The establishment of immuno-chemotherapy through the IFN-IFNAR (IFN-α receptor) signaling pathway for the intractable and advanced hepatocellular carcinoma
| Project/Area Number |
15390396
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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 |
MARUBASHI Shigeru (2004) Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20362725)
左近 賢人 (2003) 大阪大学, 医学系研究科, 助教授 (40170659)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANO Hiroaki Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 講師 (10294050)
MONDEN Morito Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00127309)
中森 正二 大阪大学, 医学系研究科, 講師 (70294080)
丸橋 繁 大阪大学, 医学系研究科, 助手 (20362725)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2004: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2003: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | hepatocellular carcinoma / IFN-α / IFN-receptor / TRAIL / NK cell / Fas-FasL / Gene Expression Profiling / 門脈内腫瘍栓 / IFN併用化学療法 / IFN受容 / STAT-phosphoSTAT / IFN / IFNAR / 5-FU / 免疫組織染色 |
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| Research Abstract |
1)The mechanism of the antitumor effect through the IFN-IFNAR signaling
The anti-tumor effect of IFN/5-FU combined therapy was significantly correlated with the strength of IFNAR expression, in the HCC cells in-vitro. This was also proved in the experiment of the IFNAR gene transfection model. In this mechanism, the upragulation of the p-STATS and Bcl-xl expression were most significantly correlated with anti-tumor effect, among the several signal transductional factors.
2)Anti tumor effect through TRAIL/TRAIL receptor and Fas/FasL
IFN-α and 5-FU enhanced TRAIL expression in peripheral mononuclear cells, and TRAIL receptor in cultured hepatoma cells. Among peripheral blood cells, NK cells were found to exert the cytotoxic effects on human hepatoma cells. In addition, the involvement of Fas/FasL system in the anti tumor effect was examined and confirmed in this study. The indirect anti-tumor effect for HCC cells through Fas/FasL system was mediated by the Caspase and FLIP.
3)The Gene Expression Profiling
Using the clinical samples treated by IFN-α and 5-FU, the gene expression profiling would be suggested to be useful for the prediction of the treatment efficacy at the over 85%.
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Report
(3 results)
Research Products
(51 results)
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[Journal Article] 進行肝癌2004
Author(s)
近藤礎, 丸橋繁, 他
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Journal Title
癌と臨床、他 81(8)
Pages: 86-89
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] 動注2004
Author(s)
大須賀慶悟, 永野浩昭, 他
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Journal Title
癌と化学療法 31(13)
Pages: 2114-2117
Description
「研究成果報告書概要(和文)」より
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