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ITO Mitsuhiro
Graduate School of Health Sciences / Faculty of Health Sciences
Professor

Researcher basic information

■ Research Keyword
  • 分子生物学
  • molecular biology
  • hematology/oncology
■ Research Areas
  • Life sciences / Hematology and oncology

Research activity information

■ Paper
  • 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)

  • 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

  • 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
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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.
    Oct. 2022, Vaccines, 10(11) (11), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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.
    Jun. 2022, Vaccines, 10(6) (6), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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.
    Jan. 2022, Vaccines, 10(2) (2), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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.
    Jan. 2022, International journal of hematology, 115(1) (1), 7 - 10, English, Domestic magazine
    Scientific journal

  • 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.
    Dec. 2020, International journal of hematology, 112(6) (6), 864 - 870, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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.
    Nov. 2020, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26(11) (11), 1216 - 1219, English, International magazine

  • 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.
    Apr. 2020, Cancer genetics, 242, 35 - 40, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kana Kuronuma, Aya Yokoi, Tomoya Fukuoka, Muneaki Miyata, Akio Maekawa, Satowa Tanaka, Leo Matsubara, Chie Goto, Miki Matsuo, Hao-Wei Han, Mai Tsuruta, Haruka Murata, Hikari Okamoto, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
    Matrix Gla protein (MGP), a modulator of the BMP-SMAD signals, inhibits arterial calcification in a Glu γ-carboxylation dependent manner but the role of MGP highly expressed in a subset of bone marrow (BM) mesenchymal stem/stromal cells is unknown. Here we provide evidence that MGP might be a niche factor for both normal and malignant myelopoiesis. When mouse BM hematopoietic cells were cocultured with mitomycin C-treated BM stromal cells in the presence of anti-MGP antibody, growth of hematopoietic cells was reduced by half, and maintenance of long-term culture-initiating cells (LTC-ICs) was profoundly attenuated. Antibody-mediated blockage of MGP also inhibited growth (by a fifth) and cobblestone formation (by half) of stroma-dependent MB-1 myeloblastoma cells. MGP was undetectable in normal hematopoietic cells but was expressed in various mesenchymal cells and was aberrantly high in MB-1 cells. MGP and bone morphogenetic protein (BMP)-4 were co-induced in stromal cells cocultured with both normal hematopoietic cells and MB-1 myeloblastoma cells in an oscillating several days-periodic manner. BMP-2 was also induced in stromal cells cocultured with normal hematopoietic cells but was barely expressed when cocultured with MB-1 cells. GST-pulldown and luciferase reporter assays showed that uncarboxylated MGP interacted with BMP-4 and that anti-MGP antibody abolished this interaction. LDN-193189, a selective BMP signaling inhibitor, inhibited growth and cobblestone formation of MB-1 cells. The addition of warfarin, a selective inhibitor of vitamin K-dependent Glu γ-carboxylation, did not affect MB-1 cell growth, suggesting that uncarboxylated MGP has a biological effect in niche. These results indicate that MGP may maintain normal and malignant hematopoietic progenitor cells, possibly by modulating BMP signals independently of Glu γ-carboxylation. Aberrant MGP by leukemic cells and selective induction of BMP-4 relative to BMP-2 in stromal cells might specify malignant niche.
    Apr. 2020, Heliyon, 6(4) (4), e03743, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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.
    Feb. 2020, Cancer genetics, 241, 72 - 76, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Leo Matsubara, Tomoya Fukuoka, Katsuko Sudo, Takako Fukunaga, Azusa Imanishi, Kana Kuronuma, Miki Matsuo, Shingo Kamoshida, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
    Translin, a ubiquitous RNA/DNA-binding protein that forms a hetero-octamer together with Translin-associated factor X (TRAX), possesses endoribonuclease activity and plays a physiological role in restricting the size and differentiation of mesenchymal precursor cells. However, the precise role of Translin in epithelial cells remains unclear. Here, we show evidence that Translin restricts the growth of pubertal mammary epithelial cells. The mammary epithelia of Translin-null females exhibited retarded growth before puberty, but highly enhanced growth and DNA synthesis with increased ramification after the onset of puberty. Primary cultures of Translin-null mammary epithelial cells showed augmented DNA synthesis in a ligand-independent and ligand-enhanced manner. Translin-null ovariectomized mice implanted with slow-release estrogen pellets showed enhanced length and ramification of the mammary glands. Mammary epithelial growth was also observed in ovariectomized Translin-null mice implanted with placebo pellets. Luciferase reporter assays using embryonic fibroblasts from Translin-null mice showed unaltered estrogen receptor α function. These results indicate that Translin plays a physiological role in restricting intrinsic growth, beyond mesenchymal cells, of pubertal mammary epithelial cells.
    Jan. 2020, Biochemical and biophysical research communications, 521(3) (3), 562 - 568, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomoya Fukuoka, Asami Kawai, Taku Takahara, Mahiro Mori, Robert G Roeder, Natsumi Hasegawa, Mitsuhiro Ito
    Transcriptional activation by PML-RARα, an acute promyelocytic leukemia-related oncofusion protein, requires pharmacological concentrations of all-trans retinoic acid (ATRA). However, the mechanism by which the liganded PML-RARα complex leads to the formation of the preinitiation complex has been unidentified. Here we demonstrate that the Mediator subunit MED1 plays an important role in the ATRA-dependent activation of the PML-RARα-bound promoter. Luciferase reporter assays showed that PML-RARα induced significant transcription at pharmacological doses (1 μM) of ATRA; however, this was submaximal and equivalent to the level of transcription driven by intact RARα at physiological doses (1 nM) of ATRA. Transcription depended upon the interaction of PML-RARα with the two LxxLL nuclear receptor recognition motifs of MED1, and LxxLL→LxxAA mutations led to minimal transcription. Mechanistically, MED1 interacted ATRA-dependently with the RARα portion of PML-RARα through the two LxxLL motifs of MED1. These results suggest that PML-RARα initiates ATRA-induced transcription through its interaction with MED1.
    Jun. 2019, Transcription, 10(3) (3), 147 - 156, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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.
    Mar. 2019, Intern Med., 58(5) (5), 707 - 712, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 急性前骨髄球性白血病の鑑別診断および治療効果判定におけるADVIA2120i の有用性の検討
    大本知佳, 米澤賢二, 天神貴子, 芳賀由美, 村山徹, Ito Mitsuhiro
    Feb. 2019, 日本検査血液学会雑誌, 20(1) (1), 52 - 61, Japanese
    [Refereed]
    Scientific journal

  • 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.
    Feb. 2019, Transpl Infect Dis., 21(1) (1), e13024, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kurata K, Nishimura S, Ichikawa H, Sakai R, Mizutani Y, Takenaka K, Kakiuchi S, Miyata Y, Kitao A, Yakushijin Kimikazu, Kawamoto Shinichiro, Yamamoto K, Ito Mitsuhiro, Matsuoka Hiroshi, Tokimatsu I, Kamei K, Minami Hironobu
    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.
    Dec. 2018, Int J Hematol., 108(6) (6), 658 - 664, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Atsushi Fukunaga, Mitsuhiro Ito, Chikako Nishigori
    Oct. 2018, Acta dermato-venereologica, 98(9) (9), 904 - 905, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 基本的転写共役因子複合体メディエーターはGATA1のN端活性化ドメインと結合する(Mediator transcriptional coregulatory complex interacts with GATA1 N-terminal activation domain)(英語)
    松尾美希, 福岡知也, 堤光, 平野希依, 辻真奈美, 久常友実, レーダー・ロバート, 長谷川菜摘, Ito Mitsuhiro
    Sep. 2018, 臨床血液, 59(9号) (9号), 1695, Japanese
    [Refereed]
    Research society

  • Ikeuchi Y, Imanishi A, Sudo K, Fukunaga T, Yokoi A, Matsubara L, Goto C, Fukuoka T, Kuronuma K, Kono R, Hasegawa N, Asano S, Ito Mitsuhiro
    Translin, a highly conserved DNA/RNA binding protein that forms a hetero-octamer together with Translin-associated factor X (TRAX), possesses a broad variety of functions, including RNA processing and DNA repair. Recent studies have reported that Translin is involved in mesenchymal cell physiology. Thus, here we analyzed the intrinsic role of Translin in mesenchymal cell proliferation and differentiation. Translin-deficient E11.5 mouse embryonic fibroblasts showed enhanced growth. Translin-deficient bone marrow-derived mesenchymal stem cells showed substantial expansion in vivo and enhanced proliferation in vitro. These cells also showed enhanced osteogenic and adipocytic differentiation. Histological analyses showed adipocytic hypertrophy in various adipose tissues. Translin knockout did not affect the growth of subcutaneous white adipose tissue-derived stem cells, but enhanced adipocytic differentiation was observed in vitro. Contrary to previous reports, in vitro-fertilized Translin-null mice were not runted and exhibited normal metabolic homeostasis, indicating the fragility of these mice to environmental conditions. Together, these data suggest that Translin plays an intrinsic role in restricting mesenchymal cell proliferation and differentiation.
    Sep. 2018, Biochem Biophys Res Commun., 504(1) (1), 115 - 122, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • MGPはBMP-4と結合し正常および悪性造血幹・前駆細胞を支持する(MGP interacts with BMP-4 and supports normal and malignant hematopoietic stem/progenitor cells)(英語)
    黒沼加菜, 横井彩, 福岡知也, 後藤千恵, 安達枝里, 松尾美希, 堤光, 岡田尚子, 梶谷未来野, 浅野茂隆, Ito Mitsuhiro
    Sep. 2018, 臨床血液, 59(9号) (9号), 1638, Japanese
    [Refereed]
    Research society

  • 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
    Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), and it has been suggested that lymphocyte recovery affects survival after HSCT. However, few studies have examined lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease. We retrospectively evaluated early lymphocyte recovery after HSCT among Japanese adults who received MMF prophylaxis. Patients were divided into two groups according to their median absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the “low ALC group” (≤ 0.22 × 109 cells/L) and the “high ALC group” (& gt 0.22 × 109 cells/L). With a median follow-up of 317 days, the high ALC group showed significantly better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02). The high ALC group also tended to have better non-relapse mortality than the low ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P = 0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC on day 28 after HSCT was effective in predicting overall survival and non-relapse mortality.
    Springer Tokyo, Jul. 2018, International Journal of Hematology, 108(1) (1), 58 - 65, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 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)

  • 転写共役因子MED1の核内受容体結合能は低温環境での体温維持に必須である
    平野希依, 物延沙耶, 安達枝里, 長崎洋樹, 福岡知也, 峰松侑希, 後藤千恵, 横井彩, 松尾美希, レーダー・ロバート, 長谷川菜摘, Ito Mitsuhiro
    Dec. 2017, 生命科学系学会合同年次大会 2017年度, [4P2T15 - 05(3P-0634, Japanese
    [Refereed]
    Research society

  • 転写共役因子MED1によるIL-33誘導性の2型自然リンパ球の動員調節
    安達枝里, 長谷川菜摘, 前川茜, 物延沙耶, 平野希依, 後藤千恵, 横井彩, 黒沼加菜, 宮田宗明, 高井義美, RoederRobert, Ito Mitsuhiro
    Dec. 2017, 生命科学系学会合同年次大会 2017年度, [4P2T15 - 04(3P-0633, Japanese
    [Refereed]
    Research society

  • 新規造血ニッチ分子MGPは正常および悪性造血幹・前駆細胞を調節する(英語)
    横井彩, 後藤千恵, 黒沼加菜, 前川昌保, 松原怜央, 福永貴子, 長谷川菜摘, 原田雅充, 浅野茂隆, Ito Mitsuhiro
    Dec. 2017, 生命科学系学会合同年次大会 2017年度, [2P - 0808], Japanese
    [Refereed]
    Research society

  • MED1の核内受容体結合能を廃絶した変異マウスにおける脂質代謝制御分子の発現
    物延沙耶, 平野希依, 安達枝里, 峰松侑希, 松尾美希, 後和佳澄, 服部美咲, 黒沼加菜, RoederRobert, 長谷川菜摘, Ito Mitsuhiro
    Dec. 2017, 生命科学系学会合同年次大会 2017年度, [4LT15 - 01(3P-0621, Japanese
    [Refereed]
    Research society

  • GATA1のN端活性化ドメインを介する転写活性化におけるメディエーターの関与の可能性
    福岡知也, 松尾美希, 後和佳澄, 森真洋, 河合麻美, 水田駿平, 峰松侑希, 服部美咲, RoederRobertG, 長谷川菜摘, Ito Mitsuhiro
    Dec. 2017, 生命科学系学会合同年次大会 2017年度, [1P - 0747], Japanese
    [Refereed]
    Research society

  • 全自動尿中有形成分分析装置UF-5000による尿中細菌測定の有用性
    牧亜矢子, 金山敦子, 河野江利子, 柴田有理子, 池本敏行, Ito Mitsuhiro, 岡田仁克
    Oct. 2017, 臨床病理, 65(補冊) (補冊), 221, Japanese
    [Refereed]
    Research society

  • 全自動尿中有形成分分析装置UF-5000の性能評価 細菌グラム染色情報、異型細胞検出情報および浸透圧測定能の評価
    牧亜矢子, 金山敦子, 井地陽子, 河野江利子, 池本敏行, Ito Mitsuhiro, 岡田仁克
    Jun. 2017, 日本医学検査学会抄録集 66回, 385, Japanese
    Research society

  • 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
    To identify strategies for reducing emesis induced by the CHOP regimen, which includes high-dose steroids, we prospectively evaluated the efficacy of palonosetron in Japanese patients. Palonosetron was administered at a dose of 0.75 mg via intravenous injection over 30 min before chemotherapy on day 1. Patients kept diaries of chemotherapy-induced nausea and vomiting (CINV) incidence from the start of chemotherapy until 168 h afterwards, in which they documented the occurrence and severity of nausea, vomiting, anorexia, and the use of rescue medication. The primary endpoint was the overall occurrence rate of nausea, vomiting, and anorexia; these rates were 56, 12, and 62 %, respectively, including all grades. The rates and severity of symptoms tended to worsen 120-168 h after completing oral prednisolone. We defined complete response (CR) as no vomiting and no use of rescue therapy. The CR rates of post palonosetron 0.75 mg treatment in the acute (0-24 h), delayed (24-168 h), and overall phases (0-168 h) were 86, 66, and 62 %, respectively. Antiemetic strategies of CHOP regimen for day 6 and, thereafter, should be investigated.
    SPRINGER JAPAN KK, Dec. 2016, INTERNATIONAL JOURNAL OF HEMATOLOGY, 104(6) (6), 682 - 691, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Satowa Tanaka, Akio Maekawa, Leo Matsubara, Azusa Imanishi, Masaya Yano, Robert G. Roeder, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
    The expression of extracellular matrix protein periostin (POSTN) was attenuated in Med1(-/-) mouse embryonic fibroblasts (MEFs), which exhibited a decreased capability to support hematopoietic progenitor cells (HPCs) in vitro. When bone marrow (BM) cells were cocultured with mitomycin C-treated Med1(+/+) MEFs, or OP-9 or MS-5 BM stromal cells, in the presence of anti-POSTN antibody, the growth of BM cells and number of long-term culture-initiating cells (LTC-ICs) were attenuated. When BM cells were cocultured with Med1(-/-) MEFs in the presence of recombinant POSTN, the growth of BM cells and the number of LTC-ICs were restored. Moreover, antibody-mediated blockage of stromal cells-derived POSTN markedly reduced the growth and cobblestone formation, a leukemic stem cell feature, of stromal cell dependent MB-1 myeloblastoma cells. POSTN was expressed both in BM cells and variably in different BM stromal cells. Expression in the latter cells was increased by physical interaction with hematopoietic cells. The receptor for POSTN, integrin alpha v beta 3, was expressed abundantly in BM stromal cells. The addition of recombinant POSTN to BM stromal cells induced intracellular signaling downstream of integrin alpha v beta 3. These results suggest that stromal cell POSTN supports both normal HPCs and leukemia-initiating cells in vitro, at least in part, indirectly by acting on stromal cells in an autocrine or paracrine manner. (C) 2016 Elsevier Inc. All rights reserved.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Sep. 2016, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 478(4) (4), 1706 - 1712, English
    [Refereed]
    Scientific journal

