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大﨑 博之
大学院保健学研究科 保健学専攻
准教授

研究者基本情報

■ 学位
  • 博士（医学）, 香川大学
■ 研究ニュース
■ 委員歴
  • 2022年06月 - 現在, 日本臨床検査学教育協議会, 科目別分科会（一般検査）会長
  • 2022年04月 - 現在, 泌尿器細胞診カンファレンス, 理事
  • 2018年06月 - 現在, 兵庫県臨床検査技師会, 理事（組織部長）
  • 2017年05月 - 現在, 日本臨床検査学教育協議会, 国際協力委員会委員（副委員長）
  • 2017年04月 - 現在, NPO法人 ラオス保健医療・医学協力協会, 理事
  • 2017年04月 - 現在, 日本臨床検査学教育学会, 評議員
  • 2009年05月 - 現在, The International Academy of Cytology, Cytotechnologist Fellow, The International Academy of Cytology
  • 2009年04月 - 現在, 日本臨床細胞学会, 評議員
  • 2021年04月 - 2023年03月, 日本臨床検査学教育協議会近畿中国四国部会, 会長
  • 2015年04月 - 2022年03月, 泌尿器細胞診カンファレンス, 幹事
  • 2020年04月 - 2021年03月, 日本臨床検査学教育協議会近畿中国四国部会, 幹事
  • 2009年04月 - 2015年03月, 日本細胞診断学推進協会, 代議員
  • 2009年04月 - 2011年03月, 細胞検査士会, 都道府県代表者委員会委員
  • 2006年04月 - 2009年03月, 四国臨床検査技師会, 病理細胞診研究班班長
  • 2006年04月 - 2008年03月, 日本臨床衛生検査技師会, 精度管理調査部会ワーキンググループ委員

研究活動情報

■ 受賞
■ 論文
  • Hiroko Ose, Akihiro Nakamura, Takuhisa Nukaya, Tadashi Sofue, Reiji Haba, Tomoo Itoh, Shingo Kamoshida, Hiroyuki Ohsaki
    INTRODUCTION: Urine cytology is an indispensable test for detecting high-grade urothelial carcinoma (HGUC); however, the distinction between HGUC cells and morphologically similar benign atypical cells poses clinical challenges. In this study, we performed double immunostaining for p53 and vimentin to establish a diagnostic method to accurately distinguish HGUC cells from benign atypical cells. METHODS: This study included 41 cases of HGUC, 11 of urolithiasis, and 22 of glomerular disease diagnosed histopathologically or clinically. After preparing urine cytology specimens from voided urine samples, p53 immunostaining was performed, and the p53-positive intensity and p53 positivity rate were calculated. Subsequently, vimentin immunostaining was performed on the same specimens to calculate the rate of vimentin positivity. RESULTS: The HGUC cell group had a mean p53-positive intensity of 2.40, a mean p53 positivity rate of 73.2%, and a mean vimentin positivity rate of 5.1%. In contrast, the mean p53-positive intensity, p53 positivity rate, and vimentin positivity rate were 1.63, 36.7%, and 66.2%, respectively, in the benign atypical cell group. There were significant differences between the two groups for each parameter. Moreover, two multiple logistic regression models combining the results of these three parameters exhibited higher sensitivity and specificity than solely assessing the p53-positive intensity, positivity rate, and vimentin positivity rate. CONCLUSION: Since double immunostaining with p53 and vimentin distinguishes HGUC cells from benign atypical cells, it could be to improve the diagnostic accuracy of urine cytology.
    2024年10月, Acta cytologica, 68(4) (4), 359 - 367, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Kazuma Sakumo, Juri Tamura, Akihiro Nakamura, Takuhisa Nukaya, Tadashi Sofue, Reiji Haba, Tomoo Itoh, Shingo Kamoshida, Hiroyuki Ohsaki
    OBJECTIVE: Recently, the nuclear area has attracted attention as a morphological parameter to differentiate high-grade urothelial carcinoma (HGUC) cells from benign reactive cells. The nuclear long diameter (NLD) strongly correlates with the nuclear area and is easy to subjectively estimate. Therefore, this study examined the usefulness of the NLD-to-neutrophil diameter ratio for detecting HGUC cells in urine cytology. METHODS: This study included 29, 26 and 18 patients with HGUC, glomerular disease and urolithiasis respectively. An image analysis system was used to measure the NLD of HGUC and benign reactive cells (reactive renal tubular cells and reactive urothelial cells) and the neutrophil diameter that appeared in the voided urine in these cases. The NLD index was calculated using the NLD-to-neutrophil diameter ratio. We subsequently compared HGUC and benign reactive cells with respect to NLD and NLD indices. In addition, the HGUC cell group and benign reactive cell group were compared by selecting the five cells with the largest NLD and NLD index on each slide. RESULTS: The NLD and NLD indices of HGUC cells were significantly higher than those of benign reactive cells in all cells and in the five cells with the largest NLD and NLD indices. The cut-off value of the NLD index for detecting HGUC cells was 1.25 in all cells and 1.80 in the five cells with the largest NLD index. CONCLUSIONS: The NLD index is a useful parameter that can be introduced into routine microscopic examinations to differentiate HGUC cells from benign reactive cells.
    2024年09月, Cytopathology : official journal of the British Society for Clinical Cytology, 35(5) (5), 642 - 647, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Kaung Htet Nay Win, Yoshihiro Kushida, Keiji Yamana, Sota Iwatani, Makiko Yoshida, Nanako Nino, Cho Yee Mon, Hiroyuki Ohsaki, Shingo Kamoshida, Kazumichi Fujioka, Mari Dezawa, Noriyuki Nishimura
    BACKGROUND: Bleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients with bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Although no curative therapies for these lung diseases exist, stem cell therapy has emerged as a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- and macrophage-like stem cells distributed in various adult and fetal tissues as stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue by sensing sphingosine-1-phosphate and replace the damaged/apoptotic cells by in vivo differentiation. Clinical trials for some human diseases suggest the safety and therapeutic efficacy of intravenously injected human leukocyte antigen-mismatched allogenic Muse cells from adult bone marrow (BM) without immunosuppressant. Here, we evaluated the therapeutic effects of human Muse cells from preterm and term umbilical cord (UC), and adult BM in a rat BLM-induced lung injury model. METHODS: Rats were endotracheally administered BLM to induce lung injury on day 0. On day 3, human preterm UC-Muse, term UC-Muse, or adult BM-Muse cells were administered intravenously without immunosuppressants, and rats were subjected to histopathologic analysis on day 21. Body weight, serum surfactant protein D (SP-D) levels, and oxygen saturation (SpO2) were monitored. Histopathologic lung injury scoring by the Ashcroft and modified American Thoracic Society document scales, quantitative characterization of engrafted Muse cells, RNA sequencing analysis, and in vitro migration assay of infused Muse cells were performed. RESULTS: Rats administered preterm- and term-UC-Muse cells exhibited a significantly better recovery based on weight loss, serum SP-D levels, SpO2, and histopathologic lung injury scores, and a significantly higher rate of both Muse cell homing to the lung and alveolar marker expression (podoplanin and prosurfactant protein-C) than rats administered BM-Muse cells. Rats receiving preterm-UC-Muse cells showed statistically superior results to those receiving term-UC-Muse cells in many of the measures. These findings are thought to be due to higher expression of genes related to cell migration, lung differentiation, and cell adhesion. CONCLUSION: Preterm UC-Muse cells deliver more efficient therapeutic effects than term UC- and BM-Muse cells for treating BLM-induced lung injury in a rat model.
    2024年05月, Stem cell research & therapy, 15(1) (1), 147 - 147, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Satoshi Morito, Hiroshi Yasui, Tomoo Itoh, Shingo Kamoshida, Hiroyuki Ohsaki
    In this brief report, we described some uncommon cytomorphological features of malignant mesothelioma (MM) cells in pleural effusions. The tumor cells exhibited abundant cytoplasmic vacuolization, with presence of single or multiple eccentric nuclei in several cells. In the Giemsa-stained smear, we observed a glossy spherical material in some cells, which tested positive in Sudan III stain. In immunocytochemical analysis, tumor cells were positive for calretinin, podoplanin, epithelial membrane antigen, and methylthioadenosine phosphorylase; tumor cells were negative for BRCA1-associated protein 1, CD68, and desmin. The intracytoplasmic vacuoles were positive for adipophilin expression.
    2023年12月, Diagnostic cytopathology, 51(12) (12), E328-E331, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Kenta Suzuki, Daisuke Ogawa, Takahiro Kanda, Takeshi Fujimori, Yuki Shibayama, Asadur Rahman, Juanjuan Ye, Hiroyuki Ohsaki, Kazuya Akimitsu, Ken Izumori, Takashi Tamiya, Akira Nishiyama, Keisuke Miyake
    Abstract Recent studies have shown that D-allose, a rare sugar, elicits antitumor effects on different types of solid cancers, such as hepatocellular carcinoma, non-small-cell lung cancer, and squamous cell carcinoma of the head and neck. In this study, we examined the effects of D-allose on the proliferation of human glioblastoma (GBM) cell lines (i.e., U251MG and U87MG) in vitro and in vivo and the underlying mechanisms. D-allose treatment inhibited the proliferation of U251MG and U87MG cells in a dose-dependent manner (3–50 mM). However, D-allose treatment did not affect cell cycles or apoptosis in these cells but significantly decreased the cell division frequency in both GBM cell lines. In a subcutaneous U87MG cell xenograft model, intraperitoneal injection of D-allose (100 mg/kg/day) significantly reduced the tumor volume in 28 days. These data indicate that D-allose-induced reduction in cell proliferation is associated with a subsequent decrease in the number of cell divisions, independent of cell-cycle arrest and apoptosis. Thus, D-allose could be an attractive additive to therapeutic strategies for GBM.
    Springer Science and Business Media LLC, 2023年11月, Scientific Reports, 13(1) (1)
    [査読有り]
    研究論文（学術雑誌）

