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Development of novel diagnostic system using exsomes

Research Project

Project/Area Number 20K07817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

Ito Masafumi  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (80393114)

Co-Investigator(Kenkyū-buntansha) 川上 恭司郎  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (90589227)
水谷 晃輔  岐阜大学, 医学部附属病院, 准教授 (80397356)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsエクソソーム / 細胞外小胞 / アルツハイマー病 / 診断法
Outline of Research at the Start

細胞から分泌されるエクソソームは由来する細胞の特徴を反映することから、体液中エクソソームは新たなタイプのバイオマーカーとして期待されている。本研究では、新規方法を用いて血清から単離したエクソソーム中のアミロイドベータ・p-Tauの検出によりアルツハイマー病と対照の鑑別が可能かどうかを検証するとともに、プロテオーム解析を行い、新規診断マーカーの候補を同定する。続いて、マーカーの検出システム構築した後に多検体で解析を行い、アルツハイマー病・MCI(軽度認知機能障害)と対照症例の鑑別における臨床的有用性を検証する。

Outline of Final Research Achievements

The purpose of this study was to purify exosomes from serum and identify novel biomarkers for Alzheimer's disease (AD) by proteomic analysis. Sera from AD patients and healthy subjects were used as samples. (1) Proteomic analysis of exosomes purified by the phosphatidylserine affinity method using stable isotope labeling identified 15 proteins that were significantly increased or decreased in AD patients. (2) Proteomic analysis of exosomes purified by antibodies against exosome marker proteins using label-free strategy identified 13 proteins that were significantly increased or decreased in AD patients. We will validate the significance of these selected biomarker candidates and develop a novel serum exosome-based diagnostic system for AD.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会を迎えているわが国では認知症の早期診断は喫緊の課題である。本研究では、血清中のエクソソームに焦点を当て、アルツハイマー病の新規バイオマーカーの探索を行った。本研究により、アミロイドβ、リン酸化タウなど既知のバイオマーカー以外の候補タンパク質を同定した。本研究を発展させることにより、将来的には血清中のエクソソームを用いたアルツハイマー病の診断が可能になることが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2020

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] miRNA-93 in Serum Extracellular Vesicles Before and After Low Dose Rate Prostate Brachytherapy.2021

    • Author(s)
      Iinuma K, Kawakami K, Mizutani K, Fujita Y, Yamaguchi T, Ito M, Kumano T, Matsuo M, Nakano M, Koie T, Ito M, Kato T
    • Journal Title

      Anticancer Res.

      Volume: 41(5) Issue: 5 Pages: 2411-2418

    • DOI

      10.21873/anticanres.15016

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Profiling of Serum Extracellular Vesicles Reveals miRNA-4525 as a Potential Biomarker for Advanced Renal Cell Carcinoma2021

    • Author(s)
      MURAMATSU-MAEKAWA YUKA、KAWAKAMI KYOJIRO、FUJITA YASUNORI、TAKAI MANABU、KATO DAIKI、NAKANE KEITA、KATO TAKU、TSUCHIYA TOMOHIRO、KOIE TAKUYA、MIURA YURI、ITO MASAFUMI、MIZUTANI KOSUKE
    • Journal Title

      Cancer Genomics - Proteomics

      Volume: 18 Issue: 3 Pages: 253-259

    • DOI

      10.21873/cgp.20256

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomic analysis of extracellular vesicles identified PI3K pathway as a potential therapeutic target for cabazitaxel‐resistant prostate cancer2021

    • Author(s)
      Hishida Seiji、Kawakami Kyojiro、Fujita Yasunori、Kato Taku、Takai Manabu、Iinuma Koji、Nakane Keita、Tsuchiya Tomohiro、Koie Takuya、Miura Yuri、Ito Masafumi、Mizutani Kosuke
    • Journal Title

      The Prostate

      Volume: 81 Issue: 9 Pages: 592-602

    • DOI

      10.1002/pros.24138

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies.2021

    • Author(s)
      Kawakami, K. Fujita, Y. Kato, T. Horie, K. Koie, T. Umezawa, K. Tsumoto, H. Miura, Y. Katagiri, Y. Miyazaki, T. Ohsawa, I. Mizutani, K. Ito, M.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 15000-15000

    • DOI

      10.1038/s41598-021-94603-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD44v8-10 mRNA contained in serum exosomes as a diagnostic marker for docetaxel resistance in prostate cancer patients2020

    • Author(s)
      Taku Kato、Kosuke Mizutani、Kyojiro Kawakami、Yasunori Fujita、Hidetoshi Ehara、Masafumi Ito
    • Journal Title

      Heliyon

      Volume: 6(7) Issue: 7 Pages: e04138-e04138

    • DOI

      10.1016/j.heliyon.2020.e04138

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum Exosomal Gamma-Glutamyltransferase Activity Increased in Patients with Renal Cell Carcinoma with Advanced Clinicopathological Features2020

    • Author(s)
      Kengo Horie、Kyojiro Kawakami、Yasunori Fujita、Yoko Matsuda、Tomio Arai、Natsuko Suzui、Tatsuhiko Miyazaki、Takuya Koie、Kosuke Mizutani、Masafumi Ito
    • Journal Title

      Oncology

      Volume: 98(10) Issue: 10 Pages: 734-742

    • DOI

      10.1159/000508688

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Proteomic analysis of serum extracellular vesicles derived from follicular thyroid cancer patients2022

    • Author(s)
      Kawakami, K., EDO, N., Morita, K., Ishikawa, T., Onose, H., Fukumori, T., Tsumoto, H., Umezawa, K., Miura, Y., Fujita, Y., Ohsawa, I., Ito, M.
    • Organizer
      第45回日本基礎老化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 前立腺特異的膜抗原(PSMA)を発現する細胞外小胞の測定系構築と前立腺および腎がんの診断における臨床的有用性2021

    • Author(s)
      川上 恭司郎, 藤田 泰典, 加藤 卓, 堀江 憲吾, 古家 琢也, 梅澤 啓太郎, 津元 裕樹, 三浦 ゆり, 片桐 恭雄, 宮崎 龍彦, 大澤 郁朗, 水谷 晃輔, 伊藤 雅史
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 細胞外小胞のプロテオーム解析によるカバジタキセル耐性因子の解明2021

    • Author(s)
      水谷晃輔、菱田勢始、川上恭司郎、藤田泰典、加藤卓、高井学、飯沼光司、中根慶太、土屋朋大、三浦ゆり、伊藤雅史、古家卓也
    • Organizer
      第30回泌尿器科分子・細胞研究会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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