  • Yukinari Sanada, Kimikazu Yakushijin, Tetsuhiko Nomura, Naoko Chayahara, Masanori Toyoda, Yosuke Minami, Naomi Kiyota, Toru Mukohara, Shinichiro Kawamoto, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami
    Objective: Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. Two-dose vaccination is a proposed strategy for increasing vaccination efficacy; however, this has yet to be confirmed in this population. The purpose of this study was to clarify the efficacy and safety of this strategy. Methods: We conducted a multicentre prospective study on a two-dose vaccination regimen in cancer patients receiving chemotherapy. Second vaccinations were performed in patients who did not respond to all three viral strains after the first vaccination. Serum haemagglutination inhibition titres were measured to determine the patients' immunological response, 2 weeks prior to the first vaccination, 3-5 weeks after each vaccination, and at the end of the influenza season. Results: We enrolled 109 patients, including 70 with solid tumours, 36 with haematological malignancies, and 3 with both cancer types. Among the total patients, the proportion of patients with protective titres against the three viral strains increased significantly from 3 to 27% (P<0.01) following vaccination. Among the 79 patients who received a second vaccination, the proportion of those with protective titres against the individual strains increased by 10% (H1N1), 8% (H3N2), and 3% (B) compared with after the first vaccination. Serious adverse events were not observed. Conclusions: We recommend influenza vaccinations for cancer patients, including those receiving chemotherapy. Also, the additional benefit of the second vaccination may be limited.
    OXFORD UNIV PRESS, May 2016, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 46(5) (5), 448 - 452, English
    [Refereed]
    Scientific journal

  • 末梢血中に形質細胞の増加を伴い白血化を伴った血管免疫芽球性T細胞性リンパ腫の1症例(A case of angioimmunoblastic T cell lymphoma with increased plasma cells in peripheral blood)(英語)
    足立靖, 日野拓也, 大澤政彦, 植木一仁, 村尾智子, 李銘, 沖垣光彦, Ito Mitsuhiro, 池原進
    Apr. 2016, 日本病理学会会誌, 105(1号) (1号), 360, Japanese
    [Refereed]
    Research society

  • Hiroki Sekine, Keito Okazaki, Nao Ota, Hiroki Shima, Yasutake Katoh, Norio Suzuki, Kazuhiko Igarashi, Mitsuhiro Ito, Hozumi Motohashi, Masayuki Yamamoto
    The KEAP1-NRF2 system plays a central role in cytoprotection. NRF2 is stabilized in response to electrophiles and activates transcription of antioxidant genes. Although robust induction of NRF2 target genes confers resistance to oxidative insults, how NRF2 triggers transcriptional activation after binding to DNA has not been elucidated. To decipher the molecular mechanisms underlying NRF2-dependent transcriptional activation, we purified the NRF2 nuclear protein complex and identified the Mediator subunits as NRF2 cofactors. Among them, MED16 directly associated with NRF2. Disruption of Med16 significantly attenuated the electrophile-induced expression of NRF2 target genes but did not affect hypoxia-induced gene expression, suggesting a specific requirement for MED16 in NRF2-dependent transcription. Importantly, we found that 75% of NRF2-activated genes exhibited blunted inductions by electrophiles in Med16-deficient cells compared to wild-type cells, which strongly argues that MED16 is a major contributor supporting NRF2-dependent transcriptional activation. NRF2-dependent phosphorylation of the RNA polymerase II C-terminal domain was absent in Med16-deficient cells, suggesting that MED16 serves as a conduit to transmit NRF2-activating signals to RNA polymerase II. MED16 indeed turned out to be essential for cytoprotection against oxidative insults. Thus, the KEAP1-NRF2-MED16 axis has emerged as a new regulatory pathway mediating the antioxidant response through the robust activation of NRF2 target genes.
    AMER SOC MICROBIOLOGY, Feb. 2016, MOLECULAR AND CELLULAR BIOLOGY, 36(3) (3), 407 - 420, English
    [Refereed]
    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]

  • 乳癌発症が遺伝要因と環境要因に依存する可能性 乳癌モデルマウスの検討
    井之上菜名子, 長谷川菜摘, 神田織江, 峰松侑希, 武元優允, 丹後元太郎, 前川茜, 長崎洋樹, 今西梓, Ito Mitsuhiro
    Dec. 2015, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回, [2P1095], Japanese
    [Refereed]
    Research society

  • 骨髄間質細胞が産生するオステオポンチンは造血幹・前駆細胞をCD44を介して支持する
    矢野雅也, 今西梓, 松原怜央, 前川晶保, 田中里和, 長崎洋樹, 河合麻美, 長谷川菜摘, 浅野茂隆, Ito Mitsuhiro
    Dec. 2015, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回, [1P0171], Japanese
    [Refereed]
    Research society

  • ぺリオスチンは正常および異常造血幹・前駆細胞を支持する(英語)
    前川晶保, 田中里和, 今西梓, 矢野雅也, 松原怜央, 長谷川菜摘, 浅野茂隆, Ito Mitsuhiro
    Dec. 2015, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回, [1P0698], Japanese
    [Refereed]
    Research society

  • NRF2-MED16を介した抗酸化遺伝子群の転写活性化機構
    岡崎慶斗, 関根弘樹, 鈴木教郎, 加藤恭丈, 五十嵐和彦, Ito Mitsuhiro, 本橋ほづみ, 山本雅之
    (公社)日本生化学会, Dec. 2015, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回, 88回・38回, [4T14L - 01(3P0701)], Japanese
    [Refereed]
    Research society

  • MED1結合蛋白CCAR1とCoCoAはPPARγ2誘導性の白色脂肪細胞分化を司る
    武元優允, 松井啓治, 前川茜, 長崎洋樹, 井之上菜名子, 物延沙耶, 今西梓, 長谷川菜摘, RoederRobertG, Ito Mitsuhiro
    Dec. 2015, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回, [1P0705], Japanese
    [Refereed]
    Research society

  • MED1は高濃度レチノイン酸とPML-RARα融合蛋白による転写活性化に必要である(英語)
    高原拓, 河合麻美, 森真洋, 丹後元太郎, 武元優允, 前川茜, 浦浜憲永, 長谷川菜摘, Ito Mitsuhiro
    Dec. 2015, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回, [2P0727], Japanese
    [Refereed]
    Research society

  • GATA1による転写活性化におけるMED1依存性と非依存性の機序
    森真洋, 河合麻美, 水田駿平, 高原拓, 丹後元太郎, 矢野雅也, RoederRobertG, 長谷川菜摘, Ito Mitsuhiro
    Dec. 2015, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回, [4T5L - 11(3P0699), Japanese
    [Refereed]
    Research society

  • 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
    No optimum treatment of iatrogenic immunodeficiency-associated lymphoproliferative disorders due to methotrexate in patients with rheumatoid arthritis (MTX-LPD) has yet been established, although MTX withdrawal is known to have a substantial effect on tumor regression. Here, we retrospectively analyzed 20 cases of MTX-LPD. Tumor shrinkage occurred in 18 of 20 cases, but only following MTX withdrawal. This tumor regression ratio was considerably better than in previous reports, and appeared due to longer "watchful waiting." Lymphocyte recovery at 2 weeks after MTX withdrawal was significantly higher in cases with tumor regression in 1 month than in those without tumor regression (p = 0.001). Median time to maximal efficacy after MTX cessation in cases without chemotherapy was 12 weeks (range 2-76). In conclusion, watchful waiting for a longer period after MTX cessation with observation of early lymphocyte recovery and uninterrupted continuation of other anti-rheumatoid drugs may be an acceptable management plan for MTX-LPD.
    TAYLOR & FRANCIS LTD, Nov. 2015, LEUKEMIA & LYMPHOMA, 56(11) (11), 3045 - 3051, English
    [Refereed]
    Scientific journal

  • Yasushi Adachi, Takuya Hino, Masahiko Ohsawa, Kazuhito Ueki, Tomoko Murao, Ming Li, Yunze Cui, Mitsuhiko Okigaki, Mitsuhiro Ito, Susumu Ikehara
    Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma, known to express CD3 and CD4, and, frequently, also CD10 and c-Maf-1. Hypergamma-globulinemia is not particularly rare in patients with AITL. However, AITL in conjunction with plasmacytosis in the peripheral blood is rare. The current report presents a case of CD10-negative AITL demonstrating leukemic change and plasmacytosis in the peripheral blood mimicking plasma cell leukemia. A 78-year-old male was admitted to hospital due to systemic lymph node enlargement, high serum IgG and IgA, and increased counts of plasmacytoid cells and lymphoid cells with atypical nuclei in the peripheral blood. Initially, plasma cell leukemia was suspected, due to the extreme increase in the number of plasma cells in the peripheral blood. However, the plasma cells did not show clonal expansion on examination by flow cytometry. Based on histological analyses, following a biopsy of an enlarged lymph node, the patient was diagnosed with AITL. This case suggests that when hypergammaglobulinemia and increases in B-lineage cells are observed, AITL should be considered in addition to disorders of B-lineage cells.
    SPANDIDOS PUBL LTD, Sep. 2015, ONCOLOGY LETTERS, 10(3) (3), 1555 - 1560, English
    [Refereed]
    Scientific journal

  • Seiji Kakiuchi, Kimikazu Yakushijin, Katsuya Yamamoto, Hideo Tomioka, Yumiko Inui, Atsuo Okamura, Shinichiro Kawamoto, Yosuke Minami, Tohru Murayama, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami
    Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.
    JAPAN SOC INTERNAL MEDICINE, 2015, INTERNAL MEDICINE, 54(16) (16), 2057 - 2060, English
    [Refereed]
    Scientific journal

  • Shumpei Mizuta, Tomoya Minami, Haruka Fujita, Chihiro Kaminaga, Keiji Matsui, Ruri Ishino, Azusa Fujita, Kasumi Oda, Asami Kawai, Natsumi Hasegawa, Norinaga Urahama, Robert G. Roeder, Mitsuhiro Ito
    The MED1 subunit of the Mediator transcriptional coregulator complex coactivates GATA1 and induces erythropoiesis. Here, we show the dual mechanism of GATA1- and MED1-mediated transcription. MED1 expression levels in K562 erythroleukemia cells paralleled the levels of GATA1-targeted gene transcription and erythroid differentiation. An N-terminal fragment of MED1, MED1(1-602), which is incapable of interacting with GATA1, enhanced GATA1-targeted gene transcription and erythroid differentiation, and introduction of MED1(1-602) into Med1(-/-) mouse embryonic fibroblasts (MEFs) partially rescued GATA1-mediated transcription. The C-terminal zinc-finger domain of GATA1 interacts with the MED1(1-602)-interacting coactivator CCAR1, CoCoA and MED1(681-715). CCAR1 and CoCoA synergistically enhanced GATA1-mediated transcription from the gamma-globin promoter in MEFs. Recombinant GATA1, CCAR1, CoCoA and MED1(1-602) formed a complex in vitro, and GATA1, CCAR1, CoCoA and MED1 were recruited to the gamma-globin promoter in K562 cells during erythroid differentiation. Therefore, in addition to the direct interaction between GATA1 and MED1, CoCoA and CCAR1 appear to relay the GATA1 signal to MED1, and multiple modes of the GATA1-MED1 axis may help to fine-tune GATA1 function during GATA1-mediated homeostasis events.
    WILEY-BLACKWELL, Jan. 2014, GENES TO CELLS, 19(1) (1), 28 - 51, English
    [Refereed]
    Scientific journal

  • Shumpei Mizuta, Tomoya Minami, Haruka Fujita, Chihiro Kaminaga, Keiji Matsui, Ruri Ishino, Azusa Fujita, Kasumi Oda, Asami Kawai, Natsumi Hasegawa, Norinaga Urahama, Robert G. Roeder, Mitsuhiro Ito
    The MED1 subunit of the Mediator transcriptional coregulator complex coactivates GATA1 and induces erythropoiesis. Here, we show the dual mechanism of GATA1- and MED1-mediated transcription. MED1 expression levels in K562 erythroleukemia cells paralleled the levels of GATA1-targeted gene transcription and erythroid differentiation. An N-terminal fragment of MED1, MED1(1-602), which is incapable of interacting with GATA1, enhanced GATA1-targeted gene transcription and erythroid differentiation, and introduction of MED1(1-602) into Med1(-/-) mouse embryonic fibroblasts (MEFs) partially rescued GATA1-mediated transcription. The C-terminal zinc-finger domain of GATA1 interacts with the MED1(1-602)-interacting coactivator CCAR1, CoCoA and MED1(681-715). CCAR1 and CoCoA synergistically enhanced GATA1-mediated transcription from the gamma-globin promoter in MEFs. Recombinant GATA1, CCAR1, CoCoA and MED1(1-602) formed a complex in vitro, and GATA1, CCAR1, CoCoA and MED1 were recruited to the gamma-globin promoter in K562 cells during erythroid differentiation. Therefore, in addition to the direct interaction between GATA1 and MED1, CoCoA and CCAR1 appear to relay the GATA1 signal to MED1, and multiple modes of the GATA1-MED1 axis may help to fine-tune GATA1 function during GATA1-mediated homeostasis events.
    WILEY-BLACKWELL, Jan. 2014, GENES TO CELLS, 19(1) (1), 28 - 51, English
    [Refereed]
    Scientific journal

  • Keiji Matsui, Kasumi Oda, Shumpei Mizuta, Ruri Ishino, Norinaga Urahama, Natsumi Hasegawa, Robert G. Roeder, Mitsuhiro Ito
    The MEDI subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor beta (TR beta) on the TSH beta gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MEDI is a ligand-dependent positive cofactor on this promoter. TSH beta gene transcription was attenuated in MEDI mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSH beta gene promoter activity in a ligand-independent manner in cultured cells. MEDI also stimulated transcription from the TSH beta gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSH beta gene promoter. (C) 2013 Elsevier Inc. All rights reserved.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Oct. 2013, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 440(1) (1), 184 - 189, English
    [Refereed]
    Scientific journal

  • Keiji Matsui, Kasumi Oda, Shumpei Mizuta, Ruri Ishino, Norinaga Urahama, Natsumi Hasegawa, Robert G. Roeder, Mitsuhiro Ito
    The MEDI subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor beta (TR beta) on the TSH beta gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MEDI is a ligand-dependent positive cofactor on this promoter. TSH beta gene transcription was attenuated in MEDI mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSH beta gene promoter activity in a ligand-independent manner in cultured cells. MEDI also stimulated transcription from the TSH beta gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSH beta gene promoter. (C) 2013 Elsevier Inc. All rights reserved.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Oct. 2013, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 440(1) (1), 184 - 189, English
    [Refereed]
    Scientific journal

  • Ruri Ishino, Kaori Minami, Satowa Tanaka, Mami Nagai, Keiji Matsui, Natsumi Hasegawa, Robert G. Roeder, Shigetaka Asano, Mitsuhiro Ito
    FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MEDI subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1(+/+) MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1(-/-) MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1(+/+) and Med1(-/-) MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells. (C) 2013 Elsevier Inc. All rights reserved.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Oct. 2013, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 440(1) (1), 125 - 131, English
    [Refereed]
    Scientific journal

  • Ruri Ishino, Kaori Minami, Satowa Tanaka, Mami Nagai, Keiji Matsui, Natsumi Hasegawa, Robert G. Roeder, Shigetaka Asano, Mitsuhiro Ito
    FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MEDI subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1(+/+) MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1(-/-) MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1(+/+) and Med1(-/-) MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells. (C) 2013 Elsevier Inc. All rights reserved.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Oct. 2013, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 440(1) (1), 125 - 131, English
    [Refereed]
    Scientific journal

  • Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE: Contribution to the self-organized criticality theory
    Yumi Miyazaki, Ken Tsumiyama, Takashi Yamane, Mitsuhiro Ito, Shunichi Shiozawa
    We have developed a systems biology concept to explain the origin of systemic autoimmunity. From our studies of systemic lupus erythematosus (SLE) we have concluded that this disease is the inevitable consequence of over-stimulating the host's immune system by repeated exposure to antigen to levels that surpass a critical threshold, which we term the system's "self-organized criticality". We observed that overstimulation of CD4 T cells in mice led to the development of autoantibody-inducing CD4 T cells (aiCD4 T) capable of generating various autoantibodies and pathological lesions identical to those observed in SLE. We show here that this is accompanied by the significant expansion of a novel population of effector T cells characterized by expression of programmed death-1 (PD-1)-positive, CD27low, CD127low, CCR7low and CD44highCD62Llow markers, as well as increased production of IL-2 and IL-6. In addition, repeated immunization caused the expansion of CD8 T cells into fully-matured cytotoxic T lymphocytes (CTL) that express Ly6ChighCD122high effector and memory markers. Thus, overstimulation with antigen leads to the expansion of a novel effector CD4 T cell population that expresses an unusual memory marker, PD-1, and that may contribute to the pathogenesis of SLE.
    2013, Kobe Journal of Medical Sciences, 59(2) (2), E64 - E71, English
    [Refereed]
    Scientific journal

  • Natsumi Hasegawa, Akiko Sumitomo, Azusa Fujita, Nami Aritome, Shumpei Mizuta, Keiji Matsui, Ruri Ishino, Kana Inoue, Norinaga Urahama, Junko Nose, Toru Mukohara, Shingo Kamoshida, Robert G. Roeder, Mitsuhiro Ito
    The Mediator subunit MED1 is essential for mammary gland development and lactation, whose contribution through direct interaction with estrogen receptors (ERs) is restricted to involvement in pubertal mammary gland development and luminal cell differentiation. Here, we provide evidence that the MED24-containing submodule of Mediator functionally communicates specifically with MED1 in pubertal mammary gland development. Mammary glands from MED1/MED24 double heterozygous knockout mice showed profound retardation in ductal branching during puberty, while single haploinsufficient glands developed normally. DNA synthesis of both luminal and basal cells were impaired in double mutant mice, and the expression of ER-targeted genes encoding E2F1 and cyclin D1, which promote progression through the G(1)/S phase of the cell cycle, was attenuated. Luciferase reporter assays employing double mutant mouse embryonic fibroblasts showed selective impairment in ER functions. Various breast carcinoma cell lines expressed abundant amounts of MED1, MED24, and MED30, and attenuated expression of MED1 and MED24 in breast carcinoma cells led to attenuated DNA synthesis and growth. These results indicate functional communications between the MED1 subunit and the MED24-containing submodule that mediate estrogen receptor functions and growth of both normal mammary epithelial cells and breast carcinoma cells.
    AMER SOC MICROBIOLOGY, Apr. 2012, MOLECULAR AND CELLULAR BIOLOGY, 32(8) (8), 1483 - 1495, English
    [Refereed]
    Scientific journal

  • Significance of the neutrophil myeloperoxidase index in patients with atherosclerotic diseases
    Kenji Yonezawa, Natsumi Morimoto, Keiji Matsui, Takako Tenjin, Masako Yoneda, Takuo Emoto, Takahiro Sawada, Tetsuhiko Nomura, Hiroshi Okamoto, Akira Takarada, Hisataka Ikeda, Ito Mitsuhiro
    The pattern of changes in the neutrophil myeloperoxidase (MPO) levels in various atherosclerotic conditions was analyzed by assessing the mean myeloperoxidase index (MPXI), which is calculated during the routine complete blood count (CBC) performed using the flow-cytochemistry blood autoanalyzer ADVIA120/2120 (Siemens), and plasma MPO concentrations. MPXI values of ischemic heart disease (IHD) patients did not differ from those of healthy volunteers. However, MPXI values of IHD patients with arteriosclerosis obliterans (ASO) (-6.1 ± 1.8) were significantly lower than those of IHD patients without ASO (0.8 ± 0.5). In contrast, the MPO values in IHD patients with ASO were significantly elevated. In subjects without IHD, while the MPXI values in mild cases of ASO (Fontaine's stages I/II, 3.4 ± 0.8) were significantly higher than those of healthy volunteers (0.4 ± 0.4), the values of those with severe ASO (stages III/IV, 0.3 ± 0.8) were significantly lower than those of mild cases. However, when ASO patients developed IHD, the MPXI values dramatically decreased (stages I/II, -7.3 ± 1.9 stages III/IV, -5.2 ± 1.6). These results indicate that MPXI is elevated in mild, but not in severe, ASO cases, and that MPXI decreases dramatically when ASO patients develop IHD. MPXI may constitute an informative independent biomarker for diagnosis and follow-up of IHD complicated by ASO. © 2005 by Kobe Journal of Medical Sciences.
    2012, Kobe Journal of Medical Sciences, 58(5) (5), E128 - E137, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tamotsu Irino, Munehiro Uemura, Humitsugu Yamane, Shigeto Umemura, Takahiko Utsumi, Naoki Kakazu, Taku Shirakawa, Mitsuhiro Ito, Takayo Suzuki, Kazuo Kinoshita
    Myeloproliferative neoplasms (MPN) are multiple disease entities characterized by clonal expansion of one or more of the myeloid lineages (i.e. granulocytic, erythroid, megakaryocytic and mast cell). JAK2 mutations, such as the common V617F substitution and the less common exon 12 mutations, are frequently detected in such tumor cells and have been incorporated into the diagnostic criteria published by the World Health Organization since 2008. However, the mechanism by which these mutations contribute to MPN development is poorly understood. We examined gene expression profiles of MPN patients focusing on genes in the JAK-STAT signaling pathway using low-density real-time PCR arrays. We identified the following 2 upregulated genes in MPN patients: a known target of the JAK-STAT axis, SOCS3, and a potentially novel target, SPI1, encoding PU.1. Induction of PU. 1 expression by JAK2 V617F in JAK2-wildtype K562 cells and its downregulation by JAK2 siRNA transfection in JAK2 V617F-positive HEL cells supported this possibility. We also found that the ABL1 kinase inhibitor imatinib was very effective in suppressing PU. 1 expression in BCR-ABL1-positive K562 cells but not in HEL cells. This suggests that PU. 1 expression is regulated by both JAK2 and ABL1. The contribution of the two kinases in driving PU. 1 expression was dominant for JAK2 and ABL1 in HEL and K562 cells, respectively. Therefore, PU. 1 may be a common transcription factor upregulated in MPN. PU. 1 is a transcription factor required for myeloid differentiation and is implicated in erythroid leukemia. Therefore, expression of PU. 1 downstream of activated JAK2 may explain why JAK2 mutations are frequently observed in MPN patients.
    PUBLIC LIBRARY SCIENCE, Jul. 2011, PLOS ONE, 6(7) (7), e22148, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tamotsu Irino, Munehiro Uemura, Humitsugu Yamane, Shigeto Umemura, Takahiko Utsumi, Naoki Kakazu, Taku Shirakawa, Mitsuhiro Ito, Takayo Suzuki, Kazuo Kinoshita
    Myeloproliferative neoplasms (MPN) are multiple disease entities characterized by clonal expansion of one or more of the myeloid lineages (i.e. granulocytic, erythroid, megakaryocytic and mast cell). JAK2 mutations, such as the common V617F substitution and the less common exon 12 mutations, are frequently detected in such tumor cells and have been incorporated into the diagnostic criteria published by the World Health Organization since 2008. However, the mechanism by which these mutations contribute to MPN development is poorly understood. We examined gene expression profiles of MPN patients focusing on genes in the JAK-STAT signaling pathway using low-density real-time PCR arrays. We identified the following 2 upregulated genes in MPN patients: a known target of the JAK-STAT axis, SOCS3, and a potentially novel target, SPI1, encoding PU.1. Induction of PU. 1 expression by JAK2 V617F in JAK2-wildtype K562 cells and its downregulation by JAK2 siRNA transfection in JAK2 V617F-positive HEL cells supported this possibility. We also found that the ABL1 kinase inhibitor imatinib was very effective in suppressing PU. 1 expression in BCR-ABL1-positive K562 cells but not in HEL cells. This suggests that PU. 1 expression is regulated by both JAK2 and ABL1. The contribution of the two kinases in driving PU. 1 expression was dominant for JAK2 and ABL1 in HEL and K562 cells, respectively. Therefore, PU. 1 may be a common transcription factor upregulated in MPN. PU. 1 is a transcription factor required for myeloid differentiation and is implicated in erythroid leukemia. Therefore, expression of PU. 1 downstream of activated JAK2 may explain why JAK2 mutations are frequently observed in MPN patients.
    PUBLIC LIBRARY SCIENCE, Jul. 2011, PLOS ONE, 6(7) (7), English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • K. Yonezawa, O. Horie, A. Yoshioka, S. Matsuki, T. Tenjin, Y. Tsukamura, M. Yoneda, K. Shibata, Y. Koike, T. Nomura, M. Yokoyama, N. Urahama, M. Ito
    P>The mean myeloperoxidase index (MPXI) is calculated during the routine complete blood count performed using the autoanalyzer ADVIA120/2120. The pattern of changes in the neutrophil myeloperoxidase levels in patients with specific infectious diseases was analyzed by assessing the MPXI levels. In patients with bacterial sepsis, identified by positive blood-culture tests, with (n = 29) and without (n = 51) systemic inflammatory response syndrome, the mean MPXI significantly reduced to -3.18 and -2.06, respectively. In contrast, among patients with nontuberculous nonseptic bacterial infections (n = 40), the mean MPXI significantly elevated to 5.51, while tuberculosis patients (n = 37) and patients with viral infection (n = 60) showed an unchanged MPXI (mean values, -0.46 and -1.06, respectively). Among the parameters of inflammation, only the C-reactive protein values showed a weak correlation with the MPXI levels. [Conclusion] These results indicate that MPXI is correlated with some specific infectious states, i.e. MPXI is low in bacterial sepsis and high in nontuberculous nonseptic bacterial infections. MPXI appears to be an independent and useful biomarker for the diagnosis and follow-up of infectious diseases, especially when the MPXI values are obtained at regular intervals during the disease courses of the patients.
    WILEY-BLACKWELL, Dec. 2010, INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 32(6) (6), 598 - 605, English
    Scientific journal

  • Akiko Sumitomo, Ruri Ishino, Norinaga Urahama, Kana Inoue, Kenji Yonezawa, Natsumi Hasegawa, Osamu Horie, Hiroshi Matsuoka, Toru Kondo, Robert G. Roeder, Mitsuhiro Ito
    MED1/TRAP220, a subunit of the transcriptional Mediator/TRAP complex, is crucial for various biological events through its interaction with distinct activators, such as nuclear receptors and GATA family activators. In hematopoiesis, MED1 plays a pivotal role in optimal nuclear receptor-mediated myelomonopoiesis and GATA-1-induced erythropoiesis. In this study, we present evidence that MED1 in stromal cells is involved in supporting hematopoietic stem and/or progenitor cells (HSPCs) through osteopontin (OPN) expression. We found that the proliferation of bone marrow (BM) cells cocultured with MED1 knockout (Med1(-/-)) mouse embryonic fibroblasts (MEFs) was significantly suppressed compared to the control. Furthermore, the number of long-term culture-initiating cells (LTC-ICs) was attenuated for BM cells cocultured with Med1(-/-) MEFs. The vitamin D receptor (VDR)- and Runx2-mediated expression of OPN, as well as Mediator recruitment to the Opn promoter, was specifically attenuated in the Med1(-/-) MEFs. Addition of OPN to these MEFs restored the growth of cocultured BM cells and the number of LTC-ICs, both of which were attenuated by the addition of the anti-OPN antibody to Med1(+/+) MEFs and to BM stromal cells. Consequently, MED1 in niche appears to play an important role in supporting HSPCs by upregulating VDR- and Runx2-mediated transcription on the Opn promoter.
    AMER SOC MICROBIOLOGY, Oct. 2010, MOLECULAR AND CELLULAR BIOLOGY, 30(20) (20), 4818 - 4827, English
    Scientific journal

  • 造血幹細胞移植後患者の末梢血細胞傷害性因子の測定を用いたGVHDおよびGVL効果の出現予測の可能性
    Ito Mitsuhiro
    Sep. 2010, 臨床血液, 51巻, 9号, pp. 1095-1095, Japanese
    [Refereed]
    International conference proceedings

  • 造血幹細胞/前駆細胞の支持に間質細胞における転写メディエーターが関与する(Transcriptional Mediator in stromal cells is involved in hematopoietic stem/progenitor cell support)(英語)
    Ito Mitsuhiro
    Sep. 2010, 臨床血液, 51巻, 9号, pp. 910-910, Japanese
    [Refereed]
    International conference proceedings

  • Pingping Jiang, Qiuping Hu, Mitsuhiro Ito, Sara Meyer, Susan Waltz, Sohaib Khan, Robert G. Roeder, Xiaoting Zhang
    Mediator recently has emerged as a central player in the direct transduction of signals from transcription factors to the general transcriptional machinery. In the case of nuclear receptors, in vitro studies have shown that the transcriptional coactivator function of the Mediator involves direct ligand-dependent interactions of the MED1 subunit, through its two classical LxxLL motifs, with the receptor AF2 domain. However, despite the strong in vitro evidence, there currently is little information regarding in vivo functions of the LxxLL motifs either in MED1 or in other coactivators. Toward this end, we have generated MED1 LxxLL motif-mutant knockin mice. Interestingly, these mice are both viable and fertile and do not exhibit any apparent gross abnormalities. However, they do exhibit severe defects in pubertal mammary gland development. Consistent with this phenotype, as well as loss of the strong ligand-dependent estrogen receptor (ER)alpha-Mediator interaction, expression of a number of known ER alpha-regulated genes was down-regulated in MED1-mutant mammary epithelial cells and could no longer respond to estrogen stimulation. Related, estrogen-stimulated mammary duct growth in MED1-mutant mice was also greatly diminished. Finally, additional studies show that MED1 is differentially expressed in different types of mammary epithelial cells and that its LxxLL motifs play a role in mammary luminal epithelial cell differentiation and progenitor/stem cell determination. Our results establish a key nuclear receptor- and cell-specific in vivo role for MED1 LxxLL motifs, through Mediator-ER alpha interactions, in mammary gland development.
    NATL ACAD SCIENCES, Apr. 2010, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(15) (15), 6765 - 6770, English
    Scientific journal

  • Involvement of Transcriptional Mediator Subunit TRAP220/MED1 in Action of Niche Cells to Support Hematopoietic Stem/Progenitor Cells.
    Kana Inoue, Akiko Sumitomo, Natsumi Hasegawa, Ayuko Kasai, Kenji Yonezawa, Norinaga Urahama, Mitsuhiro Ito
    AMER SOC HEMATOLOGY, Nov. 2008, BLOOD, 112(11) (11), 1225 - 1225, English
    [Refereed]
    Research society

  • GATA-1-Specific Coactivator MEDI/TRAP220, Transcriptional Mediator Subunit, Mediates Erythroid Differentiation in K562 Erythroleukemia Cells
    Tomoya Minami, Osamu Horie, Kana Inoue, Sawako Toji, Norinaga Urahama, Mitsuhiro Ito
    AMER SOC HEMATOLOGY, Nov. 2008, BLOOD, 112(11) (11), 788 - 788, English
    [Refereed]
    Research society

  • Role of transcriptional coactivator MED1/TRAP220 in hemin-induced erythroid differentiation of K562 erythroleukemia cells.
    Minami T, Inoue K, Toji S, Kasai A, Urahama N, Horie O, Ito Mitsuhiro
    Oct. 2008, J HEMATOL TRANSF MED, 18(Sup.) (Sup.), 15, English
    [Refereed]
    Research society