  • Satoshi Irino, Hiroko Ose, Naoki Takata, Shingo Kamoshida, Hiroyuki Ohsaki
    In most developed countries, cervical cancer screening and human papillomavirus vaccination have reduced cervical cancer incidence. However, the incidence has been increasing in Japan, possibly because of the low screening rate. Although cervical cancer incidence has increased in people in their 20s, the screening rate among 20-24-year-olds in Japan is only 10.2%, meaning that cervical cancer screening rates should be increased among young Japanese women. We conducted a questionnaire survey among students at health sciences universities to determine their knowledge of cervical cancer, screening rates, and barriers to screening. Students taking specialized medical courses were highly knowledgeable; recognition of the facts that "cervical cancer can be prevented through screening" and that "the risk of cervical cancer increases in one's 20s" was significantly high among those who underwent screening. On the other hand, only 7.5% of students used the free coupons provided for screening. Knowledge of cervical cancer improves screening rates. Therefore, educational programs to raise awareness of the importance of cervical cancer screening among non-medical and health sciences university students and young women in general are required.
    2023年09月, Nursing & health sciences, 25(3) (3), 466 - 473, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Kazuma Sakumo, Kenta Morihashi, Akihiro Nakamura, Takuhisa Nukaya, Makoto Sumitomo, Tadashi Sofue, Reiji Haba, Tomoo Itoh, Shingo Kamoshida, Hiroyuki Ohsaki
    OBJECTIVE: The Paris System for Reporting Urinary Cytology considered the nuclear-to-cytoplasmic (N:C) ratio as the most important cytomorphological feature for detecting high-grade urothelial carcinoma (HGUC) cells. Few quantitative studies have been conducted on other features although quantitative studies on the N:C ratio have been reported. Therefore, this study quantitatively analysed important cytomorphological features in distinguishing benign reactive cells from HGUC cells. METHODS: We analysed 2866 cells from the urine of 52 patients. A digital image analyser was used to quantitatively measure the nuclear area, cell area, N:C ratio, and nuclear roundness for HGUC cells and benign reactive cells. Additionally, the diagnostic value of quantitative cytomorphological criteria in HGUC cells was evaluated by the receiver operating characteristic curve. RESULTS: The area under the curve for the prediction of HGUC cells for all cells and the top five cells was in the following order: nuclear area (0.920 and 0.992, respectively), N:C ratio (0.849 and 0.977), cell area (0.781 and 0.920), and nuclear roundness (0.624 and 0.605). The best cutoff value of the N:C ratio to differentiate HGUC cells from benign reactive cells was 0.438, and using the N:C ratio of 0.702, the positive predictive value obtained was 100%. CONCLUSIONS: Our study indicated that nuclear area is a more important cytomorphological criterion than the N:C ratio for HGUC cell detection. Moreover, extracted data of the top five cells were more valuable than the data of all cells, which can be helpful in the routine practice and future criteria definition in urine cytology.
    2023年07月, Cytopathology : official journal of the British Society for Clinical Cytology, 34(4) (4), 295 - 301, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Nourin Jahan, Hiroyuki Ohsaki, Kiyoko Kaneko, Asadur Rahman, Takeshi Nishiyama, Makoto Koizumi, Shuichiro Yamanaka, Kento Kitada, Yuki Sugiura, Kenji Matsui, Takashi Yokoo, Takayuki Hamano, Makoto Kuro-O., Takuya Itou, Miwa Suzuki, Keiichi Ueda, Akira Nishiyama, Co-first author
    This study aimed to investigate whether phosphate contributes to the pathogenesis of chronic kidney disease (CKD) in dolphins. Renal necropsy tissue of an aged captive dolphin was analyzed and in vitro experiments using cultured immortalized dolphin proximal tubular (DolKT-1) cells were performed. An older dolphin in captivity died of myocarditis, but its renal function was within the normal range until shortly before death. In renal necropsy tissue, obvious glomerular and tubulointerstitial changes were not observed except for renal infarction resulting from myocarditis. However, a computed tomography scan showed medullary calcification in reniculi. Micro area X-ray diffractometry and infrared absorption spectrometry showed that the calcified areas were primarily composed of hydroxyapatite. In vitro experiments showed that treatment with both phosphate and calciprotein particles (CPPs) resulted in cell viability loss and lactate dehydrogenase release in DolKT-1 cells. However, treatment with magnesium markedly attenuated this cellular injury induced by phosphate, but not by CPPs. Magnesium dose-dependently decreased CPP formation. These data support the hypothesis that continuous exposure to high phosphate contributes to the progression of CKD in captive-aged dolphins. Our data also suggest that phosphate-induced renal injury is mediated by CPP formation in dolphins, and it is attenuated by magnesium administration.
    2023年03月, Scientific reports, 13(1) (1), 5161 - 5161, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Kiriko Maekawa, Sayaka Kotera, Hiroyuki Ohsaki
    BACKGROUND: Competency is used to channel abilities into successful processes and is employed in the medical field. Globally, several laboratory competencies exist, but the job descriptions of Japanese medical laboratory scientists differ from those of other countries and little evidence-based information on novice medical laboratory scientist competency is available in Japan. This study clarified the competencies of novice medical laboratory scientists based on various expert opinions in Japan. METHODS: The Delphi method was used to achieve an expert consensus on novice medical laboratory scientist competencies. We asked the participants to evaluate the importance of each item using the Likert scale and set 70% as the final consensus rate. RESULTS: We obtained 106/400 (26.5%) and 95/106 (89.6%) responses from participants in rounds 1 and 2, respectively. Their professional experience mean ± standard deviation was 32.4 ± 6.0 years (range: 13-41). The average of each category consensus rate was > 99.1%. Ninety-five expert opinions converged and agreed that the competency comprised 8 categories and 54 items. CONCLUSIONS: The survey results revealed that novice medical laboratory scientists were expected to have relatively higher main laboratory skill competencies in the 'Preparation and analysis' category than in other categories. Nevertheless, competencies in other categories required basic skills. In addition, our competencies contained unique competencies compared with others due to their divergent roles and their environment. Further research is warranted to explore assessment tools by developing a competency scale, thereby helping clarify the differences between ability and correlated factors. The unique competencies scale can help assess the efficacy of educational programmes for Japanese medical laboratory scientists.
    2022年12月, BMC medical education, 22(1) (1), 875 - 875, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Mai Hattori, Asadur Rahman, Satoshi Kidoguchi, Nourin Jahan, Yoshihide Fujisawa, Norihiko Morisawa, Hiroyuki Ohsaki, Hideki Kobara, Tsutomu Masaki, Akram Hossain, Akumwami Steeve, Akira Nishiyama
    BACKGROUND: The nonsteroidal mineralocorticoid receptor blocker esaxerenone is effective in reducing blood pressure (BP). OBJECTIVE: In this study, we investigated esaxerenone-driven sodium homeostasis and its association with changes in BP in Dahl salt-sensitive (DSS) hypertensive rats. METHODS: In the different experimental setups, we evaluated BP by a radiotelemetry system, and sodium homeostasis was determined by an approach of sodium intake (food intake) and excretion (urinary excretion) in DSS rats with a low-salt diet (0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD plus 0.001% esaxerenone (w/w), and HSD plus 0.05% furosemide. RESULTS: HSD-fed DSS rats showed a dramatic increase in BP with a non-dipper pattern, while esaxerenone treatment, but not furosemide, significantly reduced BP with a dipper pattern. The cumulative sodium excretion in the active period was significantly elevated in esaxerenone- and furosemide-treated rats compared with their HSD-fed counterparts. Sodium content in the skin, skinned carcass, and total body tended to be lower in esaxerenone-treated rats than in their HSD-fed counterparts, while these values were unchanged in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. Histological evaluation showed that esaxerenone, but not furosemide, treatment attenuated glomerulosclerosis, tubulointerstitial fibrosis, and urinary protein excretion induced by high salt loading. CONCLUSIONS: Collectively, these findings suggest that an esaxerenone treatment-induced reduction in BP and renoprotection are associated with body sodium homeostasis in salt-loaded DSS rats.
    2022年08月, International journal of molecular sciences, 23(16) (16), 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Masahiro Izutsu, Takanori Domoto, Shingo Kamoshida, Hiroyuki Ohsaki, Hiroshi Matsuoka, Yusuke Umeki, Kazuya Shiogama, Masaya Hirayama, Koichi Suda, Ichiro Uyama
    BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. DNA-damaging drugs, such as cisplatin (CDDP) and 5-fluorouracil (5-FU), are most frequently used in preoperative chemotherapy for ESCC. However, the response to preoperative chemotherapy varies among patients. p53, encoded by TP53, participates in apoptotic pathways following chemotherapy with DNA-damaging drugs, and mutation of TP53 contributes to chemoresistance. Organic cation transporter 1 (OCT1) participates in the uptake of CDDP, and its reduced expression is associated with CDDP resistance. The aim of this study was to evaluate the predictive impact of the expression status of p53 and OCT1 in response to preoperative chemotherapy in ESCC. METHODS: We retrospectively assessed 66 ESCC patients who received preoperative chemotherapy with CDDP/5-FU (CF) or docetaxel/CDDP/5-FU (DCF). p53 and OCT1 expression in pretreatment biopsy specimens was immunohistochemically determined and correlated with histological response to preoperative chemotherapy. RESULTS: p53 with wild-type (p53WT-ex) and mutant-type (p53MT-ex) expression patterns was identified in 40.9% and 59.1% of patients, respectively. High expression of OCT1 (OCT1High) was detected in 45.5%, and the remaining 54.5% showed low expression (OCT1Low). In a univariate analysis of the entire cohort, p53MT-ex was significantly correlated with poor response (P = 0.026), whereas OCT1Low showed marginal significance (P = 0.091). In a combined analysis, tumors with either p53MT-ex or OCT1Low showed a significant correlation with poor response compared with tumors with both p53WT-ex and OCT1High (P < 0.001). The sensitivity, specificity, and accuracy of combined p53/OCT1 were 93.9%, 47.1%, and 81.8%, respectively. Multivariate analysis identified p53 (P = 0.017), OCT1 (P = 0.032), and combined p53/OCT1 (P < 0.001) as independent predictors of histological response. When samples were stratified according to chemotherapy regimen in the univariate analysis, combined p53/OCT1 was the only significant factor for poor response in the CF (P = 0.011) and DCF (P = 0.021) groups, whereas p53 showed no statistical significance. CONCLUSIONS: Our results suggest that either p53MT-ex or OCT1Low expression in pretreatment biopsy specimens may be a potential predictor of poor response to preoperative chemotherapy with the CF-based regimens in ESCC, although the specificity needs to be improved.
    2022年04月, World journal of surgical oncology, 20(1) (1), 105 - 105, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Junichi Sakane, Hirotsugu Kitayama, Takashi Inoue, Akihiro Nakamura, Masayoshi Yamada, Yudai Miyama, Hideki Kawamura, Hideto Iwafuchi, Shingo Kamoshida, Hiroyuki Ohsaki
    INTRODUCTION: This study investigated whether our urinary podocyte detection method using podocalyxin (PDX) and Wilms tumor 1 (WT1) immunoenzyme staining combined with liquid-based cytology can serve as a noninvasive routine laboratory test for glomerular disease. METHODS: The presence of PDX- and WT1-positive cells was investigated in 79 patients with glomerular disease and 51 patients with nonglomerular disease. RESULTS: The frequencies and numbers of PDX- and WT1-positive cells were significantly higher in the glomerular disease group than in the nonglomerular disease group. The best cutoffs for PDX- and WT1-positive cell counts for identifying patients with glomerular disease were 3.5 (sensitivity = 67.1% and specificity = 100%) and 1.2 cells/10 mL (sensitivity = 43.0% and specificity = 100%), respectively. CONCLUSION: Because our urinary podocyte detection method using PDX immunoenzyme staining can be standardized and it detected glomerular disease with high accuracy, it can likely serve as a noninvasive routine laboratory test for various glomerular diseases.
    2022年03月, Acta cytologica, 66(5) (5), 434 - 440, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Tatsuya Morinishi, Yasunori Tokuhara, Kazuki Kajihara, Shunsei Kawakami, Shinichi Tanaka, Hiroyuki Ohsaki, Toru Matsunaga, Emi Ibuki, Eiichiro Hirakawa
    Gastric carcinoma is one of the most common types of cancer worldwide and a leading cause of cancer-related mortality. Gastric carcinoma is histologically subdivided into differentiated and undifferentiated carcinoma, with the latter including poorly differentiated carcinoma and signet ring cell carcinoma (SRCC). Poorly differentiated carcinoma and SRCC have a worse prognosis compared with differentiated carcinoma. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and the PPAR-α subtype regulates important cellular functions, including cell proliferation, energy metabolism, oxidative stress, immune responses and cell differentiation. The aim of the present study was to elucidate the associations between clinicopathological factors and PPAR-α expression in patients with gastric carcinoma. The immunohistochemical staining of specimens obtained from 57 patients showed that PPAR-α expression was slightly weaker in undifferentiated carcinoma than in differentiated carcinoma (P<0.01). PPAR-α expression also significantly differed between poorly differentiated carcinoma (both positive and negative: 14/20, 70%) and SRCC (not expressed: 0/7, 0%) (P<0.01). However, PPAR-α expression was not significantly affected by age, lymph node invasion, venous invasion, lymph node metastasis, depth of invasion or stage. Collectively, the present results demonstrated that the downregulated expression of PPAR-α may play a key role in the biological transformation of tumors. Therefore, PPAR-α appears to be an important protein related to histology and may hold promise as a prognostic marker. Further studies with a larger number of subjects are needed to elucidate the relationship between PPAR-α expression and tumor progression and to analyze long-term clinical survival.
    2022年02月, Molecular and clinical oncology, 16(2) (2), 51 - 51, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Shinichi Tanaka, Yasunori Tokuhara, Sho Hosokawa, Hiroyuki Ohsaki, Tatsuya Morinishi, Tamami Yamamoto, Norihiro Teramoto, Eiichiro Hirakawa
    Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a well-known nuclear receptor that is activated in the nucleus to regulate several transcription factors. Its expression patterns have been examined in various types of cancer. The present study investigated the expression patterns of PPAR-γ in non-muscle-invasive urothelial carcinoma. The expression rates of PPAR-γ, p53 and Ki-67 were compared to determine whether PPAR-γ may be considered as an immunobiomarker for bladder cancer. The intensity and extent of PPAR-γ expression were evaluated in 79 cases of non-muscle-invasive urothelial carcinoma (30 cases of papillary carcinoma low-grade, 30 cases of high-grade and 19 cases of carcinoma in situ) and 30 non-malignant cases. The nuclear overexpression of PPAR-γ was frequently observed in non-muscle-invasive urothelial carcinoma (63/79 cases) but was rarely detected in non-malignant cases (2/30 cases). The histological proliferation types of non-muscle-invasive urothelial carcinoma revealed that PPAR-γ was more frequently overexpressed in papillary carcinoma (54/60 cases) than in carcinoma in situ (9/19 cases). Immunohistochemical staining demonstrated that PPAR-γ was more useful as an immunobiomarker than p53 or Ki-67 (diagnostic odds ratios; 55.13, 16.82 and 11.13, respectively). In summary, this study demonstrated that the expression patterns of PPAR-γ were associated with histological proliferation type and that PPAR-γ was expressed in the nuclei of papillary carcinoma cells. These findings suggested that immunohistochemical staining for PPAR-γ may be used to comprehensively detect non-muscle-invasive urothelial carcinoma.
    2022年02月, Molecular and clinical oncology, 16(2) (2), 36 - 36, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Satoshi Kidoguchi, Kento Kitada, Kazuki Nakajima, Daisuke Nakano, Hiroyuki Ohsaki, Wararat Kittikulsuth, Hideki Kobara, Tsutomu Masaki, Takashi Yokoo, Kazuo Takahashi, Jens Titze, Akira Nishiyama
    AIMS: The number of cancer survivors with cardiovascular disease is increasing. However, the effect of cancer on body fluid regulation remains to be clarified. In this study, we evaluated body osmolyte and water imbalance in rats with hepatocellular carcinoma. MAIN METHODS: Wistar rats were administered diethylnitrosamine, a carcinogenic drug, to establish liver cancer. We analyzed tissue osmolyte and water content, and their associations with aldosterone secretion. KEY FINDINGS: Hepatocellular carcinoma rats had significantly reduced body mass and the amount of total body sodium, potassium, and water. However, these rats had significantly increased relative tissue sodium, potassium, and water content per tissue dry weight. Furthermore, these changes in sodium and water balance in hepatocellular carcinoma rats were significantly associated with increased 24-h urinary aldosterone excretion. Supplementation with 0.25% salt in drinking water improved body weight reduction associated with sodium and water retention in hepatocellular carcinoma rats, which was suppressed by treatment with spironolactone, a mineralocorticoid receptor antagonist. Additionally, the urea-driven water conservation system was activated in hepatocellular carcinoma rats. SIGNIFICANCE: These findings suggest that hepatocellular carcinoma induces body mass loss in parallel with activation of the water conservation system including aldosterone secretion and urea accumulation to retain osmolyte and water. The osmolyte and water retention at the tissue level may be a causative factor for ascites and edema formation in liver failure rats.
    2022年01月, Life sciences, 289, 120192 - 120192, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Kaori Enomoto, Toru Matsunaga, Tadashi Sofue, Akihiro Nakamura, Eiichiro Hirakawa, Emi Ibuki, Reiji Haba, Shingo Kamoshida, Hiroyuki Ohsaki
    BACKGROUND: p53 immunostaining is routinely used as a surrogate marker for TP53 mutational status. In urine cytology, p53 immunocytochemistry is reportedly useful in detecting urothelial carcinoma cells as well as in improving the detection sensitivity and specificity. However, to the best of our knowledge, p53 expression in repair/reactive renal tubular cells (RRTCs) from urine cytologic specimens has not been assessed to date. METHODS: We evaluated the immunoexpression of p53 and homogentisate 1,2-dioxygenase (HGD) antibody, a renal tubular cells marker, in RRTCs using voided urine and renal biopsy samples from 80 patients who were histologically diagnosed with glomerular disease. RESULTS: Repair/reactive renal tubular cells were detected in 68 (68/80, 85%) samples at a mean count of 141.1 cells per sample (range, 5-4220). Immunocytochemical analysis found p53-positive RRTCs in all the samples (68/68, 100%) with an average p53 positivity rate of RRTCs per sample at 47.7% (range, 3.8%-96.5%). Of the 68 p53-positive RRTC samples, 38 (55.9%) included cells that were HGD positive for cytoplasm. Similarly, renal biopsy analysis revealed p53-positive RRTCs in all the specimens (68/68, 100%). All 68 (100%) cases showed RRTCs that were positive for both p53 and HGD. CONCLUSION: To avoid false positives of p53 immunocytochemistry, cytologists must consider the fact that RRTCs from patients with glomerular disease are positive for p53.
    2021年11月, Cancer medicine, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Ruben Rodriguez, Andrew Y Lee, Jose A Godoy-Lugo, Bridget Martinez, Hiroyuki Ohsaki, Daisuke Nakano, David G Parkes, Akira Nishiyama, Jose Pablo Vazquez-Medina, Rudy M Ortiz
    Inappropriate activation of the renin-angiotensin system decreases glucose uptake in peripheral tissues. Chronic angiotensin receptor type 1 (AT1) blockade increases glucose uptake in skeletal muscle, decreases the abundance of large adipocytes, and macrophage infiltration in adipose. However, the contributions of each tissue to the improvement in hyperglycemia in response to AT1 blockade are not known. Therefore, we determined the static and dynamic responses of soleus muscle, liver, and adipose to an acute glucose challenge following the chronic blockade of AT1. We measured adipocyte morphology along with TNF-α expression, F4/80 and CD11c positive cells in adipose and measured insulin receptor (IR) phosphorylation and AKT phosphorylation in soleus muscle, liver, and retroperitoneal fat before (T0), 60 (T60), and 120 (T120) minutes after an acute glucose challenge in the following groups of male rats: LETO (lean control; n = 5/time point), (2) obese OLETF (n = 7-8/time point) and (3) OLETF + ARB (ARB; 10 mg olmesartan/kg/d; n = 7-8/time point). AT1 blockade decreased adipocyte TNF-α expression and F4/80 and CD11c positive cells. In retroperitoneal fat at T60, IR phosphorylation was 155% greater in ARB than in OLETF. Furthermore, in retroperitoneal fat AT1 blockade increased GLUT4 protein expression in ARB compared to OLETF. IR phosphorylation and AKT phosphorylation were not altered in the liver of OLETF, but AT1 blockade decreased hepatic PCK1 and G6PC1 mRNA expressions. Collectively, these results suggest that chronic AT1 blockade improves obesity-associated hyperglycemia in OLETF rats by improving adipocyte function and by decreasing hepatic glucose production via gluconeogenesis.
    2021年10月, American journal of physiology. Endocrinology and metabolism, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Hiroyuki Ohsaki, Keiichi Ueda, Tomoko Minakawa, Mariko Oshiro, Shingo Kamoshida, Yuki Sugiura, Miwa Suzuki, Akira Nishiyama
    Although oral cytology using Papanicolaou stain is useful for the early detection of oral premalignant lesions and squamous cell carcinoma (SCC) in people, little work has been conducted on this topic in veterinary medicine. This paper describes the features of oral cytology using Papanicolaou stain and immunocytochemistry on liquid-based cytology slides in a case of oral SCC in an Indo-Pacific bottlenose dolphin (Tursiops aduncus). In this case, dysplastic cells with koilocyte-like changes and SCC cells were identified using the Papanicolaou stain. These cells were positive for p53 using an immunocytochemistry analysis. A cytologic diagnosis of SCC was made. We believe that the early detection of premalignant oral lesions and SCC in dolphins can be significantly improved with cytology using liquid-based cytology, Papanicolaou staining, and immunocytochemistry.
    2021年09月, Veterinary clinical pathology, 50(3) (3), 404 - 409, 英語, 国際誌
    [査読有り]
    神戸大学リポジトリ（Kernel）へのリンク

