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Investigating the new strategy to suppress lung metastasis of sarcomas

Research Project

Project/Area Number 18K09051
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research Institution医療法人徳洲会野崎徳洲会病院(附属研究所)

Principal Investigator

Sasagawa Satoru  医療法人徳洲会野崎徳洲会病院(附属研究所), 研究所, 主任研究員 (80345115)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords滑膜肉腫 / 転移 / Twist1 / MICA/B / 免疫監視 / HDAC阻害剤 / 免疫回避 / がん微小環境 / NK細胞 / 骨軟部腫瘍 / 免疫療法
Outline of Final Research Achievements

Synovial sarcoma, classified as rare cancer, is known as one of the cancers with a poor prognosis due to its high incidence of metastasis. In this study, we demonstrated that Twist1 and metastasis-promoting environmental conditions suppress MICA/B expression, and low-dose HDAC inhibitors restore MICA/B expression. We also experimentally demonstrated that Twist1 is responsible for drug resistance to HDAC inhibitors; we identified SN38 as a drug that suppresses Twist1 expression and showed that it can be used in combination with HDAC inhibitors to improve drug efficacy. The results of this study clearly indicate the direction of novel molecular targeted therapy for synovial sarcoma metastasis.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、滑膜肉腫の転移に対して有効な治療法として、低用量HDAC阻害剤とイリノテカン(もしくはその代謝産物SN38)を併用することで、転移巣でもMICA/Bの発現を回復させ、NK細胞による腫瘍免疫反応により細胞死を誘導することを提案した。いずれの薬剤もいくつかのがんで承認されているものであることから、滑膜肉腫治療における臨床応用へのハードルは高くないと推測される。これまでに、滑膜肉腫の転移を抑制する、転移巣に於いても有効に作用する化学療法はほとんど無いため、本研究の成果は臨床応用への重要な礎になると期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2022 2021 2020 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The CDK4/6-UCHL5-BRD4 axis confers resistance to BET inhibitors in MLL-rearranged leukemia cells by suppressing BRD4 protein degradation2022

    • Author(s)
      Amari Keigo、Sasagawa Satoru、Imayoshi Natsuki、Toda Yuki、Hosogi Shigekuni、Imamura Toshihiko、Ashihara Eishi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 588 Pages: 147-153

    • DOI

      10.1016/j.bbrc.2021.12.063

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lung fibrosis is a novel therapeutic target to suppress lung metastasis of osteosarcoma2022

    • Author(s)
      Yui Yoshihiro、Kumai Jun、Watanabe Kenta、Wakamatsu Toru、Sasagawa Satoru
    • Journal Title

      International Journal of Cancer

      Volume: - Issue: 5 Pages: 739-751

    • DOI

      10.1002/ijc.34008

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Method for Polyacrylamide Gel Preparation Using N-hydroxysuccinimide-acrylamide Ester to Study Cell-Extracellular Matrix Mechanical Interactions2021

    • Author(s)
      Kumai Jun、Sasagawa Satoru、Horie Masanobu、Yui Yoshihiro
    • Journal Title

      Frontiers in Materials

      Volume: 8 Pages: 637278-637278

    • DOI

      10.3389/fmats.2021.637278

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular evidence of IGFBP-3 dependent and independent VD3 action and its nonlinear response on IGFBP-3 induction in prostate cancer cells2020

    • Author(s)
      Igarashi Ko、Yui Yoshihiro、Watanabe Kenta、Kumai Jun、Nishizawa Yasuko、Miyaura Chisato、Inada Masaki、Sasagawa Satoru
    • Journal Title

      BMC Cancer

      Volume: 20 Issue: 1 Pages: 802-802

    • DOI

      10.1186/s12885-020-07310-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low-dose eribulin reduces lung metastasis of osteosarcoma in vitro and in vivo.2019

    • Author(s)
      Watanabe K, Yui Y, Sasagawa S, Suzuki K, Kanamori M, Yasuda T, Kimura T.
    • Journal Title

      Oncotarget

      Volume: 10(2) Issue: 2 Pages: 161-174

    • DOI

      10.18632/oncotarget.26536

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium butyrate induces senescence and inhibits the invasiveness of glioblastoma cells.2018

    • Author(s)
      Nakagawa H, Sasagawa S, Itoh K.
    • Journal Title

      Oncology letter

      Volume: 15(2) Pages: 1495-1502

    • DOI

      10.3892/ol.2017.7518

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evidence for intrathecal sodium butyrate as a novel option for leptomeningeal metastasis.2018

    • Author(s)
      Nakagawa H, Yui Y, Sasagawa S, Itoh K.
    • Journal Title

      Journal of Neuro-Oncology

      Volume: 印刷中 Issue: 1 Pages: 43-50

    • DOI

      10.1007/s11060-018-2852-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 滑膜肉腫における転移環境条件とTwist1によるMICA/Bの発現抑制とHDAC阻害剤による MICA/Bの発現回復2021

    • Author(s)
      笹川覚、熊井準、由井理洋
    • Organizer
      日本癌学会 第80回学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 滑膜肉腫におけるMICA/Bの発現調節とそれを利用した免疫療法による転移抑制の検討2019

    • Author(s)
      笹川覚
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Vitamin D can enhance the effects of Anti-tumor treatment in prostate tumor cells.2019

    • Author(s)
      Satoru Sasagawa
    • Organizer
      ASCB|EMBO 2019 meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 滑膜肉腫におけるNKG2Dリガンドの発現調節と転移制御2018

    • Author(s)
      笹川覚、由井理洋、渡邉健太、伊藤和幸、水本篤志、中川秀光
    • Organizer
      日本癌学会第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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