  • Kai Ge, Young-Wook Cho, Hong Guo, Teresa B. Hong, Mohamed Guermah, Mitsuhiro Ito, Hong Yu, Markus Kalkum, Robert G. Roeder
    Mediator is a general coactivator complex connecting transcription activators and RNA polymerase II. Recent work has shown that the nuclear receptor-interacting MED1/TRAP220 subunit of Mediator is required for peroxisome pro] iferator-activated receptor gamma (PPAR gamma)-stimulated adipogenesis of mouse embryonic fibroblasts (MEFs). However, the molecular mechanisms remain undefined. Here, we show an intracellular PPAR gamma-Mediator interaction that requires the two LXXLL nuclear receptor recognition motifs on MED1/TRAP220 and, furthermore, we show that the intact LXXLL motifs are essential for optimal PPAR gamma function in a reconstituted cell-free transcription system. Surprisingly, a conserved N-terminal region of MED1/TRAP220 that lacks the LXXLL motifs but gets incorporated into Mediator fully supports PPAR gamma-stimulated adipogenesis. Moreover, in undifferentiated MEFs, MED1/TRAP220 is dispensable both for PPAR gamma-mediated target gene activation and for recruitment of Mediator to a PPAR response element on the aP2 target gene promoter. However, PPAR gamma shows significantly reduced transcriptional activity in cells deficient for a subunit (MED24/ TRAP100) important for the integrity of the Mediator complex, indicating a general Mediator requirement for PPAR gamma function. These results indicate that there is a conditional requirement for MED1/TRAP220 and that a direct interaction between PPAR gamma and Mediator through MED1/TRAP220 is not essential either for PPAR gamma-stimulated adipogenesis or for PPAR gamma target gene expression in cultured fibroblasts. As Mediator is apparently essential for PPAR gamma transcriptional activity, our data indicate the presence of alternative mechanisms for Mediator recruitment, possibly through intermediate cofactors or other cofactors that are functionally redundant with MED1/TRAP220.
    AMER SOC MICROBIOLOGY, Feb. 2008, MOLECULAR AND CELLULAR BIOLOGY, 28(3) (3), 1081 - 1091, English
    Scientific journal

  • Role of transcriptional coactivator MED1/TRAP220 in hematopoietic niche
    Inoue K, Sumitomo A, Iwasaki C, Hasegawa N, Yonezawa K, Horie O, Urahama N, Ito Mitsuhiro
    2008, J HEMATOL TRANSF MED, 18, 12, English
    [Refereed]
    Research society

  • Kentaro Minagawa, Katsuya Yamamoto, Shinichiro Nishikawa, Mitsuhiro Ito, Akiko Sada, Kimikazu Yakushijin, Atsuo Okamura, Manabu Shimoyama, Yoshio Katayama, Toshimitsu Matsui
    BLACKWELL PUBLISHING, Oct. 2007, BRITISH JOURNAL OF HAEMATOLOGY, 139(1) (1), 161 - 163, English
    Scientific journal

  • 基本的転写共役因子MED1/TRAP220による造血前駆細胞の支持
    Ito Mitsuhiro
    Sep. 2007, 臨床血液, 48巻, 9号, pp. 996-996, Japanese
    [Refereed]
    International conference proceedings

  • Expression of proteinase inhibitor 9 (PI-9) and cytotoxic molecule granzyme B in leukocytes after allogeneic hernatopoietic stem cell transplantation
    Osamu Horie, Tohru Murayama, Katsuyasu Saigo, Kana Inoue, Ryukichi Ryo, Mitsuhiro Ito
    BLACKWELL PUBLISHING, Jun. 2007, INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 29, 106 - 107, English
    [Refereed]
    International conference proceedings

  • 同種造血幹細胞移植後患者のgranzyme B,perforinおよびPI-9のmRNA量測定の意義
    Ito Mitsuhiro
    Apr. 2007, 医学検査, 56巻, 4号, pp. 656-656, Japanese
    [Refereed]
    International conference proceedings

  • A kinase subunit of the human mediator complex, CDK8, positively regulates transcriptional activation.
    Tadashi Furumoto, Aki Tanaka, Mitsuhiro Ito, Sohail Malik, Yutaka Hirose, Fumio Hanaoka, Yoshiaki Ohkuma
    The human thyroid hormone receptor-associated proteins (TRAP)/Mediator and related complexes mediate transcription through regulatory factors. To further understand the structural and functional diversity of these complexes we established three HeLa cell lines each expressing one of three epitope-tagged human TRAP/Mediator subunits, MED6, MED7, and CDK8 and isolated the complexes in which these subunits were contained by affinity and HPLC-gel filtration chromatography. The largest complexes from each cell line had a molecular mass of 1.5 MDa and possessed almost identical subunit compositions; we designated these complexes TRAP/Mediator-like complex 1 (TMLC1). Two potential subcomplexes were additionally observed: a 1-MDa complex from the CDK8-cell line (TMLC2) and a 600-kDa complex from the MED6-cell line (TMLC3). All three complexes regulated transcription in vitro; TMLC1 and TMLC3 augmented transcriptional activation, whereas TMLC2 repressed it. TMLC1 and TMLC2 phosphorylated RNA polymerase II (Pol II), but TMLC3 did not. Furthermore, TMLC1 predominantly interacted with the general transcription factors TFIIE, TFIIF, and TFIIH, which function during transcription initiation and the transition to elongation. In a final experiment, knockdown of CDK8 using RNA interference prevented transcriptional activation by Gal4-VP16 in a luciferase-assay. This, together with the effect of TMLC1 on transcription in vitro, suggests that CDK8 play positive roles in transcriptional activation.
    Jan. 2007, Genes to cells : devoted to molecular & cellular mechanisms, 12(1) (1), 119 - 32, English, International magazine
    [Refereed]
    Scientific journal

  • The role of proteinase inhibitor 9 (PI-9) in granzyme B/perforin-mediated cytotoxicity induced by cytotoxic T cells in allogeneic hematopoietic stem cell transfusion.
    Osamu Horie, Tohru Murayama, Katsuyasu Saigo, Yasushi Utsunomiya, Ryukichi Ryo, Mitsuhiro Ito
    AMER SOC HEMATOLOGY, Nov. 2006, BLOOD, 108(11) (11), 808A - 808A, English
    [Refereed]
    International conference proceedings

  • HIV-I TatコアクチベーターTIP30はリンパ球の異常増殖を抑制する
    ITO MITSUHIRO
    Sep. 2006, 日本癌学会65回総会記事, pp. 167-168, Japanese
    [Refereed]
    International conference proceedings

  • HIV-I TatコアクチベーターTIP30はc-mycの発現とリンパ球の異常増殖を抑制する
    ITO MITSUHIRO, HORIE OSAMU
    Sep. 2006, 臨床血液, 47巻, 9号, pp. 1081-1081, Japanese
    [Refereed]
    International conference proceedings

  • N Urahama, M Ito, A Sada, K Yakushijin, K Yamamoto, A Okamura, K Minagawa, A Hato, K Chihara, RG Roeder, T Matsui
    The TRAP220 subunit of the thyroid hormone receptor-associated polypeptide transcription coactivator complex (TRAP/Mediator complex), mammalian counterpart of the yeast Mediator complex, is proposed to act on a variety of major and specific biological events through physical interactions with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. In this study, we present the functional role of TRAP220 in nuclear receptor-mediated monopoiesis and granulopoiesis. The mouse Trap220(-/-) yolk sac hematopoietic progenitor cells were resistant to 1,25-dihydroxyvitamin D-3-stimulated differentiation into monocytes/macrophages. Furthermore, flow cytometric analyses showed that HL-60 cells, human promyelocytic leukemia cell line, wherein TRAP220 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25-dihydroxyvitamin D-3 and all-trans retinoic acid, correspondingly. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells. These results indicated a crucial role of TRAP220 in the optimal VDR- and RAR-mediated myelomonocytic differentiation processes in mammalian hematopoiesis.
    BLACKWELL PUBLISHING, Dec. 2005, GENES TO CELLS, 10(12) (12), 1127 - 1137, English
    Scientific journal

  • K Yamamoto, M Ito, K Minagawa, N Urahama, A Sada, A Okamura, T Matsui
    Deletions or translocations of chromosome band 13q14, the locus of the retinoblastoma gene (RB1), have been observed in a variety of hematological malignancies including myelodysplastic syndrome (MDS). We describe here a novel unbalanced translocation der(13)t(7;13)(p13;q14) involving 13q14 in a patient with MDS. A 66-year-old woman was diagnosed as having NIDS, refractory anemia with excess of blasts (RAEB-1) because of 7.4% blasts and trilineage dysplasia in the bone marrow cells. G-banding and spectral karyotyping analyses showed complex karyotypes as follows: 46,XX,der(6)t(6;7)(q11;?),der(7)de](7)(?p13)t(6;7)(q?;q11)t(6;I3)(q?;q?),der(13)t(7;13)(pl3;q14). Fluorescence in situ hybridization (FISH) analyses demonstrated that one allele of the RB I gene and the microsatellite locus D13S319, located at 13q14 and telomeric to the RB1 gene, was deleted. Considering other reported cases, our results indicate that submicroscopic deletions accompanying 13q 14 translocations are recurrent cytogenetic aberrations in NIDS. The RB1 gene or another tumor suppressor gene in the vicinity of D13S319, or both, may be involved in the pathogenesis of NIDS with 13q14 translocations by monoallelic deletion. (c) 2005 Elsevier Inc. All rights reserved.
    ELSEVIER SCIENCE INC, Oct. 2005, CANCER GENETICS AND CYTOGENETICS, 162(2) (2), 160 - 165, English
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 初診時に巨大縦隔腫瘤を合併した急性前骨髄球性白血病の一例
    ITO MITSUHIRO
    Sep. 2005, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集67回47回, pp. 950-950, Japanese
    [Refereed]
    International conference proceedings

  • 骨髄球系前駆細胞の分化における転写共役因子TRAP220の役割
    ITO MITSUHIRO
    Sep. 2005, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集67回47回, pp. 819-819, Japanese
    [Refereed]
    International conference proceedings

  • 基本的転写共役因子TRAP220による骨髄系細胞の分化調節
    ITO, Mitsuhiro, MATSUI, Toshimitsu, CHIHARA, Kazuo
    Sep. 2005, 日本癌学会64回総会記事, pp.64-65, Japanese
    International conference proceedings

  • ケイシンキナーゼIεによる造血細胞の細胞生存調節機構
    ITO MITSUHIRO
    Sep. 2005, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集67回47回, pp. 792-792, Japanese
    [Refereed]
    International conference proceedings

  • ephrin B1,B2はT細胞レセプター(TCR)シグナル伝達の強力な負の制御因子である
    薬師神公和, 横山和明, 西川真一郎, 定明子, 波戸章郎, 皆川健太郎, 浦浜憲永, 岡村篤夫, 山本克也, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Sep. 2005, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集 67回47回, pp.881-881, Japanese
    International conference proceedings

  • auto-PBSCT後に発症したinv(16), I型CBFβ/MYH11陽性t-MDS:移植前幹細胞中にCBFβ/MYH11は検出されない
    ITO MITSUHIRO
    Sep. 2005, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集67回47回, pp. 950-950, Japanese
    [Refereed]
    International conference proceedings

  • Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation
    Kimikazu Yakushijin, Toshimitsu Matsui, Atsuo Okamura, Katsuya Yamamoto, Mitsuhiro Ito, Kazuo Chihara
    Sinusoidal obstruction syndrome (SOS) (formerly known as hepatic veno-occlusive disease (VOD)) is a life-threatening complication subsequent to hematopoietic stem cell transplantation. However, no completely satisfactory strategies for the treatment of SOS have been established yet. Defibrotide is a single-stranded polydeoxyribonucleotide with anti-thrombotic, anti-ischemic, anti-inflammatory and thrombolytic properties, but without systemic anticoagulant effects, and some encouraging results have been reported in western countries. We treated four patients with defibrotide for SOS, since there seemed to be no possibility to cure the patients with conventionally available treatments in Japan. All patients showed evidence of multiple organ failure at the start of the treatment. Defibrotide was administered intravenously in normal saline in four divided doses for 14 to 27 days. Three patients (75%) responded to the therapy, while one died of SOS and cytomegalovirus infection despite intensive therapy. None of the patients suffered from significant adverse effects such as severe hemorrhage. This is the first report dealing with the treatment with defibrotide of Japanese patients with SOS. Because defibrotide is considered to be promising for the treatment of SOS, it is important to start a phase II study as soon as possible.
    2005, Kobe Journal of Medical Sciences, 51(4) (4), 55 - 65, English
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • K Yamamoto, A Hato, K Minagawa, K Yakushijin, N Urahama, A Sada, A Okamura, M Ito, T Matsui
    ELSEVIER SCIENCE INC, Dec. 2004, CANCER GENETICS AND CYTOGENETICS, 155(2) (2), 154 - 155, English
    [Refereed]
    Scientific journal

  • K Yamamoto, A Hato, K Minagawa, K Yakushijin, N Urahama, H Gomyo, A Sada, A Okamura, M Ito, T Matsui
    Cytogenetic abnormalities are observed in approximately one half of cases of myelodysplastic syndrome (MDS). Partial or complete chromosome losses and chromosome gains are frequently found, but there is a relatively high incidence of unbalanced translocations in MDS. We describe here two cases of MDS with an unbalanced translocation, der(11)t(11;12)(q23;q13). Both patients were 69 years of age and diagnosed with refractory anemia with excess of blasts in transformation (RAEB-t) according to the high percentage of blasts in the peripheral blood. Cytoplasmic hypogranulation of neutrophils was evident as a dysplastic change. The blasts were positive for CD4 and CD41a as well as CD 13, CD33, CD34 and HLA-DR in both cases. Chromosome analysis showed complex karyotypes including a der(11)t(1;11)(q11;p15)t(11;12)(q23;q13) in case 1 and der(11)t(11;12)(q23;q13) in case 2 plus several marker chromosomes. Spectral karyotyping confirmed the der(11)t(11; 12)(q23;q13) and clarified the origin of marker chromosomes, resulting in del(5q) and del(7q). Fluorescence in situ hybridization (FISH) analyses with a probe for the MLL gene demonstrated that the breakpoints at 11q23 were telomeric to the MLL gene in both cases. FISH also showed that the breakpoint at 11p15 of the case 1 was telomeric to the NUP98 gene. Considering another reported case, our results indicate that the der(11)t(11;12)(q23;q13) is a recurrent cytogenetic abnormality and may be involved in the pathogenesis of advanced-stage MDS. (C) 2004 Elsevier Inc. All rights reserved.
    ELSEVIER SCIENCE INC, Nov. 2004, CANCER GENETICS AND CYTOGENETICS, 155(1) (1), 67 - 73, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 基本的転写共役因子TRAP/Mediator複合体による造血調節機構
    浦浜憲永, ITO, Mitsuhiro, 岡村篤夫, 薬師神公和, 皆川健太郎, 定明子, 波戸章郎, 山本克也, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Sep. 2004, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集66回46回, pp. 874-874, Japanese
    International conference proceedings

  • リンパ腫診断におけるFDG-PETの有用性と問題点:当院での83例の後視的解析
    波戸章郎, 山本克也, 皆川健太郎, 浦浜憲永, 薬師神公和, 定明子, 岡村篤夫, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Sep. 2004, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集66回46回, pp. 742-742, Japanese
    International conference proceedings

  • AML寛解導入療法中Clostridium perfingens敗血症による溶血性貧血を発症し,早期治療にて救命し得た一例
    定明子, 山本克也, 波戸章郎, 皆川健太郎, 薬師神公和, 浦浜憲永, 岡村篤夫, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Sep. 2004, 日本血液学会・日本臨床血液学会回総会プログラム・抄録集66回46回, pp. 930-930, Japanese
    International conference proceedings

  • C Jiang, M Ito, Piening, V, K Bruck, RG Roeder, H Xiao
    Deregulation of c-myc expression is implicated in the pathogenesis of many neoplasias. Estrogen receptor alpha (ERalpha) can increase the rate of c-myc transcription through the recruitment of a variety of cofactors to the promoter, yet the precise roles of these cofactors in transcription and tumorigenesis are largely unknown. We show here that a putative tumor suppressor TIP30, also called CC3 or Htatip2, interacts with an ERalpha-interacting coactivator CIA. Using chromatin immunoprecipitation assays, we demonstrate that TIP30 and CIA are distinct cofactors that are dynamically associated with the promoter and downstream regions of the c-myc gene in response to estrogen. Both TIP30 and CIA are recruited to the c-myc gene promoter by liganded ERalpha in the second transcription cycle. TIP30 overexpression represses ERalpha-mediated c-myc transcription, whereas TIP30 deficiency enhances c-myc transcription in both the absence and presence of estrogen. Ectopic CIA cooperates with TIP30 to repress ERalpha-mediated c-myc transcription. Moreover, virgin TIP30 knockout mice exhibit increased c-myc expression in mammary glands. Together, these results reveal an important role for TIP30 in the regulation of ERalpha-mediated c-myc transcription and suggest a mechanism for tumorigenesis promoted by TIP30 deficiency.
    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, Jun. 2004, JOURNAL OF BIOLOGICAL CHEMISTRY, 279(26) (26), 27781 - 27789, English
    [Refereed]
    Scientific journal