  • Satoshi Morito, Takao Nitanda, Ryuko Tsukamoto, Shingo Kamoshida, Hiroshi Yasui, Tomoo Itoh, Hiroyuki Ohsaki
    Immunocytochemistry (ICC) is an important ancillary technique in clinical cytology for not only identifying and characterizing tumor cells but also gaining prognostic or therapeutic information. Although cell blocks are often prepared for immunocytochemical evaluation of body cavity fluid and fine-needle aspiration specimens, they are not suitable for hypocellular samples. Liquid-based cytology can help prepare additional smears from residual cytological specimens. However, since conventional methods are used for nongynecological specimens in most laboratories, ICC is often limited by the number of cytological smears. Cell transfer methods permit to evaluate several immunocytochemical markers in a single cytological smear. Yet, these methods have some limitations; for example, they are time-consuming (about 3-40 h) and medium membranes with their attached cells are occasionally stretched or torn when peeled off the slides. Therefore, in an attempt to solve these problems, we developed a rapid and reliable cell transfer method using a nylon mesh. Our method requires no special equipment or reagent and can significantly reduce the turnaround time, as compared to previous methods.
    2021年09月, Acta cytologica, 65(5) (5), 424 - 429, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Chihiro Okuda, Aiko Kyotake, Akihiro Nakamura, Tomoo Itoh, Shingo Kamoshida, Hiroyuki Ohsaki
    OBJECTIVE: In The Paris System for Reporting Urinary Cytology (TPS), the important cytomorphological features for diagnosing high-grade urothelial carcinoma (HGUC) are a nuclear-to-cytoplasmic (N:C) ratio exceeding 0.7, hyperchromasia, coarse chromatin, and irregular nuclear borders. However, quantitative cytomorphological assessments of HGUC cells using SurePath slides are rare. Therefore, we evaluated HGUC cells on SurePath slides quantitatively using a digital image analysis system and compared these data with ThinPrep data. METHODS: The same urine samples were divided into two aliquots and used to prepare SurePath and ThinPrep slides. We used ImageJ to measure the N:C ratio, hyperchromasia, and irregular nuclear borders for HGUC cells on SurePath and ThinPrep slides. RESULTS: The total number of analysed HGUC cells on SurePath slides was 981, versus 889 on ThinPrep slides. Hyperchromasia and irregular nuclear borders were significantly more severe on SurePath than on ThinPrep slides. Conversely, the N:C ratio did not differ between the methods. Additionally, HGUC cells with N:C ratios exceeding 0.7 were present on almost all slides for both methods. CONCLUSIONS: Our data indicated the reasonableness of using the N:C ratio as the major criterion for TPS on both SurePath and ThinPrep slides, and an N:C ratio cut-off of 0.7 as suitable for identifying HGUC cells. However, the severity of hyperchromasia and irregular nuclear borders differed between the processing methods.
    2021年05月, Cytopathology : official journal of the British Society for Clinical Cytology, 32(5) (5), 654 - 659, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Asadur Rahman, Tatsuya Sawano, Anupoma Sen, Akram Hossain, Nourin Jahan, Hideki Kobara, Tsutomu Masaki, Shinji Kosaka, Kento Kitada, Daisuke Nakano, Takeshi Imamura, Hiroyuki Ohsaki, Akira Nishiyama
    We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats.
    2021年02月, International journal of molecular sciences, 22(4) (4), 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Lei Li, Daisuke Nakano, Anqi Zhang, Wararat Kittikulsuth, Norihiko Morisawa, Hiroyuki Ohsaki, Norio Suzuki, Masayuki Yamamoto, Akira Nishiyama
    The kidneys are the major organs for erythropoietin (EPO) production in adults, and thus, kidney damage results in reduced EPO levels and anemia. Inhibitors of Hypoxia-inducible factor-prolyl hydroxylase domain-containing protein (HIF-PHD) are awaited as new therapeutic options for renal anemia. It can be predicted that most patients who receive HIF-PHD inhibitors have renal dysfunction as a cause of anemia. Therefore, in the present study, we investigated the effects of the HIF-PHD inhibitor molidustat on anemia and renal dysfunction when initiated after the onset of renal anemia. Male C57BL/6J mice received adenine orally to induce nephropathy. After the onset of nephropathy, the mice were treated with either vehicle or molidustat. After 4 weeks of administration, vehicle-treated mice displayed significant anemia, and molidustat ameliorated this anemia. Vehicle-treated mice exhibited reduced creatinine clearance and body weight, increased blood urea nitrogen levels, histopathological changes, immune cell infiltration, and dehydration. Molidustat reversed immune cell infiltration, dehydration, and renal fibrosis without improving renal functional parameters. In conclusion, molidustat treatment initiated after the onset of nephropathy and renal anemia reversed anemia in mice. Molidustat improved some parameters of renal abnormality, but it did not restore renal function.
    2020年12月, Journal of pharmacological sciences, 144(4) (4), 229 - 236, 英語, 国内誌
    [査読有り]
    研究論文（学術雑誌）

