The development of novel treatment through the hepatocellular carcinoma (HCC) specific siginaling pathway and molecular based gene expression profiling for advanced HCC

1)IFN/5-FU联合治疗肝癌细胞的抗肿瘤作用与IFN-α R的表达强度密切相关。在这一机制中，IFNAR基因甲基化与抗肿瘤效应显著相关，在多种因素中。2）通过IFN和5 FU代谢的关系抗肿瘤效应在IFN和5 FU的抗肿瘤效应中，IFN会诱导5 FU代谢中的TS-1抑制率。3）通过外周血细胞中的Fas/FasL抗肿瘤效应。发现NK细胞对人肝癌细胞具有细胞毒作用。在IFN的抗血管生成作用中，Ang-2是最重要的因子之一，在几种抗血管生成分子中，TSP，Ang-1，VEGF，Tie 2，5）基因表达谱分析以IFN-α和5-FU联合治疗的临床标本为例，基因表达谱分析可用于预测85%以上的疗效。

1) The mechanism of the antitumor effect through the IFN-IFNAR signalingThe 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 metabolismIn 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/FasLAmong 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 actionAbout 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 ProfilingUsing 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%.