Research of the induction of autophagy and the suppression mechanism in MGMT activity by vorinostat

• Project/Area Number: 26861141
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Niigata University
• Principal Investigator: Ogura Ryosuke 新潟大学, 医歯学総合病院, 医員 (70626423)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ボリノスタット / MGMT / 局在 / テモゾロミド / シャペロン介在性オートファジー / 核外移行

Outline of Final Research Achievements

Vorinostat, a histone deacetylase inhibitor, suppress O6-methylguanine-DNA methyltransferase (MGMT) activity, but the mechanism is unknown. In this study, we found that it was necessary to resistant to temozolomide that MGMT localized in nucleus. And MGMT overexpression in cytoplasm may be degraded by chaperone-mediated autophagy. It can be new treatment strategy to change MGMT localization by vorinostat.

Research Products

• [Journal Article] Chemical screening identifies EUrd as a novel inhibitor against Temozolomide-resistant glioblastoma-initiating cells. (2016)
  • Author(s): Tsukamoto Y, Ohtsu N, Echizenya S, Otsuguro S, Ogura R, Natsumeda M, Isogawa M, Aoki H, Ichikawa S, Sakaitani M, Matsuda A, Maenaka K, Fujii Y, Kondo T.
  • Journal Title: Stem Cells Volume: - Issue: 8 Pages: 2016-2025
  • DOI: 10.1002/stem.2380
  • Peer Reviewed
• [Journal Article] Immunohistochemical profiles of IDH1, MGMT and p53: Practical significance for prognostication of patients with diffuse gliomas. (2015)
  • Author(s): Ogura R, Tsukamoto Y, Natsumeda M, Isogawa M, Aoki H, Kobayashi T, Yoshida S, Okamoto K, Takahashi H, Fujii Y, Kakita A.
  • Journal Title: Neuropathology Volume: - Issue: 4 Pages: 324-335
  • DOI: 10.1111/neup.12196
  • Peer Reviewed
• [Journal Article] Cortico-cortical activity between the primary and supplementary motor cortex: An intraoperative near-infrared spectroscopy study. (2015)
  • Author(s): Fukuda M, Takao T, Hiraishi T, Aoki H, Ogura R, Sato Y, Fujii Y
  • Journal Title: Surg Neurol Int Volume: - Issue: 1 Pages: 44-44
  • DOI: 10.4103/2152-7806.153872
  • Peer Reviewed / Open Access
• [Journal Article] Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy. (2014)
  • Author(s): Natsumeda M, Igarashi H, Nomura T, Ogura R, Tsukamoto Y, Kobayashi T, Aoki H, Okamoto K, Kakita A, Takahashi H, Nakada T, Fujii Y
  • Journal Title: Acta Neuropathol Commun. Volume: -
  • Peer Reviewed / Open Access
• [Presentation] ボリノスタットによるオートファジー誘導とMGMT抑制効果に関する研究 (2014)
  • Author(s): 小倉良介、塚本佳広、棗田学、五十川瑞穂、青木洋、藤井幸彦
  • Organizer: 第15回 日本分子脳神経外科学会
  • Place of Presentation: 大手門パルズ
  • Year and Date: 2014-09-25 – 2014-09-26