2003 Fiscal Year Final Research Report Summary
Mechanistic Investigation and future clinical application of anti-angiogenic theraphy in hepatacellular carcinoma
| Project/Area Number |
14570498
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Nara Medical University |
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Principal Investigator |
YOSHIJI Hitoshi Nara Medical University, 3rd Dept of Int Med, Research Associate, 医学部, 助手 (40336855)
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| Co-Investigator(Kenkyū-buntansha) |
IMAZU Hiroo Nara Medical University, 3rd Dept of Int Med, Research Associate, 助手 (60336857)
KOJIMA Hideyuki Nara Medical University, 3rd Dept of Int Med, Research Associate, 助手 (60326345)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Angiogenesis / VFGF / Hepatocellular Carcinoma / Angiotensin-II |
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| Research Abstract |
In the current granted-project., we elucidated the in vivo role of vascular endothelial growth factor (VEGF) on hepatocellular carcinoma (HCC) development. We examined the combined effect of VEGF and basic fibroblast growth factor (bFGF), which is also known as a potent angiogenic factor in HCC, overexpression by means of a combination of a retroviral tetracycline (tet)-regulated gene expression system. We found that VEGF and bFGF synergistically increased tumor growth and angiogenesis in murine HCC cells, at least partly induction of VEGF by bFGF overexpression through VEGFR-2. We also found that clinically used angiotensin converting enzyme inhibitor (ACE-I), perindopril (PE) and interferon (IFN) at clinical compatible low doses significantly suppressed the HCC development and angiogenesis associated with suppression of VEGF. We reported these results in several journals, such as Hepatology and Clinical Cancer Research.
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[Publications] Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Nobuchi R, Hicklin DJ, Wu Y, Yanase K, Namisaki T, Yamazaki M, Tsujinoue H, Imazu H, Masaki T, Fukui H.: "Vascular endothilial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis"GUT. 52(9). 1347-1354 (2003)
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[Publications] Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Yanase K, Namisaki T, Kitade K, Yamazaki M, Tsujinoue H, Fukui H.: "Angiotensin-II induces the tissue inhibitor of metalloproteinases-1 through the protein kinase-C signaling pathway in rat liver fibrosis development"Hepatol Res. 27. 51-56 (2003)
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[Publications] Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Yanase K, Namisaki T, Yamazaki M, Tsujinoue H, Imazu H, Fukui H: "Extracellular matrix remodeling may predominate over hepatocyte injury in hepatocellular carcinoma development"ONCOLOGY REPORTS. 10. 957-962 (2003)
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[Publications] Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Yanase K, Namisaki T, Yamazaki M, Tsujinoue H, Imazu H, Fukui H.: "The copper-chelating agent, trientine, attenuates liver enzymealtered preneoplastic lesions in rats by angiogenesis suppression"ONCOLOGY REPORTS. 10. 1369-1373 (2003)
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[Publications] Noguchi R, Yoshiji H, kuriyama S, Yoshii J, Ikenaka Y, Yanase K, Namisaki T, Yamazaki M, Tsujinoue H, Imazu H, Masaki T, Fukui H.: "Combination of interferon-beta and the angiotensin-converting enzyme inhibitor, perindopril, attenuates murine hepatocellular carcinoma development and angiogenesis"Clin Cancer Res. 9. 6038-6045 (2003)
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[Publications] Ikenaka Y, Yoshiji H, Kuriyama S, Yoshii J, Noguchi R, Tsujinoue H, Yanase K, Namisaki T, Imazu H, Masaki T, Fukui H.: "Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model"Int.J.Cancer. 105. 340-346 (2003)
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