  • Yuki Shibayama, Kazuo Takahashi, Hisateru Yamaguchi, Jun Yasuda, Daisuke Yamazaki, Asadur Rahman, Takayuki Fujimori, Yoshihide Fujisawa, Shinji Takai, Toru Furukawa, Tsutomu Nakagawa, Hiroyuki Ohsaki, Hideki Kobara, Jing Hao Wong, Tsutomu Masaki, Yukio Yuzawa, Hideyasu Kiyomoto, Shinichi Yachida, Akihiro Fujimoto, Akira Nishiyama
    (Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.
    2020年11月, Communications biology, 3(1) (1), 724 - 724, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Sho Hosokawa, Kenichi Shukuya, Keisuke Sogabe, Yasukazu Ejima, Tatsuya Morinishi, Eiichiro Hirakawa, Hiroyuki Ohsaki, Tatsuo Shimosawa, Yasunori Tokuhara
    Gentisic acid (GA), a metabolite of acetylsalicylic acid (ASA), and homogentisic acid (HGA), which is excreted at high levels in alkaptonuria, are divalent phenolic acids with very similar structures. Urine containing HGA is dark brown in color due to its oxidation. We recently reported a new oxidation method of HGA involving the addition of sodium hydroxide (NaOH) with sodium hypochlorite pentahydrate (NaOCl·5H2O), which is a strong oxidant. In the present study, we attempted to oxidize GA, which has a similar structure to HGA, using our method. We herein observed color changes in GA solution and analyzed the absorption spectra of GA after the addition of NaOH with NaOCl·5H2O. We also examined the oxidation reaction of GA using a liquid chromatography time-of-flight mass spectrometer (LC/TOF-MS). The results obtained indicated that GA solution had a unique absorption spectrum with a peak at approximately 500 nm through an oxidation reaction following the addition of NaOH with NaOCl·5H2O. This spectrophotometric method enables GA to be detected in sample solutions without expensive analytical instruments or a complex method.
    2020年, PloS one, 15(4) (4), e0232263, 英語, 国際誌
    [査読有り]
    神戸大学リポジトリ（Kernel）へのリンク

