Clinical Application of Anti-angiogenetic Therapy on Hepatocarcinogenesis and Hepatocellular carcinoma -With Special Reference to Matrix Metalloproteinases and Cytokines network-

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To purpose of this study is to control a tumor-related angiogenesis of hepatocellular carcinoma (HCC). In this particular study, angiogenesis-related matrix metallojroteinases (MMPs), vascular endothelial growth factor (VEGF) and angiogenesis-related cytokines network were forcused. In the examination using a diethylnitrosamine-induced rat HCC model, enhanced expression of MMP-2 and MT1-MMP, compatibility of these sites and enhanced expression of MMP-9 in HCC invasive lesion were observed together with its fibronation and carcinogenesis. In clinical cases, enhanced expression of MMP-7 was interestingly observed in HCC viable cells after transcatheter arterial embolization with its suspected involvement in the proliferation of MMP-3,7 in addition to similar results as those described above. Furthermore, MT1 -MMP seemed to be a key factor of HCC. It was noteworthy in the correlation of VEGF and MMPs that compatibility of VEGF and MMP-9 was often observed. In clinical cases, decreased IFN-γ and increased IL-8 were characteristically observed before and after carcinogenesis. it was also suggested from in vitro studies that I-ICV has a close relation to angiogenesis in particular. In the fundamental study, MMP inhibitor and vascular endothelial proliferation inhibitor showed tumor dormancy, tumor shrinkage and chemoprevention effects on HCC. The clinical application of antiangiogenetic therapy is greatly expected.