• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Foundation of chemotherapy for malignant glioma targeting mTOR

Research Project

Project/Area Number 17K08304
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionNiigata University

Principal Investigator

EDA TAKEYOSHI  新潟大学, 医歯学総合病院, 薬剤師 (90772038)

Co-Investigator(Kenkyū-buntansha) 棗田 学  新潟大学, 脳研究所, 助教 (00515728)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsGlioblastoma / mTOR / xenograft / drug repositioning / translational research / glioma / グリオーマ / 神経膠腫(グリオーマ) / 薬理学
Outline of Final Research Achievements

Glioblastoma (GBM) accounts for the majority of primary brain tumors. Multimodal therapy such as surgical removal, radiotherapy, and temozolomide (TMZ) chemotherapy is performed, whereas the prognosis is still poor. There is an urgent need to develop effective chemotherapy. In primary assessment, we performed a screened for drugs that regulated the proliferation and differentiation against GBM cell lines. Approved macrolides, clindamycin (CLD) reduced cell viability in cultures. Here, we demonstrated that CLD regulated the proliferation of GBM. CLD attenuated the phosphorylation of p70S6K in a dose dependent manner. These effects were synergistically enhanced by the combination with CLD and TMZ. In vivo experiment, repeated administration of CLD and TMZ suppressed tumor growth. These results indicate that CLD shows synergistic activity and sensitization in combination with conventional chemotherapy in xenografts.

Academic Significance and Societal Importance of the Research Achievements

CLDはGBM細胞に対し、高い抗腫瘍効果を示した。mTOR制御がその機序と考える。in vivo実験では、CLDとTMZ併用による作用を検証し、腫瘍は縮小を維持した。腫瘍制御におけるmTOR抑制については、フィードバック機構の存在が知られ、再発に関与するとされるが、CLDはTMZとの併用によりこれを回避している。GBM治療に重要な知見を提示する。
GBM治療への応用の際、CLDは既存薬であることから、ヒトでの安全性が確保されている。また、従来の抗悪性腫瘍薬とは作用機序も異なるため、骨髄抑制など強力な副作用を回避できる。薬価は分子標的薬と比べると安価で、医療費削減の一助となるなど意義は大きい。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (2 results)

All 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] EGFRvIII Is Expressed in Cellular Areas of Tumor in a Subset of Glioblastoma2019

    • Author(s)
      Nozawa T , Okada M, Natsumeda M, Eda T, Abe H, Tsukamoto Y, Okamoto K, Oishi M, Takahashi H, Fujii Y, Kakita A
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 59 Issue: 3 Pages: 89-97

    • DOI

      10.2176/nmc.oa.2018-0078

    • NAID

      130007612662

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] mTORシグナルを標的とした悪性グリオーマに対する新規化学療法の基盤研究2019

    • Author(s)
      江田岳誉、金丸優、岡田正康、棗田学、大石誠、藤井幸彦
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2019 Research-status Report 2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi