimizu, K. Morishita, T. Ohtsu, K. Itoh, H. Minami, H. Fujii, Y. Sasaki, K. Mukai

  Oxford University Press (OUP), Nov. 1998, Japanese Journal of Clinical Oncology, 28(11) (11), 688 - 695

  Scientific journal


• Study of cohort-specific consent and patient control in phase I cancer trials.

  C K Daugherty, M J Ratain, H Minami, D M Banik, N J Vogelzang, W M Stadler, M Siegler

  PURPOSE To address the challenging ethical dilemmas created from the participation of advanced cancer patients in phase I trials, we assessed the feasibility of a clinical trial design that uses an interactive informed consent process in which patient-subjects can choose to become directly involved in decisions of dose escalation. PATIENTS AND METHODS Subjects were advanced cancer patients in the Hematology/Oncology Clinics at the University of Chicago who were eligible to participate in a phase I trial in which they underwent a three-step informed consent process that used cohort-specific consent and allowed them the option to choose their own doses of the chemotherapeutic agents under study, vinorelbine (NVB) and paclitaxel (TAX), within predetermined limits. NVB and TAX were administered in conventional 21- to 28-day cycles for two cycles while on study. Dose escalation occurred when a patient-subject chose a higher untested dose after they received information on all previously assessable patient-subjects. In addition to the phase I trial itself, a survey that consisted of structured interviews, which sought to evaluate patients' experiences with the interactive subject-choice phase I trial design and consent process, was conducted with participating subjects. The phase I trial itself sought to determine the associated toxicities of the agents under study. The survey results were compared with a similar survey of a matched control population of subjects who participated in other concurrently active conventional phase I trials at our institution. RESULTS Twenty-nine patient-subjects participated in the phase I trial, with 24 who agreed to and completed the survey interviews. Seventy-six percent of patient-subjects opted to choose their dose of the agents under study, and 28% chose the highest available doses. More than half of the patient-subjects (56%) felt some degree of comfort in being asked to choose their dose of chemotherapy, with 53% stating that being asked to choose their dose made them feel in control, fully informed, or content. However, there were no statistically significant improvements in objective measures of the informed consent process, which included surveyed subjects' stated understanding of either provided information about phase I trials and alternatives to trial participation or of the research purpose of phase I trials. By making choices, the group of patients in the interactive subject choice trial changed the size of the dose cohorts and modified the process of dose escalation in this phase I study. CONCLUSION Although complex, our innovative phase I trial design is feasible. In addition to the use of cohort-specific consent, the trial design may reduce the magnitude of many of the commonly recognized ethical dilemmas associated with this form of clinical research, which include difficulties with information provision and the understanding of possible risks and benefits of phase I trial participation, through direct subject involvement in research decision making by otherwise potentially vulnerable cancer patients.

  American Society of Clinical Oncology (ASCO), Jul. 1998, Journal of Clinical Oncology, 16(7) (7), 2305 - 2312

  Scientific journal


• Successful Treatment with Nedaplatin in Patients with Ovarian Cancer that Recurred After Platinum-containing Chemotherapy: Report of Two Cases

  K. Itoh, T. Yamashita, H. Wakita, Y. Watanabe, K. Kodama, H. Fujii, H. Minami, T. Ohtsu, T. Igarashi, Y. Sasaki

  Oxford University Press (OUP), May 1998, Japanese Journal of Clinical Oncology, 28(5) (5), 343 - 346

  Scientific journal


• Determination of Cytosol c-erbB-2 Protein in Breast Cancer by Sandwich Enzyme Immunoassay

  S. Imoto, H. Ohkura, K. Sugano, Y. Sasaki, K. Ito, T. Igarashi, T. Ohtsu, H. Fujii, H. Minami, T. Hasebe, K. Mukai

  Oxford University Press (OUP), Feb. 1998, Japanese Journal of Clinical Oncology, 28(2) (2), 92 - 96

  Scientific journal


• Successful Treatment by Radiation and Hormone Therapy of Isolated Local Recurrence of Breast Cancer 24 Years after Mastectomy Accompanied by Immune Thrombocytopenia: A Case Report

  Tadahiko Igarashi, Kuniaki Itoh, Hirofumi Fuji, Tomoko Ohtsu, Hironobu Minami, Yasutsuna Sasaki, Wakako Shimizu, Takashi Ogino, Masahisa Muramatsu

  Oxford University Press, 1998, Japanese Journal of Clinical Oncology, 28(4) (4), 270 - 275, English

  Scientific journal


• Adjustment of creatinine clearance improves accuracy of Calvert's formula for carboplatin dosing

  Y Ando, H Minami, H Saka, M Ando, S Sakai, K Shimokata

  Springer Science and Business Media LLC, Oct. 1997, British Journal of Cancer, 76(8) (8), 1067 - 1071

  Scientific journal


• Re: Prediction of Carboplatin Clearance From Standard Morphological and Biological Patient Characteristics

  H. Minami, Y. Ando, H. Saka, K. Shimokata

  Oxford University Press (OUP), Jul. 1997, JNCI Journal of the National Cancer Institute, 89(13) (13), 968 - 969

  Scientific journal


• Pharmacokinetic Study of Carboplatin Given on a 5‐Day Intravenous Schedule

  Yuichi Ando, Hironobu Minami, Hideo Saka, Masahiko Ando, Seiji Sugiura, Shuzo Sakai, Kaoru Shimokata

  We investigated whether carboplatin pharmacokinetics is altered when the drug is delivered daily over 5 days, compared to a single‐day infusion. Carboplatin was infused in 11 patients with lung cancer, who were randomly assigned to 2 groups. In the first group, the agent was administered on a conventional single‐day schedule in the first course and then on a 5‐day schedule in the second course. In the second group, the order was reversed (crossover design). The dose was calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min) as a substitute for glomerular filtration rate (GFR): carboplatin (mg) = AUC X (Ccr+25), where AUC denotes the area under the concentration versus time curve (mg ml^–1 min). No difference of carboplatin clearance between the single‐day and 5‐day schedule was observed (94.8± 19.9 versus 96.1+29.9 ml/min, P=0.818, paired t test). The formula systematically overestimated the carboplatin clearance; the ratio of estimated clearance/ observed clearance ranged from 1.01 to 1.58 (median 1.28; 95% confidence interval, 1.18 to 1.39). We concluded that the individual dosing strategy based on renal function can be applied with a 5‐day schedule as well as a single‐day schedule. Carboplatin is overdosed when Ccr is substituted for GFR in Calvert's formula.

  Wiley, May 1997, Japanese Journal of Cancer Research, 88(5) (5), 517 - 521

  Scientific journal


• A Phase II Study of Carboplatin and Prolonged Administration of Oral Etoposide in Patients with Small-Cell Lung Cancer

  Hironobu Minami, Hideo Saka, Shuzo Sakai, Masashi Yamamoto, Kaoru Shimokata

  Informa UK Limited, Jan. 1997, Acta Oncologica, 36(7) (7), 765 - 769

  Scientific journal


• Prognostic value of pleural effusion in patients with non-small cell lung cancer.

  Sugiura S., Ando Y., Minami H., Ando M., Sakai S., Shimokata K.

  Jan. 1997, Clin Cancer Res, 3(1) (1), 47 - 50

  [Refereed]


• Pharmacodynamic modeling of prolonged administration of etoposide

  H. Minami, Mark J. Ratain, Yuichi Ando, K. Shimokata

  Springer Science and Business Media LLC, Nov. 1996, Cancer Chemotherapy and Pharmacology, 39(1-2) (1-2), 61 - 66

  Scientific journal


• Acceptability of Patients with Brain Metastases for Clinical Trials of Chemotherapy for Metastatic Non-Small-Cell Lung Cancer

  Yuichi Ando, Seiji Sugiura, Masahiko Ando, Hironobu Minami, Fumio Nomura, Shuzo Sakai, Kaoru Shimokata

  Ovid Technologies (Wolters Kluwer Health), Oct. 1996, American Journal of Clinical Oncology, 19(5) (5), 478 - 482

  Scientific journal


• Therapeutic Drug Monitoring in 21‐Day Oral Etoposide Treatment for Lung Cancer

  Yuichi Ando, Hironobu Minami, Hideo Saka, Masahiko Ando, Shuzo Sakai, Kaoru Shimokata

  We aimed to determine whether or not therapeutic drug monitoring is applicable to 21‐day oral etoposide treatment for lung cancer. As the starting dose, a 25‐mg capsule of etoposide was taken orally three times daily (75 mg/body). To achieve the target concentration range of 1.0 to 1.5 μg/ml, the dose was changed to two (50 mg/body) or four (100 mg/body) times a day from day 5, depending on the mean concentration obtained on days 3 and 4 (C_before). The mean concentration was calculated by use of a limited sampling model we constructed previously. Among 26 courses in 15 patients, two patients experienced grade 4 leukopenia plus neutropenia, and one of them died on day 20. Because nausea/emesis prevented the planned dose escalation in one patient, we excluded two courses of this patient from the pharmacokinetic analysis of dose modification. Among 5 courses with dose reduction, the C_before of 1.7±0.1 (μg/ml, mean±SE) was decreased to 1.3±0.2 after day 5 (C_after). Among 7 courses with dose escalation, the C_before of 0.9±0.0 was increased to the C_after of 1.2±0.1. Among the remaining 12 courses without dose modification, the C_before and the C_after were 1.2±0.0 and 1.3±0.1, respectively. Hematologic toxicities tended to correlate with the drug concentration. TDM is thus applicable to oral etoposide given according to this schedule, and a larger study is now needed to confirm that the therapeutic efficacy is improved by introducing TDM.

  Wiley, Aug. 1996, Japanese Journal of Cancer Research, 87(8) (8), 856 - 861

  Scientific journal


• Is there a circadian variation in plasma concentrations of etoposide given by prolonged continuous infusion?

  Yuichi Ando, Hironobu Minami, Shuzo Sakai, K. Shimokata

  Springer Science and Business Media LLC, Mar. 1996, Cancer Chemotherapy and Pharmacology, 37(6) (6), 616 - 618

  Scientific journal


• Therapeutic Drug Monitoring of Etoposide in a 14‐Day Infusion for Non‐small‐cell Lung Cancer

  Yuichi Ando, Hironobu Minami, Hideo Saka, Masahiko Ando, Shuzo Sakai, Kaoru Shimokata

  We investigated whether a constant plasma concentration could be obtained by the individualized administration of low‐dose, prolonged‐infusional etoposide. Etoposide was infused for 14 days at 40 mg/m²day initially in patients with inoperable non‐small‐cell lung cancer. The infusion rate was modified based upon the etoposide concentration at 24 h following the initiation of the infusion (C₂₄) to achieve a target concentration of 1.5 μg/ml. We postulated that severe toxicities could be avoided by maintaining the steady‐state concentration at less than 2 7mu;g/ml, while antitumor activity could be expected if the steady‐state concentration was maintained at more than 1 μg/ml. In a total of 21 courses in 12 patients, the mean etoposide dose was 35±6 mg/m² daily. The C₂₄ was 1.8±0.4 μg/ml and ranged from 1.1 to 2.9 μg/ml. Following dose modification, the mean concentration from 96 to 336 h (C_mean) was 1.6±0.2 μg/ml and ranged from 1.2 to 2.0 μg/ml. The toxicities were well‐tolerated except for one patient with WHO grade 4 leukopenia and neutropenia who developed infectious complications. There were no treatment‐related deaths. Following dose modification, the inter‐patient variability was decreased successfully. Although this pharmacologically‐guided method needs to be validated using more patients, it could be used for therapeutic drug monitoring.

  Wiley, Feb. 1996, Japanese Journal of Cancer Research, 87(2) (2), 200 - 205

  Scientific journal


• Limited sampling model for area under the concentration-time curve of total topotecan

  Minami H., Beijnen JH, Verweij J., Ratain MJ

  Jan. 1996, Clin Cancer Res, 2(1) (1), 43 - 46


• 153 広範な癌性気管狭窄に対し気管切開口よりダイナミックステントを挿入した一例(ステント 3)

  下野 洋平, 安藤 昌彦, 杉浦 誠治, 南 博信, 野村 史郎, 酒井 秀造

  特定非営利活動法人 日本呼吸器内視鏡学会, 1996, 気管支学, 18(3) (3), 300 - 300, Japanese


• Occult Thymic Carcinoma Presenting as Malignant Cardiac Tamponade

  ANDO Yuichi, HIRABAYASHI Norio, MINAMI Hironobu, NOMURA Fumio, SAKAI Shuzo

  A 66-year-old woman who presented with malignant cardiac tamponade of unknown origin was eventually found to have a tiny squamous cell carcinoma of the thymus. Thus, even a small thymic carcinoma can exhibit highly aggressive behavior. It should be included in the differential diagnosis of malignant cardiac tamponade of unknown origin.
  (Internal Medicine 34: 393-395, 1995)

  The Japanese Society of Internal Medicine, May 1995, Japanese Journal of Medicine, 34(5) (5), 393 - 395, English

  Scientific journal


• Clinical and pharmacologic analysis of hyperfractionated daily oral etoposide.

  H Minami, Y Ando, S Sakai, K Shimokata

  PURPOSE The antitumor effect of etoposide is increased by maintaining a low blood level, whereas high peak levels may cause myelotoxicity. We investigated whether a constant low blood level could be obtained by the administration of oral etoposide three times daily. PATIENTS AND METHODS Nineteen patients with non-small-cell lung cancer were treated with oral etoposide (25 mg three times daily for 21 days) as monotherapy or in combination with cisplatin 80 mg/m2. A pharmacokinetic model that predicted the mean blood concentration (Cmean) was developed in the 10 patients on etoposide monotherapy and validated in the nine patients on combination chemotherapy. Pharmacodynamic relationships were evaluated in each group. RESULTS Etoposide dose per body-surface area ranged from 45 to 63 mg/m2/d (median, 53), but did not correlate with plasma level. Cmean was 1.1 +/- 0.3 micrograms/mL. Peak concentrations ranged from 0.6 to 2.5 micrograms/mL. The intrapatient coefficient of variation for plasma etoposide concentrations was 22% +/- 10%. Cmean was accurately estimated as follows: Cmean = 0.098 + 0.413 x C0 + 0.458 x C2 (r = .97, P = .0001), where C0 and C2 represent concentrations before and 2 hours after administration. This model was unbiased (mean predictive error [MPE], 0.0 microgram/mL) and precise (root mean square error [RMSE], 0.1 microgram/mL). Leukopenia was the major toxicity. The surviving fraction of leukocytes (SF; nadir count/pretreatment count) was correlated to Cmean as follows: SF = 0.87 - 0.34 x Cmean (r = .67, P = .03) in the monotherapy group and SF = 0.64 - 0.33 x Cmean (R = .77, P = .03) in the combination chemotherapy group. Two and four patients treated with monotherapy and combination chemotherapy showed responses, respectively. All responders had a Cmean > or = 1.0 microgram/mL. CONCLUSION Hyperfractionated oral etoposide achieveda stable plasma level that could be predicted by measurement at only two times.

  American Society of Clinical Oncology (ASCO), Jan. 1995, Journal of Clinical Oncology, 13(1) (1), 191 - 199

  Scientific journal


• Rupture of Thoracic Aorta Caused by Penetrating Aortic Ulcer

  Yuichi Ando, Hironobu Minami, Hideyuki Muramoto, Michihiko Narita, Shuzo Sakai

  Elsevier BV, Aug. 1994, Chest, 106(2) (2), 624 - 626

  Scientific journal


• Interbronchoscopist Variability in the Diagnosis of Lung Cancer by Flexible Bronchoscopy

  Hironobu Minami, Yuichi Ando, Fumio Nomura, Shuzo Sakai, Kaoru Shimokata

  Elsevier BV, Jun. 1994, Chest, 105(6) (6), 1658 - 1662

  Scientific journal


• Endobronchial Mucosal Bridges as Evidence of Residual Malignancy

  Yuichi Ando, Hironobu Minami, Fumio Nomura, Shuzo Sakai

  S. Karger AG, 1994, Respiration, 61(1) (1), 58 - 60

  Scientific journal


• Phase I clinical and pharmacokinetic study of a 14-day infusion of etoposide in patients with lung cancer.

  H Minami, K Shimokata, H Saka, H Saito, Y Ando, K Senda, F Nomura, S Sakai

  PURPOSE A phase I study was conducted to determine the maximum-tolerated dose (MTD) of a 14-day continuous infusion of etoposide, and to evaluate the pharmacokinetics in patients with lung cancer. PATIENTS AND METHODS Etoposide was administered continuously through a central venous catheter using a pump. The starting dose level was 300 mg/m2 over 14 days, with dose escalations of 100 mg/m2 over 14 days until unacceptable toxicities occurred. Pharmacokinetic studies were performed in all patients. RESULTS Twenty-one patients, 20 with non-small-cell lung cancer and one with refractory small-cell lung cancer, received 37 courses. No World Health Organization (WHO) grade III or greater toxicity occurred at doses up to 400 mg/m2 over 14 days. At 700 mg/m2 over 14 days, all four patients experienced grade III or IV leukocytopenia, and two developed grade III stomatitis. No cumulative toxicity was observed. A steady concentration of etoposide was achieved 24 hours after the start of chemotherapy, and it was significantly correlated with surviving fractions of leukocytes (r = -.64, P = .001) and platelets (r = -.68, P < .001). The leukocyte count at the termination of chemotherapy predicted the nadir count (r = .93, P < .001). CONCLUSION Steady blood levels of etoposide were maintained for prolonged periods, during 14-day continuous infusions. Leukocytopenia and stomatitis were dose-limiting. Nadir counts and surviving fractions of leukocytes were predicted by the leukocyte count at the end of chemotherapy and the concentration of etoposide, respectively. The recommended dose for phase II trials is 600 mg/m2 over 14 days.

  American Society of Clinical Oncology (ASCO), Aug. 1993, Journal of Clinical Oncology, 11(8) (8), 1602 - 1608

  Scientific journal


• 55 再検査気管支鏡による肺癌の診断率(気管支鏡検査の肺癌診断率)(第 16 回日本気管支学会総会)

  南 博信, 安藤 昌彦, 安藤 雄一, 千田 一嘉, 野村 史郎, 酒井 秀造

  特定非営利活動法人 日本呼吸器内視鏡学会, 1993, 気管支学, 15(4) (4), 342 - 342, Japanese


• Small Caliber Catheter Drainage for Spontaneous Pneumothorax

  Hironobu Minami, Kazuyoshi Senda, Tsuyoshi Iwahara, Fumio Nomura, Shuzo Sakai, Hideo Saka, Yoshitsugu Horio, Kaoru Shimokata

  Elsevier BV, Dec. 1992, The American Journal of the Medical Sciences, 304(6) (6), 345 - 347

  Scientific journal


• 11 気管支鏡による肺癌の診断率 : 術者による差(気管支鏡診断 II)

  南 博信, 安藤 雄一, 千田 一嘉, 岩原 毅, 野村 史郎, 酒井 秀造

  特定非営利活動法人 日本呼吸器内視鏡学会, 1992, 気管支学, 14(3) (3), 235 - 235, Japanese


• Pharmacokinetics of an etoposide infused over three days: concomitant infusion with cisplatin

  Minami H., Horio Y., Sakai S., Saka H., Shimokata K.

  Lead, Dec. 1991, Jpn J Clin Oncol, 21(6) (6), 400 - 405

  [Refereed]


• Check-valve Mechanism as a Cause of Bilateral Spontaneous Pneumothorax Complicating Bronchioloalveolar Cell Carcinoma

  Hironobu Minami, Shuzo Sakai, Atsushi Watanabe, Kaoru Shimokata

  Elsevier BV, Sep. 1991, Chest, 100(3) (3), 853 - 855

  Scientific journal


• Hyperfractionated radiotherapy combined with chemotherapy (cisplatin, vinblastine, mitomycin C) for inoperable non-small cell lung cancer.

  Watanabe Atsushi, Shimokata Kaoru, Nomura Fumio, Saka Hideo, Horio Yoshitsugu, Minami Hironobu, Iwahara Tsuyoshi, Shibagaki Tomohisa, Sakai Shuzo

  Eleven cases of inoperable non-small cell lung cancer were treated with hyperfractionated radiotherapy combined with chemotherapy. Hyperfractionated radiotherapy consisted of 1.6 Gy per fraction, 2 fractions a day with 6 hours between fractions, 5 days a week for a total of 60.8 Gy. After 38.4 Gy of irradiation to the primary tumor, hilar, and mediastinal lymph nodes, an additional 22.4 Gy was given to primary lesion. Chemotherapy consisted of cisplatin, 80 mg/m² day 1, mitomycin C, 10 mg/m² day 1, and vinblastine, 5mg/m², days 1 and 15. At least 2 courses were administered. The combination of radiotherapy and chemotherapy was sequential. Of 6 patients in whom hyperfractionated radiotherapy was performed first, 5 achieved PR. Of 5 patients in whom chemotherapy was performed first, 2 achieved PR. Median survival time was 300 days. Nine of the eleven patients experienced esophagitis, but in all patients this was controlled easily by oral antacids and/or H₂ blockers. In regard to radiation pneumonitis, fibrosis occurred in seven of nine cases, but they did not require corticosteroids. Levels of hematological toxicity were similar to previous reports, but were somewhat severe in cases receiving chemotherapy after irradiation. We conclude that hyperfractionated radiotherapy combined with chemotherapy including cisplatin is safe, but further evaluation to determine optimal dose and combination methods is necessary.

  The Japan Lung Cancer Society, 1991, JJLC, 31(1) (1), 61 - 67, Japanese


• P-35 化学療法後に Mucosal Bridge を生じた肺小細胞癌の二例(肺癌 4 P-6)

  南 博信, 安藤 雄一, 千田 一嘉, 堀尾 芳嗣, 岩原 毅, 酒井 秀造

  特定非営利活動法人 日本呼吸器内視鏡学会, 1991, 気管支学, 13, 159 - 159, Japanese


• Cytomegalovirus-induced gastritis in a bone marrow transplant patient.

