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Development of novel mouse brain tumor model using in vivo electroporation and piggyBac system

Research Project

Project/Area Number 16K07125
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionKeio University

Principal Investigator

Onishi Nobuyuki  慶應義塾大学, 医学部(信濃町), 訪問研究員 (40534540)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsマウス脳腫瘍モデル / In vivoエレクトロポレーション / piggyBacシステム / 神経幹細胞
Outline of Final Research Achievements

Glioblastoma multiforme (GBM), is one of the most malignant brain tumors, has highly-proliferative and invasive characters. To understand these malignant characters of GBM, an appropriate carcinogenesis model is required. Loss of INK4A/ARF and stimulation of common signal transduction pathways involving RAS are frequently found in GBM. Previously, we have established a stable mouse models of brain tumors, transplanting the genetically modified neural stem cells (NSCs). Recently, for the purpose of reproducing a clinical tumor initiating process, we are developing a novel mouse model of brain tumors by gene transfer into mouse brain directly. Using in vivo electroporation and piggyBac system, transduction of activated-H-RAS and shInk4a/Arf into NSCs in mouse brain, efficiently formed highly proliferative, invasive and heterogeneous brain tumors. Based on these findings, we propose this in vivo carcinogenesis technique is efficient method to generate appropriate mouse brain tumor models.

Academic Significance and Societal Importance of the Research Achievements

悪性脳腫瘍、特にグリオブラストーマ(glioblastoma multiforme: GBM)は原発性脳腫瘍のうち悪性度が最も高く、浸潤の早さから手術による全摘は困難とされており、平均生存期間は約1年と極めて予後不良な悪性腫瘍である。GBMは放射線・化学療法に抵抗性を持ち、効果的な治療は未だ確立されていない。GBMの性状を理解し、新たな治療戦略を考案するためには適切な発がんモデルの構築が必須である。本研究で構築したマウス脳腫瘍モデルは、ヒトGBMに酷似した特徴を有する脳腫瘍を簡便な方法で作製することができ、最も予後が悪く難治性のがんの一つであるGBMの治療を目指した研究を促進するものである。

Report

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

    (11 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (6 results)

  • [Journal Article] Development of a functional thyroid model based on an organoid culture system.2018

    • Author(s)
      Saito Y, Onishi N, Takami H, Seishima R, Inoue H, Hirata Y, Kameyama K, Tsuchihashi K, Sugihara E, Uchino S, Ito K, Kawakubo H, Takeuchi H, Kitagawa Y, Saya H, Nagano O.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 497 Issue: 2 Pages: 783-789

    • DOI

      10.1016/j.bbrc.2018.02.154

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells.2017

    • Author(s)
      Ishimoto T, Miyake K, Nandi T, Yashiro M, Onishi N, Huang KK, Joyce LN, Kalpana R, Tay ST, Suzuki Y, Cho BC, Kuroda D, Arima K, Izumi D, Iwatsuki M, Baba Y, Oki E, Watanabe M, Saya H, Hirakawa K, Baba H, Tan P.
    • Journal Title

      Gastroenterology

      Volume: in press Issue: 1 Pages: 191-204

    • DOI

      10.1053/j.gastro.2017.03.046

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Simvastatin-Induced Apoptosis in Osteosarcoma Cells: A Key Role of RhoA-AMPK/p38 MAPK Signaling in Antitumor Activity.2017

    • Author(s)
      Kamel WA, Sugihara E, Nobusue H, Yamaguchi-Iwai S, Onishi N, Maki K, Fukuchi Y, Matsuo K, Muto A, Saya H, Shimizu T.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 16 Issue: 1 Pages: 182-192

    • DOI

      10.1158/1535-7163.mct-16-0499

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-)2016

    • Author(s)
      Tsuchihashi K, Okazaki S, Ohmura M, Ishikawa M, Sampetrean O, Onishi N, Wakimoto H, Yoshikawa M, Seishima R, Iwasaki Y, Morikawa T, Abe S, Takao A, Shimizu M, Masuko T, Nagane M, Furnari FB, Akiyama T, Suematsu M, Baba E, Akashi K, Saya H, Nagano O.
    • Journal Title

      Cancer Research

      Volume: in press Issue: 10 Pages: 2954-2963

    • DOI

      10.1158/0008-5472.can-15-2121

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumour resistance in induced pluripotent stem cells derived from naked mole-rats2016

    • Author(s)
      Miyawaki S, Kawamura Y, Oiwa Y, Shimizu A, Hachiya T, Bono H, Koya I, Okada Y, Kimura T, Yoshihiro Tsuchiya, Suzuki S, Onishi N, Kuzumaki N, Matsuzaki Y, Narita M, Ikeda E, Okanoya K, Seino K, Saya H, Okano H & Miura K
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 11471-11471

    • DOI

      10.1038/ncomms11471

    • NAID

      120006535074

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] In vivoエレクトロポレーションを用いたマウス発がんモデルならびに簡便な遺伝子改変マウス作製法の開発2018

    • Author(s)
      大西 伸幸、大塚 正人、佐藤 正宏、佐谷 秀行
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of novel mouse brain tumor model using in vivo electroporation and piggyBac system2016

    • Author(s)
      Nobuyuki Onishi, Hideyuki Saya
    • 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)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] In vivoエレクトロポレーションを用いた新規マウス脳腫瘍モデルの開発2016

    • Author(s)
      大西 伸幸
    • Organizer
      平成28年度新学術領域研究「学術研究支援基盤形成【先端モデル動物支援プラットフォーム】」若手支援技術講習会
    • Place of Presentation
      蓼科グランドホテル滝の湯(長野)
    • Year and Date
      2016-09-14
    • Related Report
      2016 Research-status Report
  • [Presentation] In vivoエレクトロポレーションを用いた新規マウス脳腫瘍モデルの開発ならびに性状解析2016

    • Author(s)
      大西 伸幸、佐谷 秀行
    • Organizer
      第4回 がんと代謝研究会
    • Place of Presentation
      かごしま県民交流センター(鹿児島)
    • Year and Date
      2016-07-07
    • Related Report
      2016 Research-status Report
  • [Presentation] In vivoエレクトロポレーションを用いた新規マウス脳腫瘍モデルの開発2016

    • Author(s)
      大西 伸幸、佐谷 秀行
    • Organizer
      第43回 BMSコンファレンス (BMS2016)
    • Place of Presentation
      ホテル ニューアカオ(静岡)
    • Year and Date
      2016-07-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Development of mouse brain tumor model using in vivo electroporation and piggyBac system2016

    • Author(s)
      Nobuyuki Onishi, Hideyuki Saya
    • Organizer
      第14回 幹細胞シンポジウム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Research-status Report

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

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