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Remodeling of altered epigenetic regulation via targeting epigenetic factor during glioma formation

Research Project

Project/Area Number 16K20003
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionNagoya University

Principal Investigator

Ohka Fumiharu  名古屋大学, 医学系研究科, 助教 (10725724)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords悪性脳腫瘍 / エピゲノム異常 / 悪性神経膠腫 / エピゲノム治療 / 神経膠腫 / 脳腫瘍学
Outline of Final Research Achievements

We established MADM mouse model which generates malignant glioma spontaneously. From an early stage of tumor formation, expression level of EZH2 was highly upregulated. Using glioma cell lines which are derived from MADM mice tumors, we found that EZH2 inhibitor (EPZ6438) inhibited cell growth of tumor cells. Also MRI imaging revealed that both oral administration of EPZ6438 and genetic depletion of EZH2 inhibited tumor growth in MADM mice significantly. We harvested tumor tissue of EZH2 knock-out MADM mice tumors, EZH2-intact MADM mice tumors and normal mice brains. Gene expression analysis with microarray revealed that expression levels of genes which are associated with neuronal differentiation are retained by knock out of EZH2 gene. These data indicated that EZH2 plays pivotal roles in glioma formation via dysregulation of histone modifications.

Academic Significance and Societal Importance of the Research Achievements

悪性脳腫瘍に対する治療薬は未だ少なく、極めて予後不良疾患である。本研究では悪性脳腫瘍の一部のサブグループではエピゲノム因子であるEZH2が腫瘍形成に重要な役割を果たしており、EZH2を阻害することで腫瘍の増大を抑制することができた。細胞実験のみでなく動物実験でも有望な効果が見られており、予後不良である悪性脳腫瘍の有望な新規治療薬の候補として今後さらに研究を発展していくための基礎となる知見を得ることができたと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016

All Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] マウスモデルを用いたIDH野生型グレードIIIグリオーマ形成に寄与するエピゲノム異常の解析2018

    • Author(s)
      大岡史治、出口彰一 、鈴木啓道、青木恒介、加藤 彰、山道 茜、勝島啓佑、新城恵子、若 林俊彦 、近藤 豊 、夏目敦至
    • Organizer
      第19回日本分子脳神経外科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Epigenetic treatment for IDH-wildtype lower grade glioma, targeting dysregulation of EZH2-H3K27me32017

    • Author(s)
      Fumiharu Ohka, Atsushi Natsume, Hiromichi Suzuki, Shoichi Deguchi, Keisuke Katsushima, Keiko Shinjo, Toshihiko Wakabayashi, Yutaka Kondo
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Epigenetic treatment strategy for IDH-wildtype grade III glioma2017

    • Author(s)
      Fumiharu Ohka, Shoichi Deguchi, Hiromichi Suzuki, Kosuke Aoki, Keisuke Katsushima, Keiko Shinjo, Toshihiko Wakabayashi, Yutaka Kondo, Atsushi Natsume  
    • Organizer
      日本脳神経外科学会第76回学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] IDH野生型グレードIIIグリオーマ形成におけるエピゲノムリプログラミング2017

    • Author(s)
      大岡史治、出口彰一、山道茜、鈴木啓道、青木恒介、加藤 彰、勝島啓佑、新城恵子、若林俊彦、近藤 豊、夏目敦至
    • Organizer
      第35回日本脳腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] IDH野生型グレード3グリオーマに対する新規エピジェネティクス治療の開発2016

    • Author(s)
      大岡史治, 出口彰一, 鈴木啓道, 青木恒介, 加藤 彰,勝島啓佑, 新城恵子, 若林俊彦, 近藤豊, 夏目敦至
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      甲府富士屋ホテル(山梨県甲府市)
    • Year and Date
      2016-12-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Epigenomic treatment for IDH wild-type grade III glioma, targeting dysregulation of EZH2-H3K27me32016

    • Author(s)
      Fumiharu Ohka, Atsushi Natsume, Hiromichi Suzuki, Kosuke Aoki, Shoichi Deguchi, Keisuke Katsushima, Keiko Shinjo, Toshihiko Wakabayashi, Yutaka Kondo
    • Organizer
      2016 SNO annual meeting
    • Place of Presentation
      Scottsdale (USA)
    • Year and Date
      2016-11-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] EZH2を標的としたIDH1野生型グリオーマの新規治療戦略2016

    • Author(s)
      大岡史治, 夏目敦至, 鈴木啓道, 出口彰一,勝島啓佑, 新城恵子, 若林俊彦, 近藤豊
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] IDH野生型グレード3グリオーマ形成に寄与するエピゲノム異常を標的とした新規治療2016

    • Author(s)
      大岡史治, 出口彰一, 鈴木啓道, 青木恒介, 加藤 彰,勝島啓佑, 新城恵子, 若林俊彦, 近藤豊, 夏目敦至
    • Organizer
      日本脳神経外科学会第75回学術総会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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