  Hironobu MINAMI, Tadashi MATSUSHITA, Takurou SUGIHARA, Yoshihisa KODERA, Shuzo SAKAI, Kaoru SHIMOKATA

  Lead, Japanese Society of Internal Medicine, 1990, Japanese Journal of Medicine, 29(4) (4), 433 - 435

  [Refereed]

  Scientific journal

• Performance status is a useful predictor of SOS/VOD progression

  市川大哉, 藥師神公和, 飯田幸太郎, 福井さくら, 梁間敢, 岡副結梨, 高橋瑠里, 松本咲耶, 坂井里奈, 倉田啓史, 北尾章人, 北尾章人, 宮田吉晴, 齊藤泰之, 川本晋一郎, 山本克也, 伊藤光宏, 村山徹, 村山徹, 松岡広, 南博信

  2025, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 47th


• Efficacy of the refined EBMT diagnostic criteria 2023 for sinusoidal obstruction syndrome

  市川大哉, 藥師神公和, 辻高寛, 武本奈緒子, ジョイス美紀, 岡副結梨, 高橋瑠里, 松本咲耶, 坂井里奈, 倉田啓史, 北尾章人, 宮田吉晴, 齊藤泰之, 川本晋一郎, 山本克也, 伊藤光宏, 村山徹, 松岡広, 南博信, 北尾章人, 宮田吉晴, 齊藤泰之, 川本晋一郎, 伊藤光宏, 村山徹, 松岡広

  2024, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 46th


• A case of suspected false-positive or mosaic MLH1 pathogenic variant in the germline finding in a cancer genomic profiling

  田中敬子, 花房宏昭, 花房宏昭, 金原史朗, 金原史朗, 松本久幸, 松本久幸, 坊亮輔, 坊亮輔, 國久智成, 國久智成, 清田尚臣, 清田尚臣, 久保亮治, 久保亮治, 南博信, 南博信, 野津寛大, 野津寛大

  2024, 日本遺伝カウンセリング学会誌, 45(2) (2)


• 抗HLA抗体陽性患者がHLA適合PCで副反応を発症した1症例

  栗岡綾, 田淵匠, 上田真弘, 生戸健一, 廣垣鼓, 籔内温子, 早川郁代, 平川結梨, 川本晋一郎, 南博信

  2024, 日本輸血細胞治療学会誌, 70(2) (2)


• びまん性胃癌における遺伝子変異と腫瘍免疫微小環境から考える複合免疫療法

  長谷善明, 船越洋平, 南博信

  2024, 日本消化器病学会雑誌(Web), 121


• 進行・再発・転移の固形腫瘍における血栓塞栓症と出血リスク:PROVE-emboli試験post-hoc解析

  今村善宣, 能勢拓, 大幡真也, 乙井一典, 乙井一典, 森健太, 辻高寛, 宮田吉晴, 金原史朗, 長谷善明, 小山泰司, 船越洋平, 清田尚臣, 清田尚臣, 南博信, 南博信

  2024, 日本血栓止血学会誌, 35(2) (2)


• がんゲノムプロファイル検査でRAD51Dが検出され、事前のリスク低減卵管卵巣摘出術についての情報交換が有用であった症例

  花房 宏昭, 田中 敬子, 濱 真奈美, 金原 史朗, 益子 尚久, 坊 亮輔, 國久 智成, 粟野 宏之, 清田 尚臣, 久保 亮治, 南 博信, 野津 寛大

  (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 139 - 139, Japanese


• Adipocyte regulation of cancer stem cell properties

  下野洋平, 後藤秀彰, 林孝典, ハレディアン ベフヌーシュ, 前田真男, 渋谷尚樹, 河野誠之, 船越洋平, 掛地吉弘, 南博信

  2023, 日本消化器癌発生学会総会プログラム・抄録集, 34th


• がん関連静脈血栓塞栓症に対するアピキサバン療法の出血リスク予測:多施設共同第2相臨床試験副次的解析

  今村善宣, 能勢拓, 宮田吉晴, 小山泰司, 長谷善明, 金原史朗, 船越洋平, 清田尚臣, 藥師神公和, 南博信

  2023, 日本内科学会雑誌, 112


• 進行・再発・転移の未治療固形がん患者における静脈血栓塞栓症の前向き観察研究の統合解析

  今村善宣, 能勢拓, 大幡真也, 森健太, 乙井一典, 宮田吉晴, 金原史朗, 長谷善明, 小山泰司, 船越洋平, 清田尚臣, 清田尚臣, 南博信, 南博信

  2023, 日本血栓止血学会誌, 34(2) (2)


• 小児がん経験者の移行期医療の現状およびがん治療歴と心機能に関する解析

  平川結梨, 藥師神公和, 松本咲耶, 坂井里奈, 倉田啓史, 今村善宜, 北尾章人, 船越洋平, 田中秀和, 清田尚臣, 南博信

  2023, 日本腫瘍循環器学会学術集会抄録集(Web), 6th


• がん治療前の悪性腫瘍関連下肢静脈血栓塞栓症のリスク因子に関する検討:PROVE-emboli study

  能勢拓, 今村善宣, 大幡真也, 森健太, 乙井一典, 小山泰司, 長谷義明, 金原史朗, 船越洋平, 清田尚臣, 清田尚臣, 南博信, 南博信

  2023, 日本腫瘍循環器学会学術集会抄録集(Web), 6th


• SARS-CoV-2PCRが持続陽性となったDLBCLの1症例

  佐伯美紀, 北尾章人, 臼井佑太郎, 高倉嗣丈, 渡部まりか, 松本咲耶, 水谷優, 坂井里奈, 船越洋平, 藥師神公和, 南博信

  2022, 臨床血液, 63(2) (2)


• Safety and Efficacy of SARS-CoV-2 Vaccine (BNT162b2) in Allogeneic HSCT Patients

  渡部まりか, 藥師神公和, 船越洋平, 大路剛, 酒井博則, 北條渉, 佐伯美紀, 平川結梨, 松本咲耶, 坂井里奈, 北尾章人, 宮田吉晴, 伊藤光宏, 松岡広, 南博信

  2022, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 44th


• オルガノイドが駆動するがん研究 オルガノイドの乳がん研究への展開

  下野 洋平, 西村 建徳, 河野 誠之, 渋谷 尚樹, 林 孝典, 柳 久乃, 渡辺 崇, 前田 真男, 掛地 吉弘, 河田 健司, 浅井 直也, 高尾 信太郎, 南 博信, 喜島 祐子, 鈴木 元, 後藤 典子

  (一社)日本癌学会, Sep. 2021, 日本癌学会総会記事, 80回, [CS4 - 3], English


• 癌ゲノム医療 神戸大学医学部附属病院におけるがんゲノム医療の現状と課題

  篠山 隆司, 田中 一寛, 金原 史朗, 小松 正人, 児玉 良典, 山本 暢之, 長嶋 宏明, 南 博信, 廣瀬 隆則, 伊藤 智雄

  日本脳腫瘍病理学会, May 2021, Brain Tumor Pathology, 38(Suppl.) (Suppl.), 067 - 067, Japanese


• Immunological analysis of the combination therapy of nivolumab, paclitaxel and bevacizumab in patients with HER2negative MBC in NEWBEAT trial (WJOG9917BTR)

  Yukinori Ozaki, Shigehisa Kitano, Junji Tsurutani, Tsutomu Iwasa, Masato Takahashi, Toru Mukohara, Norikazu Masuda, Manabu Futamura, Hironobu Minami, Koji Matsumoto, Hidetaka Kawabata, Makiko Yamashita, Kenichi Yoshimura, Toshimi Takano

  Feb. 2021, CANCER RESEARCH, 81(4) (4), English

  Summary international conference


• NivoCUP: An open-label phase II study on the efficacy of nivolumab in cancer of unknown primary.

  Junko Tanizaki, Kan Yonemori, Kohei Akiyoshi, Hironobu Minami, Hiroki Ueda, Yuichi Takiguchi, Chihiro Nakayama Kondoh, Yoshihiko Segawa, Shin Takahashi, Yasuo Iwamoto, Yasuhiro Kidera, Kazuya Fukuoka, Yasushi Nakamura, Yasutaka Chiba, Kazuto Nishio, Kazuhiko Nakagawa, Hidetoshi Hayashi

  May 2020, JOURNAL OF CLINICAL ONCOLOGY, 38(15) (15), English

  Summary international conference


• Pharmacokinetic study of the oral fluorouracil antitumor agent S-1 in patients with impaired renal function (vol 110, pg 1987, 2019)

  Keiko Goto, Yutaka Fujiwara, Takeshi Isobe, Naoko Chayahara, Naomi Kiyota, Toru Mukohara, Yukari Tsubata, Takamasa Hotta, Kenji Tamura, Noboru Yamamoto, Hironobu Minami

  Apr. 2020, CANCER SCIENCE, 111(4) (4), 1437 - 1437, English

  Others


• A multicenter phase II study evaluating the efficacy of nivolumab plus paclitaxel plus bevacizumab triple-combination therapy as a first-line treatment in patients with HER2-negative metastatic breast cancer: WJOG9917B NEWBEAT trial

  Yukinori Ozaki, Toru Mukohara, Junji Tsurutani, Masato Takahashi, Koji Matsumoto, Manabu Futamura, Norikazu Masuda, Shigehisa Kitano, Kenichi Yoshimura, Hironobu Minami, Toshimi Takano

  Feb. 2020, CANCER RESEARCH, 80(4) (4), English

  Summary international conference


• 日本人悪性腫瘍関連静脈血栓塞栓症に対するapixaban療法の第II相臨床試験

  今村善宣, 乙井一典, 森健太, 喜多川浩一, 岡田秀明, 秦明登, 林秀敏, 能勢拓, 大幡真也, 宮田吉晴, 船越洋平, 豊田昌徳, 藥師神公和, 清田尚臣, 清田尚臣, 松岡広, 南博信, 南博信

  2020, 日本血液学会学術集会抄録(Web), 82nd


• リソソーム機能活性化を介した抗体薬物複合体であるゲムツズマブオゾガマイシンの殺細胞効果増強法

  水谷優, 稲瀬安希, マイマイテイリイマム, 宮田吉晴, 北尾章人, 松本久幸, 後藤秀彰, 藥師神公和, 松岡広, 南博信

  2020, 日本内科学会雑誌, 109


• An mTORC1/2 dual inhibitor, AZD2014, enhances gemtuzumab ozogamicin-induced apoptosis in primary AML cells

  稲瀬安希, 南博信, 松岡広

  2019, 日本癌学会学術総会抄録集(Web), 78th


• 当院における高頻度マイクロサテライト不安定性大腸癌のスクリーニング方法の検討

  高井亮, 山下公大, 須藤洋崇, 豊田昌徳, 船越洋平, 今村善宣, 清田尚臣, 清田尚臣, 井上潤, 田中心和, 松田武, 児玉裕三, 南博信, 南博信, 掛地吉弘