  • Involvement of casein kinase I epsilon in cytokine-induced granulocytic differentiation
    A Okamura, N Iwata, A Nagata, A Tamekane, M Shimoyama, H Gomyo, K Yakushijin, N Urahama, M Hamaguchi, C Fukui, K Chihara, M Ito, T Matsui
    Two closely related casein kinase I (CKI) isoforms, CKIdelta and CKIepsilon, are ubiquitously expressed in many human tissues, but their specific biologic function remains to be clarified. Here, we provide the first evidence that CKIepsilon is involved in hematopoietic cell differentiation. CKIepsilon, but not CKIdelta, was down-regulated along with human granulocytic differentiation. The specific down-regulation was observed in granulocyte colony-stimulating factor (G-CSF)-induced cell differentiation of murine interleukin-3 (IL-3)dependent myeloid progenitor 32D cells. Introduction of wild-type (WT)-CKIepsilon into 32D cells inhibited the G-CSF-induced cell differentiation, whereas kinase-negative (KN)-CKIepsilon promoted the differentiation. Neither WT- nor KN-CKIepsilon affected IL-3-dependent cell growth. Moreover, introduction of WT- or KN-CKIdelta did not affect the cytokine-induced cell growth and differentiation. While G-CSF-induced activation of signal transducers and activators of transcription 3 (STAT3) was sustained by KN-CKIepsilon, STAT3 activation was attenuated by WT-CKIepsilon. This may be explained by the fact that the suppressor of cytokine signaling 3 (SOCS3) was stabilized by its physical association with CKIepsilon. Such stabilization by CKIepsilon was also seen in IL-3-induced beta-catenin. The stabilization of downstream components of cytokine and Writ signaling by CKIepsilon might be critical for integration of several intracellular signaling pathways to a cell-specific biologic response in hematopoietic cell self-renewal. (C) 2004 by The American Society of Hematology.
    AMER SOC HEMATOLOGY, Apr. 2004, BLOOD, 103(8) (8), 2997 - 3004, English
    [Refereed]
    Scientific journal

  • 核内情報受容から遺伝子発現への機構-病態とその治療の分子レベルでのアプローチ TRAP/Mediator複合体の核内受容体情報伝達における生理的役割
    ITO, Mitsuhiro, 浦浜憲永, MATSUI, Toshimitsu, CHIHARA, Kazuo
    Mar. 2004, 日本薬学会124年会講演要旨集, 1号, pp. 152-152, Japanese
    International conference proceedings

  • Development and sex differences in social communication from primary school to adolescence: Formulation of an advanced test of theory of mind, Japanese version
    ITO, Mitsuhiro, TAKADA, Satoshi
    Mar. 2004, Bulletin Of Health Sciences Kobe, Vol. 19, No. , pp. 63-79, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • TIP30 deficiency increases susceptibility to tumorigenesis
    M Ito, C Jiang, K Krumm, Zhang, X, J Pecha, Zhao, X, YJ Guo, RG Roeder, H Xiao
    TIP30, also called CC3 or Htatip2, is a putative metastasis suppressor that promotes apoptosis and inhibits angiogenesis. Although TIP30 has several characteristic features of a tumor suppressor in in vitro analyses, tumor development as a result of TIP30 inactivation has not been demonstrated in vivo, and abnormal expression of TIP30 in human cancer has not been reported. Using genetically engineered mice and cells deficient in TIP30, we show that TIP30-deficient mice have a high incidence of hepatocellular carcinoma and other tumors, and loss of TIP30 enhances susceptibility of fibroblasts to transformation by the SV40 large T antigen. Furthermore, immunohistochemical analysis. indicates that reduced TIP30 expression is associated with 33% of human hepatocellular carcinomas. Some of these carcinomas harbor missense mutations in the Tip30 gene, which cause abnormal expression of TIP30. Together, these results demonstrate that the Tip30 gene is a tumor susceptibility gene playing an important role in the suppression of hepatocarcinogenesis.
    AMER ASSOC CANCER RESEARCH, Dec. 2003, CANCER RESEARCH, 63(24) (24), 8763 - 8767, English
    [Refereed]
    Scientific journal

  • Morphologic, flow cytometric and cytogenetic evaluation of bone marrow involvement in B-cell lymphoma
    H Gomyo, M Shimoyama, K Minagawa, K Yakushijin, N Urahama, A Okamura, K Yamamoto, M Ito, K Chihara, Y Hayashi, T Matsui
    Background and Objectives. Flow cytometric immunophenotypic analysis (FC) and cytogenetic analysis are essential techniques for the diagnosis and classification of many hematologic disorders. The roles of these analyses in B-cell lymphoma to detect bone marrow (BM) involvement in clinical staging and to evaluate the effectiveness of treatments have not yet been determined. The aim of this study was to evaluate the usefulness of FC and cytogenetic analysis in the assessment of BM involvement in B-cell lymphoma. Design and Methods. We retrospectively analyzed the usefulness of three-color FC and cytogenetic analysis in detecting BM involvement by examing 104 BM specimens from patients with B-cell lymphoma. Results. By morphologic evaluation of BM biopsy (BMB), the BM was involved in 11 specimens (10.6%), not involved in 92 specimens (88.5%) and involvement could not be determined in 1 specimen (0.9%). FC identified a monoclonal B-cell population in 24 samples (23.1%). FC detected BM involvement in all but one BMB positive sample, and showed negative results in a BMB undetermined sample. Conclusively, FC found a monoclonal B-cell population in 14 of 92 BMB negative samples (15.2%). In particular, FC detected smaller amounts of BM involvement than did morphologic evaluation. Cytogenetic analysis revealed clonal abnormalities in only 9 of 104 samples (8.7%). However, 2 of these 9 samples were from patients with aggressive lymphoma with complex structural chromosomal abnormalities detectable only by cytogenetic analysis. Interpretation and Conclusions. Although morphologic evaluation of adequate amounts of BMB specimens remains essential for the evaluation of BM involvement, three-color FC is more sensitive in detecting BM disease than morphologic or cytogenetic analysis. Cytogenetic analysis seems to have low sensitivity and specificity, but this method may improve the detection of BM involvement in a small number of aggressive lymphomas that have many mitotic cells.
    FERRATA STORTI FOUNDATION, Dec. 2003, HAEMATOLOGICA, 88(12) (12), 1358 - 1365, English
    [Refereed]
    Scientific journal

  • Hiroshi Gomyo, Manabu Shimoyama, Kentaro Minagawa, Kimikazu Yakushijin, Norinaga Urahama, Atsuo Okamura, Katsuya Yamamoto, Mitsuhiro Ito, Kazuo Chihara, Toshimitsu Matsui
    A rheumatoid arthritis (RA) patient treated with low-dose methotrexate (MTX) therapy suffered from hemophagocytic syndrome (HPS) associated with B-cell lymphoma (B-LAHS). Administration of acyclovir and intravenous immunoglobulin promptly resolved laboratory test abnormalities accompanied with HPS. Moreover, hemophagocytic histiocytes and lymphoma cells in the bone marrow disappeared without anti-cancer therapy. Two months after reintroduction of MTX for RA flare, lymphoma re-grew rapidly without bone marrow involvement and HPS. Two cycles of combination chemotherapy induced the lymphoma to a complete remission/unconfirmed (CRu), but then the chemotherapy was discontinued due to severe side effects. In this case, on the basis of RA and MTX induced immunosuppressive state, Epstein-Barr virus (EBV) infection was associated with the development of HPS and lymphoma. Anti-viral therapy alone was effective against HPS and lymphoma at initial presentation and improved her general condition. This case indicates that anti-cancer therapy should be preceded by anti-viral therapy and withdrawal of immunosuppressive therapy in patients under immunosuppressive therapy, as long as the clinical situation permits.
    Oct. 2003, Leukemia and Lymphoma, 44(10) (10), 1807 - 1810, English
    [Refereed]
    Scientific journal

  • 瀰漫性リンパ腫への移行時に新たな転座t(2;6)(p12;q23)が出現したt(18;22)(q21;q11)陽性濾胞性リンパ腫
    山本克也, 岡村篤夫, 皆川健太郎, 薬師神公和, 浦浜憲永, 五明広志, SHIMOYAMA, Manabu, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Aug. 2003, 臨床血液, 44巻, 8号, pp. 853-853, Japanese
    International conference proceedings

  • 骨髄生検,フローサイトメトリー,染色体検査によるB細胞リンパ腫の骨髄浸潤の評価
    五明広志, SHIMOYAMA, Manabu, 皆川健太郎, 浦浜憲永, 薬師神公和, 岡村篤夫, 山本克也, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Aug. 2003, 臨床血液, 44巻, 8号, pp. 854-854, Japanese
    International conference proceedings

  • 胸腺形成及びT細胞活性化におけるEphB6の役割 EphB6欠損マウスを用いた解析
    SHIMOYAMA,Manabu, 薬師神公和, 五明広志, 皆川健太郎, 浦浜憲永, 岡村篤夫, 山本克也, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Aug. 2003, 臨床血液, 44巻, 8号, pp. 724-724, Japanese
    International conference proceedings

  • Development and sex differences in understanding simile, sarcasm, and persuasion; Formulation of an advanced test of theory of mind,Japanese version
    ITO, Mitsuhiro, TAKADA, Satoshi, Kneko T
    Aug. 2003, Proceedings of 16th Asian Conference on Mental Retardation, Vol. 16, No. , pp. 344-352, English
    [Refereed]
    Scientific journal

  • Auto-PBSCT後に発症したt-MDSにnon-TBIレジメンでの臍帯血移植が奏効した1成人例
    皆川健太郎, 山本克也, 浦浜憲永, 薬師神公和, 五明広志, 岡村篤夫, SHIMOYAMA, Manabu, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    Aug. 2003, 臨床血液, 44巻, 8号, pp. 871-871, Japanese
    International conference proceedings

  • M Shimoyama, H Matsuoka, A Nagata, N Iwata, A Tamekane, A Okamura, H Gomyo, M Ito, K Jishage, N Kamada, H Suzuki, TT Noda, T Matsui
    A member of the largest family of receptor protein kinases, EphB6, lacks its intrinsic kinase activity, but it is expressed in normal human tissues. To investigate the physiological function of EphB6, we generated EphB6 deficient mice. EphB6(-/-) mice developed normally, revealed no abnormality in general appearance, and were fertile. Although a developmental increase of EphB6 in the fetal thymus was confirmed, T-cell development in various lymphoid organs of EphB6(-/-) mice was comparable to those of EphB6(+/+). Even in fetal thymus organ cultures, any developmental differences of EphB6(-/-) and EphB6(+/+) thymocytes were undetectable. The different binding characteristics to ephrin-Fc proteins between EphB6(-/-) and EphB6(+/+) thymocytes demonstrated that ephrin-B2 is the unique ligand for EphB6 among eight known ephrins. While EphB6 was a dominant receptor that binds to ephrin-B2 in adult thymocytes, fetal ones also expressed another EphB that binds to ephrin-B2. Overlapping expression of the EphB subfamily in the fetal thymus might compensate for the loss of EphB6 during the thymic development.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Oct. 2002, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 298(1) (1), 87 - 94, English
    [Refereed]
    Scientific journal

  • Hiroshi Matsuoka, Nobuko Iwata, Mitsuhiro Ito, Manabu Shimoyama, Aki Nagata, Kazuo Chihara, Setsuo Takai, Toshimitsu Matsui
    We have identified a human Eph-family protein, HEP, gene located in human chromosomal region 7q33→q35. The deduced amino acid sequence shared primary structural properties of Eph-family receptor tyrosine kinases. However, six invariant amino acids such as a lysine in the ATP-binding site and an aspartic acid in the phosphotransfer site of a conserved catalytic domain were substituted with other amino acid residues in HEP. Thus, no intrinsic tyrosine kinase activity was detectable in the catalytic domain expressed in CHO-K1 cell transfectants. Although most kinase-defective mutants of growth factor receptors have been reported as pathogenic receptors, its transcript was abundantly expressed in normal human adult tissues. A 135-kDa HEP protein was expressed in the human brain as much as in CHO-K1 cells transfected with a HEP cDNA expression vector. HEP is the first description of a kinase-defective Eph-family protein expressed abundantly in normal human tissues.
    Academic Press Inc., Jun. 1997, Biochemical and Biophysical Research Communications, 235(3) (3), 487 - 492, English
    Scientific journal

  • Ito Mitsuhiro, Matsui Toshimitsu, Taniguchi Taizo, Chihara Kazuo
    We screened Drosophila melanogaster genomic and cDNA libraries by low-stringency hybridization with a probe representing the protein tyrosine kinase (TyK) domain encoded by a human α-platelet-derived growth factor receptorencoding cDNA. The complete sequences of the open reading frames and 3′-untranslated regions (UTR) of some crosshybridizing clones were identical to the recently published sequence of DFR1, encoding the novel D. melanogaster fibroblast growth factor receptor homolog. However, two species of DFR1 cDNAs were isolated that differed with respect to their 5′-UTR. Analysis of the genomic organization revealed that DFR1 is composed of three exons. The entire coding region is contained within the third exon. S1 mapping and RNase-protection assays demonstrated that two distinct DFR1 transcripts possessing either the first or the second exon in combination with the third exon are generated by alternative splicing. This suggests that the transcriptional, as well as posttranscriptional, regulation of fibroblast growth factor receptor (FGFR)-encoding genes during D. melanogaster development is likely to be complex. © 1994.
    Feb. 1994, Gene, 139(2) (2), 215 - 218, English
    [Refereed]
    Scientific journal

■ MISC
  • 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

  • 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

  • 急性前骨髄球性白血病とその他の急性骨髄性白血病の鑑別診断におけるmyeloperoxidase indexの有用性
    米澤賢二, 大本知佳, 水田あずさ, 天神貴子, 八木智恵, 升村京子, 足立綾, 三村喜彦, 富永亮, 五明広志, 前田彰男, 水野石一, 村山徹, Ito Mitsuhiro
    Sep. 2015, 臨床血液, 56(9号) (9号), 1693, Japanese
    [Refereed]
    Meeting report

  • 再生医学と基礎研究―Festina lente!―
    Ito Mitsuhiro
    2015, オベリスク, 20, 5 - 12, Japanese
    Introduction scientific journal

  • 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
    AMER SOC HEMATOLOGY, Dec. 2014, BLOOD, 124(21) (21), English
    Summary international conference

  • Yumi Miyazaki, Ken Tsumiyama, Takashi Yamane, Mitsuhiro Ito, Shunichi Shiozawa
    FRONTIERS RESEARCH FOUNDATION, 2013, FRONTIERS IN IMMUNOLOGY, 4(87) (87), English
    [Refereed]
    Others

  • The Role of Proteinase Inhibitor 9 (PI-9) and Granzyme B in Peripheral Leukocytes for GVL and GVHD After Allogeneic Hematopoietic Stem Cell Transplantation
    Osamu Horie, Kaori Minami, Sawako Toji, Kenji Yonezawa, Hiroshi Gomyo, Akio Maeda, Ishikazu Mizuno, Tohru Murayama, Mitsuhiro Ito
    AMER SOC HEMATOLOGY, Nov. 2011, BLOOD, 118(21) (21), 866 - 866, English
    Summary international conference

  • 骨髄増殖性腫瘍患者末梢血におけるJAK2V617変異依存的なPU.1発現上昇(JAK2 V617F-dependent upregulation of PU.1 expression in the Deripheral blood of mveloproliferative neoplasm patients)(英語)
    Shirakawa Taku, Ito Mitsuhiro
    (一社)日本癌学会, Sep. 2011, 日本癌学会総会記事, 70回(70回) (70回), 462 - 462, Japanese
    [Refereed]
    Meeting report

  • 転写メディエーターサブユニットMED1のPPARγ結合能を廃絶したマウスでインスリン抵抗性が改善する
    Ito Mitsuhiro
    Dec. 2010, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集83回・33回, 2P - 0530, Japanese
    [Refereed]
    Meeting report

  • 赤白血病細胞K562のGATA1誘導性赤芽球分化におけるMED1/TRAP220の役割
    Ito Mitsuhiro
    Dec. 2010, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集83回・33回, 1P - 0688, Japanese
    [Refereed]
    Meeting report

