Matsushita, Maiko

写真a

Affiliation

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

Position

Associate Professor

External Links
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Career 【 Display / hide 】

  • 2000.04
    -
    2006.06

    慶応義塾大学医学部内科学教室助手

  • 2001.04
    -
    2004.03

    米国スローンケタリング記念癌研究所研究員

  • 2006.07
    -
    2010.03

    慶応義塾大学医学部先端医科学研究所助手

  • 2010.04
    -
    2014.03

    慶応義塾大学薬学部専任講師

  • 2015.04
    -
    Present

    慶應義塾大学薬学部准教授

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Academic Background 【 Display / hide 】

  • 1995.03

    Keio University, Faculty of Medicine

    University, Graduated

  • 2000.03

    Keio University, Graduate School, Division of Medicine

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 医学, Keio University, Coursework, 2001.10

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Research Areas 【 Display / hide 】

  • Immunology

  • General internal medicine (including psychosomatic medicine) (General Internal Medicine (includes Psychosomatic Medicine))

  • Hematology

  • Oncology

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Research Themes 【 Display / hide 】

  • Development of novel immunotherapy against cancer, 

    2010.04
    -
    Present

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Papers 【 Display / hide 】

  • Characteristics of a Novel Target Antigen Against Myeloma Cells for Immunotherapy

    Maiko Matsushita, Saku Saito, Shinya Yokoe, Daiju Ichikawa and Yutaka Hattori

    Vaccines （MDPI)  8 （ 4 ） 579 - 591 2020.10

    Research paper (scientific journal), Accepted

  • A Study on the Description of Anticancer Drug Combination Therapy in Package Insert

    Shibata S, Matsushita M, Tsukamoto K, Chiba K, Ozaki K, Suzuki T

    BPB Reports （The Pharmaceutical Society of Japan)  3 （ 5 ） 157 - 165 2020.10

    Joint Work, Accepted

  • 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.

  • A novel derivative (GTN024) from a natural product, komaroviquinone, induced the apoptosis of high-risk myeloma cells via reactive oxygen production and ER stress.

    Okayama M, Kitabatake S, Sato M, Fujimori K, Ichikawa D, Matsushita M, Suto Y, Iwasaki G, Yamada T, Kiuchi F, Hirao M, Kunieda H, Osada M, Okamoto S, Hattori Y

    Biochem Biophys Res Commun （Biochemical and Biophysical Research Communications)  505 （ 3 ） 787 - 793 2018.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0006291X

    　View Summary

    © 2018 Elsevier Inc. New drugs have significantly improved the survival of patients with multiple myeloma (MM), but the prognosis of MM patients with high-risk cytogenetic changes such as t(4; 14), t(14; 16) or del17p remains very poor. A natural product, komaroviquinone (KQN), was originally isolated from the perennial semi-shrub Dracocephalum komarovi and has anti-protozoal activity against Trypanosoma cruzi, the organism causing Chagas’ disease. Here we demonstrate that a novel KQN-derivative, GTN024, has an anti-MM effect both in vitro and in vivo. GTN024 induced the apoptosis of MM cell lines including those with high-risk cytogenetic changes. GTN024 produced reactive oxygen species (ROS) and increased phosphorylated eIF2α. The ROS production and subsequent endoplasmic reticulum (ER) stress are thought to play a key role in GTN024-induced apoptosis, as the apoptosis was completely abrogated by anti-oxidant treatment. In a mouse xenograft model, an intraperitoneal injection of 20 mg/kg of GTN024 significantly delayed tumor growth. Hematological toxicity and systemic toxicity as indicated by weight loss were not observed. These results suggest that the novel KQN-derivative GTN024 could become a candidate drug for treating high-risk MM.

  • Anticancer Drug Prescription Patterns in Japan: Future Directions in Cancer Therapy

    Shoyo Shibata,Maiko Matsushita,Yoshimasa Saito,Takeshi Suzuki

    Therapeutic Innovation & Regulatory Science （Therapeutic Innovation and Regulatory Science)  52 （ 6 ） 718 - 723 2018.03

    Joint Work, Accepted,  ISSN  21684790

    　View Summary

    © The Author(s) 2018. Background: Despite their benefits, the rapid development of new cancer treatments has been a significant driver of increasing health care expenditures in the face of limited health care budgets. In this study, we analyzed the prescribing trends for anticancer drugs from 2010 through 2016 in Japan and sought to identify unique trends that could provide a basis for future medical economic research aiming to develop more efficacious and cost-effective cancer therapies. Methods: We used publicly available marketing data for anticancer drugs in Japan for 2010-2016. The drugs selected for this research were categorized according to the Anatomical Therapeutic Chemical Classification System. We investigated the overall anticancer drug market size, the number of anticancer drugs, the top 30 selling anticancer categories, sales and prescription volumes, and changes in sales and prescription volumes between 2010 and 2016 in the country. Results: The anticancer agent market expanded each year from 2010 to 2016, with sales exceeding 1 trillion yen in 2015. The proportion of molecular targeted drugs (antineoplastic mAbs and protein kinase inhibitors) among the top 30 selling anticancer categories has continued to increase, and both the sales and prescription volumes of these drugs exceeded those of drugs in other categories, suggesting that these treatments play a dominant role in cancer pharmacotherapy. Conclusion: The availability and increasing use of innovative but more expensive targeted therapies were major drivers of increases in pharmaceutical expenditures for cancer treatment in Japan. Therefore, the effective use of genetic testing can mitigate these rising costs.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Immunomodulatory effects of drugs for effective cancer immunotherapy.

