| Project/Area Number |
09470132
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tokyo |
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Principal Investigator |
SHIRATORI Yasushi Faculty of Medicine, University of Tokyo, Lecturer, 医学部・附属病院, 講師 (70196624)
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| Co-Investigator(Kenkyū-buntansha) |
KOMATSU Yutaka Faculty of Medicine, University of Tokyo, Assistant, 医学部・附属病院, 助手 (90301100)
KANAI Fumihiko Faculty of Medicine, University of Tokyo, Assistant, 医学部・附属病院, 医員
MATSUMURA Masayuki Faculty of Medicine, University of Tokyo, Assistant, 医学部・附属病院, 医員
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Adenovirus / Sinusoida cells / ONIYX / TGF-β / signal / PKC / collagen / angiogenesis / gene therapy / stellate cells / endothelial cells / Adenovirus vector / colon cancer / IL-2 / IL-12 / Stellate cells / Enclothelil cells / hepatic metastasis / 細胞外基質 / transcription |
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| Research Abstract |
(Liver-direced genetherapy) An administration of Liver-directed-adenovirus vector encoded with IL-2 or IL-12 gene inhibit hepatic metastasis of colorectal carcinoma in vivo using murine model. A combination administration of adenovirus vectors encoded with these cytokines and those with cytosine deaminase (CD) gene is more efficiently inhibit hepatic metastasis of colon carcinoma. Other adenovirus vector system using ONIYX or encoded p53, Bad, or Bax induced cytotoxicity (apoptosis) of the tumor cells. These vectors may be useful for clinical trial.
(Regulation of collagen synthesis) TGF-beta signaling pathway for the collagen production in fibroblasts and stellate cells has been clarified using dual luciferase assay, indicating the signal interaction of smad system in the cells. Regulation of these molecules using dominant negative gene transfection inhibit collage synthesis. Other intracellular signaling pathway are under investigation. Furthermore, endothelial cells cultured in three dimentional culture system in vitro are found to activate cellular PKC signaling pathway including Raf and MAPKK signaling pathway. These studies may be related to the angiogenesis of endothelial cells. In addition, enrollment of NF-kB in induction of adherent molecules is also found in hepatic endothelial cells in vitro.
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