| Project/Area Number |
17390367
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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 |
UMESHITA Koji Osaka University, Hospital, Assistant, 医学部附属病院, 助手 (60252649)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANO Hiroaki Osaka University, Graduate School of Medicine, lecturer, 医学系研究科, 講師 (10294050)
DONO Keizo Osaka University, Graduate School of Medicine, lecturer, 医学系研究科, 講師 (60283769)
YAMAMOTO Hirofumi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (30322184)
TAKEMASAO Ichiro Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (50379252)
MONDEN Morito Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00127309)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2005: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | hepatocellular carcinoma / advanced cancer / portal venous thrombus / IFN-α / chemotherapy / IFN-receptor / angiogenesis / Gene Expression Profiling / IFN併用化学療法 / TRAIL / NK細胞 / Fas / Fas-L / Angiopoietin / 難治性進行癌 |
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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. In this mechanism, the methylation of IFNAR gene was significantly correlated with anti-tumor effect, among the several factors.
2) Anti tumor effect through the relationship between IFN and 5FU metabolism
In the anti-tumor effect of IFN and 5FU, IFN would induce the TS-1 inhibitory rate in 5FU metabolism.
3) Anti tumor effect through Fas/FasL
Among peripheral blood cells, NK cells were found to exert the cytotoxic effects on human hepatoma cells. In addition, the involvement of CTL system in the anti tumor effect was examined and confirmed in terms of the relationship of apoptosis in this study.
4) Anti tumor effect through the anti-angiogenic action
About the anti-angiogenic action of IFN, Ang-2 was the one of most important factor, among several anti-angiogenic molecules, TSP, Ang-1, VEGF, Tie2, HIF1-α.
5) 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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