    Matsushita M,Kawaguchi M.

    Journal of Oncology    ID 8653489 2018.10

    Introduction and explanation (scientific journal), Joint Work

  • Immunotherapy Targeting Leukemia Stem Cells.

    Matsushita M

    International Journal of Hematological Disorders (Science and Education Publishing)     39 - 42 2015.07

    Introduction and explanation (scientific journal), Single Work

  • 造血器腫瘍における免疫療法.

    松下麻衣子.

    産科と婦人科 (診断と治療社)  81(2)   217-222 2014.02

    Introduction and explanation (commerce magazine), Single Work

  • がん幹細胞を標的とした免疫療法.

    河上裕, 松下麻衣子, 植田良, 塚本信夫, 大多茂樹.

    日本臨牀 (日本臨牀)  70(12)   p2142-2146 2012.12

    Introduction and explanation (commerce magazine), Joint Work

  • Quantitative analysis of PRAME for detection of minimal residual disease in leukemia.

    Matsushita M*, Yamazaki R, Kawakami Y.

    Methods Mol Med (Human Press Inc.)  97   267-275 2004.02

    Introduction and explanation (scientific journal), Joint Work

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Presentations 【 Display / hide 】

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

    Maiko Matsushita, Saku Saito, Kanae Mori, Shinya Yokoe, Daiju Ichikawa, Yutaka Hattori

    An AACR Special Conference on Tumor Immunology and Immunotherapy, 2019.11, Poster (general)

  • 骨髄腫細胞においてリプログラミング遺伝子による脱分化が薬剤抵抗性とクローン増殖性を増強する

    辻宏樹,不藤 拓海, 佐俣 光一, 山元 智史, 市川 大樹, 松下 麻衣子, 服部 豊

    第81回日本血液学会学術集会 (東京) , 2019.10, Media report,etc., 日本血液学会

  • 多発性骨髄腫細胞のレナリドミド耐性に関する多様な分子メカニズム

    不藤拓海、宇於崎 凉, 山口 高史, 山元 智史, 辻 宏樹, 佐俣 光一, 市川 大, 松下 麻衣子, 服部 豊

    第81回日本血液学会学術集会 (東京) , 2019.10, Oral Presentation(general), 日本血液学会

  • komaroviquinoneという天然物由来の新規化合物がin vivoにおいて抗MM活性を示す

    佐俣光一,岡山幹夫,藤森宏太,山元智史,市川大樹,松下麻衣子,須藤豊,岩崎源司,山田健人,服部豊　

    第78回日本癌学会学術総会 (京都) , 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, 2019.06, Oral Presentation(general)

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

  • Development of novel combined immunotherapy using in silico screening system

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 松下　麻衣子, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • Development of novel immunotherapy targeting leukemic stem cells.

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 松下　麻衣子, Grant-in-Aid for Scientific Research (C), Principal Investigator

    　View Summary

    Novel cancer antigen, CXorf48, was highly expressed in patients-derived leukemic stem cells. Cytotoxic T cells induced with HLA-A24-restricted epitope could recognize these leukemic stem cells from leukemic patients. We also found the correlation between existence of anti-CXorf48 CTL in peripheral blood of leukemic patients and their clinical courses.
    Moreover, demethylating agent up-regulated expression of CXorf48 gene in leukemic cells, but not in normal blood cells, suggesting that combination of demethylating agent with immunotherapy might be effective. Therefore, immnotherapy targeting CXorf48 would be a promising treatment for leukemia by eradicating leukemic stem cells.

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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医薬組成物

    Application No.： 2016-207402  2016.10 

    Patent, Joint, National application

  • 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.： 2016-031897  2016.02 

    Publication No.： 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.： 2013-194119  2013.09 

    Announcement No.： 2015-71543  2015.04 

    Registration No.： 6204130  2017.09

    Patent, Joint, National application

  • がん免疫療法

    Application No.： 2012-132288  2012.06 

    Announcement No.： 2013-256454(P2013-256454A)  2013.12 

    Registration No.： 5984113  2016.08

    Patent, Joint, National application

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Awards 【 Display / hide 】

  • 日本骨髄腫学会奨励賞

    松下麻衣子, 2015.05, 日本骨髄腫学会, 新規ホメオボックス蛋白由来抗原を用いた多発性骨髄腫に対する複合的免疫治療法の開発

    Type of Award： Awards of National Conference, Council and Symposium

  • 日本白血病研究基金一般研究賞

    松下麻衣子, 2013.11, 日本白血病研究基金, 新規癌抗原を標的とした多発性骨髄腫に対する免疫治療法の開発

    Type of Award： Awards of Publisher, Newspaper Company and Foundation

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Courses Taught 【 Display / hide 】

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

    2020

  • SEMINAR: (CLINICAL PHYSIOLOGY AND THERAPEUTICS)

    2020

  • RESEARCH FOR BACHELOR'S THESIS 1

    2020

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2020

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2020

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