  • Salman Mahmud Siddique, Koji Kubouchi, Yuka Shinmichi, Nana Sawada, Reiko Sugiura, Yasushi Itoh, Shunsuke Uehara, Kanae Nishimura, Shunsuke Okamura, Hiroyuki Ohsaki, Shingo Kamoshida, Yusuke Yamashita, Shinobu Tamura, Takashi Sonoki, Hiroshi Matsuoka, Tomoo Itoh, Hideyuki Mukai
    Protein kinase N1 (PKN1) knockout (KO) mice spontaneously form germinal centers (GCs) and develop an autoimmune-like disease with age. Here, we investigated the function of PKN1 kinase activity in vivo using aged mice deficient in kinase activity resulting from the introduction of a point mutation (T778A) in the activation loop of the enzyme. PKN1[T778A] mice reached adulthood without external abnormalities; however, the average spleen size and weight of aged PKN1[T778A] mice increased significantly compared to aged wild type (WT) mice. Histologic examination and Southern blot analyses of spleens showed extramedullary hematopoiesis and/or lymphomagenesis in some cases, although without significantly different incidences between PKN1[T778A] and WT mice. Additionally, flow cytometry revealed increased numbers in B220+, CD3+, Gr1+ and CD193+ leukocytes in the spleen of aged PKN1[T778A] mice, whereas the number of lymphocytes, neutrophils, eosinophils, and monocytes was reduced in the peripheral blood, suggesting an advanced impairment of leukocyte trafficking with age. Moreover, aged PKN1[T778A] mice showed no obvious GC formation nor autoimmune-like phenotypes, such as glomerulonephritis or increased anti-dsDNA antibody titer, in peripheral blood. Our results showing phenotypic differences between aged Pkn1-KO and PKN1[T778A] mice may provide insight into the importance of PKN1-specific kinase-independent functions in vivo.
    2019年09月, Scientific reports, 9(1) (1), 13977 - 13977, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Sakanashi F, Shintani M, Tsuneyoshi M, Ohsaki H, Kamoshida S
    OBJECTIVE: Cleaved caspase-3 (CC3), phosphorylated-mixed-lineage kinase domain-like protein (p-MLKL), and microtubule-associated protein-1 light chain-3B (LC3B) have pivotal functions in apoptosis, necroptosis, and autophagy, respectively. In vitro studies have shown that interaction of these proteins are complex and their roles in cancer can be influenced by many factors. However, these findings are not adequately assessed in human tissues. Here, we determined CC3, p-MLKL, and LC3B expression in colorectal cancers (CRCs), and assessed their associations with clinicopathological parameters, and with KRAS and p53 status. METHODS: We immunohistochemically assessed 113 CRC specimens for levels of CC3, p-MLKL, LC3B, and p53. KRAS gene status was analyzed using the Scorpion- amplification refractory mutation system. RESULTS: High levels of CC3 (CC3High) and LC3B (LC3BHigh) were detected in 38% and 35% of the 113 CRCs, respectively, but no or only a few p-MLKL-positive cells were observed in any of the tumors. CC3High was significantly associated with high pT status (P = 0.03), vascular invasion (P = 0.03) and high pStage (P = 0.04) and was marginally associated with lymph node (P = 0.06) and distant metastases (P = 0.06). LC3BHigh was also significantly associated with high pT status (P = 0.02) and lymphatic invasion (P = 0.002), and was marginally associated with nerve plexus invasion (P = 0.06). In combined analysis, compared with CC3Low/LC3BLow tumors, tumors that were either CC3High, LC3BHigh, or both were significantly associated with high pT status (P = 0.0007), lymphatic invasion (P = 0.03), vascular invasion (P = 0.003), distant metastasis (P = 0.04) and high pStage (P = 0.04). LC3BHigh was significantly associated with a mutant-type expression pattern of p53 (P = 0.003). CONCLUSION: To the best of our knowledge, this is the first study to examine the combination of CC3/LC3B and p-MLKL expression in clinical CRC samples and to correlate these expression data with clinicopathological parameters and EGFR and p53 status. Our results suggest that necroptosis is a rare process in CRC, apoptosis and autophagy are upregulated in aggressive CRCs, and p53 mutation may lead to the upregulation of autophagy.
    2019年07月, Pathology, research and practice, 215(7) (7), 152425 - 152425, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Ryuko Tsukamoto, Hiroyuki Ohsaki, Sho Hosokawa, Yasunori Tokuhara, Shingo Kamoshida, Toshiko Sakuma, Tomoo Itoh, Chiho Ohbayashi
    OBJECTIVE: Anaplastic lymphoma kinase (ALK) positive (+) lung cancers are predictive for response to crizotinib and alectinib. There are many cases of lung cancer in which surgery cannot be performed, and such cases require diagnosis by cytological specimen or biopsy. Estimating ALK (+) lung cancer from cytomorphology would allow molecular testing to proceed without the waste of a small amount of specimen. The purpose of this study was to assess whether qualitative and quantitative cytomorphological features are sufficient for distinguishing primary ALK (+) from ALK (-) lung cancer. METHODS: We examined eight qualitative cytomorphological parameters and three quantitative nuclear morphometric parameters in 17 cases of primary ALK (+) lung cancer, diagnosed by fluorescence in situ hybridisation (FISH) using histological specimens, and in 41 cases of ALK (-) lung cancer. Quantitative nuclear morphometric parameters were analysed by a computer-assisted image analysis system. RESULTS: In ALK (+) lung cancer, three qualitative parameters (signet ring cells, nuclear grooves and single type nucleoli) and two quantitative parameters (large nuclear area and irregular nuclear shape) were observed in significantly higher proportions. However, in ALK (-) lung cancer, one qualitative parameter (unclear and multiple type nucleoli) was seen significantly more often. CONCLUSIONS: These results show that the cytomorphological features of signet ring cells, nuclear grooves and nucleoli shape can help to triage a small amount of cytological and biopsy specimens for appropriate molecular testing of primary ALK (+) lung cancer.
    2019年05月, Cytopathology : official journal of the British Society for Clinical Cytology, 30(3) (3), 295 - 300, 英語, 国際誌
    [査読有り]

  • Morinishi T, Tokuhara Y, Ohsaki H, Ibuki E, Kadota K, Hirakawa E
    Peroxisome proliferator-activated receptor alpha (PPAR-α) belongs to the PPAR family and plays a critical role in inhibiting cell proliferation and tumorigenesis in various tumors. However, the role of PPAR-α in colorectal tumorigenesis is unclear. In the present study, we found that fenofibrate, a PPAR-α agonist, significantly inhibited cell proliferation and induced apoptosis in colorectal carcinoma cells. In addition, PPAR-α was expressed in the nucleus of colorectal carcinoma cells, and the expression of nuclear PPAR-α increased in colorectal carcinoma tissue compared with that of normal epithelium tissue (P<0.01). The correlation between the expression of nuclear PPAR-α and clinicopathological factors was evaluated in human colorectal carcinoma tissues, and the nuclear expression of PPAR-α was significantly higher in well-to-moderately differentiated adenocarcinoma than in mucinous adenocarcinoma (P<0.05). These findings indicate that activation of PPAR-α may be involved in anticancer effects in colorectal carcinomas, and nuclear expression of PPAR-α may be a therapeutic target for colorectal adenocarcinoma treatment.
    2019年, PPAR research, 2019, 7486727 - 7486727, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Okamura S, Osaki T, Nishimura K, Ohsaki H, Shintani M, Matsuoka H, Maeda K, Shiogama K, Itoh T, Kamoshida S
    2019年01月, Biotechnic & histochemistry : official publication of the Biological Stain Commission, 94(1) (1), 60 - 64
    [査読有り]
    神戸大学リポジトリ（Kernel）へのリンク

