Brain tumor research by using accurate mouse models

• Project/Area Number: 16K08731
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Center for Geriatrics and Gerontology (2018-2019); The University of Tokyo (2016-2017)
• Principal Investigator: Momota Hiroyuki 国立研究開発法人国立長寿医療研究センター, 病院, 医長 (60469971)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脳腫瘍 / マウスモデル / 生体イメージング / ウイルス療法

Outline of Final Research Achievements

We utilized the RCAS/tv-a system to create histologically accurate brain tumors in immune-competent mice. The RCAS viruses were injected into the brain of tv-a-expressing mice and malignant gliomas generated were monitored by using bioluminescence imaging. We tested new drugs for brain tumors in mice, elucidated the mechanism of tumor initiation and development using this system, and reported a novel brain tumor mouse model.

Academic Significance and Societal Importance of the Research Achievements

RCAS/tv-aシステムによる脳腫瘍マウスモデルは、研究代表者が国内へ初めて導入した正確性の高い（ヒトの腫瘍に近い）モデルであり、脳腫瘍発生機構の解明から新たな治療薬の開発まで、幅広い用途に応用できる。本研究により、目標とした新規薬剤の開発はできなかったが、ウイルス療法などの新規性のある治療法の効果をマウスで試験することができた。また、共同研究により、脳腫瘍の新たな病態解明や、新規脳腫瘍マウスモデルの開発を行い、論文発表することができた。

Research Products

• [Journal Article] Foxr2 promotes formation of CNS-embryonal tumors in a Trp53-deficient background (2019)
  • Author(s): Poh Boonmin、Koso Hideto、Momota Hiroyuki、Komori Takashi、Suzuki Yutaka、Yoshida Nobuaki、Ino Yasushi、Todo Tomoki、Watanabe Sumiko
  • Journal Title: Neuro-Oncology Volume: 21 Issue: 8 Pages: 993-1004
  • DOI: 10.1093/neuonc/noz067
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enhancement of malignant properties of human glioma cells by ganglioside GD3/GD2. (2018)
  • Author(s): Taiji Iwasawa, Pu Zhang, Yuki Ohkawa, Hiroyuki Momota, Toshihiko Wakabayashi, Yuhsuke Ohmi, Robiul H. Bhuiyan, Keiko Furukawa, Koichi Furukawa
  • Journal Title: Int. J. Oncol. Volume: 52 Pages: 1255-1266
  • DOI: 10.3892/ijo.2018.4266
  • Peer Reviewed
• [Journal Article] Significance of perivascular tumour cells defined by CD109 expression in progression of glioma (2017)
  • Author(s): Shiraki Yukihiro、Mii Shinji、Enomoto Atsushi、Momota Hiroyuki、Han Yi-Peng、Kato Takuya、Ushida Kaori、Kato Akira、Asai Naoya、Murakumo Yoshiki、Aoki Kosuke、Suzuki Hiromichi、Ohka Fumiharu、Wakabayashi Toshihiko、Todo Tomoki、Ogawa Seishi、Natsume Atsushi、Takahashi Masahide
  • Journal Title: The Journal of Pathology Volume: 243 Issue: 4 Pages: 468-480
  • DOI: 10.1002/path.4981
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] RCAS/tv-aマウスモデルを用いた脳腫瘍研究 (2017)
  • Author(s): 百田洋之、稲生靖、藤堂具紀
  • Organizer: 第76回日本脳神経外科学会学術総会
• [Presentation] タンパク発現で見るグリオーマの分子異常とPDGFシグナルの関係 (2016)
  • Author(s): 百田洋之、稲生靖、伊藤博崇、金山政作、田中実、藤堂具紀
  • Organizer: 第34回日本脳腫瘍学会学術総会
  • Place of Presentation: 山梨県・甲府市
  • Year and Date: 2016-12-04
• [Presentation] RCAS/tv-a mouse model system for the development of oncolytic virus therapy for brain tumors (2016)
  • Author(s): 百田洋之、稲生靖、藤堂具紀
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川県・横浜市
  • Year and Date: 2016-10-06