  2019, 日本消化器癌発生学会総会プログラム・抄録集, 30th


• 本邦における高頻度マイクロサテライト不安定性大腸癌のスクリーニング方法の検討

  須藤洋崇, 豊田昌徳, 船越洋平, 今村善宣, 清田尚臣, 清田尚臣, 井上潤, 田中心和, 高瀬信尚, 長谷川寛, 山下公大, 松田武, 鈴木知志, 児玉裕三, 掛地吉弘, 南博信, 南博信

  2019, 日本家族性腫瘍学会学術集会プログラム・抄録集, 25th


• EGFR阻害薬に伴うざ瘡様皮疹へのアダパレンゲル予防投与のプラセボ対照左右ランダム化比較試験

  土井 久容, 茶屋原 菜穂子, 清田 尚臣, 豊田 昌徳, 立原 素子, 山本 正嗣, 藤島 佳未, 飛松 和俊, 福永 淳, 川口 淳, 向原 徹, 南 博信

  (一社)日本がん看護学会, Jan. 2019, 日本がん看護学会誌, 33(Suppl.) (Suppl.), 173 - 173, Japanese


• Coexpression ofETV6/MDS1/EVI1andETV6/EVI1fusion transcripts in acute myeloid leukemia with t(3;12)(q26.2;p13) and thrombocytosis

  Katsuya Yamamoto, Kimikazu Yakushijin, Hiroya Ichikawa, Atsuo Okamura, Shigeki Nagao, Seiji Kakiuchi, Keiji Kurata, Shinichiro Kawamoto, Keiji Matsui, Yuji Nakamachi, Jun Saegusa, Hiroshi Matsuoka, Hironobu Minami

  Last, Informa UK Limited, 11 Dec. 2018, Leukemia & Lymphoma, 60(5) (5), 1294 - 1298, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• A phase II study on the efficacy of Nivolumab in Japanese patients with cancer of unknown primary (CUP) (NivoCUP)

  Junko Tanizaki, Hidetoshi Hayashi, Hironobu Minami, Makoto Arai, Shin Takahashi, Yoshihiko Segawa, Yukinori Ozaki, Hiroki Ueda, Kohei Akiyoshi, Yasuo Iwamoto, Kan Yonemori, Yasuhiro Kidera, Kazuya Fukuoka, Kazuto Nishio, Kazuhiko Nakagawa

  Oct. 2018, ANNALS OF ONCOLOGY, 29, English

  Summary international conference


• Epigenetic regulation of colorectal cancer stem cells by the miR-221/QKI5 axis

  Junko Mukohyama, Yohei Shimono, Piero Dalerba, Taichi Isobe, Qingjiang Hu, Debashis Sahoo, Naoki Shibuya, Hironobu Minami, Koshi Mimori, Yoshihiro Kakeji, Akira Suzuki

  Jul. 2018, CANCER RESEARCH, 78(13) (13), English

  Summary international conference


• Phase II study of a combination therapy of nivolumab, bevacizumab and paclitaxel in patients with HER2-negative metastatic breast cancer as a first-line treatment (WJOG9917B, NEWBEAT trial).

  Yukinori Ozaki, Koji Matsumoto, Masato Takahashi, Toru Mukohara, Manabu Futamura, Norikazu Masuda, Junji Tsurutani, Kenichi Yoshimura, Hironobu Minami, Toshimi Takano

  May 2018, JOURNAL OF CLINICAL ONCOLOGY, 36(15) (15), English

  Summary international conference


• Pazopanibにより長期病勢安定が得られた肺動脈原発血管内膜肉腫の一例

  崔諭司, 今村善宣, 清田尚臣, 清田尚臣, 重岡學, 豊田昌徳, 船越洋平, 兵庫寧子, 須藤洋崇, 金原史朗, 奥田祐亮, 吉田賢史, 南博信

  2018, 日本臨床腫瘍学会学術集会(CD-ROM), 16th


• リソソーム機能を介したAMLに対する新規治療戦略

  INASE Aki, MAIMAITILI Yimamu, MIZUTANI Yu, MINAMI Hironobu, MATSUOKA Hiroshi

  2018, 日本分子生物学会年会プログラム・要旨集(Web), 41st, ROMBUNNO.3LBA‐115 (WEB ONLY), English


• Remarkable response to cetuximab-containing chemotherapy for tongue cancer refractory to immune checkpoint inhibitors

  Hirotaka Suto, Naomi Kiyota, Yoshinori Imamura, Yasuko Hyogo, Kei Takenaka, Yoshiaki Nagatani, Meiko Nishimura, Masanori Toyoda, Toru Mukohara, Hironobu Minami

  Oct. 2017, ANNALS OF ONCOLOGY, 28, English

  Summary international conference


• 【転移性脊椎腫瘍に対する最小侵襲脊椎安定術(MISt)】 転移性脊椎腫瘍に対する出張型骨転移Cancer Boardの取り組み

  Kakutani Kenichiro, Sakai Yoshitada, 伊藤雅明, Kawamoto Teruya, Hara Hitomi, 深瀬直政, Okada Takuya, Sugimoto Koji, Miyawaki Daisuke, Sasaki Ryohei, Kiyota Naomi, Minami Hironobu, 秋末敏宏, Kuroda Ryosuke, 西田康太郎

  (株)全日本病院出版会, Sep. 2017, 整形外科最小侵襲手術ジャーナル, (84) (84), 79 - 83, Japanese

  [Refereed]

  Introduction scientific journal


• Detection of EBV BamHI W region in surgical cancer specimen is a useful method to evaluate the risk of lymphomagenesis in patient-derived tumor xenografts

  Junko Mukohyama, Dai Iwakiri, Yoh Zen, Toru Mukohara, Hironobu Minami, Yoshihiro Kakeji, Yohei Shimono

  Jul. 2017, CANCER RESEARCH, 77, English

  Summary international conference


• MicroRNA-mediated upregulation of the WNT signaling activities in human breast cancer stem cells

  Yohei Shimono, Taichi Isobe, Andrei Turtoi, Junko Mukohyama, Toru Mukohara, Akira Suzuki, Vincent Castronovo, Hironobu Minami

  Jul. 2017, CANCER RESEARCH, 77, English

  Summary international conference


• Phase I/II trial of glasdegib in patients with primary or secondary myelofibrosis.

  Aaron Thomas Gerds, Tetsuzo Tauchi, Ellen K. Ritchie, Michael W. N. Deininger, Catriona H. M. Jamieson, Ruben A. Mesa, Mark L. Heaney, Norio Komatsu, Hironobu Minami, Yun Su, Mohammed Naveed Shaik, Xiaoxi Zhang, Christine DiRienzo, Mirjana Zeremski, Adrian Woolfson, Geoffrey Chan, Moshe Talpaz

  May 2017, JOURNAL OF CLINICAL ONCOLOGY, 35, English

  Summary international conference


• マイクロRNAによる原発巣および転移巣のがん幹細胞制御機構

  Shimono Yohei, 渋谷尚樹, 向山順子, 西村建徳, 後藤典子, Minami Hironobu, Kakeji Yoshihiro, 鈴木聡

  腫瘍の発生、進展さらには転移にも重要な働きをもつがん幹細胞の機能制御に関わるマイクロRNAの働きについて、特に乳がんおよび大腸がんに着目して概説した。多彩な機能をもつマイクロRNAは、がんの転移にも関わっている。例えば、miR-33bはHMGA2、転写因子であるSALL4やTwistを標的とし、乳がんの転移や浸潤を抑制する。また、miR-7はc-mycやtwist、miR9の発現を抑制し乳がん細胞の転移を抑制する。さらには、miR-181cやmiR-200のようにエクソソーム内に内包され細胞外に放出されることで細胞間の情報伝達を行っているマイクロRNAも同定されてきた。

  (一社)日本サイトメトリー学会, May 2017, Cytometry Research, 27(1号) (1号), 33 - 39, Japanese

  [Refereed]

  Introduction scientific journal


• 【Precision Medicine】 Imprecision medicineからprecision medicineへ

  Minami Hironobu

  Mar. 2017, がん分子標的治療, 15(1号) (1号), 6 - 10, Japanese

  Introduction scientific journal


• 自家末梢血幹細胞移植における栄養状態と予後に関する後方視的解析

  水谷優, 藥師神公和, 市川大哉, 坂井里奈, 後藤秀彰, 倉田啓史, 西村明子, 北尾章人, 田渕聡子, 瓜生恭章, 垣内誠司, 宮田吉晴, 乾由美子, 眞田幸尚, 今村善宣, 船越洋平, 高橋路子, 高橋路子, 岡村篤夫, 川本晋一郎, 山本克也, 伊藤光宏, 松岡広, 南博信, 南博信

  2017, 日本造血細胞移植学会総会プログラム・抄録集, 40th


• 未治療原発不明癌に対するDNAチップを用いた原発巣推定に基づく治療効果の意義を問う無作為化第II相試験

  倉田宝保, 武田晃司, 滝口裕一, 松本光史, 向井博文, 南博信, 小野澤祐輔, 山中康弘, 西尾和人, 中川和彦

  2017, 日本臨床腫瘍学会学術集会(CD-ROM), 15th


• PHASE 2 STUDY OF LENVATINIB IN PATIENTS WITH DIFFERENTIATED, MEDULLARY AND ANAPLASTIC THYROID CANCER: FINAL ANALYSIS RESULTS

  Shunji Takahashi, Naomi Kiyota, Tomoko Yamazaki, Naoko Chayahara, K. Nakano, Lina Inagaki, Kazuhisa Toda, Tomohiro Enokida, Hironobu Minami, Yoshinori Imamura, Tatsuya Sasaki, Takuya Suzuki, Katsuki Fujino, Corina Dutcus, Louise Young, Makoto Tahara

  Nov. 2016, ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, 12, 134 - 134, English

  Summary international conference


• 【新しいチロシンキナーゼ阻害薬】 各臓器がんに対する新しいチロシンキナーゼ阻害薬 原発性骨髄線維症、甲状腺がん

  垣内誠司, Minami Hironobu

  Oct. 2016, がん分子標的治療, 14(3号) (3号), 290 - 294, Japanese

  Introduction scientific journal


• HLAと分子標的薬の薬物有害反応

  西村明子, Minami Hironobu

  Oct. 2016, がん分子標的治療, 14(3号) (3号), 325 - 328, Japanese

  Introduction scientific journal


• 【がん免疫療法 腫瘍免疫学の最新知見から治療法のアップデートまで 免疫学の基礎知識と、免疫チェックポイント阻害薬、T細胞療法、個別化・複合免疫療法、臨床開発の最前線】(第II部)がん免疫療法の開発と臨床試験 (第4章)各種がん免疫療法の臨床試験と実際 免疫チェックポイント阻害療法 非小細胞肺がん

  今村善宣, Minami Hironobu

  (株)羊土社, Aug. 2016, 実験医学, 34(12) (12), 2014 - 2018, Japanese

  Introduction scientific journal


• Pharmacokinetic study of S-1, an oral fluorouracil antitumor agent in Japanese patients with impaired renal function

  Keiko Goto, Yutaka Fujiwara, Takeshi Isobe, Yukari Tsubata, Takamasa Hotta, Naoko Chayahara, Naomi Kiyota, Toru Mukohara, Noboru Yamamoto, Hironobu Minami

  Jul. 2016, ANNALS OF ONCOLOGY, 27, English

  Summary international conference


• Upregulation of Oncogenic miR-221 in Human Colon Cancer Stem Cells

  Junko Mukohyama, Yohei Shimono, Toru Mukohaya, Yoshihiro Kakeji, Hironobu Minami

  Jul. 2016, ANNALS OF ONCOLOGY, 27, English

  Summary international conference


• Relationship between Adverse Events and Efficacy of Lenvatinib for Thyroid Cancer

  Hideaki Goto, Naomi Kiyota, Naoko Chayahara, Kei Takenaka, Yoshinori Imamura, Meiko Nishimura, Masanori Toyoda, Toru Mukohara, Hironobu Minami

  Jul. 2016, ANNALS OF ONCOLOGY, 27, English

  Summary international conference


• 【がん標的分子と治療開発-現状と将来】 各臓器別の新薬開発の現状と将来 乳がん治療開発の現状と将来

  北尾章人, Minami Hironobu

  Jul. 2016, 医学のあゆみ, 258(5号) (5号), 553 - 559, Japanese

  Introduction scientific journal


• Phase II study of lenvatinib in patients with differentiated, medullary, and anaplastic thyroid cancer: Final analysis results.