  • Juan Wang, Yuki Shibayama, Anqi Zhang, Hiroyuki Ohsaki, Eisuke Asano, Yasuyuki Suzuki, Yoshio Kushida, Hideki Kobara, Tsutomu Masaki, Zhiyu Wang, Akira Nishiyama
    BACKGROUND: Although constitutive activating mutations in the Wnt/β-catenin signalling pathway are important for colorectal cancer development, canonical signalling through Wnt ligands is essential for β-catenin activation. Here, we investigated the role of (pro)renin receptor ((P)RR), a component of the Wnt receptor complex, in the pathogenesis of colorectal cancer. METHODS: (P)RR silencing was performed in human colorectal cancer cells containing constitutive activating mutations in the Wnt/β-catenin pathway. (P)RR overexpression was induced in normal colon epithelial cells. Protein and mRNA levels of pathway components were detected, and Wnt signalling activity was measured using a β-catenin reporter. Cell proliferative activity and apoptosis were evaluated using WST-1 assay and flow cytometry. Xenografts were induced in nude mice. RESULTS: (P)RR expression was greater in colorectal cancer tissues and cells than in normal colorectal samples. Patients with strong (P)RR expression took more proportion in groups with poorly-differentiated, advanced and rapidly-progressing cancers. (P)RR silencing attenuated the pathway in colorectal cancer cells, impaired their proliferation in vitro and vivo. (P)RR overexpression enhanced the pathway and proliferation of normal colon epithelial cells. CONCLUSIONS: Aberrant (P)RR expression promotes colorectal cancer through the Wnt/β-catenin signalling pathway despite constitutive pathway-activating mutations. (P)RR is a potential diagnostic and therapeutic target for colorectal cancer.
    2019年01月, British journal of cancer, 120(2) (2), 229 - 237, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Tokuhara Y, Shukuya K, Tanaka M, Sogabe K, Ejima Y, Hosokawa S, Ohsaki H, Morinishi T, Hirakawa E, Yatomi Y, Shimosawa T
    Springer Science and Business Media LLC, 2018年07月, Scientific reports, 8(1) (1), 11364
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Hiroyuki Ohsaki, Toru Matsunaga, Taishi Fujita, Yasunori Tokuhara, Shingo Kamoshida, Tadashi Sofue
    In glomerular disease, podocytes and parietal epithelial cells (PECs) are shed in the urine. Therefore, urinary podocytes and PECs are noninvasive biomarkers of glomerular disease. The purpose of this protocol is to employ immunocytochemistry to detect podocytes and PECs, using the WT1 antibody on liquid-based cytology slides.
    2018年05月, Bio-protocol, 8(9) (9), e2827, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Tadashi Sofue, Yoshio Kushida, Taro Ozaki, Masahiro Moritoki, Yoko Nishijima, Hiroyuki Ohsaki, Nobufumi Ueda, Yoshiyuki Kakehi, Akira Nishiyama, Tetsuo Minamino
    BACKGROUND: It is uncertain whether kidneys from marginal donors are suitable for live kidney transplantation. In deceased donor kidneys, tubular cell senescence affects allograft function. However, the degree of cell senescence in a living donor kidney with marginal factors has not been reported. In this study, we assessed the association of tubular cell senescence with allograft and remnant kidney function by a prospective observational clinical study. METHODS: Thirty-eight living donor kidney transplantations were analyzed prospectively. Tissue sections obtained from preimplantation kidney biopsies were immunostained for p16INK4a to indicate cell senescence. Various kidney biomarkers were analyzed in urine and blood samples. RESULTS: Of the 38 donors, 21 had marginal factors. Severe tubular senescence was found in living donors with overlapping marginal criteria. Tubular senescence in living donor kidneys was significantly related to donor age and lower recipient kidney function at 1 year after transplantation independently of donor age (β = -0.281; p = 0.050) but did not affect remnant kidney function after donation. Pretransplantation donor pre-estimated glomerular filtration rate and hypertension did not show a significant area under the curve (AUC) for prediction of high tubular senescence. High plasma levels of soluble αKlotho were associated with a higher predictive value for low tubular cell senescence with an AUC of 0.78 (95% CI 0.62-0.93; p < 0.01). CONCLUSIONS: The nuclear p16-staining rate in donated kidney tubules is a predictor for allograft kidney function but not donor remnant kidney function. Detection of tubular cell senescence may facilitate selection of appropriate living donor candidates.
    2018年, American journal of nephrology, 47(1) (1), 8 - 17, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Yasunori Tokuhara, Tatsuya Morinishi, Toru Matsunaga, Manabu Sakai, Takayoshi Sakai, Hiroyuki Ohsaki, Kyuichi Kadota, Yoshio Kushida, Reiji Haba, Eiichiro Hirakawa
    Spandidos Publications, 2018年01月, Oncology Letters, 15(1) (1), 99 - 108, 英語
    [査読有り]
    研究論文（学術雑誌）

  • T. Fujita, T. Sofue, M. Moritoki, Y. Nishijima, Y. Tokuhara, H. Wakisaka, Y. Kushida, R. Haba, H. Ohsaki
    2017年12月, CYTOPATHOLOGY, 28(6) (6), 524 - 530, 英語
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • Rana Mashud, Akira Nomachi, Akihide Hayakawa, Koji Kubouchi, Sally Danno, Takako Hirata, Kazuhiko Matsuo, Takashi Nakayama, Ryosuke Satoh, Reiko Sugiura, Manabu Abe, Kenji Sakimura, Shigeharu Wakana, Hiroyuki Ohsaki, Shingo Kamoshida, Hideyuki Mukai
    2017年08月, SCIENTIFIC REPORTS, 7(1) (1), 7663, 英語
    [査読有り]
    研究論文（学術雑誌）
    神戸大学リポジトリ（Kernel）へのリンク

  • H. Ohsaki, T. Sofue, K. Kawakami, Y. Nishijima, T. Hara, T. Matsunaga, Y. Kushida, R. Haba, Y. Shigematsu, S. Irino
    2016年02月, Cytopathology, 27(1) (1), 43 - 49, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yasunori Tokuhara, Tatsuya Morinishi, Toru Matsunaga, Hiroyuki Ohsaki, Yoshio Kushida, Reiji Haba, Eiichiro Hirakawa
    2015年07月, ONCOLOGY LETTERS, 10(1) (1), 93 - 98, 英語
    [査読有り]
    研究論文（学術雑誌）

  • T. T. Yamanushi, M. R. Boyett, Y. Yamamoto, H. Ohsaki, E. Hirakawa, H. Dobrzynski
    2015年05月, FOLIA MORPHOLOGICA, 74(2) (2), 258 - 261, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Namiki Kawanishi, Yoshiaki Norimatsu, Hiroyuki Ohsaki, Tsutomu Yuminamochi, Ryohei Katoh, Ken Okusaki, Yukio Sato, Tadao K. Kobayashi
    2014年09月, DIAGNOSTIC CYTOPATHOLOGY, 42(9) (9), 823 - 826, 英語
    [査読有り]

  • Kento Kitada, Daisuke Nakano, Hiroyuki Ohsaki, Hirofumi Hitomi, Tohru Minamino, Junichi Yatabe, Robin A. Felder, Hirohito Mori, Tsutomu Masaki, Hiroyuki Kobori, Akira Nishiyama
    2014年09月, JOURNAL OF DIABETES AND ITS COMPLICATIONS, 28(5) (5), 604 - 611, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Ohsaki H, Shigematsu Y, Irino S
    2014年05月, Diagnostic cytopathology, 42(5) (5), 423 - 427, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Satoshi Nishioka, Daisuke Nakano, Kento Kitada, Tadashi Sofue, Hiroyuki Ohsaki, Kumiko Moriwaki, Taiga Hara, Koji Ohmori, Masakazu Kohno, Akira Nishiyama
    2014年04月, KIDNEY INTERNATIONAL, 85(4) (4), 871 - 879, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Norimatsu Y, Ohsaki H, Masuno H, Kagawa A, Teramoto N, Kobayashi TK
    S. Karger AG, 2014年, Acta cytologica, 58(1) (1), 76 - 82, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yoshiaki Norimatsu, Hiroyuki Ohsaki, Kenji Yanoh, Namiki Kawanishi, Tadao K. Kobayashi
    2013年04月, DIAGNOSTIC CYTOPATHOLOGY, 41(4) (4), 303 - 307, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yoshiaki Norimatsu, Yumie Shigematsu, Shingo Sakamoto, Hiroyuki Ohsaki, Kenji Yanoh, Namiki Kawanishi, Tadao K. Kobayashi
    2013年02月, DIAGNOSTIC CYTOPATHOLOGY, 41(2) (2), 120 - 125, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Ohsaki H, Hirouchi T, Hayashi N, E Okanoue, M Ohara, N Kuroda, E Hirakawa
    2013年02月, Cytopathology, 24(1) (1), 52 - 57, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yoshiaki Norimatsu, Shingo Sakamoto, Hiroyuki Ohsaki, Satoru Ozaki, Toshiro Yokoyama, Keiko Shimizu, Kenji Yanoh, Minoru Akiyama, Masamichi Bamba, Tadao K. Kobayashi
    2013年, Diagnostic Cytopathology, 41(8) (8), 673 - 681, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yoshiaki Norimatsu, Yumie Shigematsu, Shingo Sakamoto, Hiroyuki Ohsaki, Kenji Yanoh, Namiki Kawanishi, Tadao K. Kobayashi
    2012年12月, DIAGNOSTIC CYTOPATHOLOGY, 40(12) (12), 1077 - 1082, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Tadashi Sofue, Hideyasu Kiyomoto, Hiroyuki Kobori, Maki Urushihara, Yoko Nishijima, Kumiko Kaifu, Taiga Hara, Sachiko Matsumoto, Atsuhiko Ichimura, Hiroyuki Ohsaki, Hirofumi Hitomi, Hiroshi Kawachi, Melvin R. Hayden, Adam Whaley-Connell, James R. Sowers, Sadayoshi Ito, Masakazu Kohno, Akira Nishiyama
    2012年05月, AMERICAN JOURNAL OF HYPERTENSION, 25(5) (5), 604 - 611, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yoshiaki Norimatsu, Miho Kawai, Akira Kamimori, Tsutomu Yuminamochi, Hiroyuki Ohsaki, Kenji Yanoh, Namiki Kawanishi, Tadao K. Kobayashi
    2012年03月, DIAGNOSTIC CYTOPATHOLOGY, 40(3) (3), 204 - 209, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Hiroyuki Ohsaki, Muneo Nakamura, Keiji Arie, Eiichiro Hirakawa, Reiji Haba, Yoshiaki Norimatsu
    2012年02月, DIAGNOSTIC CYTOPATHOLOGY, 40(2) (2), 159 - 162, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yu-Yan Fan, Masakazu Kohno, Hirofumi Hitomi, Kento Kitada, Yoshihide Fujisawa, Junichi Yatabe, Midori Yatabe, Robin A. Felder, Hiroyuki Ohsaki, Kazi Rafiq, Shamshad J. Sherajee, Takahisa Noma, Akira Nishiyama, Daisuke Nakano
    2011年02月, ENDOCRINOLOGY, 152(2) (2), 680 - 688, 英語
    [査読有り]
    研究論文（学術雑誌）