  • 間質細胞のメディエーターサブユニットMED1/TRAP220はオステオポンチン発現を介する造血幹細胞/前駆細胞の支持に関与する(Mediator subunit MED1/TRAP220 in stromal cells is involved in hematopoietic stem/progenitor cell support through osteopontin expression)(英語)
    Horie Osamu, Matsuoka Hiroshi, Ito Mitsuhiro
    Dec. 2010, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集83回・33回, 1P - 0662, Japanese
    [Refereed]
    Meeting report

  • MediatorのサブユニットMED1とMED24はエストロゲン受容体機能と乳腺の発達に協調的に寄与する
    Ito Mitsuhiro
    Dec. 2010, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集83回・33回, 2P - 0531, Japanese
    [Refereed]
    Meeting report

  • The role of transcriptional coactivator TRAP220/MED1 in nuclear receptor-mediated myelomonocytic differentiation.
    M Ito, N Urahama, A Sada, K Yakushijin, K Yamamoto, A Okamura, K Minagawa, A Hato, K Chihara, RG Roeder, T Matsui
    AMER SOC HEMATOLOGY, Nov. 2005, BLOOD, 106(11) (11), 765A - 765A, English
    Summary international conference

  • Casein kinase I epsilon downregulates PI3K/Akt signaling, followed by genotoxic stress-induced apoptosis of hematopoietic cells.
    A Okamura, K Yamamoto, K Yakushijin, N Urahama, K Minagawa, A Sada, A Hato, S Nishikawa, K Yokoyama, M Ito, T Matsui
    AMER SOC HEMATOLOGY, Nov. 2004, BLOOD, 104(11) (11), 360A - 360A, English
    Summary international conference

  • Morphologic, flow cytometric and cytogenetic evaluation of bone marrow involvement in B-cell lymphoma.
    H Gomyo, M Shimoyama, A Hato, K Minagawa, K Yakushijin, N Urahama, A Sada, A Okamura, K Yamamoto, M Ito, K Chihara, Y Hayashi, T Matsui
    AMER SOC HEMATOLOGY, Nov. 2003, BLOOD, 102(11) (11), 263B - 263B, English
    Summary international conference

  • Stabilization of SOCS3 and beta-catenin by casein kinase I epsilon to regulate hematopoietic cell differentiation.
    A Okamura, M Shimoyama, H Gomyo, K Yakushijin, N Urahama, K Minagawa, A Sada, A Hato, K Yamamoto, M Ito, T Matsui
    AMER SOC HEMATOLOGY, Nov. 2003, BLOOD, 102(11) (11), 837A - 837A, English
    Summary international conference

  • 【甲状腺疾患研究の最前線 基礎研究から治療への応用】 転写共役因子異常と甲状腺機能
    ITO, Mitsuhiro, CHIHARA, Kazuo
    最新医学社, Jul. 2003, 最新医学, 58巻, 7号, pp. 1687-1694(7) (7), 1629 - 1742, Japanese
    Introduction scientific journal

  • Antiproliferative Effect of a Novel Cholecystokinin-B/Gastrin Receptor Antagonist, YM022
    MURAYAMA Tohru, MATSUMORI Yoshinobu, IWATA Nobuko, ITO Mitsuhiro, TANIGUCHI Taizo, CHIHARA Kazuo, MATSUI Toshimitsu
    31 Jul. 1996, Jpn. J. Cancer Res., 87(7) (7), 743 - 750, English

■ Books And Other Publications
  • 遺伝子発現制御機構
    田村 隆明, 浦 聖惠, Ito Mitsuhiro, 他
    Joint work, 東京化学同人, 2017, Japanese
    Scholarly book

■ Lectures, oral presentations, etc.
  • 非血縁者間骨髄移植前の病勢コントロールとしてGCD療法が有効であった肝脾原発T細胞性リンパ腫の一例
    大國まりか, 市川大哉, 須藤洋崇, 橋本朗子, 田中康博, 新里偉咲, 長尾茂樹, 坂井里奈, 水谷優, 北尾章人, 倉田啓史, 垣内誠司, 宮田吉晴, 乾由美子, 齊藤 泰之, Yakushijin Kimikazu, Kawamoto Shinichiro, Ito Mitsuhiro, 山本克也, Matsuoka Hiroshi, Minami Hironobu
    第40回日本造血細胞移植学会総会, Feb. 2018, Japanese, 日本造血細胞移植学会, 札幌, Domestic conference
    Poster presentation

  • 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方視的解析
    水谷 優, Yakushijin Kimikazu, 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, Takahashi Michiko, 岡村 篤夫, Kawamoto Shinichiro, 山本 克也, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    第40回日本造血細胞移植学会総会, Feb. 2018, Japanese, 日本造血細胞移植学会, 札幌, Domestic conference
    Poster presentation

  • A Case of Refractory Chronic GVHD of Lips Successfully Treated with Wrap Therapy
    市川 大哉, 奥野 真紀子, 坂井 里奈, 水谷 優, 倉田 啓史, 須藤 洋崇, 垣内 誠司, 北尾 章人, 宮田 吉晴, 眞田 幸尚, 乾 由美子, 瓜生 恭章, Saito Yasuyuki, Yakushijin Kimikazu, Kawamoto Shinichiro, 田村 恵利, 岸本 恵実, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    The 39th Annual Meeting of the Japan Socitey for Hematopoietic Cell Transplantation, Mar. 2017, Japanese, The Japan Society for Hematopoietic Cell Transplantation, 島根, Domestic conference
    Poster presentation

  • Nuclear receptor binding capacity of MED1 is required for maintaining body temperature at cold environment
    平野希依, Kie Hirano, 物延沙耶, Saya Mononobe, Natsumi Hasegawa, Mitsuhiro Ito
    第40回日本分子生物学会, 2017, Japanese, Domestic conference
    Poster presentation

  • MED1 regulates mobilization of IL-33 indused type 2 innate lymphoid cells
    ERI ADACHI, NATSUMI HASEGAWA, 前川茜(Akane Maekawa, 物延沙耶, Saya Mononobe, 平野希依(Kie Hirano, 後藤千恵(Chie Goto, 横井彩(Aya Yokoi, 黒沼加菜, Kana Kuronuma, MITSUHIRO ITO
    第40回日本分子生物学会, 2017, Japanese, Domestic conference
    Poster presentation

  • Metabolic markers expressed in mice where MED1 nuclear receptor recognition motifs are defeated
    SAYA MONONOBE, KIE HIRANO, ERI ADACHI, YUKI MINEMATSU, MIKI MATSUO, KASUMI GOWA, MISAKI HATTORI, KANA KURONUMA, NATSUMI HASEGAWA, MITSUHIRO ITO
    第40回日本分子生物学会, 2017, Japanese, Domestic conference
    Poster presentation

  • Mediator may be involved in transcriptional activation through N-terminal activation domain of GATA1
    福岡知也, Tomoya Fukuoka, 松尾美希(Miki Matsuo, 後和佳澄, Kasumi Gowa, 森真洋(Mahiro Mori, 河合麻美, Asami Kawai, 水田駿平, Shunpei Mizuta, 峰松侑希, Yuki Minematsu, 服部美咲, Misaki Hattori, HASEGAWA NATSUMI, Mitsuhiro Ito
    第40回日本分子生物学会, 2017, Japanese, Domestic conference
    Poster presentation

  • The antiemetic effect of palonosetron in malignant lymphoma patients treated with the CHOP regimen
    宮田 吉晴, Yakushijin Kimikazu, 乾 由美子, 今村 善宣, 後藤 秀彰, 水谷 優, 倉田 啓史, 垣内 誠司, 眞田 幸尚, Minami Yosuke, Kawamoto Shinichiro, Ito Mitsuhiro, 富永 亮, 五明 広志, 水野 石一, 野村 哲彦, 喜多川 浩一, 杉本 健, 村山 徹, Matsuoka Hiroshi, Minami Hironobu
    The 78th Annual Meeting of the Japanese Society of Hematology, Oct. 2016, Japanese, The Japanese Society of Hematology, 横浜, Domestic conference
    Poster presentation

  • BRAF V600E mutation-specific antibody for the diagnosis of hairy cell leukemia .
    Akihito Kitao, Yakushijin Kimikazu, Eriko Honda, Hiroya Ichikawa, Yu Mizutani, Yoshiharu Miyata, Kiyoaki Uryu, Yumiko Inui, Kawamoto Shinichiro, Matsuoka Hiroshi, Ito Mitsuhiro, Tomoo Ito, Minami Hironobu
    The 78th annual meeting of the japanese society of hematology, Oct. 2016, Japanese, Japanese Society of Hematology, 横浜, Domestic conference
    Poster presentation

  • 同種造血幹細胞移植後のリンパ球回復と予後に関する後方視的解析
    倉田 啓史, Yakushijin Kimikazu, 乾 由美子, 岡村 篤夫, Kawamoto Shinichiro, Minami Yosuke, 山本 克也, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    第14回日本臨床腫瘍学会学術集会, Jul. 2016, Japanese, 日本臨床腫瘍学会, 神戸, Domestic conference
    Oral presentation

  • Treatment strategies for double primary neoplasm patients who develop malignant lymphoma and solid tumors
    北尾 章人, 水谷 優, 後藤 秀彰, 乾 由美子, Kawamoto Shinichiro, Yakushijin Kimikazu, Minami Yosuke, Matsuoka Hiroshi, Ito Mitsuhiro, Minami Hironobu
    第14回日本臨床腫瘍学会学術集会, Jul. 2016, English, 日本臨床腫瘍学会, 神戸, Domestic conference
    Oral presentation

  • Delayed Absolute Lymphocyte Count Recovery after Allogeneic Hematopoietic Stem Cell Transplantation with Mycophenolate Mofetil
    Keiji Kurata, Yakushijin Kimikazu, Ishikazu Mizuno, Yumiko Inui, Hiroshi Gomyo, Atsuo Okamura, Ryo Tominaga, Kawamoto Shinichiro, Minami Yosuke, Akio Maeda, Katsuya Yamamoto, Tohru Murayama, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    7th, JSH International Symposium, May 2016, English, Japan Society of Hematology, Awaji, Japan, International conference
    Poster presentation

  • Absolute Lymphocyte Count Recovery Predicts Clinical Outcome after Allogeneic Hematopoietic Stem Cell Transplantation in a Japanese Population
    Keiji Kurata, Yakushijin Kimikazu, Ishikazu Mizuno, Yumiko Inui, Hiroshi Gomyo, Atsuo Okamura, Hiroya Ichikawa, Yu Mizutani, Seiji Kakiuchi, Yoshiharu Miyata, Ryo Tominaga, Akihito Kitao, Yukinari Sanada, Saito Yasuyuki, Minami Yosuke, Kawamoto Shinichiro, Akio Maeda, Katsuya Yamamoto, Tohru Murayama, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    42nd, Annual Meeting of the European Society for Blood and Marrow Transplantation, Apr. 2016, English, European Society for Blood and Marrow Transplantation, Valencia, Spain, International conference
    Poster presentation

  • 自律神経ストームを伴った造血幹細胞移植後HHV-6脳炎
    乾 由美子, Yakushijin Kimikazu, 水谷 優, 市川 大哉, 倉田 啓史, 垣内 誠司, 宮田 吉晴, 眞田 幸尚, 北尾 章人, Minami Yosuke, Kawamoto Shinichiro, 田中 康博, 新里 偉咲, 山本 克也, 村山 徹, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    第38回日本造血幹細胞移植学会総会, Mar. 2016, Japanese, 日本造血細胞移植学会, 名古屋, Domestic conference
    Oral presentation

  • 乳癌発症が遺伝要因と環境要因に依存する可能性−乳癌モデルマウスの検討
    INOUE NANAKO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • 骨髄間質細胞が産生するオステオポンチンは造血幹・前駆細胞をCD44を介して支持する
    YANO MASAYA, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • The role of MED1 in breast carcinogenesis and progression
    MINEMATSU YUKI, INOUE NANAKO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第39回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • RAR-binding ability of MED1 is required for high-concentrationATRA-dependent activation of PML-RARα
    TAKAHARA TAKU, KAWAI ASAMI, MORI MAHIRO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第78回日本血液学会学術集会, 2016, Japanese, Domestic conference
    Poster presentation

  • Periostin supports normal and malignant hematopoietic stem/progenitor cells in vitro.
    MAEKAWA AKIO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • Periostin supports hematopoietic stem/progenitor cells and niche-dependent myeloblastoma cells.
    TANAKA SATOWA, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • Periostin supports hematopoietic stem:progenitor cells and niche-dependent myeloblastoma cells in vitro
    MAEKAWA AKIO, HASEGAWA NATSUMI, ITO MITSUHIRO
    58th ASH Annual Meeting and Exposition, 2016, English, International conference
    Poster presentation

  • Mediator subunit MED1 is required for PML-RARα fusion protein-induced transcriptional activation in response high concentration all-trans retinoic acid.
    TAKAHARA TAKU, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • MED1結合蛋白CCAR1とCoCoAはPPARγ2誘導性の白色脂肪細胞分化を司る
    TAKEMOTO YUSUKE, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • MED1-dependent and -independent coactivation mechanism of Mediator for GATA1 action
    MORI MAHIRO, KAWAI ASAMI, TAKAHARA TAKU, HASEGAWA NATSUMI, ITO MITSUHIRO
    第78回日本血液学会学術集会, 2016, Japanese, Domestic conference
    Poster presentation

  • High-concentration ATRA-dependent activation of PML-RARα requires Mediator subunit MED1.
    KAWAI ASAMI, HASEGAWA NATSUMI, ITO MITSUHIRO
    日本血液学会, 2016, Japanese, Domestic conference
    Poster presentation

  • GATA1による転写活性化におけるMED1依存性と非依存性の機序
    MORI MAHIRO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2016, Japanese, Domestic conference
    Poster presentation

  • Periostin supports normal and malignant hematopoietic stem/progenitor cells in vitro.
    TANAKA SATOWA, HASEGAWA NATSUMI, ITO MITSUHIRO
    International Conference on The Tumour Microenvironment in the Haematological Malignancies and its Therapeutic Targeting, European, May 2015, English, International conference
    Poster presentation

  • Absolute Lymphocyte Count Recovery Predicts Clinical Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation
    Keiji Kurata, Yakushijin Kimikazu, Atsuo Okamura, Yukinari Sanada, Hideaki Goto, Yu Mizutani, Seiji Kakiuchi, Yoshiharu Miyata, Yumiko Inui, Yohei Funakoshi, Kiyoaki Uryu, Kawamoto Shinichiro, Minami Yosuke, Katsuya Yamamoto, Tohru Murayama, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    the 6th JSH International Symposium, May 2015, English, 日本血液学会, 軽井沢, Domestic conference
    Poster presentation

  • 骨髄非破壊的造血幹細胞移植後の非感染性心内膜炎
    眞田 幸尚, Yakushijin Kimikazu, 垣内 誠司, 宮田 吉晴, 船越 洋平, Minami Yosuke, Kawamoto Shinichiro, 山本 克也, Ito Mitsuhiro, Matsuoka Hiroshi, Minami Hironobu
    第38回日本造血幹細胞移植学会総会, Mar. 2015, Japanese, 日本造血細胞移植学会, 名古屋, Domestic conference
    Oral presentation

  • 乳癌発症が遺伝要因と環境要因に依存する可能性−乳癌モデルマウスの検討
    INOUE NANAKO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2015, Japanese, Domestic conference
    Poster presentation

  • 骨髄間質細胞が産生するオステオポンチンは造血幹・前駆細胞をCD44を介して支持する
    YANO MASAYA, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2015, Japanese, Domestic conference
    Poster presentation

  • Periostin supports normal and malignant hematopoietic stem:progenitor cells in vitro.
    MAEKAWA AKIO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2015, Japanese, Domestic conference
    Poster presentation

  • Periostin supports hematopoietic stem:progenitor cells and niche-dependent myeloblastoma cells.
    TANAKA SATOWA, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2015, Japanese, Domestic conference
    Poster presentation

  • Mediator subunit MED1 is required for PML-RARα fusion protein-induced transcriptional activation in response high concentration all-trans retinoic acid.
    TAKAHARA TAKU, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2015, Japanese, Domestic conference
    Poster presentation

