Hattori, Yutaka

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 病態生理学講座 (Shiba-Kyoritsu)

Position

Professor

External Links

Career 【 Display / hide

  • 1984.04
    -
    1986.04

    慶應義塾大学病院, 内科, 研修医

  • 1986.05
    -
    1988.03

    川崎市立川崎病院, 内科, 医員

  • 1988.10
    -
    1996.04

    国立がんセンター研究所, 分子腫瘍学部, 研究員

  • 1993.03
    -
    1995.07

    Memorial Sloan-Kettering Cancer Center, Hematologic Oncology

  • 1996.05
    -
    2006.09

    慶應義塾大学医学部内科学教室, 血液・感染・リウマチ内科, 助手

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Academic Background 【 Display / hide

  • 1978.04
    -
    1984.03

    Keio University, School of Medicine

    University, Graduated

Academic Degrees 【 Display / hide

  • 医学博士, Keio University, 1991.02

    K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes.

Licenses and Qualifications 【 Display / hide

  • 医師免許, 1984.06

  • 日本内科学会認定内科医, 1987.12

  • 日本内科学会指導医, 2000.05

  • 日本血液学会認定血液専門医, 2004.10

  • 日本臨床腫瘍学会暫定指導医, 2005.09

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Books 【 Display / hide

  • 多発性骨髄腫 新規治療薬の使い方・考え方

    HATTORI YUTAKA, 先端医学社(東京), 2017.06

    Scope: 開発中の薬剤 pp174-179

  • 骨髄腫治療を理解するためのMyeloma Biology

    HATTORI YUTAKA, 医薬ジャーナル社(大阪), 2017.05

    Scope: 肝細胞増殖因子(HGF)およびその受容体(c-MET) pp137-144

  • 悪性腫瘍の薬、病態、治療 スタンダード薬学シリーズ 医療薬学 IV.薬理、病態・薬物治療(4) 日本薬学会編

    服部 豊, 東京化学同人, 2017.04

    Scope: pp207-218

  • 多発性骨髄腫の診療指針 第4版 日本骨髄腫学会編

    HATTORI YUTAKA, 文光堂, 2016.08

  • 低分子化合物 免疫調節薬 サリドマイド

    HATTORI YUTAKA, 日本臨床社, 2016.07

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Papers 【 Display / hide

  • Antibody drug separation using thermoresponsive anionic polymer brush modified beads with optimised electrostatic and hydrophobic interactions

    Nagase K., Ishii S., Ikeda K., Yamada S., Ichikawa D., Akimoto A.M., Hattori Y., Kanazawa H.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

     View Summary

    © 2020, The Author(s). Antibody drugs play an important role in biopharmaceuticals, because of the specificity for target biomolecules and reduction of side effects. Thus, separation and analysis techniques for these antibody drugs have increased in importance. In the present study, we develop functional chromatography matrices for antibody drug separation and analysis. Three types of polymers, poly(N-isopropylacrylamide (NIPAAm)-co-2-acrylamido-2-methylpropanesulfonic acid (AMPS)-co-N-phenyl acrylamide (PhAAm)), P(NIPAAm-co-AMPS-co-n-butyl methacrylate (BMA)), and P(NIPAAm-co-AMPS-co-tert-butylacrylamide (tBAAm)), were modified on silica beads through atom transfer radical polymerisation. Rituximab elution profiles were observed using the prepared beads-packed column. Rituximab adsorption at high temperature and elution at low temperature from the column were observed, as a result of the temperature-modulated electrostatic and hydrophobic interactions. Using the column, rituximab purification from contaminants was performed simply by changing the temperature. Additionally, three types of antibody drugs were separated using the column through temperature-modulated hydrophobic and electrostatic interactions. These results demonstrate that the temperature-responsive column can be applied for the separation and analysis of biopharmaceuticals through a simple control of the column temperature.

  • Characteristics of a novel target antigen against myeloma cells for immunotherapy

    Matsushita M., Saito S., Yokoe S., Ichikawa D., Hattori Y.

    Vaccines (Vaccines)  8 ( 4 ) 1 - 13 2020.12

     View Summary

    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by reverse transcription polymerase chain reaction (RT-PCR) using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and51 Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells, and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.

  • A phenylphthalimide derivative, TC11, induces apoptosis by degrading MCL1 in multiple myeloma cells

    Ichikawa D., Nakamura M., Murota W., Osawa S., Matsushita M., Yanagawa H., Hattori Y.

