The evalution of target moleculein glioma stem-like cells

• Project/Area Number: 25861262
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: TAMASE Akira 金沢大学, 医学系, 協力研究員 (10595458)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: グリオーマ幹細胞 / Notch / 分子標的療法 / 増殖

Outline of Final Research Achievements

Notch was selected as an important signaling molecule for cancer stem/initiating cells to maintain stemness, induce cell proliferation and regulate apoptosis. Notch signal inhibition by γ-secretase inhibitor may be effective strategy for the treatment of cancer stem/initiating cells. We analyzed 3 patient’s derived GBM stem-like cells with treatment by MRK003, a novel clinically available γ-secretase inhibitor. Notch 1 and 2 were expressed in all cells. MRK003 suppressed Notch signaling in all cells. Akt signaling which is downstream of Notch was strongly inhibited in two species of cells. These cells showed strong effect of MRK in terms of inhibition of proliferation and sphere formation. On the contrary, the cell without alteration of Akt signaling by MRK showed low effect of MRK. Taken together, the effect of MRK003 may depend on the inhibition of Akt pathway.

Research Products

• [Journal Article] High-resolution magnetic resonance imaging findings of basilar artery plaque in a patient with branch atheromatous disease: a case report. (2014)
  • Author(s): Miyaji Y, Kawabata Y, Joki H, Seki S, Mori K, Kamide T, Tamase A, Nomura M, Kitamura Y, Tanaka F
  • Journal Title: J Med Case Rep Volume: 8 Issue: 1 Pages: 395-395
  • DOI: 10.1186/1752-1947-8-395
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Isolated index finger palsy due to cortical infarction (2014)
  • Author(s): Kawabata Y, Miyaji Y, Joki H, Seki S, Mori K, Kamide T, Tamase A, Nomura M, Kitamura Y, Tanaka F
  • Journal Title: J Stroke Cerebrovasc Dis Volume: 23 Issue: 10 Pages: e475-e476
  • DOI: 10.1016/j.jstrokecerebrovasdis.2014.07.042
  • Peer Reviewed / Open Access
• [Journal Article] Cerebellar hemorrhage after embolization of ruptured vertebral dissecting aneurysm proximal to PICA including parent artery. (2014)
  • Author(s): Tamase A, Kamide T, Mori K, Kitamura Y, Shima H, Seki S, Nomura M
  • Journal Title: Surg Neurol Int Volume: 5 Issue: 1 Pages: 59-59
  • DOI: 10.4103/2152-7806.131187
  • Peer Reviewed / Open Access
• [Journal Article] A chronic intracerebral fluid hematoma (2014)
  • Author(s): Nomura M, Miyashita K, Tamase A, Kamide T, Mori K, Kitamura Y, Seki S, Shima H, Yanagimoto K
  • Journal Title: Neuroradiol J Volume: 27 Issue: 2 Pages: 191-4
  • DOI: 10.15274/nrj-2014-10030
  • Peer Reviewed / Open Access
• [Journal Article] Arterial spin-labeling magnetic resonance imaging for diagnosis of late seizure after stroke. (2014)
  • Author(s): Miyaji Y, Yokoyama M, Kawabata Y, Joki H, Kushi Y, Yokoi Y, Sasame J, Seki S, Mori K, Kamide T, Tamase A, Shima H, Nomura M, Kitamura Y, Tanaka F
  • Journal Title: J Neurol Sci Volume: 339 Issue: 1-2 Pages: 87-90
  • DOI: 10.1016/j.jns.2014.01.026
  • Peer Reviewed