Complete regulation of glioma stem cell by notch and Akt signal inhibition

• Project/Area Number: 15K19956
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: tanaka shingo 金沢大学, 医学系, 協力研究員 (40507084)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Notch阻害薬 / Akt阻害薬 / 膠芽腫 / Notch阻害剤 / Akt阻害剤 / 膠芽腫幹細胞

Outline of Final Research Achievements

Glioblastoma is the most malignant primary brain tumor in humans. The patinets with glioblastoma have a uniformly poor prognosis. The significance of targeting glioblastoma-stem cells may be important for successful treatment. In this study, we analyzed the efficacy of the Nothc inhibitor and Akt inhibitor for glioblastoma stem cell with Notch inhibitor resistance. Notch inhibitor concomitant Akt inhibitor treatment enhanced the effect by monothearapy such as suppression of cell proliferation and stemness maintenance, and promotion of apoptosis.

Research Products

• [Journal Article] Chronic spatial working memory deficit associated with the superior longitudinal fasciculus: a study using voxel-based lesion-symptom mapping and intraoperative direct stimulation in right prefrontal glioma surgery (2016)
  • Author(s): Kinoshita K, Hayashi Y, et al.
  • Journal Title: J Neurosurg Volume: 19 Issue: 4 Pages: 1-19
  • DOI: 10.3171/2015.10.jns1591
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells. (2015)
  • 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: 239-50
  • DOI: 10.1007/s11060-014-1630-z
  • Peer Reviewed / Open Access
• [Presentation] Notch阻害剤抵抗性膠芽腫幹細胞に対するAkt阻害剤併用の有効性 (2015)
  • Author(s): 田中慎吾、中野伊知郎、平尾敦、中田光俊
  • Organizer: 第33回日本脳腫瘍学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-12-06
• [Presentation] 膠芽腫幹細胞に対するγ－セクレターゼ阻害剤MRK003の効果と感受性マーカーの解析 (2015)
  • Author(s): 田中慎吾、平尾敦、中野伊知郎、藤堂具紀、稲生靖、中田光俊
  • Organizer: 第74回日本脳神経外科学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2015-10-14