  Shunji Takahashi, Naomi Kiyota, Tomoko Yamazaki, Naoko Chayahara, Kenji Nakano, Lina Inagaki, Kazuhisa Toda, Tomohiro Enokida, Hironobu Minami, Yoshinori Imamura, Tatsuya Sasaki, Takuya Suzuki, Katsuki Fujino, Corina Dutcus, Makoto Tahara

  May 2016, JOURNAL OF CLINICAL ONCOLOGY, 34(15) (15), English

  Summary international conference


• 【遺伝子解析に基づく新しい分子標的治療】 遺伝子解析に基づく新しい分子標的治療

  Minami Hironobu, 中島貴子, 間野博行, 松村到

  Apr. 2016, がん分子標的治療, 14(1号) (1号), 68 - 75, Japanese

  Introduction scientific journal


• 対談・第14回日本臨床腫瘍学会学術集会開催に向けて。

  西條長宏, Minami Hironobu

  2016, がん分子標的治療, 14, 170 - 173, Japanese

  Introduction scientific journal


• トラスツズマブ術後補助療法

  Minami Hironobu

  2016, Cancer Board of the Breast 2, 60, Japanese

  [Refereed]

  Introduction scientific journal


• センチネルリンパ節転移1個陽性の乳癌に対し腋窩リンパ節郭清を施行すべきか。施行すべきであるvs施行すべきでない。

  Minami Hironobu

  メディカルレビュー社, 2016, Cancer Board of the Breast 2, 35(1) (1), 42 - 46, Japanese

  [Refereed]

  Introduction scientific journal


• がん薬物療法の新時代・求められるチーム医療・期待される看護師の役割とは？

  Minami Hironobu, 川上祥子

  エス・エム・エス ; 1980-, 2016, ナース専科, 5(5) (5), 48 - 51, Japanese

  [Refereed]

  Introduction scientific journal


• エリブリンの第I相試験

  Minami Hironobu

  2016, Cancer Board of the Breast, 3, 55 - 56, Japanese

  [Refereed]

  Introduction scientific journal


• JSMO’s Best of ASCO Conference 2016

  Minami Hironobu

  2016, がん分子標的治療, 14, 290 - 294, Japanese

  [Refereed]

  Introduction scientific journal


• Imprecision medicineからprecision medicineへ

  Minami Hironobu

  2016, 分子標的治療, 15, 6 - 10, Japanese

  [Refereed]

  Introduction scientific journal


• HER2陰性乳癌の術前化学療法でpCRが得られなかった場合、術後補助化学療法を追加すべきか (JBCRG-04) を念頭に。

  Minami Hironobu

  2016, Cancer Board of the Breast, 3(31) (31), Japanese

  [Refereed]

  Introduction scientific journal


• 【チーム医療・医療連携を考える】 医療連携 甲状腺癌診療連携プログラム

  Minami Hironobu

  Jan. 2016, クリニシアン, 63(1号) (1号), 64 - 68, Japanese

  Introduction scientific journal


• がん治療の基本

  竹中圭, Minami Hironobu

  Jan. 2016, 月刊薬事, 58(2) (2), 187 - 195, Japanese

  Introduction scientific journal


• MicroRNA Regulation of Human Breast Cancer Stem Cells

  Yohei Shimono, Junko Mukohyama, Shun-ichi Nakamura, Hironobu Minami

  MicroRNAs (miRNAs) are involved in virtually all biological processes, including stem cell maintenance, differentiation, and development. The dysregulation of miRNAs is associated with many human diseases including cancer. We have identified a set of miRNAs differentially expressed between human breast cancer stem cells (CSCs) and non-tumorigenic cancer cells. In addition, these miRNAs are similarly upregulated or downregulated in normal mammary stem/progenitor cells. In this review, we mainly describe the miRNAs that are dysregulated in human breast CSCs directly isolated from clinical specimens. The miRNAs and their clusters, such as the miR-200 clusters, miR-183 cluster, miR-221-222 cluster, let-7, miR-142 and miR-214, target the genes and pathways important for stem cell maintenance, such as the self-renewal gene BMI1, apoptosis, Wnt signaling, Notch signaling, and epithelial-to-mesenchymal transition. In addition, the current evidence shows that metastatic breast CSCs acquire a phenotype that is different from the CSCs in a primary site. Thus, clarifying the miRNA regulation of the metastatic breast CSCs will further advance our understanding of the roles of human breast CSCs in tumor progression.

  MDPI AG, 25 Dec. 2015, Journal of Clinical Medicine, 5(1) (1), 2 - 2, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101)

  Yutaka Fujiwara, Shogo Kobayashi, Hiroaki Nagano, Masashi Kanai, Etsuo Hatano, Masanori Toyoda, Tetsuo Ajiki, Yuki Takashima, Kenichi Yoshimura, Akinobu Hamada, Hironobu Minami, Tatsuya Ioka

  03 Dec. 2015, PLOS ONE, 10(12) (12), e0143072 - e0143072


• A phase I b study of panobinostat and 5-azacitidine in Japanese patients with MDS, CMML, or AML

  Kimikazu Yakushijin, Hironobu Minami, Toshiki Uchida, Michinori Ogura, Masafumi Taniwaki, Tsutomu Kobayashi, Asuka Mori, Masataka Yonemura, Wataru Munakata, Yukio Kobayashi

  Nov. 2015, ANNALS OF ONCOLOGY, 26, 85 - 85, English

  Summary international conference


• A cases of pertuzumab plus trastuzumab plus docetaxel was effective for inflammatory breast cancer with HER2-positive

  Yuji Yamashita, Yuko Tanaka, Meiko Nishimura, Toru Mukohara, Seishi Kono, Shintaro Takao, Hironobu Minami

  Nov. 2015, ANNALS OF ONCOLOGY, 26, 143 - 143, English

  Summary international conference


• Comparison of 2D-and 3D-culture models as drug-testing platforms in breast cancer

  Yoshinori Imamura, Toru Mukohara, Yohei Shimono, Yohei Funakoshi, Naoko Chayahara, Masanori Toyoda, Naomi Kiyota, Shintaro Takao, Seishi Kono, Tetsuya Nakatsura, Hironobu Minami

  Aug. 2015, CANCER RESEARCH, 75, English

  Summary international conference


• 日本臨床腫瘍学会"がん薬物療法専門医"制度がめざすもの

  Minami Hironobu

  Aug. 2015, 医学のあゆみ 日本のがん診療UPDATE 連携拠点病院と最新トピックス, 254(9) (9), 757 - 762, Japanese

  Introduction scientific journal


• 新しい分子標的治療の副作用対策

  Minami Hironobu, 山口研成, 岡野晋, 山崎直也

  (株)メディカルレビュー社, Apr. 2015, がん分子標的治療, 13(1) (1), 72 - 78, Japanese

  Introduction scientific journal


• Land-Mark papers in Oncology. CMF

  Minami Hironobu

  Mar. 2015, Cancer Board of the Breast, 1(1) (1), 62 - 63, Japanese

  Introduction scientific journal


• Disappearance of double minute chromosomes with MYC amplification in relapsed acute myeloid leukemia after stem cell transplantation

  Katsuya Yamamoto, Kimikazu Yakushijin, Keiji Kurata, Yukinari Sanada, Shinichiro Kawamoto, Hiroshi Matsuoka, Hironobu Minami

  14 Feb. 2015, International Journal of Hematology, 101(5) (5), 423 - 425, English


• Coexistent t(8;21)(q22;q22) Translocation and 5q Deletion in Acute Myeloid Leukemia

  Katsuya Yamamoto, Kimikazu Yakushijin, Yukinari Sanada, Shinichiro Kawamoto, Hiroshi Matsuoka, Hironobu Minami

  Japanese Society for Lymphoreticular Tissue Research, 2015, Journal of Clinical and Experimental Hematopathology, 55(3) (3), 181 - 185


• 再発・転移粘膜悪性黒色腫に対するダカルバジン単剤療法の後方視的検討

  西村明子, 清田尚臣, 豊田昌徳, 茶屋原菜穂子, 竹中圭, 瓜生恭章, 今村善宣, 船越洋平, 向原徹, 南博信

  2015, 日本内科学会雑誌, 104


• Rhabdomyolysis Caused by <i>Candida parapsilosis</i> in a Patient with Acute Myeloid Leukemia after Bone Marrow Transplantation

  Seiji Kakiuchi, Kimikazu Yakushijin, Katsuya Yamamoto, Hideo Tomioka, Yumiko Inui, Atsuo Okamura, Shinichiro Kawamoto, Yosuke Minami, Tohru Murayama, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami

  2015, Internal Medicine, 54(16) (16), 2057 - 2060, English

  [Refereed]


• Efficacy of the Two-Dose Influenza Vaccine in Cancer Patients Receiving Chemotherapy: A Prospective Study

  Yukinari Sanada, Kimikazu Yakushijin, Tetsuhiko Nomura, Katsuya Yamamoto, Keiji Kurata, Kei Takenaka, Seiji Kakiuchi, Yoshiharu Miyata, Yoshinori Imamura, Meiko Nishimura, Yohei Funakoshi, Yuriko Iwamoto, Naoko Chayahara, Masanori Toyoda, Yosuke Minami, Naomi Kiyota, Toru Mukohara, Shinichiro Kawamoto, Yohei Shimono, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami

  Dec. 2014, BLOOD, 124(21) (21), English

  Summary international conference


• 腹部DLBCL病変出現1ヵ月前に発症したNeurolymphomatosisの1例

  井本 寛東, Kawamoto Shinichiro, 垣内 誠司, 宮田 吉晴, 眞田 幸尚, 川森 有里子, Yakushijin Kimikazu, 南 陽介, Matsuoka Hiroshi, Minami Hironobu

  (一社)日本血液学会-東京事務局, Nov. 2014, 臨床血液, 55(11号) (11号), 2339 - 2339, Japanese

  Meeting report


• Pharmacokinetic and pharmacodynamic study of adjuvant gemcitabine therapy of biliary tract cancer following major hepatectomy (KHBO1101)

  Yutaka Fujiwara, Shogo Kobayashi, Hiroaki Nagano, Masashi Kanai, Etsuo Hatano, Masanori Toyoda, Tetsuo Ajiki, Yuki Takashima, Akinobu Hamada, Hironobu Minami, Tatsuya Ioka

  Oct. 2014, CANCER RESEARCH, 74(19) (19), English

  Summary international conference


• A PROSPECTIVE STUDY OF THE EFFICACY OF INFLUENZA VACCINATION FOR CANCER PATIENTS RECEIVING CHEMOTHERAPY

  Yukinari Sanada, Kimikazu Yakushijin, Katsuya Yamamoto, Meiko Nishimura, Yohei Funakoshi, Naoko Chayahara, Masanori Toyoda, Naomi Kiyota, Toru Mukohara, Hironobu Minami

  Oct. 2014, ANNALS OF ONCOLOGY, 25, English

  Summary international conference


• A RETROSPECTIVE ANALYSIS OF DACARBAZINE MONOTHERAPY FOR RECURRENT OR METASTATIC MUCOSAL MELANOMA

  Meiko Nishimura, Naomi Kiyota, Masanori Toyoda, Naoko Chayahara, Kei Takenaka, Kiyoaki Uryu, Yoshinori Imamura, Yohei Funakoshi, Toru Mukohara, Hironobu Minami

  Oct. 2014, ANNALS OF ONCOLOGY, 25, English

  Summary international conference


• Transcriptional expression of Bcl-2 as predictive of response to neoadjuvant chemotherapy with trastuzumab in HER2-positive ER-positive breast cancer patients.

