Overcoming therapy resistance of glioma cells via modulation of mitochondrial energy metabolism

• Project/Area Number: 22791331
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Yamagata University
• Principal Investigator: TOMIYAMA Arata 山形大学, 医学部, 助教 (40385810)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: グリオーマ / エネルギー代謝 / テモゾロミド / Warburg effect

Research Abstract

In this study, we identified a chemical agent capable of promoting mitochondrial respiration of glioma cells and also confirmed that the chemical agent overcomes temozolomide resistance of glioma cells in vitro. In vivo, the chemical agent synergized with temozolomide to inhibit tumor growth in the subcutaneous xenograft model. However, the synergistic anti-tumor effect of these drugs remains to be demonstrated in the intracranial xenograft model.

Research Products

• [Journal Article] MEK-ERK signaling dictates DNA-repair gene MGMT expression and temozolomide resistance of stem-like glioblastoma cells via the MDM2-p53 axis (2011)
  • Author(s): Sato A, Sunayama J, Matsuda K, Seino S, Suzuki K, Watanabe E, Tachibana K, Tomiyama A, Kayama T, Kitanaka C
  • Journal Title: Stem Cells Volume: 29 Pages: 1942-1951
  • Peer Reviewed
• [Journal Article] FoxO 3a functions as a key integrator of cellular signals that control glioblastoma stem-like cell differentiation and tumorigenicity (2011)
  • Author(s): Sunayama J, Sato A, Matsuda KI, Tachibana K, Watanabe E, Seino S, Suzuki K, Narita Y, Shibui S, Sakurada K, Kayama T, Tomiyama A, Kitanaka C
  • Journal Title: Stem Cells Volume: 29 Pages: 1327-1337
  • Peer Reviewed
• [Journal Article] FoxO3a functions as a key integrator of cellular signals that control glioblastoma stem-like cell differentiation and tumorigenicity (2011)
  • Author(s): Sunayama J, et al.
  • Journal Title: Stem Cells Volume: 29 Pages: 1327-1337
  • Peer Reviewed
• [Journal Article] Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the maintenance of self-renewal and tumorigenicity of glioblastoma stem-like cells (2010)
  • Author(s): Sunayama J, Matsuda KI, Sato A, Tachibana K, Suzuki K, Narita Y, Shibui S, Sakurada K, Kayama T, Tomiyama A, Kitanaka C
  • Journal Title: Stem Cells Volume: 28 Pages: 1930-1939
  • Peer Reviewed
• [Journal Article] Dual blocking of mTor and PI3K elicits a pro-differentiation effect on glioblastoma stem like-cells (2010)
  • Author(s): Sunayama J, Sato A, Matsuda KI, Tachibana K, Suzuki K, Narita Y, Shibui S, Sakurada K, Kayama T, Tomiyama A, Kitanaka C
  • Journal Title: Neuro-Oncol Volume: 12 Pages: 1205-1219
  • Peer Reviewed
• [Journal Article] Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR (2010)
  • Author(s): Sato A, et al.
  • Journal Title: Neurosci Lett Volume: 470 Pages: 155-120
  • Peer Reviewed
• [Journal Article] Association of stem cell marker CD133 expression with dissemination of glioblastomas (2010)
  • Author(s): Sato A, et al.
  • Journal Title: Neurosurg Rev Volume: 33 Pages: 175-183
  • Peer Reviewed
• [Presentation] グリオーマ幹細胞におけるFoxO3aを介した分化と造腫瘍能の制御 (2011)
  • Author(s): 佐藤篤, 砂山潤, 松田憲一朗, 立花研, 渡部江梨子, 清野静香, 鈴木香, 成田善孝, 渋井壮一郎, 富山新太, 北中千史, 嘉山孝正
  • Organizer: 第29回日本脳腫瘍学会学術総会
  • Place of Presentation: 下呂(水明館)
  • Year and Date: 2011-11-27
• [Presentation] MEK inhibition enhances temozolomide sensitivity of glioma stem-like cells via MGMT down-regulation (2011)
  • Author(s): Sato A, Matsuda KI, Sunayama J, Sakurada K, Tachibana K, Tomiyama A, Kitanaka C, Kayama T
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋(古屋国際会議場)
  • Year and Date: 2011-10-03
• [Presentation] MEK inhibition enhances temozolomide sensitivity of glioma stem-like cells via MGMT down-regulation (2011)
  • Author(s): Sato A, et al.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋(名古屋国際会議場)
  • Year and Date: 2011-10-03
• [Presentation] グリオーマ幹細胞におけるMGMT発現とテモゾロミド感受性に関する検討 (2010)
  • Author(s): 佐藤篤, 松田憲一朗, 砂山潤, 清野静香, 鈴木香, 櫻田香, 立花研, 富山新太, 北中千史, 嘉山孝正
  • Organizer: 第28回日本脳腫瘍学会
  • Place of Presentation: 軽井沢(軽井沢プリンスホテル)
  • Year and Date: 2010-11-28
• [Presentation] Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the regulation of stemness of glioblastoma stem cells (2010)
  • Author(s): Sunayama J, Matsuda KI, Sato A, Tachibana K, Narita Y, Shibui S, Sakurada K, Kayama T, Tomiyama A, Kitanaka C
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2010-09-24
• [Presentation] Mechanism of heavy ion radiation-induced glioma cell death (2010)
  • Author(s): Tomiyama A, et al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24