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Development of antiangiogenic therapy targeting mTOR signaling pathway for the treatment of complicated vascular malformations

Research Project

Project/Area Number 18K16974
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56070:Plastic and reconstructive surgery-related
Research InstitutionHokkaido University

Principal Investigator

ISHIKAWA Kosuke  北海道大学, 医学研究院, 客員研究員 (60791374)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords血管奇形 / 血管新生 / 血管内皮細胞 / 硬化療法 / ラパマイシン / シロリムス / 動静脈奇形 / 脈管奇形
Outline of Final Research Achievements

The purpose of this study was to evaluate angiogenesis through the mTOR signaling pathway as a therapeutic target in vascular malformations. Histopathological examination of vascular malformations after sclerotherapy showed angiogenesis in sclerosed vessels. The vascular endothelial cells of neovasculature were immunohistochemically positive for phospho-mTOR. This study demonstrated the possibility of the antiangiogenic therapy targeting mTOR signaling pathway for the treatment of vascular malformations to prevent recanalization of sclerosed vessels.

Academic Significance and Societal Importance of the Research Achievements

血管奇形は約40%が難治性であり、その多くが小児期から生涯にわたり治療を要するため、新たな薬物療法の開発が望まれる。本研究により、血管奇形に対する硬化療法後にmTOR経路を介した血管新生が起きている可能性が示唆された。硬化療法後の血管内血管新生による血管再疎通を阻害し硬化療法の効果を高めるため、mTOR経路をターゲットにした新たな薬物療法の可能性が示された。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 1 results)

  • [Journal Article] Wound-healing problems associated with combined vascular malformations in Klippel-Trenaunay syndrome2019

    • Author(s)
      Ishikawa Kosuke、Yamamoto Yuhei、Funayama Emi、Furukawa Hiroshi、Sasaki Satoru
    • Journal Title

      Advances in Wound Care

      Volume: 8 Issue: 6 Pages: 246-255

    • DOI

      10.1089/wound.2018.0835

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Squamous cell carcinoma arising in a chronic leg ulcer in Klippel-Trenaunay syndrome after the Charles procedure: A case with 40 years of follow up2019

    • Author(s)
      Ishikawa Kosuke、Funayama Emi、Yamamoto Yuhei、Furukawa Hiroshi、Hayashi Toshihiko、Murao Naoki、Osawa Masayuki、Maeda Taku、Fujita Munezumi、Sasaki Satoru
    • Journal Title

      The Journal of Dermatology

      Volume: 46 Issue: 11

    • DOI

      10.1111/1346-8138.15001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集/患児・家族に寄り添う血管腫・脈管奇形の医療 混合型脈管奇形2019

    • Author(s)
      佐々木了, 石川耕資
    • Journal Title

      PEPARS

      Volume: 145 Pages: 53-60

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 上肢の過成長を伴う血管奇形症例の検討2019

    • Author(s)
      石川耕資, 蕨 雄大, 藤田宗純, 森山宇蘭, 舟山恵美, 山本有平, 佐々木了
    • Organizer
      第62回日本手外科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] PI3Kα阻害薬による静脈奇形とPROSの治療2019

    • Author(s)
      石川耕資
    • Organizer
      第62回日本形成外科学会総会・学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 下肢Klippel-Trenaunay症候群における創傷の検討2019

    • Author(s)
      石川耕資, 蕨 雄大, 藤田宗純, 森山宇蘭, 竹田朋弘, 三田村真太郎, 舟山恵美, 佐々木了
    • Organizer
      第11回日本創傷外科学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 下肢Klippel-Trenaunay症候群に対する治療の検討2019

    • Author(s)
      石川耕資, 藤田宗純, 竹田朋弘, 三田村真太郎, 舟山恵美, 佐々木了
    • Organizer
      第16回日本血管腫血管奇形学会学術集会
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2021-02-19  

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