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  521 ( 1 ) 252 - 258 2020.01

    ISSN  0006291X

     View Summary

    © 2019 To date, the prognosis of multiple myeloma (MM) in patients harboring cytogenetic abnormalities (CA) involving t (4; 14) and deletion of chromosome 17 remains poor despite recent advances in drug development that include the use of immunomodulatory drugs (IMiDs) such as lenalidomide for MM. To address this issue, we have developed a novel phenylphthalimide derivative, TC11, that is structurally related to IMiDs. It remains unclear how TC11 induces apoptosis of MM cells with high-risk CA. Here, we show that TC11 does not induce degradation of CRBN's substrates, IKZF1/3 and CK1α, and induces apoptosis of CRBN-silenced MM; this effect was independent of the cereblon (CRBN) pathway, which is involved in the mechanism of action of IMiDs used for the treatment of MM. We also revealed that TC11, in contrast to existing IMiDs, induced degradation of MCL1 and activation of caspase-9. Furthermore, inhibition of CDK1 by CGP74514A prevented TC11-induced MCL1 degradation, caspase-9 activation, and the subsequent apoptotic cell death. We showed that ectopic MCL1 expression rescued apoptosis of MM. These observations suggest that TC11 induces apoptotic death caused by degradation of MCL1 during prolonged mitotic arrest. Therefore, our findings suggest that TC11 is a potential drug candidate for high-risk MM.

  • Significance of peripheral mononuclear cells producing interferon-γ in response to insulin B:9–23-related peptides in subtypes of type 1 diabetes

    Oikawa Y., Sakamoto K., Satomura A., Haisa A., Katsuki T., Hattori Y., Inoue I., Noda M., Shimada A.

    Clinical Immunology (Clinical Immunology)  208 2019.11

    ISSN  15216616

     View Summary

    © 2019 Elsevier Inc. Type 1 diabetes is largely caused by β-cell destruction through anti-islet autoimmunity. Reportedly, interferon (IFN)-γ-secreting peripheral blood mononuclear cells (PBMCs) specific to four insulin B-chain amino acid 9–23-related peptides (B:9–23rPep) were increased in type 1 diabetes participants. This study aimed to investigate the PBMC frequencies in subtypes of type 1 diabetes using enzyme-linked immunospot assay. In this cross-sectional study, peripheral blood samples were obtained from 148 participants including 72 with acute-onset type 1 diabetes (AT1D), 51 with slowly progressive insulin-dependent diabetes mellitus (SPIDDM), and 25 with type 2 diabetes. The frequency of B:9–23rPep-specific IFN-γ-producing PBMCs was significantly higher in AT1D participants than in SPIDDM and type 2 diabetes participants. Meanwhile, a significant inverse correlation was observed between the PMBC frequencies and insulin secretion capacity in SPIDDM participants. These findings suggest that the increased peripheral B:9–23rPep-specific IFN-γ immunoreactivity reflects decreased functional β-cell mass and greater disease activity of type 1 diabetes.

  • Temperature-modulated cell-separation column using temperature-responsive cationic copolymer hydrogel-modified silica beads

    Nagase K., Inanaga D., Ichikawa D., Mizutani Akimoto A., Hattori Y., Kanazawa H.

    Colloids and Surfaces B: Biointerfaces (Colloids and Surfaces B: Biointerfaces)  178   253 - 262 2019.06

    ISSN  09277765

     View Summary

    © 2019 Elsevier B.V. There is strong demand for cell separation methods that do not decrease cell activity or modify cell surfaces. Here, new temperature-modulated cell-separation columns not requiring cell-surface premodification are described. The columns were packed with temperature-responsive cationic polymer hydrogel-modified silica beads. Poly(N-isopropylacrylamide-co-n-butyl methacrylate-co-N,N-dimethylaminopropyl acrylamide) hydrogels with various cationic moieties were attached to silica-bead surfaces by radical polymerization using N,Nʹ-methylenebisacrylamide as a crosslinking agent. The beads were packed into solid-phase extraction columns, and temperature-dependent cell elution from the columns was found using HL-60 and Jurkat cells. The retention HL-60 and Jurkat cells in columns containing cationic beads at 37 °C was 95.3% to 99.6% and 95.0% to 98.8%, respectively. By contrast, beads without cationic properties exhibited low cell retention (20.6% for HL-60 and 32.5% for Jurkat cells). The cells were mainly retained through both electrostatic and hydrophobic interactions. The retained HL-60 (4.9%) and Jurkat cells (40%) were eluted at 4 °C from the column with a low composition of cationic monomer (DMAPAAm, 1 mol% in copolymer), because the temperature-responsive hydrogels on the beads became hydrophilic, decreasing the hydrophobic interactions between the cells and the beads. A higher number of Jurkat cells than HL-60 cells were eluted because of differences in their electrostatic properties (Jurkat cells: −2.53 mV; HL-60 cells: −20.7 mV). The results indicated that cell retention by the hydrogel-coated beads packed in a solid phase extraction column could be modulated simply by changing the temperature.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Treatment of relapsed and refractory multiple myeloma

