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analysis of molecular mechanism of invasion in malignant gliomas and development of a novel treatment by inhibition of glioma cell migrations

Research Project

Project/Area Number 17K10872
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionOsaka Medical College (2019)
Sapporo Medical University (2017-2018)

Principal Investigator

Wanibuchi Masahiko  大阪医科大学, 医学部, 教授 (30343388)

Co-Investigator(Kenkyū-buntansha) 佐々木 祐典  札幌医科大学, 医学部, 講師 (20538136)
三上 毅  札幌医科大学, 医学部, 講師 (30372816)
三國 信啓  札幌医科大学, 医学部, 教授 (60314217)
小松 克也  札幌医科大学, 医学部, 助教 (60749498)
中崎 公仁  札幌医科大学, 医学部, 研究員 (70722461)
本望 修  札幌医科大学, 医学部, 教授 (90285007)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsglioma / glioblastoma / ACTC1 / SERPINEA1 / IL13 receptor alpha 2 / prognosis / invasion / migration / high grade glioma / 悪性神経膠腫 / 神経膠腫 / 浸潤能 / 分子メカニズム / 治療法
Outline of Final Research Achievements

Gliomas account for 24.1% of primary brain tumors. It is difficult to cure the disease with multimodality treatment combined with surgery, chemotherapy, and radiotherapy. The 5-year survival rate of glioblastoma which is the most malignant type of gliomas is only 10.1%. The reason for the poor prognosis is the invasive capacity, however, the factors and mechanisms of invasion or migration is still unknown.In this study, we found several factors which related to the prognosis of gliomas such as ACTC1 (actin alpha cardiac muscle 1), SERPINEA1, IL13 receptor alpha 2. Among these, ACTC1 was also closely related to the invasion of malignant gliomas. In addition, timelapse study of U87 malignant glioma cell line revealed gene knockdown of ACTC1 using by siRNA resulted in the inhibition of migration of glioma cells. The present study demonstrated that targeting of migration capacity of glioma cells may lead to the improvement of prognosis of malignant gliomas.

Academic Significance and Societal Importance of the Research Achievements

グリオーマの中でも、最悪性型である膠芽腫の5年生存率は10.1%と非常に予後不良である。特に周囲脳への浸潤により完治が困難であることが理由の一つである。本研究で得られた知見から、特にACTC1は予後、浸潤に関与することが明らかとなり、かつ、ACTC1は機能的にグリオーマの遊走に関与していることが明らかとなった。本研究を更に進め、予後や浸潤に関与する因子を標的とした今までにない治療法を確立することで、予後不良であるグリオーマの予後を改善できる可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results) Presentation (4 results) (of which Invited: 1 results)

  • [Int'l Joint Research] Yale University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Yale University(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Actin, alpha, cardiac muscle 1 ( ACTC1 ) knockdown inhibits the migration of glioblastoma cells in vitro2018

    • Author(s)
      Wanibuchi Masahiko、Ohtaki Shunya、Ookawa Satoshi、Kataoka-Sasaki Yuko、Sasaki Masanori、Oka Shinichi、Kimura Yusuke、Akiyama Yukinori、Mikami Takeshi、Mikuni Nobuhiro、Kocsis Jeffery D.、Honmou Osamu
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 392 Pages: 117-121

    • DOI

      10.1016/j.jns.2018.07.013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Digital Polymerase Chain Reaction Quantification of SERPINA1 Predicts Prognosis in High-Grade Glioma2018

    • Author(s)
      Satoshi Ookawa, Masahiko Wanibuchi'Correspondence information about the author Masahiko WanibuchiEmail the author Masahiko Wanibuchi, Yuko Kataoka-Sasaki, Masanori Sasaki, Shinichi Oka, Shunya Ohtaki, Shouhei Noshiro, Katsuya Komatsu, Yukinori Akiyama, Takeshi Mikami, Nobuhiro Mikuni, Jeffery D. Kocsis, Osamu Honmou
    • Journal Title

      World Neurosurg.

      Volume: e783 Pages: e783-e789

    • DOI

      10.1016/j.wneu.2017.12.166

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 認知機能障害で発症した脳腫瘍症例の検討2019

    • Author(s)
      鰐渕昌彦、秋山幸功、三國信啓
    • Organizer
      第28回 日本脳ドック学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ACTC1は膠芽腫細胞の遊走に関与している2019

    • Author(s)
      鰐渕昌彦、 大瀧隼也、大川聡史、佐々木優子、佐々木祐典、秋山幸功、三國信啓、本望修
    • Organizer
      第24回 日本脳腫瘍の外科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳腫瘍の臨床・基礎研究(教育講演)2018

    • Author(s)
      鰐渕昌彦
    • Organizer
      第81回日本脳神経外科学会北海道支部会、札幌、2018年9月29日
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Gene knockdown of ACTC1 inhibits migration of glioblastoma in vitro2017

    • Author(s)
      9.Wanibuchi M, Ohtaki S, Ookawa S, Kataoka-Sasaki Y, Sasaki M, Oka S, Kimura Y, Akiyama Y, Mikami T, Mikuni N, Kocsis JD, Honmou O
    • Organizer
      第35回日本脳腫瘍学会学術総会、高松
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-02-21  

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