Development of a new molecular target for glioma mediated ribosome synthesis inhibition (nucleolar stress)

• Project/Area Number: 26861164
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Keio University
• Principal Investigator: MIWA TOMORU 慶應義塾大学, 医学部, 助教 (20365282)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: EFTUD1 / glioma / ribosome / western blot / glioma cell line / Western blot

Outline of Final Research Achievements

EFTUD1 expression in　glioma cell lines　and tissue was higher than in normal brain tissue. Downregulating EFTUD1 induced G1 cell-cycle arrest and apoptosis, leading to reduced glioma cell proliferation.　The mechanism underlying this antitumor effect was impaired ribosome biogenesis via EFTUD1 inhibition. Additionally, protective autophagy was induced by glioma cells as an adaptive response to EFTUD1 inhibition. The antitumor effect induced by the combined treatment was significantly higher than that of either EFTUD1 inhibition　or CQ alone. These results suggest that EFTUD1 represents a novel therapeutic target and that the combination of EFTUD1 inhibition with autophagy blockade may be effective in the treatment of gliomas.

Research Products

• [Journal Article] Giant Cell Tumor of the Skull: Review of the Literature. (2016)
  • Author(s): Tamura R, Miwa T, Shimizu K, Mizutani K, Tomita H, Yamane N, Tominaga T, Sasaki S.
  • Journal Title: J Neurol Surg A Cent Eur Neurosurg. Volume: 77 Issue: 03 Pages: 239-246
  • DOI: 10.1055/s-0035-1554808
  • Peer Reviewed
• [Journal Article] Neuroendoscopic biopsy and the treatment of tumor-associated hydrocephalus of the ventricular and paraventricular region in pediatric patients: a nationwide study in Japan. (2015)
  • Author(s): Miwa T, Hayashi N, Endo S, Ohira T.
  • Journal Title: Neurosurg Rev. Volume: 38 Issue: 4 Pages: 693-704
  • DOI: 10.1007/s10143-015-0629-z
  • Peer Reviewed / Open Access
• [Journal Article] Molecular-genetic and clinical characteristics of gliomas with astrocytic appearance and total 1p19q loss in a single institutional consecutive cohort. (2015)
  • Author(s): Hayashi S, Sasaki H, Kimura T, Abe T, Nakamura T, Kitamura Y, Miwa T, Kameyama K, Hirose Y, Yoshida K.
  • Journal Title: Oncotarget. Volume: 6 Pages: 15871-15881
  • Peer Reviewed / Open Access
• [Presentation] 線維性骨異形成症手術例の検討 (2015)
  • Author(s): 三輪点 坂本好昭 大平貴之 貴志和生 吉田一成
  • Organizer: 日本脳神経外科学会第74回学術総会
  • Place of Presentation: ロイトン札幌 （北海道札幌市）
  • Year and Date: 2015-10-16
• [Presentation] Treatment strategy of the intracranial secondly cystic lesions (2015)
  • Author(s): Miwa T, Ohira T, Toda M, Yoshida K
  • Organizer: 15th Interim Meeting of the World Federation of Neurosurgical Societies
  • Place of Presentation: Rome (Italy)
  • Year and Date: 2015-09-11
  • Int'l Joint Research
• [Presentation] 小児fibrous dysplasia手術例の検討 (2015)
  • Author(s): 三輪点 坂本好昭 田村亮太 河野まや 貴志和生 吉田一成
  • Organizer: 第43回日本小児神経外科学会
  • Place of Presentation: 海峡メッセ下関 (山口県下関市）
  • Year and Date: 2015-06-12
• [Presentation] Characteristics of fetal brain tumors with genetic analysis (2014)
  • Author(s): Tomoru Miwa, Hikaru Sasaki, Kazunari Yoshida
  • Organizer: 日韓４大学Joint Conference
  • Place of Presentation: Ramada plaza jeju (Koria, Jeju Island)
  • Year and Date: 2014-07-05 – 2014-07-06
• [Presentation] Surgical indication and the natural course of intracranial infantile myofibromatosis (2014)
  • Author(s): Tomoru Miwa, Yuichiro Nonaka, Shizuo Oi, Hikaru Sasaki, Kazunari Yoshida
  • Organizer: 16th International Symposium on Pediatric Neuro Oncology
  • Place of Presentation: Suntec Singapore Convention & Exhibition Centre (Singapore. Singapore)
  • Year and Date: 2014-06-28 – 2014-07-02