  • MED1結合蛋白CCAR1とCoCoAはPPARγ2誘導性の白色脂肪細胞分化を司る
    TAKEMOTO YUSUKE, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2015, Japanese, Domestic conference
    Poster presentation

  • High-concentration ATRA-dependent activation of PML-RARα requires Mediator subunit MED1.
    KAWAI ASAMI, HASEGAWA NATSUMI, ITO MITSUHIRO
    第77回日本血液学会学術集会, 2015, Japanese, Domestic conference
    Poster presentation

  • GATA1による転写活性化におけるMED1依存性と非依存性の機序
    MORI MAHIRO, HASEGAWA NATSUMI, ITO MITSUHIRO
    第38回日本分子生物学会, 2015, Japanese, Domestic conference
    Poster presentation

  • FGF8 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro.
    RURI ISHINO, HASEGAWA NATSUMI, MITSUHIRO ITO
    Highlights of ASH in Asia, Mar. 2014, English, International conference
    [Invited]
    Invited oral presentation

  • FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro.
    KEIJI MATSUI, HASEGAWA NATSUMI, MITSUHIRO ITO
    55th Annual Meeting of the American Society of Hematology, Dec. 2013, English, International conference
    Poster presentation

  • PHYSICAL INTERACTION BETWEEN PPARγ AND MEDIATOR SUBUNIT MED1 IS CRUCIAL FOR INDUCED ADIPOCYTE HYPERTROPHY
    ITO MITSUHIRO, HASEGAWA NATSUMI
    MECHANISMS OF EUKARYOTIC TRANSCRIPTION 2013, Aug. 2013, English, Cold Spring Harbor Laboratory, International conference
    Poster presentation

  • 文部科学省科学技術戦略推進費「地域再生人材創出拠点の形成」事業 医師・コメディカル総合人材育成拠点形成 エキスパート・コメディカル育成プログラムについて
    中町 祐司, 林 伸英, 木下 承皓, Tanaka Kazushi, Ito Mitsuhiro, Arakawa Soichi, Fujisawa Masato, Kawano Seiji
    第55回日本臨床検査医学会近畿支部総会, Dec. 2012, Japanese, 京都, Domestic conference
    [Invited]
    Nominated symposium

  • Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells.
    Fujita A, Mizuta S, Matsui K, Ishino R, Mukohara T, Kamoshida S, Roeder RG, Ito M
    2012 Keystone Symposia on Molecular and Cellular Biology, Apr. 2012, English, British Columbia, International conference
    [Invited]
    Invited oral presentation

  • Pure red cell aplasia with primary screlosing cholangitis improved after liver transplantation
    Yakushijin Kimikazu, Okamura Atsuo, Shimoyama Manabu, Katayama Yoshio, Matsui Toshimitsu, Ito Mitsuhiro, Ku Yonson
    第70回日本血液学会総会, Oct. 2008, Japanese, 日本血液学会, 京都, Domestic conference
    Poster presentation

  • 造血ニッチの転写コアクチベーターMED1/TRAP220による造血細胞の増殖
    Horie Osamu, Ito Mitsuhiro
    第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007, Japanese, 日本分子生物学会、日本生化学会, 横浜, Domestic conference
    Poster presentation

  • リンパ球の細胞傷害性因子グランザイムBとその内因性インヒビターPI-9の発現比
    Horie Osamu, Saigo Katsuyasu, Ryo Ryukichi, Ito Mitsuhiro
    第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007, Japanese, 日本分子生物学会、日本生化学会, 横浜, Domestic conference
    Poster presentation

  • Inflammatory cytokines induce aberrant splicing of Dbl protooncogene as rheumatoid arthritis disease gene.
    Komai Koichiro, Ito Mitsuhiro, Hashiramoto Akira, Shiozawa Shunichi
    AmericanCollegeofRheumatology71stAnnualScientificMeeting, Nov. 2007, English, American College of Rheumatology, ボストン, アメリカ, International conference
    Oral presentation

  • 基本的転写共役因子MED1/TRAP220による造血前駆細胞の支持
    Ito Mitsuhiro, Horie Osamu
    第６９回日本血液学会・４９回日本臨床血液学会合同総会, Oct. 2007, Japanese, 日本血液学会、日本臨床血液学会, 横浜, Domestic conference
    Poster presentation

  • 移植後GVHDにおけるリンパ球の細胞傷害性因子グランザイムBとその内因性インヒビターPI-9の発現
    Horie Osamu, Saigo Katsuyasu, Ryo Ryukichi, Ito Mitsuhiro
    第６９回日本血液学会・４９回日本臨床血液学会合同総会, Oct. 2007, Japanese, 日本血液学会、日本臨床血液学会, 横浜, Domestic conference
    Poster presentation

  • 同種造血幹細胞移植後患者のgranzyme B,perforinおよびPI-9のmRNA量測定の意義
    Horie Osamu, Ito Mitsuhiro
    第５６回日本医学検査学会, May 2007, Japanese, 日本医学検査学会, 宮崎, Domestic conference
    Poster presentation

  • Expression of proteinase inhibitor 9 (PI-9) and cytotoxic molecule granzyme B in leukocytes after allogeneic hematopoietic stem cell transplantation.
    Horie Osamu, Ryo Ryukichi, Ito Mitsuhiro
    20thInternationalSymposiumonTechnologicalInnovationsinLaboratoryHematology, May 2007, English, International Society of Laboratory Hematology, フロリダ州マイアミ, アメリカ合衆国, International conference
    Poster presentation

  • The role of proteinase inhibitor 9 (PI-9) in granzyme B/perforin-mediated cytotoxicity induced by cytotoxic T cells in allogeneic hematopoietic stem cell transfusion.
    HORIE OSAMU, Ryo Ryukichi, ITO MITSUHIRO
    48th Annual Meeting of the American Society of Hematology, Dec. 2006, English, American Society of Hematology, オーランド, International conference
    Poster presentation

  • The role of proteinase inhibitor 9 (PI-9) in granzyme B/perforin-mediated cytotoxicity induced by cytotoxic T cells in allogeneic hematopoietic stem cell transfusion.
    Mitsuhiro Ito
    48th Annual Meeting of the American Society of Hematology, Dec. 2006, English, Orlando, FL, International conference
    Poster presentation

  • The role of proteinase inhibitor 9 (PI-9) in granzyme B/perforin-mediated cytotoxicity induced by cytotoxic T cells in allogeneic hematopoietic stem cell transfusion
    O. Horie, T. Murayama, K. Saigo, Y. Utsunomiya, R. Ryo, M. Ito
    48th American Society of Hematology Annual Meeting, Dec. 2006, English, American Society of Hematology, Orange County Conversation Center Orlando, Florida, International conference
    Poster presentation

  • HIV-I TatコアクチベーターTIP30はc-mycの発現とリンパ球の異常増殖を抑制する。
    Mitsuhiro Ito
    第68回日本血液学会総会および第48回臨床血液学会総会同時開催, Oct. 2006, Japanese, 福岡, Domestic conference
    Poster presentation

  • HIV-I TatコアクチベーターTIP30はc-mycの発現とリンパ球の異常増殖を抑制する
    ITO MITSUHIRO, HORIE OSAMU
    第68回日本血液学会総会および第48回臨床血液学会総会同時開催, Oct. 2006, Japanese, 日本血液学会総会および臨床血液学会, 福岡, Domestic conference
    Poster presentation

  • Establishment of a method for measurement of proteinase inhibitor 9 (PI-9) antigen in leukocytes.
    HORIE OSAMU, ITO MITSUHIRO, Ryo Ryukichi
    9th International Congress of the Asian Society of Clinical Pathology and Laboratory Medicine, Oct. 2006, English, Asian Society of Clinical Pathology and Laboratory Medicine, 神戸, International conference
    Poster presentation

  • Establishment of a method for measurement of proteinase inhibitor 9 (PI-9) antigen in leukocytes
    O. Horie, M. Nakano, Y. Utsunomiya, M. Ito, R. Ryo
    The 9th International Congress of the Asian Society Clinical Pathology and Laboratory Medicine, Oct. 2006, English, Asian Society Clinical Pathology and Laboratory Medicine, Kobe International Exhibition Hall, International conference
    Poster presentation

  • HIV-I TatコアクチベーターTIP30はリンパ球の異常増殖を抑制する。
    Mitsuhiro Ito
    第65回日本癌学会学術総会, Sep. 2006, Japanese, 横浜, Domestic conference
    Poster presentation

  • HIV-I TatコアクチベーターTIP30はリンパ球の異常増殖を抑制する
    ITO MITSUHIRO
    第65回日本癌学会学術総会, Sep. 2006, Japanese, 日本癌学会, 横浜, Domestic conference
    Poster presentation

  • The role of transcriptional coactivator TRAP220/MED1 in myelomonocytic differentiation.
    ITO MITSUHIRO
    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress., Jun. 2006, English, International Union of Biochemistry and Molecular Biology and FAOBMB, 京都, International conference
    Poster presentation

  • The role of transcriptional coactivator TRAP220/MED1 in myelomonocytic differentiation.
    Mitsuhiro Ito
    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress, Jun. 2006, English, Kyoto, International conference
    Poster presentation

  • 末梢性T細胞リンパ腫(PTCL)に同種移植が奏効した3症例。
    Mitsuhiro Ito
    第28回日本造血細胞移植学会総会, Feb. 2006, Japanese, 横浜, Domestic conference
    Oral presentation

  • 末梢性T細胞リンパ腫(PTCL)に同種移植が奏効した3症例
    松井 裕子, 皆川 健太郎, 田中 祐子, 横山 和明, 西川 真一郎, 波戸 章郎, 定 明子, 薬師神 公和, 岡村 篤夫, 山本 克也, ITO, Mitsuhiro, MATSUI, Toshimitsu
    第28回日本造血細胞移植学会総会, Feb. 2006, Japanese, 第28回日本造血細胞移植学会総会, 東京, Domestic conference
    Oral presentation

  • The role of transcriptional coactivator TRAP220/MED1 in nuclear receptor-mediated myelomonocytic differentiation.
    ITO, Mitsuhiro, 浦濱 憲永, 定 明子, 薬師神 公和, 山本 克也, 岡村 篤夫, 皆川 健太郎, 波戸 章郎, CHIHARA, Kazuo, R G Roeder, MATSUI, Toshimitsu
    第47回米国血液学会, Dec. 2005, English, 米国血液学会, アトランタ, International conference
    Oral presentation

  • The role of transcriptional coactivator TRAP220/MED1 in nuclear receptor-mediated myelomonocytic differentiation
    ITO, Mitsuhiro, N Urahama, A Sada, K Yakushijin, K Yamamoto, A Okamura, K Minagawa, A Hato, CHIHARA, Kazuo, R G Roeder, MATSUI, Toshimitsu
    Annual Meeting of the American Society of Hematology, Dec. 2005, English, American Society of Hematology, Atlanta, International conference
    Poster presentation

  • Functional studies of human mediator subunit MED18/p28b.
    Tadashi Furumoto, Sohail Malik, ITO, Mitsuhiro, Robert G, Roeder, Fumio Hanaoka, Yoshiaki Ohkuma
    第28回分子生物学会年会, Dec. 2005, English, 第28回分子生物学会年会, 福岡, Domestic conference
    Poster presentation

  • 初診時に巨大縦隔腫瘤を合併した急性前骨髄性白血病の一例
    横山 和明, 岡村 篤夫, 西川 真一郎, 波戸 章郎, 皆川 健太郎, 浦浜 憲永, 薬師神 公和, 定 明子, ITO, Mitsuhiro, MATSUI, Toshimitsu
    第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, Sep. 2005, Japanese, 第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, 横浜, Domestic conference
    Poster presentation

  • 骨髄球系前駆細胞の分化における転写共役因子TRAP220の役割
    浦浜 憲永, ITO, Mitsuhiro, 定 明子, 薬師神 公和, 皆川 健太郎, 岡村 篤夫, 西川 真一郎, 波戸 章郎, 横山 和明, 山本 克也, BABA, Hisamitsu, MATSUI, Toshimitsu
    第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, Sep. 2005, Japanese, 第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, 横浜, Domestic conference
    Poster presentation

  • 基本的転写共役因子TRAP220による骨髄系細胞の分化調節
    ITO, Mitsuhiro, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第64回日本癌学会総会, Sep. 2005, Japanese, 日本癌学会, 札幌, Domestic conference
    Oral presentation

  • 基本的転写共役因子TRAP220による骨髄系細胞の分化調節
    ITO, Mitsuhiro, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第64回日本癌学会学術総会, Sep. 2005, Japanese, 第64回日本癌学会学術総会, 札幌, Domestic conference
    Oral presentation

  • The role of coactivator TRAP220 in myelomonocytic differentiation
    ITO, Mitsuhiro, N Urahama, A Sada, R G Roeder, MATSUI, Toshimitsu
    Keystone Symposium, Tissue-specific nuclear receptor, Sep. 2005, English, Keystone Symposium, Tissue-specific nuclear receptor, Breckenridge, International conference
    Poster presentation

  • ephrin B1, B2はT細胞レセプター(TCR)シグナル伝達の強力な負の制御因子である
    薬師神 公和, 横山 和明, 西川 真一郎, 定 明子, 波戸 章郎, 皆川 健太郎, 浦浜 憲永, 岡村 篤夫, 山本 克也, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, Sep. 2005, Japanese, 第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, 横浜, Domestic conference
    Poster presentation

  • auto-PBSCT後に発症したinv(16), I型CBFb/MYH11陽性t-MDS: 移植前幹細胞中にCBFb/MYH11は検出されない
    山本 克也, 西川 真一郎, 皆川 健太郎, 薬師神 公和, 岡村 篤夫, ITO, Mitsuhiro, MATSUI, Toshimitsu
    第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, Sep. 2005, Japanese, 第67回日本血液学会総会・第47回日本臨床血液学会総会同時開催, 横浜, Domestic conference
    Poster presentation

  • 転写共役因子TRAP220による造血前駆細胞の分化調節
    ITO, Mitsuhiro, 浦浜 憲永, 定 明子, MATSUI, Toshimitsu
    第3回幹細胞シンポジウム, Apr. 2005, Japanese, 第3回幹細胞シンポジウム, 淡路島, Domestic conference
    Poster presentation

  • リンパ腫診療におけるCT併用FDG-PETの有用性
    波戸章郎, 岡村篤夫, 薬師神公和, ITO, Mitsuhiro, 山本克也, MATSUI, Toshimitsu
    第３回臨床腫瘍学会総会, Mar. 2005, Japanese, 第３回臨床腫瘍学会総会, 横浜, Domestic conference
    Oral presentation

  • Role of the TRAP220 component of the TRAP/Mediator complex in myelomonocytic differentiation
    ITO, Mitsuhiro
    日本生化学会バイオシンポジウム＆第4回転写研究会共催, Jan. 2005, English, 日本生化学会バイオシンポジウム＆第4回転写研究会共催, 草津, International conference
    Oral presentation

  • 造血前駆細胞の分化における転写コアクチベーターTRAP220の役割
    浦浜 憲永, ITO, Mitsuhiro, 定 明子, 薬師神 公和, 岡村 篤夫, 皆川 健太郎, MATSUI, Toshimitsu, CHIHARA, Kazuo, Robert G Roeder
    第27回日本分子生物学会年会, Dec. 2004, Japanese, 日本分子生物学会, 神戸, Domestic conference
    Poster presentation

  • 最近1年間に当院で施行した成人臍帯血移植における生着不全の４症例
    波戸 章郎, 山本 克也, 横山 和明, 西川 真一郎, 皆川 健太郎, 薬師神 公和, 浦浜 憲永, 定 明子, 岡村 篤夫, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    第27回日本造血細胞学会総会, Dec. 2004, Japanese, 日本造血細胞学会, 岡山, Domestic conference
    Poster presentation

  • ステロイドが著効した妊娠に伴う後天性血友病の１例
    新名 尚史, 横山 和明, 定 明子, 皆川 健太郎, 浦浜 憲永, 岡村 篤夫, 山本 克也, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    第１７５回 日本内科学会近畿地方会, Dec. 2004, Japanese, 日本内科学会, 京都, Domestic conference
    Oral presentation