  Maki Tanioka, Kazuko Sakai, Tamotsu Sudo, Toshiko Sakuma, Kouichi Hirokaga, Shintaro Takao, Hironobu Minami, Shunichi Negoro, Kazuhiko Nakagawa, Kazuto Nishio

  May 2014, JOURNAL OF CLINICAL ONCOLOGY, 32(15) (15), English

  Summary international conference


• 臨床研究/臨床試験の適正化 大規模臨床試験と治療ガイドライン がん領域

  Minami Hironobu

  May 2014, 臨床薬理, 45(3号) (3号), 115 - 118, Japanese

  Introduction scientific journal


• 閉経前（30歳代で化学療法後）のホルモン受容体陽性乳癌の術後治療で、タモキシフェンにLH-RHアナログをすぐに使用すべきか、生理再開後に併用すべきか？すぐに使用すべきである vs 生理再開後に併用すべきである。

  Minami Hironobu

  Apr. 2014, Cancer Board乳癌, 7, 42, Japanese

  Introduction commerce magazine


• 【免疫チェックポイント分子を標的とした治療の展開】

  Minami Hironobu, 藤原 豊, 山崎 直也, 中村 健一

  Apr. 2014, がん分子標的治療, 12(1号) (1号), 42 - 50, Japanese

  Introduction commerce magazine


• 気道狭窄を伴う異なる頸部悪性腫瘍の2例

  岡田希美, 眞田幸尚, 薬師神公和, 竹中圭, 船越洋平, 豊田昌徳, 向原徹, 大谷恭子, 松岡広, 南博信

  2014, 日本臨床腫瘍学会学術集会(CD-ROM), 12th


• 進行性悪性黒色腫におけるnivolumabとipilimumabの併用。論文紹介。

  Minami Hironobu

  2014, がん分子標的治療, 12, 99 - 101, Japanese

  Introduction commerce magazine


• Triple negative乳癌の治療にプラチナ製剤を使用すべきか？ 使う vs使わない

  Minami Hironobu

  2014, Cancer Board乳癌, 7, 136, Japanese

  Introduction commerce magazine


• A phase I study of single-agent BEZ235 (SDS sachet), once-or twice-daily, in Japanese patients with advanced solid tumors.

  Koichiro Watanabe, Hironobu Minami, Satoshi Otsu, Yoshinori Hirashima, Ryotaro Morinaga, Kazuo Nishikawa, Yasushi Hisamatsu, Toru Mukohara, Naomi Kiyota, Naoko Chayahara, Masanori Toyoda, Yoshinori Imamura, Yutaka Fujiwara, Cornelia Quadt, Matthew Robson, Kazuto Natsume, Takuji Aoki, Kuniaki Shirao

  Nov. 2013, MOLECULAR CANCER THERAPEUTICS, 12(11) (11), English

  Summary international conference


• 25-year experience with primary major salivary gland carcinoma at a single institution in Japan

  Y. Imamura, N. Kiyota, N. Otsuki, C. Hirai, Y. Funakoshi, T. Mukohara, D. Yamashita, T. Ito, K. Nibu, H. Minami

  Sep. 2013, EUROPEAN JOURNAL OF CANCER, 49, S753 - S753, English

  Summary international conference


• Pathologic complete response to cisplatin with dose-dense paclitaxel as neoadjuvant chemotherapy for locally advanced cervical cancer: Preliminary results of a multicenter phase II study with additional mutation analysis of adeno/adenosquamous carcinoma

  Maki Tanioka, Satoshi Yamaguchi, Shinya Sato, Shoji Nagao, Kazuhiro Takehara, Masato Nishimura, Tamotsu Sudo, Satoshi Morita, Hironobu Minami, Shunichi Negoro, Muneaki Shimada, Junzo Kigawa, Kiyoshi Fujiwara

  May 2013, JOURNAL OF CLINICAL ONCOLOGY, 31(15) (15), English

  Summary international conference


• A randomized multicenter phase II trial on efficacy of a hydrocolloid dressing containing ceramide with a low-friction external surface for hand-foot skin reaction caused by sorafenib in patients with renal cell carcinoma.

  Nobuo Shinohara, Norio Nonomura, Go Kimura, Masatoshi Eto, Hironobu Minami, Naoya Yamazaki, Seiji Naito

  May 2013, JOURNAL OF CLINICAL ONCOLOGY, 31(15) (15), English

  Summary international conference


• 抗Jka自己抗体を検出したIgA欠損症を伴うEvans症候群の一例

  Hayakawa Akira

  (一社)日本輸血・細胞治療学会, Apr. 2013, 日本輸血細胞治療学会誌, 59(2) (2), 330 - 330, Japanese

  Meeting report


• 再発・転移頭頸部がんに対するドセタキセル・シスプラチン併用(DC)療法

  島田貴信, 清田尚臣, 今村善宣, 西村明子, 船越洋平, 富岡秀夫, 豊田昌徳, 茶屋原菜穂子, 向原徹, 南博信

  2013, 日本臨床腫瘍学会学術集会(CD-ROM), 11th


• sunitinibを使用し腸管壊死をきたしたACTH産生神経内分泌腫瘍

  眞田幸尚, 向原徹, 今村善宣, 西村明子, 船越洋平, 富岡秀夫, 島田貴信, 豊田昌徳, 清田尚臣, 南博信

  2013, 日本臨床腫瘍学会学術集会(CD-ROM), 11th


• A PILOT RANDOMIZED TRIAL COMPARING STANDARD PAIN CONTROL WITH OR WITHOUT GABAPENTIN FOR THE TREATMENT OF PAIN RELATED TO RADIATION-INDUCED MUCOSITIS IN HEAD AND NECK CANCER

  T. Kataoka, N. Kiyota, T. Shimada, Y. Imamura, N. Chayahara, M. Toyoda, Y. Funakoshi, H. Tomioka, Y. Fujiwara, K. Nibu, T. Komori, H. Nishimura, R. Sasaki, T. Mukohara, H. Minami

  Oct. 2012, ANNALS OF ONCOLOGY, 23, 91 - 91, English

  Summary international conference


• 用語解説 デノスマブ

  Minami Hironobu

  Oct. 2012, Cancer Board 乳癌, 5(2号) (2号), 194 - 195, Japanese

  [Invited]

  Introduction scientific journal


• Phase I dose-escalating study of panobinostat (LBH589) Administered intravenously to Japanese patients with advanced solid tumors

  Sachi Morita, Satoshi Oizumi, Hironobu Minami, Koichi Kitagawa, Yoshito Komatsu, Yutaka Fujiwara, Megumi Inada, Satoshi Yuki, Naomi Kiyota, Ayako Mitsuma, Masataka Sawaki, Hiromi Tanii, Junko Kimura, Yuichi Ando

  Oct. 2012, INVESTIGATIONAL NEW DRUGS, 30(5) (5), 1950 - 1957, English

  Introduction scientific journal


• Cryptic insertion of BCL2 gene into immunoglobulin heavy locus in follicular lymphoma with t(6;9)(p23;p13)

  Katsuya Yamamoto, Atsuo Okamura, Yumiko Inui, Kimikazu Yakushijin, Tohru Murayama, Hiroshi Matsuoka, Hironobu Minami

  Sep. 2012, LEUKEMIA RESEARCH, 36(9) (9), E202 - E205, English

  [Refereed]

  Report scientific journal


• 頭頸部癌患者における放射線性粘膜炎による疼痛に対するガバペンチンのパイロット・ランダム化比較試験

  片岡 智子, 清田 尚臣, 島田 貴信, 今村 善宣, 茶屋原 菜穂子, 豊田 昌徳, 船越 洋平, 富岡 秀夫, 藤原 豊, 丹生 健一, 古森 孝英, 西村 英輝, 佐々木 良平, 向原 徹, 南 博信

  (一社)日本頭頸部癌学会, May 2012, 頭頸部癌, 38(2) (2), 188 - 188, Japanese


• 【遺伝性乳癌卵巣癌診療の新時代】 PARP阻害剤の臨床開発

  Toyoda Masanori, Minami Hironobu

  Apr. 2012, 癌と化学療法, 39(4号) (4号), 519 - 524, Japanese

  Introduction commerce magazine


• 臨床医学の展望2012 腫瘍内科学

  Minami Hironobu

  日本医事新報社, Mar. 2012, 日本医事新報, (4585号) (4585号), 72 - 77, Japanese

  [Invited]

  Introduction commerce magazine


• 切除不能高分化神経内分泌腫瘍に対するダカルバジン療法

  Fujiwara Yutaka, Toyoda Masanori, Chayahara Naoko, Kiyota Naomi, Mukohara Toru, Matsuoka Hiroshi, Minami Hironobu

  Feb. 2012, 日本内科学会雑誌, 101(Suppl.) (Suppl.), 174, Japanese

  [Refereed]

  Meeting report


• Extra-Pulmonary Neuroendocrine Carcinoma(EP-NEC)に対する救済化学療法としてのアムルビシン(AMR)の効果

  Toyoda Masanori, Fujiwara Yutaka, Chayahara Naoko, Kiyota Naomi, Mukohara Toru, Minami Hironobu

  Feb. 2012, 日本内科学会雑誌, 101(Suppl.) (Suppl.), 241, Japanese

  [Refereed]

  Meeting report


• 造血幹細胞移植前の眼科受診の意義

  薬師神公和, 船越洋平, 垣内誠司, 今村善宣, 乾由美子, 川森有里子, 豊田昌徳, 島田貴信, 富岡秀夫, 茶屋原菜穂子, 清田尚臣, 藤原豊, 向原徹, 岡村篤夫, 山本克也, 村山徹, 村山徹, 松岡広, 南博信

