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The regulation of glioma stem cell by the transcription factor "RBPJ" suppression in Notch signal

Research Project

Project/Area Number 17K10858
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKanazawa University

Principal Investigator

TANAKA SHINGO  金沢大学, 医学系, 助教 (40507084)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsRBPJ / Notchシグナル / グリオーマ幹細胞 / STATシグナル / 膠芽腫 / STAT3 / RBPJk / Stat3 / RBPJk
Outline of Final Research Achievements

Glioblastoma is a primary malignant brain tumor and is an intractable disease with a poor prognosis. This study is a targeted therapeutic study against glioblastoma stem cells. We focused on the nuclear transcription factor RBPJ, which is an active indicator of Notch signaling. RBPJ expression was higher in glioblastoma tissue than in normal brain, and glioblastoma stem cells had higher RBPJ expression than differentiated glioblastoma cells. RBPJ inhibition of glioblastoma stem cells results in decreased cell proliferation and loss of stem cell phenotype. As a mechanism, we found that inhibition of RBPJ induced inhibition of the downstream factors interleukin 6 and STAT signal. Tumor reduction was also checked in animal studies. It suggested that inhibition of RBPJ is effective for the regulation of glioblastoma stem cells.

Academic Significance and Societal Importance of the Research Achievements

Notchシグナルは様々な癌腫において幹細胞性の維持や細胞増殖などの機能を有するとされている。膠芽腫幹細胞においても同様であり、本研究ではNotchシグナルの活性に重要な核内転写因子RBPJが膠芽腫幹細胞で高発現していることを確認した。膠芽腫幹細胞のRBPJを抑制することにより腫瘍細胞の増殖遅延や幹細胞性維持機能の低下が認められた。従って、膠芽腫幹細胞制御にRBPJが重要な役割を果たしていることが示唆された。

Report

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

    (10 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Symptomatic delayed in-stent thrombus formation after carotid artery stenting for radiation-induced stenosis: a case report2018

    • Author(s)
      田中 慎吾、 東馬 康郎、 吉川 陽文、 木多 眞也
    • Journal Title

      Japanese Journal of Stroke

      Volume: 40 Issue: 5 Pages: 362-366

    • DOI

      10.3995/jstroke.10555

    • NAID

      130007486211

    • ISSN
      0912-0726, 1883-1923
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] The regulation of the important nuclear transcription factor “RBPJ” of Notch signal in glioblastoma cells2019

    • Author(s)
      Guangtao Zhang, Shingo Tanaka, Hemragul Sabit, Mitsutoshi Nakada
    • Organizer
      ASNO 2019 The 16th Meeting of the Asian Society for Neuro-Oncology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Notchシグナル関連核内転写因子RBPJの抑制による抗膠芽腫細胞作用2019

    • Author(s)
      張光濤、田中慎吾、淑瑠 ヘムラサビット、中田光俊
    • Organizer
      第20回日本分子脳神経外科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 小児テント上腫瘍の1例2018

    • Author(s)
      田中慎吾、宮下勝吉、木下雅史、中田光俊
    • Organizer
      第55回北陸脳腫瘍懇話会
    • Related Report
      2018 Research-status Report
  • [Presentation] 段階的治療を施行した充実性小脳虫部頭側血管芽腫の1例2018

    • Author(s)
      田中慎吾、宮下勝吉、木下雅史、見崎 孝一、笹川泰生、内山尚之、林 康彦、 中田光俊
    • Organizer
      第95回日本脳神経外科学会中部支部会
    • Related Report
      2018 Research-status Report
  • [Presentation] 充実性小脳虫部血管芽腫に対する3Dシミュレーション画像の有用性の検討2018

    • Author(s)
      田中慎吾、宮下勝吉、中田光俊
    • Organizer
      第23回日本脳腫瘍の外科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膠芽腫RPA分類クラス5における予後良好因子の検討2018

    • Author(s)
      田中慎吾、宮下勝吉、玉井 翔、木下雅史、中田光俊
    • Organizer
      第77回脳神経外科学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Analysis of prognostic factors in glioblastoma RPA class Ⅳ and Ⅴ2018

    • Author(s)
      Shingo Tanaka, Masashi kinoshita M, Katsuyoshi Miyashita K, Mitsutoshi Nakada
    • Organizer
      The 15th Meeting of the Asian Society for Neuro-Oncology,
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Notchシグナル活性化促進転写因子RBPJkの抑制による膠芽腫幹細胞悪性形質の制御2018

    • Author(s)
      田中慎吾, 中田光俊
    • Organizer
      第36回日本脳腫瘍学会学術集会
    • Related Report
      2018 Research-status Report
  • [Book] Clinical Neuroscience 脳腫瘍のゲノムとエピゲノム2018

    • Author(s)
      田中慎吾、中田光俊
    • Publisher
      中外医学社
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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