  • Casein kinase Ie downregulates PI3K/Akt signaling, followed by genotoxic stress-induced apoptosis of hematopoietic cells
    A Okamura, K Yamamoto, K Yakushijin, N Urahama, K Minagawa, A Sada, A Hato, S Nishikawa, K Yokoyama, ITO, Mitsuhiro, MATSUI, Toshimitsu
    Annual Meeting of the American Society of Hematology, Dec. 2004, English, American Society of Hematology, サンディエゴ, International conference
    Poster presentation

  • 不均衡転座der(11)t(11;12)(q23;q13)は進行期MDSで見られる新たな再発性の染色体異常である
    山本 克也, 波戸 章郎, 皆川 健太郎, 薬師神 公和, 浦浜 憲永, 定 明子, 岡村 篤夫, ITO, Mitsuhiro, MATSUI, Toshimitsu
    第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, Sep. 2004, Japanese, 第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, 京都, Domestic conference
    Poster presentation

  • 生体肝移植後に発症した末梢性T細胞性リンパ腫の1例
    薬師神 公和, 波戸 章郎, 山本 克也, 皆川 健太郎, 浦浜 憲永, 定 明子, 岡村 篤夫, 横山 和明, 西川 真一郎, ITO, Mitsuhiro, MATSUI, Toshimitsu
    第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, Sep. 2004, Japanese, 第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, 京都, Domestic conference
    Poster presentation

  • 基本的転写共役因子TRAP/Mediator複合体による造血調節機構
    浦浜 憲永, ITO, Mitsuhiro, 岡村 篤夫, 薬師神 公和, 皆川 健太郎, 定 明子, 波戸 章郎, 山本 克也, CHIHARA, Kazuo, MATSUI, Toshimitsu
    第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, Sep. 2004, Japanese, 第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, 京都, Domestic conference
    Poster presentation

  • リンパ腫診断におけるFDG-PETの有用性と問題点：当院での83例の後視的解析
    波戸 章郎, 山本 克也, 皆川 健太郎, 浦浜 憲永, 薬師神 公和, 定 明子, 岡村 篤夫, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, Sep. 2004, Japanese, 第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, 京都, Domestic conference
    Oral presentation

  • HIV-I TatコアクチベーターTIP30はc-myc発現を抑制し、癌の発生を抑制する
    ITO, Mitsuhiro
    第63回日本癌学会学術総会, Sep. 2004, Japanese, 第63回日本癌学会学術総会, 福岡, Domestic conference
    Oral presentation

  • Casein kinase I eによる造血細胞の自己複製・分化制御機構
    岡村 篤夫, 山本 克也, 薬師神 公和, 浦浜 憲永, 皆川 健太郎, 定 明子, 波戸 章郎, 西川 真一郎, 横山 和明, ITO, Mitsuhiro, MATSUI, Toshimitsu
    第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, Sep. 2004, Japanese, 第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, 京都, Domestic conference
    Poster presentation

  • AML寛解導入療法中Clostridium perfrigens敗血症による溶血性貧血を呈し、早期治療にて救命し得た一例
    定 明子, 山本 克也, 波戸 章郎, 皆川 健太郎, 薬師神 公和, 浦浜 憲永, 岡村 篤夫, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, Sep. 2004, Japanese, 第66回日本血液学会総会・第46回日本臨床血液学会総会同時開催, 京都, Domestic conference
    Poster presentation

  • 核内受容体の情報伝達におけるTRAP/Mediator複合体の役割と形態形成に及ぼす作用
    ITO, Mitsuhiro, 浦浜 憲永, ロバート・G・レーダー, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第81回日本生理学会大会, Jun. 2004, Japanese, 第81回日本生理学会大会, 札幌, Domestic conference
    [Invited]
    Invited oral presentation

  • 核内受容体の情報伝達におけるTRAP/Mediator複合体の役割と形態形成に及ぼす作用
    ITO, Mitsuhiro, 浦浜 憲永, ロバート・G・レーダー, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第81回 日本生理学会大会シンポジウム, Jun. 2004, Japanese, 日本生理学会, 札幌, Domestic conference
    Others

  • 転写共役因子TRAP/Mediator複合体と未分化前駆細胞の分化
    ITO, Mitsuhiro, 浦浜 憲永, MATSUI, Toshimitsu
    第２回幹細胞シンポジウム, Apr. 2004, Japanese, 第２回幹細胞シンポジウム, 東京, Domestic conference
    Poster presentation

  • 転写共役因子TRAP/Mediator複合体を介する造血の制御
    浦浜 憲永, ITO, Mitsuhiro, 岡村 篤夫, 薬師神 公和, 皆川 健太郎, 定 明子, 波戸 章郎, 山本 克也, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第８回遺伝子医療研究会, Mar. 2004, Japanese, 第８回遺伝子医療研究会, 東京, Domestic conference
    Oral presentation

  • TRAP/Mediator複合体の核内受容体情報伝達における生理的役割
    ITO, Mitsuhiro, 浦浜 憲永, MATSUI, Toshimitsu, CHIHARA, Kazuo
    日本薬学会第124年会, Mar. 2004, Japanese, 日本薬学会第124年会, 大阪, Domestic conference
    [Invited]
    Invited oral presentation

  • TRAP/Mediator複合体の核内受容体情報伝達における生理的役割
    ITO, Mitsuhiro, 浦浜 憲永, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第124回日本薬学会年会シンポジウム, Mar. 2004, Japanese, 日本薬学会, 大阪, Domestic conference
    Others

  • HIV-I TatコアクチベーターTIP30は腫瘍発生を抑制する
    ITO, Mitsuhiro
    第3回転写研究会, Jan. 2004, Japanese, 第3回転写研究会, つくば, Domestic conference
    Oral presentation

  • 哺乳類の造血におけるTRAP/Mediator複合体のTRAP220を介する役割
    浦浜 憲永, ITO, Mitsuhiro, 薬師神 公和, SHIMOYAMA, Manabu, 岡村 篤夫, 五明 広志, 皆川 健太郎, 山本 克也, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第26回日本分子生物学会年会, Dec. 2003, Japanese, 第26回日本分子生物学会年会, 神戸, Domestic conference
    Poster presentation

  • 成人臍帯血移植におけるnon-TBI regimenの有用性
    皆川 健太郎, 山本 克也, 波戸 章郎, 定 明子, 薬師神 公和, 浦浜 憲永, 五明 広志, 岡村 篤夫, SHIMOYAMA, Manabu, CHIHARA, Kazuo, ITO, Mitsuhiro, MATSUI, Toshimitsu
    第26回日本造血細胞移植学会総会, Dec. 2003, Japanese, 第26回日本造血細胞移植学会総会, 横浜, Domestic conference
    Poster presentation

  • Stabilization of SOCS3 and b-catenin by casein kinase Ie to regulate hematopoietic cell differentiation
    A Okamura, SHIMOYAMA, Manabu, H Gomyo, K Yakushijin, N Urahama, K Minagawa, A Sada, A Hato, K Yamamoto, ITO, Mitsuhiro, MATSUI, Toshimitsu
    Annual Meeting of the American Society of Hematology, Dec. 2003, English, American Society of Hematology, San Diego, International conference
    Poster presentation

  • RNAポリメラーゼIIのCTDリン酸化を介する核内シグナル伝達クロストーク
    大熊 芳明, 古元 義, 田中 亜紀, 林 和宏, 佐藤 千晶, ITO, Mitsuhiro, 花岡 文雄
    第26回日本分子生物学会年会, Dec. 2003, Japanese, 第26回日本分子生物学会年会, 神戸, Domestic conference
    [Invited]
    Invited oral presentation

  • 彌慢性リンパ腫への移行時に新たな転座t(2;6)(p12;q23)が出現したt(15;22)(q21;q11)陽性濾胞性リンパ腫
    山本 克也, 岡村 篤夫, 皆川 健太郎, 薬師神 公和, 浦浜 憲永, 五明 広志, SHIMOYAMA, Manabu, ITO, Mitsuhiro, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第６５回日本血液学会総会 第４５回日本臨床学会総会 同時期開催, Aug. 2003, Japanese, 日本血液学会, 大阪, Domestic conference
    Oral presentation

  • 骨髄生検、フローサイドメトリー、染色体検査によるB細胞リンパ腫の骨髄浸潤の評価
    五明 広志, SHIMOYAMA, Manabu, 皆川 健太郎, 浦浜 憲永, 薬師神 公和, 岡村 篤夫, 山本 克也, ITO, Mitsuhiro, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第６５回日本血液学会総会 第４５回日本臨床学会総会 同時期開催, Aug. 2003, Japanese, 日本血液学会, 大阪, Domestic conference
    Oral presentation

  • 胸腺形成およびＴ細胞活性化におけるEphB6の役割：EphB6欠損マウスを用いた解析
    SHIMOYAMA, Manabu, 薬師神 公和, 五明 広志, 皆川 健太郎, 浦浜 憲永, 岡村 篤夫, 山本 克也, ITO, Mitsuhiro, CHIHARA, Kazuo, MATSUI, Toshimitsu
    第６５回日本血液学会総会 第４５回日本臨床学会総会 同時期開催, Aug. 2003, Japanese, 日本血液学会, 大阪, Domestic conference
    Oral presentation

  • Auto-PBSCT後に発症したt-MDSにnon-TBIレジメンでの臍帯血移植が奏効した１成人例
    皆川 健太郎, 山本 克也, 浦浜 憲永, 薬師神 公和, 五明 広志, 岡村 篤夫, SHIMOYAMA, Manabu, ITO, Mitsuhiro, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第６５回日本血液学会総会 第４５回日本臨床学会総会 同時期開催, Aug. 2003, Japanese, 日本血液学会, 大阪, Domestic conference
    Oral presentation

  • HLA2座不一致骨髄非破壊的造血幹細胞移植の１例ーHLA遺伝子型２座以上
    皆川 健太郎, 山本 克也, 波戸 章郎, 定 明子, 薬師神 公和, 浦浜 憲永, 五明 広志, 岡村 篤夫, SHIMOYAMA, Manabu, ITO, Mitsuhiro, MATSUI, Toshimitsu, CHIHARA, Kazuo
    第１７０回 日本内科学会近畿地方会, Jun. 2003, Japanese, 日本内科学会, 大阪, Domestic conference
    Oral presentation

  • A novel mutation in the RDH5 gene in a patient with macular dystrophy without white punctata.
    YAMAMOTO,Hidehiro, Yakushijin K, KUSUHARA, Sentaro, TAMURA, Yumi, AZUMI, Atsushi, TSUKAHARA, Yasutomo, ITO, Mitsuhiro, MATSUI, Toshimitsu, NEGI, Akira
    ARVO 2003, May 2003, English, ARVO, Lauderdale, International conference
    Poster presentation

  • A novel mutation in the RDH5 gene in a patient with macular dystrophy without white punctata
    YAMAMOTO,Hiroyuki, K Yakushijin, KUSUHARA, Sentaro, A Nagai, TAMURA, Yumi, AZUMI, Atsushi, TSUKAHARA, Yasutomo, ITO, Mitsuhiro, MATSUI, Toshimitsu, NEGI, Akira
    Association for Research in Vision and Ophthalmology, May 2003, English, Association for Research in Vision and Ophthalmology, Ft. Lauderdale, International conference
    Poster presentation

  • 胸腺形成におけるEphB6の役割；EphB6遺伝子欠損マウスを用いた解析
    ITO MITSUHIRO
    第7回遺伝子医療研究会, Mar. 2003, Japanese, 第7回遺伝子医療研究会, 大阪, Domestic conference
    Oral presentation

■ Research Themes
  • 基本的転写共役因子MED1による2型自然免疫制御機構と代謝調節
    伊藤 光宏
    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, 01 Apr. 2020 - 31 Mar. 2023
    動物細胞のmRNA転写を担うRNAポリメラーゼIIを構成するメディエーターは基本的転写共役因子複合体でありつつ、サブユニット構成によってアクチベーター特異性を併せ持つ。特にMED1サブユニットは多くの転写には必要でない一方で核内受容体やGATA1等のアクチベーターによる転写を担う点で特異性が高いサブユニットである。本研究ではMED1の核内受容体特異的コアクチベーターとしての役割を主に自然免疫機構や代謝調節に焦点をあてて個体レベルで観察するため、MED1の核内受容体結合能を廃絶した変異MED1をマウス遺伝子座にノックインしたマウスを解析した。本マウスは一見正常であるが、マウス由来細胞で核内受容体機能の低下があることを確認した。自然免疫を担うリンパ球のうち、iNKT細胞はMED1ノックアウトマウスでは著明に減少するが、MED1の核内受容体結合能廃絶マウスでは明らかな変化を認めなかった。一方、これまでに2型自然リンパ球が、IL33で動員する際に特に内臓白色脂肪組織で増加することを認めている。その際に2型自然免疫が本マウスで野性型よりも増強することが考えられる。事実、組織学的に内臓白色脂肪組織を観察したところ、好酸性細胞の増加を認め、この仮説を裏付ける所見を得ている。2型自然リンパ球の増殖・分化を司る転写因子はRORαやGATA3が知られているので、MED1の核内受容体結合能がこれら転写因子の機能を抑制する可能性が考えうるが、その機序は必ずしも直接的ではないのかもしれない。

  • 伊藤 光宏
    学術研究助成基金助成金／基盤研究(C), Apr. 2017 - Mar. 2020, Principal investigator
    Competitive research funding

  • The role for Mediator subunits MED1 in the property of breast carcinomas
    Hasegawa Natsumi, ITO Mitsuhiro
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2015 - 31 Mar. 2018
    We previously reported that Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells. In order to determine the role for MED1 in the property of breast carcinomas, prognosis, and response to therapy, we have prepared, or are in the process of preparing, mice carrying various mutations in MED1 and MED1-associated factor. We have analysed these mutant mice that have been ready so far if these mice possess the ability of inhibiting breast cancer.

  • 伊藤 光宏
    学術研究助成基金助成金／基盤研究(C), Apr. 2014 - Mar. 2017, Principal investigator
    Competitive research funding

  • The role for Mediator transcriptional coregulator complex in the property of breast carcinomas
    HASEGAWA Natsumi, ITO Mitsuhiro
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Research Activity Start-up, Kobe University, 30 Aug. 2013 - 31 Mar. 2015
    We previously reported that Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells. In order to determine the role for MED1 and MED24 in the property of breast carcinomas, prognosis, and response to therapy, we have prepared, or are in the process of preparing, mice carrying various mutations in MED1, MED24, and MED1-associated factor. We have started analyses of these mutant mice that have been ready so far if these mice possess the ability of inhibiting breast cancer.

  • Epigenome analysis of cancer
    NISHIKAWA Shinichi, TARUI Hiroshi, ITO Mitsuhiro, NISHIGORI Chikako, MATSUI Toshimitsu, NAGAI Ken-ichi, MIYAZAKI Yasushi, ITO Kiminari
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (S), The Institute of Physical and Chemical Research, 2008 - 2012
    The purpose of this study is to specify the effect of de-methylating agents on myelodysplastic syndrome (MDS) patients. So far, we have constructed promoter methylomes from 4 MDS patients (2 with RCMD and 2 with RAEB-2), as well as that from two healthy donors (commercial products). Samples from the two different subtypes clustered together, and it seems likely that DNA methylation analysis could serve as a useful diagnostic. We found an enormous over-representation of transcription factors within sets of identified genes differentially methylated between the two tumor types. Most other genes identified could also be considered to have regulatory functions with many genes encoding proteins involved in signal transduction, as well as a number of microRNA genes. We also looked at biological process associated with these gene sets. For most analyses we found an even more enormous over-representation of genes associated with various developmental processes, with many genes involved in nervous system development.

  • 伊藤 光宏
    学術研究助成基金助成金／基盤研究(C), 2011, Principal investigator
    Competitive research funding

  • 伊藤 光宏
    科学研究費補助金／基盤研究(C), 2008, Principal investigator
    Competitive research funding

  • 伊藤 光宏
    科学研究費補助金／特定領域研究, 2008, Principal investigator
    Competitive research funding

  • 伊藤 光宏
    科学研究費補助金／基盤研究(C), 2006, Principal investigator
    Competitive research funding

  • 伊藤 光宏
    科学研究費補助金／基盤研究(C), 2005, Principal investigator
    Competitive research funding

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