  2012, 日本造血細胞移植学会総会プログラム・抄録集, 34th


• SMILE療法及び末梢血幹細胞移植によって良好な経過が得られた再発・難治性NK/T細胞リンパ腫の一例

  垣内誠司, 船越洋平, 豊田昌徳, 乾由美子, 川森有里子, 薬師神公和, 岡村篤夫, 山本克也, 松岡広, 南博信

  2012, 日本造血細胞移植学会総会プログラム・抄録集, 34th


• Isolated Isochromosome 17q in Myelodysplastic Syndromes with Pure Red Cell Aplasia and Basophilia

  Yumiko Inui, Katsuya Yamamoto, Atsuo Okamura, Kimikazu Yakushijin, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami

  2012, INTERNAL MEDICINE, 51(12) (12), 1579 - 1584, English

  [Refereed]

  Introduction scientific journal


• 【進化するがん免疫療法(ワクチン療法、細胞療法、抗体療法)】 抗体療法 造血器腫瘍の抗体療法

  Yakushijin Kimikazu, Minami Hironobu

  科学評論社, Nov. 2011, 腫瘍内科, 8巻, 5号, pp. 505-513(5) (5), 514 - 522, Japanese

  Introduction scientific journal


• 【RANKLシグナルと骨病変】 抗RANKL抗体による癌の骨転移の治療

  Minami Hironobu

  Jul. 2011, Clinical Calcium, 21巻, 8号, pp. 1217-1222, Japanese

  Introduction scientific journal


• 【がん患者のリハビリテーションと理学療法】 造血幹細胞移植患者における理学療法介入の意義

  井上 順一朗, 小野 玲, 牧浦 大祐, 竹腰 久容, 中田 登紀江, 石橋 有希, 岡村 篤夫, 南 博信, 三浦 靖史, 佐浦 隆一

  (株)医学書院, May 2011, 理学療法ジャーナル, Vol 45. No. 5, pp. 399-405(5) (5), 399 - 405, Japanese

  Introduction scientific journal


• 日本人癌患者のAHR遺伝子多型によるイリノテカン体内動態への影響

  佐井 君江, 福島 浩美, 坂, 斎藤 嘉朗, 鹿庭 なほ子, 白尾 国昭, 濱口 哲弥, 山本 昇, 田村 友秀, 山田 康秀, 大江 裕一郎, 吉田 輝彦, 南 博信, 松村 保広, 大津 敦, 西條 長宏, 澤田 純一, 内藤 幹彦, 奥田 晴宏

  (公社)日本薬学会, Mar. 2011, 日本薬学会年会要旨集, 131年会(3) (3), 164 - 164, Japanese


• 急性GVHD予防薬ミコフェノール酸モフェチル(MMF)使用下における移植後G-CSF至適投与量の検討

  岡村篤夫, 薬師神公和, 乾由美子, 船越洋平, 富岡秀夫, 島田貴信, 豊田昌徳, 茶屋原菜穂子, 清田尚臣, 藤原豊, 向原徹, 山本克也, 松岡広, 南博信

  2011, 日本造血細胞移植学会総会プログラム・抄録集, 33rd


• 臍帯血移植前にボリコナゾール水晶体内投与が有効であった真菌性眼内炎

  船越洋平, 薬師神公和, 明石梓, 楠原仙太郎, 土井健史, 乾由美子, 豊田昌徳, 島田貴信, 茶屋原菜穂子, 富岡秀夫, 清田尚臣, 藤原豊, 向原徹, 岡村篤夫, 山本克也, 松岡広, 村山徹, 村山徹, 南博信

  2011, 日本造血細胞移植学会総会プログラム・抄録集, 33rd


• 【がん免疫療法の進歩と問題点 ペプチドワクチン療法、抗体療法、細胞療法】 抗体療法 固形がんに対する抗体療法

  Minami Hironobu

  Dec. 2010, Mebio, 27巻, 12号, pp. 88-100, Japanese

  Introduction scientific journal


• 日本人癌患者の薬物トランスポーター遺伝子型によるイリノテカン体内動態および副作用への影響

  佐井 君江, 斎藤 嘉朗, 前川 京子, 金 秀良, 鹿庭 なほ子, 最上 知子, 巻, 内藤 幹彦, 澤田 純一, 奥田 晴宏, 白尾 国昭, 濱口 哲弥, 山本 昇, 大江 裕一郎, 田村 友秀, 山田 康秀, 松村 保広, 大津 敦, 吉田 輝彦, 西條 長宏, 南 博信

  (公社)日本薬学会, Mar. 2010, 日本薬学会年会要旨集, 130年会(3) (3), 163 - 163, Japanese


• An overview of the recent progress in irinotecan pharmacogenetics

  Yutaka Fujiwara, Hironobu Minami

  Mar. 2010, PHARMACOGENOMICS, 11(3) (3), 391 - 406, English

  [Refereed]


• PI3K inhibitors overcome resistance to HER2-targeted agents caused by PIK3CA mutations in HER2-amplified breast cancer cell lines

  Yu Kataoka, Hironobu Minami, Hiroyuki Shimada, Nagahiro Saijo, Midori Hirai, Toru Mukohara

  Dec. 2009, MOLECULAR CANCER THERAPEUTICS, 8(12) (12), English

  Summary international conference


• Effect of axitinib (AG-013736) on thyroid function and biomarkers: Results from phase studies in Japanese patients

  Yutaka Fujiwara, Naomi Kiyota, Naoko Chayahara, Akiyuki Suzuki, Yoshiko Umeyama, Toru Mukohara, Hironobu Minami

  Dec. 2009, MOLECULAR CANCER THERAPEUTICS, 8(12) (12), English

  Summary international conference


• α1-Acid glycoproteinを指標とした新たなドセタキセル投与量選択基準の提唱

  Minami Hironobu

  This study was aimed to propose a novel dosing schedule of docetaxel based on α₁-acid glycoprotein (AGP)as an index. For this purpose, we performed Monte Carlo simulation using a population pharmacokinetic/pharmacodynamic (PPK/PPD) model, which we previously developed to estimate the ANC Nadir distribution after docetaxel administration. AGP values, which were incorporated in PPK/PPD, were sampled from normal distributions (S.D. 44, range from 19 to 259), as various mean levels of 125, 150, 175 and 200 (mg/dl). Monte Carlo simulation was conducted using docetaxel doses of 40, 50 and 60 (mg/m²) for each AGP distribution. Simulation was performed 200 times, and distributions of ANC Nadir median were obtained from simulations. We accepted a dose when 20 percentile of the distribution of ANC Nadir median was greater than 500 (counts/μl), in order to avoid the grade 4 neutropenia. From the results of simulations, 40, 50, 60 and 60 doses (mg/m²) were recommended for 125, 150, 175, and 200 AGP mean (mg/dl) respectively. Secondly, to evaluate this dosing schedule, we adopted these recommended doses to 16 patients whose ANC Nadir observed is lesser than 500, and simulated the ANC Nadir. The number of patients whose simulated time below ANC=500 was higher than 6 days decreased from 8 to 2, implying that this dosing schedule might be effective to avoid neutropenia induced by docetaxel. In conclusion, we proposed a novel dosing schedule of docetaxel using AGP as an index, which might be effective to avoid neutropenia induced by docetaxel.
  

  The Pharmaceutical Society of Japan, Dec. 2009, Yakugaku Zasshi, 129巻, 12, pp. 1565-1572(12) (12), 1565 - 1572, Japanese

  [Refereed]

  Introduction scientific journal


• Pericardial synovial sarcomaの一例

  西村 明子, 神山 久信, 尾西 由美子, 松本 敬子, 野上 宗伸, 竹中 大祐, 大野 良治, 杉村 和朗, 伊藤 智雄, 大林 千穗, 小谷 義一, 藤原 豊, 南 博信

  (公社)日本医学放射線学会, Sep. 2009, 日本医学放射線学会秋季臨床大会抄録集, 45回, S547 - S547, Japanese


• 【腫瘍内科の現状と展開】 がん薬物療法の展開 抗悪性腫瘍薬の薬理遺伝学

  Minami Hironobu

  Aug. 2009, 日本内科学会雑誌, 98巻, 8, pp. 1846-1853, Japanese

  [Refereed]

  Introduction scientific journal


• 術後補助化学療法にアンスラサイクリンは必要か？必要であるVS不要である。

  Minami Hironobu

  2009, Cancer Board 乳癌, 1巻, , pp. 112-112, Japanese

  [Refereed]

  Introduction scientific journal


• 再発乳癌に対するカペシタビン単剤治療VS併用療法

  Minami Hironobu

  2009, Cancer Board 乳癌, 1巻, , pp. 44-44, Japanese

  [Refereed]

  Introduction scientific journal


• がんプロフェッショナル養成プランについて 6大学連携オンコロジーチーム養成プラン

  仲田 文造, 日野 雅之, 中川 和彦, 西村 恭昌, 西田 升三, 中野 孝司, 廣田 省三, 南 博信, 佐々木 良平, 田中 京子, 林田 裕美, 鈴木 志津枝

  (一社)日本癌治療学会, Oct. 2008, 日本癌治療学会誌, 43(2) (2), 275 - 275, Japanese


• 分子標的薬の有害事象とその管理

  Minami Hironobu

  Sep. 2008, 臨床血液, 49巻, 9号, pp. 822-822, Japanese

  Introduction scientific journal


• Report from the second Japanese Urological Association-Japanese Society of Medical Oncology joint conference, 2007: 'diagnosis and treatment of urological malignant tumors: how can we promote subspecialists?'

