Project/Area Number |
21390378
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Osaka University |
Principal Investigator |
NAGANO Hiroaki 大阪大学, 医学系・研究科, 准教授 (10294050)
|
Co-Investigator(Kenkyū-buntansha) |
MARUBASHI Sigeru 大阪大学, 医学系・研究科, 助教 (20362725)
KOBAYASHI Shougo 大阪大学, 医学系・研究科, 助教 (30452436)
TAKEMASA Ichiro 大阪大学, 医学系・研究科, 助教 (50379252)
武田 裕 大阪大学, 医学系研究科, 助教 (90397696)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
Keywords | 肝細胞癌 / 難治性進行癌 / 門脈内腫瘍栓 / インターフェロン / 化学療法 / インターフェロン受容体 / 血管新生 / トランスクリプトーム解析 / 進行癌 / 抗腫瘍効果 / apoptosis / 5FU |
Research Abstract |
SUMMARY OF RESEARCH RESULTS (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 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. (3) The Gene Expression Profiling Using the clinical samples treated by IFN-αand 5-FU, the gene expression profiling would be suggested to be useful for the prediction of the treatment efficacy. In addition, the 2 candidates of predictive factors for anti-tumor effect of IFN-αand 5-FU was identified by Gene Expression Profiling with unresponsive HCC cell lines.
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