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The effect of the Notch inhibitor and a preclinical study for glioma stem cells

Research Project

Project/Area Number 25861263
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionKanazawa University

Principal Investigator

TANAKA Shingo  金沢大学, 医学系, 協力研究員 (40507084)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords膠芽腫 / MRK-003 / Notch阻害剤 / グリオーマ幹細胞 / 膠芽腫幹細胞 / Notchシグナル
Outline of Final Research Achievements

Glioblastoma is the most malignant primary brain tumor in humans. The patients with glioblastoma have a uniformly poor prognosis. The significance of targeting glioblastoma-initiating cells (GICs) may be important for successful treatment of glioblastoma. In this study, we analyzed the effect of the Notch inhibitor MRK-003 on nine patient-derived GICs. MRK-003 suppressed GIC's proliferation and stemness maintenance, and promoted their apoptosis. Based on their sensitivities to MRK-003, the nine GICs were divided into “relatively sensitive” and “relatively resistant” GICs. The IC50(half maximal inhibitory concentration) of MRK003 in a set of GICs exhibited a negative correlation with CD44 and positive correlation with CD133. Our study suggested that MRK-003 may exhibit significant therapeutic potential for GICs with CD44-high and CD133-low expression.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013

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

  • [Journal Article] Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells2015

    • Author(s)
      Tanaka S, Nakada M, Yamada D, Nakano I, Todo T, Ino Y, Hoshii T, Tadokoro Y, Ohta K, Ali MA, Hayashi Y, Hamada J, Hirao A.
    • Journal Title

      J Neurooncol.

      Volume: 121 Issue: 2 Pages: 239

    • DOI

      10.1007/s11060-014-1630-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebral Infarction Related to Carmustine Wafers in Glioblastoma: A Case Report2015

    • Author(s)
      Nakada M, Tanaka S, Oishi M, Miyashita K, Misaki K, Mohri M, Hayashi Ya, Uchiyama N, Watanabe T, Hayashi Yu
    • Journal Title

      NMC Case Report Journal

      Volume: 2 Issue: 1 Pages: 36-39

    • DOI

      10.2176/nmccrj.2014-0080

    • NAID

      130004698823

    • ISSN
      2188-4226
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelioid glioblastoma arising from pleomorphic xanthoastrocytoma with the BRAF V600E mutation.2014

    • Author(s)
      Tanaka S, Nakada M, Nobusawa S, Suzuki SO, Sabit H, Miyashita K, Hayashi Y.
    • Journal Title

      Brain Tumor Pathology

      Volume: 31 Issue: 3 Pages: 172-6

    • DOI

      10.1007/s10014-014-0192-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of Tsc1 accelerates malignant gliomagenesis when combined with oncogenic signals.2014

    • Author(s)
      Yamada D, Hoshii T, Tanaka S, Hegazy AM, Kobayashi M, Tadokoro Y, Ohta K, Ueno M, Ali MAE, Hirao A.
    • Journal Title

      J Biochem.

      Volume: 155 Issue: 4 Pages: 227-33

    • DOI

      10.1093/jb/mvt112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] 膠芽腫幹細胞株に対するγ‐セクレターゼ阻害剤MRK003の効果2013

    • Author(s)
      田中慎吾、中田光俊、中野伊知郎、藤堂具紀、稲生靖、林裕、濵田潤一郎、平尾敦
    • Organizer
      第72回日本脳神経外科学会総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Notch阻害による膠芽腫幹細胞の制御2013

    • Author(s)
      田中慎吾、中田光俊、山田大祐、中野伊知郎、藤堂具紀、稲生靖、林裕、濵田潤一郎、平尾敦
    • Organizer
      第14回日本分子脳神経外科学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Strong therapeutic potential of γ-secretase inhibitor MRK003 for GBM stem-like cells with high CD44 and low CD133 expression2013

    • Author(s)
      Shingo Tanaka, Mitsutoshi Nakada, Daisuke Yamada, Ichiro Nakano, Tomoki Todo, Yutaka Hayashi, Jun-ichiro Hamada, Atsushi Hirao
    • Organizer
      4th Quadrennial Meeting of the World Federation of Neuro-Oncology
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Mesenchymal type GBMに対するNotch阻害剤の有効性2013

    • Author(s)
      田中慎吾、中田光俊、山田大祐、中野伊知郎、藤堂具紀、稲生靖、林裕、濵田潤一郎、平尾敦
    • Organizer
      第31回日本脳腫瘍学会
    • Place of Presentation
      宮崎シーガイア
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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