Development of a new multidisciplinary therapy for the intractable, advanced hepatocellular carcinoma, targeting the intracellular signaling molecules.
| Project/Area Number |
13470255
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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 |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SAKON Masato Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40170659)
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| Co-Investigator(Kenkyū-buntansha) |
MONDEN Morito Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00127309)
NAKAMORI Syoji Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (70294080)
NAGANO Hiroaki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10294050)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2002: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2001: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | hepatocelluklar carcinoma / interferon-α / 5-FU / angiogenesis / interferon receptor / TRAIL / TRAIL receptor / 肝細胞癌 / IFN併用化学療法 / TRAIL受容体 / NK細胞 / インターフェロン-α / 5-fluorouracil / angiopoietin / TRAIL-receptor |
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| Research Abstract |
1) Relationship between antitumor effect and suppression of angiogenesis in human hepatoma cells - implanted nude mice receiving a combined 5-FU and interferon-alpha (IFN-alpha) therapy.
In human tumor cells-implanted nude mice, antitumor effect was compared by measuring tumor diameter among 4 treatment regimens, I.e., control, 5-FU, IFN-alpha and 5-FU + IFN-alpha. The antitumor effect was best observed in 5-FU + IFN-alpha group, and was significantly correlated with micro vessel density count in tumo r tissue. In addition, the involvement of various angiogenic factors including VEGF was examined by measuring mRNA or protein expression. Among angiogenic factors examined, the expression of angiopoietin 2 was most significantly correlated with angiogenesis in tumor tissues.
2) Antitumor effect through TRAIL/TRAIL receptor.
IFN-alpha and 5-FU enhanced TRAIL expression in peripheral mononuclear cells, and TRAIL receptor in cultured hepatoma cells. Among peripheral blood cells, NK cells and mononuclear cells were found to exert the cytotoxic effects on human hepatoma cells.
3) Expression of IFN-alpha receptor (IFNR) in human hepatoma tissues.
The protein expression of IFNR in human hepatoma tissues was investigated immunohistochemically in 20 patients receiving combined intra-arterial 5-FU and systemic IFN-alpha therapy. The clinical antitumor effect was observed in all of 12 IFNR positive patients while none of 8 IFNR negative patients show the clinica; response. These results suggest the significant role of IFNR in the antitumor signaling pathway of IFN-alpha and 5-FU.
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Report
(3 results)
Research Products
(14 results)
