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Novel molecular therapy targeting aberrant glycogen synthase kinase-3 beta in soft tissue sarcoma

Research Project

Project/Area Number 16K20040
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionKanazawa University

Principal Investigator

Abe Kensaku  金沢大学, 附属病院, 医員 (60749191)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsGSK-3β / soft tissue sarcoma / GSK3β / 軟部肉腫 / 滑膜肉腫 / 線維肉腫 / 作用機序 / in vivo / 分子標的薬
Outline of Final Research Achievements

Expression of the active form of GSK3β was higher in sarcoma cells than in fibroblasts. Inhibition of GSK3β activity by pharmacological inhibitors or of its expression by RNA interference suppressed the proliferation of sarcoma cells and induced apoptosis. GSK3β inhibition suppressed the expression of cyclin D1, CDK4 and matrix metalloproteinase (MMP)-2 as well as sarcoma cell invasion of collagen gel. Treatment by intraperitoneal injection of either of the GSK3β inhibitors attenuated the proliferation of sarcoma xenografts in mice in comparison to the mice treated with dimethyl sulfoxide (diluent of GSK3β inhibitor). Pathology examination revealed marked necrosis in the tumors of mice treated with the inhibitor. No obvious side effects or adverse events were observed in the treated mice.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2018 2017 2016

All Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Novel molecular therapy targeting aberrant GSK3β in soft tissue sarcomas2018

    • Author(s)
      Kensaku Abe
    • Organizer
      American Academy of Orthopaedic Surgeons 2018 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 軟部肉腫に対するGSK3βを標的とした新しい分子標的治療2018

    • Author(s)
      阿部健作
    • Organizer
      第91回 日本整形外科災害外科学会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel molecular therapy targeting aberrant glycogen synthase kinase-3β in soft tissue sarcoma: a basic research2018

    • Author(s)
      Kensaku Abe
    • Organizer
      EFORT 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GSK3β阻害薬による軟部肉腫への新しい分子標的治療2018

    • Author(s)
      阿部健作
    • Organizer
      第51回 日本整形外科学会 骨・軟部腫瘍学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 軟部肉腫に対するGSK3β阻害による新しい分子標的治療2017

    • Author(s)
      阿部健作
    • Organizer
      第55回 日本癌治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] GSK3β阻害による軟部肉腫の新しい分子標的治療2017

    • Author(s)
      阿部健作
    • Organizer
      第36回 日本整形外科学会基礎学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] GSK3β阻害による軟部肉腫の治療効果の検討2016

    • Author(s)
      阿部 健作
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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