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RAS抑制変異体を用いた腫瘍特異的同所性遺伝子治療モデル

Research Project

Project/Area Number 12217003
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (C)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University

Principal Investigator

葛巻 暹  北海道大学, 遺伝子病制御研究所, 教授 (80091445)

Project Period (FY) 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsRAS / 抑制変異体 / 遺伝子治療 / ヌードマウス / 膀胱癌 / 膵癌
Research Abstract

1.CEAプロモーターを持つRAS抑制変異体N116Yアデノウイルスベクター(AdCEA-N116Y)は、CEA産生陽性のヒト膵癌細胞株PCI35、PCI43に対し有効な増殖抑制およびアポトーシス誘導効果を示した。ヌードマウスの脾臓にPCI43株を接種し肝転移を作るモデルにおいては、細胞接種5日目にAdCEA-N116Yを投与することで肝内転移結節数を有意に抑制できた。
2.AdCMV-N116Yはin vitroでヒト膀胱癌細胞株UMUC-2およびKU-7に対し顕著な増殖抑制効果を示した。この腫瘍形質抑制効果はJNK活性化に関わるシグナル伝達経路の抑制による可能性が示唆された。またこのベクターは、膀胱に同所生着させたUMUC-2およびKU-7の増殖を強く抑えることが示された。

Report

(1 results)
  • 2000 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] Watanabe T.: "An improved intravesical model using human bladder cancer cell lines to optimize gene and other therapies."Cancer Gene Therapy. 7. 1575-1580 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeuchi,M.: "The dominant negateive H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice"Gene Therapy. 7. 518-526 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe,T.: "Suppressive effects of dominant negative ras mutant N116Y on transformed phenotypes of human bladder cancer cells."Cancer Letters. 149. 195-200 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe,T.: "Significance of the Grb2 and Son of sevenless (Sos) proteins in human bladder cancer cell lines."IUBMB life. 49. 317-320 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe,T.: "Adenovirus-mediated gene therapy for bladder cancer in an orthotopic model using a dominant negative H-ras mutant."Int.J.Cancer. (in press).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2018-03-28  

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