  • H. Ohsaki, E. Hirakawa, K. Kagawa, M. Nakamura, H. Kiyomoto, R. Haba
    2010年10月, CYTOPATHOLOGY, 21(5) (5), 334 - 338, 英語
    [査読有り]
    研究論文（学術雑誌）

  • H. Ohsaki, E. Hirakawa, Y. Kushida, S. Yokoshita, M. Nakamura, H. Kiyomoto, R. Haba
    2010年10月, CYTOPATHOLOGY, 21(5) (5), 326 - 333, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Yoshiaki Norimatsu, Namiki Kawanishi, Yumie Shigematsu, Tamiaki Kawabe, Hiroyuki Ohsaki, Tadao K. Kobayashi
    2010年09月, DIAGNOSTIC CYTOPATHOLOGY, 38(9) (9), 702 - 704, 英語
    [査読有り]

  • Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte.
    Yu-Yan Fan, Masakazu Kohno, Daisuke Nakano, Hiroyuki Ohsaki, Hiroyuki Kobori, Diah Suwarni, Naro Ohashi, Hirofumi Hitomi, Katsuhiko Asanuma, Takahisa Noma, Yasuhiko Tomino, Toshiro Fujita, Akira Nishiyama
    OBJECTIVES: Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB), cilnidipine, on the progression of proteinuria in hypertensive patients compared with an L-type CCB, amlodipine. In the present study, we examined the effects of cilnidipine and amlodipine on the renal injury in spontaneously hypertensive rat/ND mcr-cp (SHR/ND) and their underlying mechanism. METHODS AND RESULTS: SHR/ND were treated with vehicle (nU10), cilnidipine [33 mg/kg per day, orally (p.o.); nU11] or amlodipine (20 mg/kg per day, p.o.; nU9) for 20 weeks. SHR/ND developed proteinuria in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilm's tumor factor, a marker of podocyte, were co-expressed. SHR/ND had significantly greater desmin staining, an indicator of podocyte injury, with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content, the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast, amlodipine failed to change these renal parameters. CONCLUSION: These data suggest that cilnidipine suppressed the development of proteinuria greater than amlodipine possibly through inhibiting N-type calcium channel-dependent podocyte injury in SHR/ND.
    2010年05月, Journal of hypertension, 28(5) (5), 1034 - 43, 英語, 国際誌
    [査読有り]
    研究論文（学術雑誌）

  • Yu-Yan Fan, Masakazu Kohno, Daisuke Nakano, Hiroyuki Ohsaki, Hiroyuki Kobori, Suwarni Diah, Naro Ohashi, Hirofumi Hitomi, Katsuhiko Asanuma, Takahisa Noma, Yasuhiko Tomino, Toshiro Fujita, Akira Nishiyama
    2010年05月, JOURNAL OF HYPERTENSION, 28(5) (5), 1034 - 1043, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Hiroyuki Ohsaki, Eiichiro Hirakawa, Yoshio Kushida, Kyuichi Kadota, Masashi Ishikawa, Reiji Haba
    2009年09月, DIAGNOSTIC CYTOPATHOLOGY, 37(9) (9), 676 - 679, 英語
    [査読有り]
    研究論文（学術雑誌）

  • H. Ohsaki, R. Haba, T. Matsunaga, M. Nakamura, H. Kiyomoto, E. Hirakawa
    2009年08月, CYTOPATHOLOGY, 20(4) (4), 224 - 230, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Association of Metastin/a G-protein-coupled Receptor Signaling and Down Syndrome Critical Region 1 in Epithelial Ovarian Cancer
    Kohkichi Hata, Yoh Watanabe, Hidekatsu Nakai, Takashi Minami, Hiroyuki Ohsaki, Eiichiro Hirakawa, Hiroshi Hoshiai
    2009年02月, ANTICANCER RESEARCH, 29(2) (2), 617 - 623, 英語
    [査読有り]
    研究論文（学術雑誌）

  • H. Ohsaki, M. Nakamura, A. Kagawa, T. T. Yamanushi, Y. Kushida, R. Haba, E. Hirakawa
    2008年12月, CYTOPATHOLOGY, 19(6) (6), 389 - 393, 英語
    [査読有り]
    研究論文（学術雑誌）

  • Hiroyuki Ohsaki, Reiji Haba, Toru Matsunaga, Muneo Nakamura, Hideyasu Kiyomoto, Eiichiro Hirakawa
    2008年05月, ACTA CYTOLOGICA, 52(3) (3), 297 - 303, 英語
    [査読有り]
    研究論文（学術雑誌）

  • T Tonai, K Shiba, Y Taketani, Y Ohmoto, K Murata, M Muraguchi, H Ohsaki, E Takeda, T Nishisho
    2001年09月, JOURNAL OF NEUROCHEMISTRY, 78(5) (5), 1064 - 1072, 英語
    [査読有り]
    研究論文（学術雑誌）

■ 書籍等出版物
  • ~基礎から学ぶ~ 細胞診のすすめ方〈第5版〉
    分担執筆, 近代出版, 2025年03月, ISBN: 4874023045

  • 見て学ぶ 一般検査アトラス（外観検査から顕微鏡検査まで）
    分担執筆, 医学書院, 2024年07月, 日本語, ISBN: 4260056638

  • 臨床検査技師 臨地実習ハンドブック
    分担執筆, 医歯薬出版, 2024年03月, 日本語, ISBN: 4263226992

  • 染色法のすべて
    分担執筆, 医歯薬出版, 2021年03月, 日本語, ISBN: 4263226909

  • 顕微鏡検査ハンドブック 臨床に役立つ形態学
    分担執筆, 医学書院, 2012年07月, 日本語, ISBN: 4260015540

  • 臨床検査学実習書シリーズ病理検査学 実習書
    日本臨床検査学教育協議会
    分担執筆, 医歯薬出版, 2011年06月, 日本語, ISBN: 4263223276

  • アトラス細胞診と病理診断
    分担執筆, 医学書院, 2010年06月, 日本語, ISBN: 4260009419

■ 共同研究・競争的資金等の研究課題
  • ラオスにおける悪性中皮腫の実態解明 －新たに開発した細胞診断法を用いて－
    大崎 博之
    日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2025年04月 - 2029年03月

  • 過酷環境における「夏眠様反応」による体液制御法の開発
    西山 成, 杉浦 悠毅, 鈴木 美和, 植田 啓一, 大崎 博之
    日本学術振興会, 科学研究費助成事業, 挑戦的研究(萌芽), 香川大学, 2024年06月28日 - 2026年03月31日

  • 老化・加齢性疾患の予防に向けた「夏眠様反応」制御メカニズム解明のための基盤研究
    西山 成, 大崎 博之, 高橋 和男
    日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 香川大学, 2022年04月 - 2026年03月, 研究分担者

  • 子宮頸がん予防に向けた市民へのアプローチ方法に関する研究
    大崎 博之, 入野 了士
    神戸市, 市の健康課題の解決に繋がる研究, 2024年10月 - 2025年12月, 研究代表者

  • 子宮頸癌検診の HPV 検査における検体自己採取キットの開発
    大崎 博之, 松井 三明
    （株）神戸大学イノベーション, 神戸大学 GAP ファンドプログラム, 2024年08月 - 2025年07月, 研究代表者
    競争的資金

  • 第22回 国際細胞学会（イタリア）における発表
    大崎博之
    （公社）日本臨床細胞学会, ICCトラベルグラント, 2025年05月
    競争的資金

  • IgA 腎症の新たな非侵襲的検査法の開発 －腎生検と透析を回避するために－
    大崎 博之, 鴨志田 伸吾
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2022年04月 - 2025年03月, 研究代表者
    競争的資金

  • 体腔液細胞診検体を用いた肺癌 PD-L1 発現の評価
    森藤 哲史, 安井 寛, 大崎 博之
    （公財）政策医療振興財団, 令和５年度 研究助成金, 神戸大学大学院 保健学研究科, 2023年06月 - 2024年05月, 研究分担者