    Hisako Kunieda, Maki Hirao, Yutaka Hattori

    Hematological Malignancies (ver. 2) (Nihon Rinsho Co. Ltd)  78 ( 増刊号3 ) 638 - 644 2020.08

    Introduction and explanation (others), Joint Work

     View Summary

    Treatment strategies and regimen for relapsed or refractory multiple myeloma are summarized. Newly developed drugs or methods were also introduced.

  • A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma.

    Yamamoto T, Kosaka N, Hattori Y, Ochiya T.

    J Clin Med. 7 ( 3 ) E55 2018.03

    Introduction and explanation (scientific journal), Joint Work

  • 下痢の受診勧奨のポイント

    HATTORI YUTAKA

    日本薬剤師会雑誌 (日本薬剤師会)  67 ( 10 ) 1439 - 1441 2015

    Introduction and explanation (scientific journal), Single Work

  • 便秘の受診勧奨のポイント

    HATTORI YUTAKA

    日本薬剤師会雑誌 (日本薬剤師会)  67 ( 7 ) 957 - 961 2015

    Introduction and explanation (scientific journal), Single Work

  • 多発性骨髄腫の生物学、最近の話題

    HATTORI YUTAKA

    臨床血液 (日本血液学会)  54 ( 8 ) 692 - 695 2013

    Introduction and explanation (scientific journal), Single Work

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Presentations 【 Display / hide

  • A novel candidate for immunological target in treatment of multiple myeloma.

    Matsushita M, Saito S, Mori K, Yokoe S, Ichikawa D, Hattori Y

    An AACR Special Conference on Tumor Immunology and Immunotherapy (Boston, U.S.A.) , 2019.11, Poster (general), American Association of Cancer Research

  • Diverse molecular mechanisms of lenalidomide resistance in multiple myeloma cells

    Futo T, Uozaki R, Yamaguchi T, Yamamoto T, Tsuji H, Samata K, Ichikawa D, Matsushita M, Hattori Y

    81th Annual meeting of the Japanese Society of Hematology (Tokyo) , 2019.10, Oral Presentation(general), Japanese Society of Hematology

  • Dedifferentiation by reprogramming genes augmented drug resistance and clonal growth in myeloma cells

    Tsuji H, Futo T, Samata K, Yamamoto T, Ichikawa D, Matsushita M, Hattori Y

    81th annual meeting of the Japanese Society of Hematology (Tokyo) , 2019.10, Poster (general), Japanese Society of Hematology

  • Novel compound derived from natural products, komaroviquinone, showed anti-myeloma activity in vivo

    Samata K, Okayama M, Fujimori K, Yamamoto T, Ichikawa D, Matsushita M, Suto Y, Iwasaki G, Yamada T, Hattori Y

    78th annual meeting of the Japanese cancer association, 2019.09, Oral Presentation(general)

  • 天然物由来成分komaroviquinone及びその誘導体群はin vivoにおいて抗骨髄腫活性を示す

    佐俣光一、岡山幹夫、藤森宏太、西山沙織、辻宏樹、不藤拓海、市川大樹、松下麻衣子、岩崎源司、須藤豊、山田健人、平尾磨樹、国枝尚子、長田眞、服部豊

    日本薬学会生物系薬学部会第20回Pharmaco-Hematologyシンポジウム (東京) , 2019.06, Oral Presentation(general), 日本薬学会生物系薬学部会

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 新たな概念によるハイリスク骨髄腫の予後不良に関わる分子機構の探索と克服薬の開発

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 服部 豊, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • ハイリスク造血器腫瘍の髄外病変に着目した新規ターゲットの探索と創薬研究

    2017.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 服部 豊, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • Drug discovery based on novel concept for overcoming high-risk myeloma which is still intractable despite of recent progress in the treatment

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 服部 豊, Grant-in-Aid for Scientific Research (C), Principal Investigator

     View Summary

    Despite of the use of newly developed drugs, multiple myeloma (MM) with high-risk cytogenetic changes revealed significantly poor prognosis. Most patients acquired drug resistance and developed extra-medullary diseases.We found that N-cadherin and other mesenchymal genes were highly expressed in t(4;14)-positive high-risk MM patients, and E-cadherin and other epithelial genes were expressed in MM patients with normal karyotype. Those cadherin-positive MM cells demonstrated tumorigenicity to SCID mice.We also developed a new immunomudulatory drug (IMiDs), TC11, which showed anti-tumor activity via cereblon-independent pathway unlike previously developed IMiDs.In addition, we tried structural modification of TC11 and succeeded in significantly increasing water-solublity of TC11.