  Minami Hironobu

  May 2008, International journal of urology, Vol. 15, No. 5, pp. 389-93(5) (5), 389 - 393, English

  Introduction scientific journal


• 【薬物動態・薬理遺伝学】 イリノテカンのPK/PD/PGx

  Minami Hironobu

  科学評論社, Apr. 2008, 腫瘍内科, 2巻, 2号, pp. 107-111(2) (2), 130 - 135, Japanese

  Introduction scientific journal


• CYP3A4遺伝子多型の日本人癌患者におけるイリノテカン薬物動態への影響

  佐井 君江, 斎藤 嘉朗, 福島 浩美, 坂, 鹿庭 なほ子, 最上 知子, 巻, 白尾 国昭, 濱口 哲弥, 山本 昇, 国頭 英夫, 大江 裕一郎, 田村 友秀, 山田 康秀, 南 博信, 松村 保広, 大津 敦, 吉田 輝彦, 西條 長宏, 澤田 純一

  (公社)日本薬学会, Mar. 2008, 日本薬学会年会要旨集, 128年会(3) (3), 111 - 111, Japanese


• 日本人におけるSLCO1B1遺伝子の多型解析及び主要ハプロタイプ解析

  金 秀良, 斎藤 嘉朗, 佐井 君江, 黒瀬 光一, 前川 京子, 鹿庭 なほ子, 小澤 正吾, 鎌谷 直之, 白尾 国昭, 山本 昇, 濱口 哲弥, 國頭 英夫, 大江 裕一郎, 山田 康秀, 田村 友秀, 吉田 輝彦, 南 博信, 大津 敦, 西條 長宏, 澤田 純一

  (公社)日本薬学会, Mar. 2008, 日本薬学会年会要旨集, 128年会(3) (3), 112 - 112, Japanese


• 【肺癌UPDATE 研究と臨床の最前線】 治療 高齢者肺癌の薬物療法

  Minami Hironobu

  Mar. 2008, 医学のあゆみ, 224巻, 13号, pp. 1133-1136, Japanese

  Introduction scientific journal


• 日本人癌患者のイリノテカン個別化治療実現に向けて：UGT1A1遺伝子多型（＊28および＊6）の意義について

  Minami Hironobu

  2008, 薬学雑誌, 128巻, 128, pp. 575-584, Japanese

  [Refereed]

  Introduction scientific journal


• HER2陽性再発乳癌に対するトラスツズマブ 単剤治療vs併用療法

  Minami Hironobu

  2008, Cancer Board乳癌, 1巻, , pp. 36-36, Japanese

  Introduction scientific journal


• プロテアソーム阻害剤ボルテゾミブの臨床導入 再発または難治性の多発性骨髄腫患者を対象としたボルテゾミブの国内臨床第I/II相試験

  OGAWA YOSHIAKI, TOBINAI KENSEI, OGURA MICHINORI, ANDO KIYOSHI, TSUCHIYA TAKAHIDE, KOBAYASHI YUKIO, WATANABE TAKASHI, MARUYAMA DAI, MORISHIMA YASUO, KAGAMI YOSHITOYO, TAJI HIROSHI, MINAMI HIRONOBU, ITO KUNIAKI, NAKATA MASANOBU, HOTTA TOMOMITSU

  (有)科学評論社, 28 Sep. 2007, 月刊血液・腫よう科, 55(3) (3), 298 - 305, Japanese


• Multifaceted psychosocial intervention program for breast cancer patients after first recurrence: Feasibility study

  T. Akechi, K. Taniguchi, S. Suzuki, M. Okamura, H. Minami

  Oct. 2006, PSYCHO-ONCOLOGY, 15(2) (2), S153 - S154, English

  Summary international conference


• Pharmacokinetics and pharmacodynamics of protein-unbound docetaxel in cancer patients

  MINAMI Hironobu, KAWADA Kenji, SASAKI Yasutsuna, IGARASHI Tadahiko, SAEKI Toshiaki, TAHARA Makoto, ITOH Kuniaki, FUJII Hirofumi

  10 Mar. 2006, Cancer Sci., 97(3) (3), 235 - 241, English


• 日本人におけるUGT1As(1A9-1A7-1A1)遺伝子多型のイリノテカン薬物動態への影響

  佐井 君江, 佐伯 真弓, 鹿庭 なほ子, 斎藤 嘉朗, 小澤 正吾, 澤田 純一, 白尾 国昭, 南 博信, 大津 敦, 山本 昇, 田村 友秀, 濱口 哲弥, 吉田 輝彦, 西條 長宏

  (公社)日本薬学会, Mar. 2006, 日本薬学会年会要旨集, 126年会(3) (3), 112 - 112, Japanese


• パクリタキセル代謝に影響を与える遺伝子および血清学的因子について

  香取 典子, 中島 由起子, 吉谷 隆志, 祖山 晃子, 福島 浩実, 坂, 黒瀬 光一, 鹿庭 なほ子, 斎藤 嘉朗, 小澤 正吾, 青柳 伸男, 山本 昇, 南 博信, 田村 友秀, 西條 長宏, 澤田 純一

  (公社)日本薬学会, Mar. 2006, 日本薬学会年会要旨集, 126年会(3) (3), 113 - 113, Japanese


• Population pharmacokinetics of docetaxel in patients treated in an oncology practice: A proposal for dose adjustment in hepatic dysfunction

  Hironobu Minami, Kenji Kawada, Yasutsuna Sasaki, Makoto Tahara, Tadahiko Igarashi, Kuniaki Itoh, Hirofumi Fujii, Toshiaki Saeki

  2006, ANNALS OF ONCOLOGY, 17, 139 - 139, English

  Summary international conference


• Pharmacokinetics of escalating doses of darbepoetin alfa in patients with solid tumors undergoing chemotherapy

  Gyo Asai, Nobuyuki Yamamoto, Yasutsuna Sasaki, Hironobu Minami, Tomohide Tamura, Kazuhiko Nakagawa, Kiyohiko Hatake, Nagahiro Saijo, Yusuke Tanigawara, Tomomitsu Hotta

  2006, ANNALS OF ONCOLOGY, 17, 291 - 291, English

  Summary international conference


• Doxorubicin+Cyclophosphamide→Paclitaxel術前化学療法の臨床効果及び病理学的完全奏効例の検討

  藤井 知紀, 向井 博文, 河田 健司, 中島 光, 南 博信, 和田 徳昭, 井本 滋, 黒木 嘉典, 長谷部 孝裕

  (一社)日本乳癌学会, May 2005, 日本乳癌学会総会プログラム抄録集, 13回, 188 - 188, Japanese


• A phase I study of GW572016 in patients with solid tumors

  H Minami, K Nakagawa, K Kawada, H Mukai, M Tahara, T Kurata, H Uejima, T Nogami, Y Sasaki, M Fukuoka

  Jul. 2004, JOURNAL OF CLINICAL ONCOLOGY, 22(14) (14), 207S - 207S, English

  Summary international conference


• Research on development of new treatment technique: new pharmacotherapy for cancer.

  西条長宏, 江角浩安, 西尾和人, 桑野信彦, 福岡正博, 松村保広, 松本邦夫, 杉本芳一, 南博信

  2003, がん克服新10か年戦略プロジェクト研究報告書 平成14年度


• 1990年代に開発された新規抗癌剤のEBMと将来への展望 Taxotereの臨床試験のエビデンスレベル

  佐伯 俊昭, 高嶋 成光, 佐々木 康綱, 伊藤 國明, 五十嵐 忠彦, 南 博信, 藤井 博文, 石澤 賢一, 久保田 馨, 井本 滋

  (株)癌と化学療法社, Jul. 2000, 癌と化学療法, 27(8) (8), 1288 - 1293, Japanese


• 50. Chemo-endocrine therapyが奏効した原発不明癌の多発性骨転移例(第985回千葉医学会例会・第二内科例会)

  五十嵐 忠彦, 伊藤 国明, 南 博信, 藤井 博文, 大津 智子, 佐々木 康綱, 遠藤 伸行

  千葉大学, 01 Dec. 1999, 千葉医学雑誌, 75(6) (6), 359 - 359, Japanese


• 51. 抗癌剤の第一相試験における増量法について(第985回千葉医学会例会・第二内科例会)

  伊藤 国明, 五十嵐 忠彦, 南 博信, 藤井 博文, 大津 智子, 佐々木 康綱

  千葉大学, 01 Dec. 1999, 千葉医学雑誌, 75(6) (6), 359 - 359, Japanese


• 48. 進行乳癌に対するDocetaxel-Doxorubicin併用療法(第968回千葉医学会例会・第二内科例会)

  伊藤 国明, 五十嵐 忠彦, 藤井 博文, 南 博信, 大津 智子, 佐々木 康綱

  千葉大学, 01 Dec. 1998, 千葉医学雑誌, 74(6) (6), 530 - 530, Japanese


• Toxicity and efficacy of ifosfamide, carboplatin and etoposide (modified ICE) as a salvage chemotherapy in Japanese patients with relapsed or refractory aggressive non-Hodgkin's lymphoma

  ITOH Kuniaki, IGARASHI Tadahiko, OHTSU Tomoko, WAKITA Hisashi, WATANABE Yuko, FUJII Hirofumi, MINAMI Hironobu, SASAKI Yasutsuna

  01 Dec. 1998, Int J Hematol, 68(4) (4), 431 - 437, English


• 7. 抗がん剤の第I相試験参加患者のアンケート調査(第947回千葉医学会例会・第二内科例会)

  伊藤 国明, 五十嵐 忠彦, 藤井 博文, 南 博信, 大津 智子, 佐々木 康綱

  千葉大学, 01 Feb. 1998, 千葉医学雑誌, 74(1) (1), 46 - 46, Japanese


• A-5 新規抗癌剤TOP-53の第一相試験

  佐々木 康綱, 大橋 靖雄, 南 博信, 藤井 博文, 渡辺 裕子, 大津 智子, 五十嵐 忠彦, 伊藤 國明

  日本肺癌学会, 05 Oct. 1997, 肺癌, 37(5) (5), 620 - 620, Japanese


• Therapeutic Drug Monitoring によるエトポシド14日間持続静注療法 : 化学療法(4)

  安藤 雄一, 安藤 昌彦, 杉浦 誠治, 南 博信, 野村 史郎, 酒井 秀造

  日本肺癌学会, 10 Oct. 1994, 肺癌, 34(5) (5), 658 - 658, Japanese


• 非小細胞肺癌IIIB期胸水症例の予後の検討 : 病期診断

  杉浦 誠治, 安藤 昌彦, 安藤 雄一, 南 博信, 野村 史郎, 酒井 秀造

  日本肺癌学会, 10 Oct. 1994, 肺癌, 34(5) (5), 649 - 649, Japanese


• P-306 小型進行肺癌の検討

  藤田 興一, 服部 龍夫, 安藤 雄一, 杉浦 誠治, 南 博信, 野村 史郎, 酒井 秀造

  日本肺癌学会, 10 Oct. 1993, 肺癌, 33(5) (5), 781 - 781, Japanese


• 8 非小細胞肺癌に対する多分割放射線療法と化学療法の併用についての検討

  野村 史郎, 渡邊 篤, 安藤 雄一, 杉浦 誠治, 南 博信, 酒井 秀造, 下方 薫

  日本肺癌学会, 10 Oct. 1993, 肺癌, 33(5) (5), 641 - 641, Japanese


• 34 経口エトポシドの1日多分割投与の薬物動態学的検討

  南 博信, 安藤 雄一, 杉浦 誠治, 野村 史郎, 酒井 秀造

  日本肺癌学会, 10 Oct. 1993, 肺癌, 33(5) (5), 647 - 647, Japanese


• W-IV-5 Dose Intensityを高める自家骨髄移植療法

  野村 史郎, 南 三郎, 安藤 雄一, 千田 一嘉, 南 博信, 酒井 秀造, 小寺 良尚

  日本肺癌学会, 05 Oct. 1992, 肺癌, 32(5) (5), 615 - 615, Japanese


• Gc-49 肺癌剖検例の消化管転移の検討

  千田 一嘉, 安藤 雄一, 南 博信, 岩原 毅, 野村 史郎, 酒井 秀造

  日本肺癌学会, 01 Oct. 1991, 肺癌, 31(5) (5), 770 - 770, Japanese


• Ga-62 気管支鐃による肺癌の診断率術者、経験年数による差

  南 博信, 安藤 雄一, 千田 一嘉, 岩原 毅, 野村 史郎, 酒井 秀造

  日本肺癌学会, 01 Oct. 1991, 肺癌, 31(5) (5), 734 - 734, Japanese