  • 新たな診断技術を用いたラオスの悪性中皮腫の実態解明 ーアスベスト禁止法の成立のためにー
    大崎 博之
    （公財）平和中島財団, 2023年度 国際学術研究助成, 2023年04月 - 2024年03月, 研究代表者, 国際共著している
    競争的資金

  • 移植腎老化に着目した移植腎予後予測モデル構築に関する前向き観察研究
    祖父江 理, 大崎 博之
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 香川大学, 2021年04月 - 2024年03月
    移植腎生検を行う生体腎移植後レシピエントにおいて、通常診療で得られる血液、尿データに加え、研究用血清・尿・パラフィン腎標本を採取、尿細管核におけるP16染色度を計測し、CNI腎毒性(細動脈硝子化)や移植腎予後との関連性を検討するために、香川大学単施設による前向きコホート研究を実施中である。 目標症例数は前向きコホート200例(生体腎移植を施行するドナー・レシピエント各50例と移植腎生検を施行する100名）である。 令和2年8月よりすでに登録開始しており、現在23例の登録を得ている。令和5年8月までの登録を予定している。 移植腎における尿細管細胞核のP16陽性率・CNI腎毒性発生率(輸入細動脈における細動脈硝子化)・尿沈査尿細管細胞P16染色率を評価している。 また、多施設共同横断研究(移植腎病理レジストリ)によるバイオマーカー研究では、189例の登録症例の血清にてαKlotho値を測定しており、CNI腎毒性の発生との関連をROC解析にて評価予定である 大規模レジストリを用いた予後予測モデル作成に関してはJ-CKD-DB-EX研究のデータクリーニング作業を待っている

  • SLCトランスポーターの免疫組織化学染色による食道癌術前化学療法の効果予測
    鴨志田 伸吾, 松岡 宏, 大崎 博之
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2020年04月 - 2023年03月
    パラフィンブロック長期保管の影響を受けなかったOCT1について解析すると、反応群の54.5%、非反応群の37.5%が高発現であった。治療レジメン別にみると、CF群では反応群の62.5%、非反応群の44.8%、DCF群では反応群の33.3%、非反応群の18.2%がOCT1高発現を示した。反応群でOCT1高発現率が高かったが、統計学的に有意ではなかった。次に、DCF群を対象としてOATP1A2およびOATP1B3の発現を検討したが、すべての症例でOATP1A2高発現、OATP1B3低発現であった。以上から、SLCトランスポーターのみでは食道癌術前薬物療法の効果を予測するのは難しいと考えられた。 さらにCNT1、OAT1、OCT6およびOCTN2の発現についても解析した。CNT1高発現は反応群の18.2%、非反応群の22.5%に認められた（有意差なし）。他3種のトランスポーターはほぼすべての症例で低発現であった。したがって、SLCトランスポーターの発現に基づいて、非反応群に有効性が期待される殺細胞性薬剤を推定するのは困難と考えられた。 食道癌術前薬物療法の効果は薬剤トランスポーターのみに依存しているわけではないことが示唆されたため、DNA障害性抗癌剤によるアポトーシス誘導に重要な役割を果たすp53の免疫組織化学染色も実施し、p53の発現パターンからのアプローチも加えることにした。p53変異型発現を示す症例は非反応群に有意に多かった。p53とOCT1を組合せると、p53変異型発現またはOCT1低発現を示す症例はより強い有意性をもって非反応群に多く、p53/OCT1組合せは唯一の独立予測因子であった。以上から、食道癌におけるp53変異型/OCT1低発現のパターンは術前薬物療法の抵抗性予測因子である可能性が示唆された。

  • 健康長寿をもたらす夏眠反応同定とその制御
    西山 成, 杉浦 悠毅, 鈴木 美和, 植田 啓一, 大崎 博之
    日本学術振興会, 科学研究費助成事業 挑戦的研究(萌芽), 挑戦的研究(萌芽), 香川大学, 2020年07月 - 2022年03月
    本研究プロジェクトでは、最近、申請者らが見つけた生物が備え持つ適応能力「夏眠(aestivation)反応」に着目し、それを制御することで老化防止や生活習慣病の未病に挑戦する。上記全体構想の中で、本研究期間の2年間において、げっ歯類の「夏眠」モデルを使用した「夏眠反応」の制御メカニズムの解析（課題①）、宇宙空間での微小重力環境を利用したヒトでの急激なストレス暴露による「夏眠反応」の同定（課題②）、潜水などの急激なストレスに対する適応能力（防御反応）を有している海生哺乳類・イルカでの「夏眠反応」の同定（課題③）に挑む。 最終年度において課題①では、ラットの肝不全モデルにて「夏眠様反応」を生じ、体液を保持しようとしていることが明らかとなった(Kidoguchi et al. Life Sci. 2022に発表)。また、これ夏眠様反応がうまく作動しないと、血圧が上昇することも報告した（Ogura et al. Hypertens Res. 2022）。課題②では、2018年度JAXAマウスサンプルシェア・プロジェクトで実施したの宇宙空間で飼育されたマウスの実験データをKidney Int. 2022に発表した(Nishiyama et al.)。これに引き続き、現在、2025年度以降に国際宇宙ステーションでの宇宙飛行士において検証するプロジェクトについてJAXAと計画中である（最終外部評価終了）。課題③についての研究はCOVID-19の影響を受け、予定通りに実験が進んでおらず、現在も進行中である。

  • 尿中ポドサイトによる糸球体腎炎の各種判定基準の確立
    大﨑 博之, 坂根 潤一, 鴨志田 伸吾, 北山 浩嗣
    （公社）日本臨床細胞学会, 班研究課題研究助成, 2020年04月 - 2022年03月, 研究代表者
    競争的資金

  • 尿中ポドサイトによるIgA腎症の早期発見と病態評価
    大﨑 博之
    （公財）政策医療振興財団, 平成30年度研究助成金, 2018年03月 - 2019年04月, 研究代表者
    競争的資金

  • VEGF依存性腫瘍血管の同定と大腸癌ベバシズマブ療法の効果予測
    鴨志田 伸吾, 新谷 路子, 伊藤 智雄, 大﨑 博之, 岡村 俊佑, 尾崎 達司, 塩竈 和也, 西村 奏絵, 前田 耕太郎, 松岡 宏
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2016年04月 - 2019年03月
    大腸癌組織のTK1陽性血管率（TK1-PVR；TK1/CD31二重免疫染色を利用）とKi67-PVRは正常組織よりも有意に高かったが、正常組織のTK1-PVRはKi67-PVRより有意に低かった。術前化学療法（NAC）後の大腸癌肝転移において、低血管密度群の全生存期間（OS）は有意に延長しており、低TK1-PVR群に死亡例はなかった。一方、腫瘍細胞におけるCC3やCCK18の高発現群、高CC3-PVR群のOSは有意に短縮していた。TK1/CD31二重免疫染色は腫瘍血管の同定に有用であること、NAC後の腫瘍血管やアポトーシスの解析により大腸癌肝転移患者の予後を予測できる可能性が示唆された。

  • 非侵襲的バイオマーカーによる腎移植後再発性腎炎の発症・活動性予測法の確立
    祖父江 理, 鈴木 仁, 大崎 博之
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 香川大学, 2015年04月 - 2018年03月
    新規バイオマーカー糖鎖異常IgA1による腎移植後IgA沈着症・腎症の非侵襲的診断・病態解明・予後予測・治療効果判定を目的に前向きコホート研究を行った。血清糖鎖異常IgA1、抗糖鎖異常IgA1-IgG、糖鎖異常IgA1-IgG免疫複合体ともにIgA沈着の有無で有意差は認めなかった。1年目にはIgA沈着症を認めるものの3年後には消失した症例では1年時の免疫複合体濃度は低い傾向にあり、糖鎖異常IgA1-IgG免疫複合体定量はIgA沈着症の予後予測に有用である可能性が示唆された。また、尿細管老化が移植腎機能に与える影響に関しても検討を行った。

  • 大崎 博之
    日本学術振興会 科学研究費助成事業 基盤研究(C), 基盤研究(C), 2015年04月 - 2018年03月
    競争的資金

  • ２０歳代女性のセクシャリティを育む子宮頸がん検診受診行動啓発プログラムの開発
    中越 利佳, 岡村 絹代, 山口 利子, 大崎 博之
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 愛媛県立医療技術大学, 2012年04月 - 2017年03月
    本研究は、20歳代女性の子宮頸がんに対する心理・社会的特徴を明らかにし、子宮頸がん予防冊子配布型啓発による効果を検証するものである。 子宮頸がん検診に対する思いは、「検診不安」、「リプロダクティブヘルス意識」、「検診煩わしさ」が抽出され、「リプロダクティブヘルス意識」が高い者は、子宮頸がん予防の理解と行動がとれることが明らかになった。そこで、リプロダクティブヘルス、セクシャリティ向上に着目した子宮頸がん予防パンフレットを作成し配布した。対象者の背景に即した内容の啓発媒体は、子宮頸がん予防の意識を向上させる効果が示された。

  • 糸球体腎炎患者の尿中に出現する各種細胞の出現状況による病態推定 －Liquid-based cytology を用いた形態学的・免疫細胞化学的検討－
    大﨑博之
    （公財）日本腎臓財団, 若手研究者助成, 2012年06月 - 2013年05月, 研究代表者
    競争的資金

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