  • 難治性多発性骨髄腫に対する骨髄腫瘍血管新生を標的とした遺伝子治療法の開発と実践.

    2003.05
    -
    2004.03

    慶應義塾大学, Keio Gijuku Academic Development Funds, Research grant

  • 腫瘍血管新生を標的とした難治性多発性骨髄腫の新規治療法の開発と実践.

    2003.03
    -
    2004.03

    財団法人 がん研究振興財団, 第35回がん研究助成金, Research grant

Works 【 Display / hide

  • 教育上の業績

    HATTORI YUTAKA

     

    Other

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    Direct contribution to education of clinical residents in the management of in & out-patients of Keio University Hospital.

Intellectual Property Rights, etc. 【 Display / hide

  • フェニルフタルイミド修飾体及びそれを有効成分とする抗癌剤

    Application No.: 2016-207402  2016.10 

    Patent, Joint

  • 化合物もしくはその薬理学的に許容される塩、抗腫瘍剤、又は活性酸素産生剤

    Application No.: 特願2016-031897  2016.02 

    Publication No.: 特開2017-149658  2017.08 

    Patent, Joint

  • ペプチド、樹状細胞、細胞傷害性T細胞、白血病ワクチン、及び白血病受動免疫療法剤

    Application No.: 特願2013-194119  2013.09 

    Publication No.: 特開2015-71543  2015.04 

    Registration No.: 特許第6204130号  2017.09

    Patent, Joint

  • がん免疫療法

    Application No.: 特願2012-132288  2012.06 

    Publication No.: 特開2013-256454  2013.12 

    Registration No.: 特許第5984113号  2016.08

    Patent, Joint

  • 多発性骨髄腫に伴う骨融解症状を診断するための診断剤及びその使用法.

    Application No.: P2011-17058  2011.01 

    Publication No.: 特開2012-159297  2012.08 

    Patent, Joint

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Awards 【 Display / hide

  • がん集学的治療研究財団第29回一般研究助成

    服部豊., 2008.12, がん集学的治療研究財団, サリドマイドを用いた多発性骨髄腫に対する自家造血幹細胞移植後の維持・強化療法.

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  • 日本白血病研究基金平成20年度一般研究賞

    服部豊., 2008.10, 日本白血病研究基金, 多発性骨髄腫の再発の分子機構とその克服.

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  • 高松宮妃癌研究癌研究基金研究助成受賞

    服部豊., 2008.01, 高松宮妃癌研究癌研究基金, 難治性造血器腫瘍に対するポストサリドマイド世代の画期的治療法の開発.

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  • がん集学的治療研究財団 第29回一般研究助成受賞

    2008

  • 日本白血病研究基金一般研究賞受賞

    2008

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Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD: (CLINICAL PHYSIOLOGY AND THERAPEUTICS)

    2021

  • SPECIALIZED CANCER CLINICAL TRAINING

    2021

  • SEMINAR: (CLINICAL PHYSIOLOGY AND THERAPEUTICS)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • PRIOR LEARNING FOR CLINICAL PRACTICE 5

    2021

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Memberships in Academic Societies 【 Display / hide

  • The Pharmaceutical Society of Japan, 

    2008
    -
    Present
  • The Japanese Society of Myeloma, 

    2005
    -
    Present
  • American Society of Hematology, 

    1995
    -
    Present
  • The Japanese Cancer Association, 

    1988
    -
    Present
  • The Japanese Society of Hematology, 

    1985
    -
    Present

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Committee Experiences 【 Display / hide

  • 2020.04
    -
    2021.03

    president, The 45th Annual Meeting of the Japanese Society of Hematology

  • 2005
    -
    Present

    director, Japanese Society of Myeloma

  • 2000
    -
    Present

    Editorial Board, Japanese Journal of Clinical Oncology

  • 1985
    -
    Present

    Board of Councillors、Editorial provision committee , Japanese Society of Hematology