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

抗血管生成治疗在肝癌发生和肝细胞癌中的临床应用-特别参考基质金属蛋白酶和细胞因子网络-

基本信息

批准号：
12671268
负责人：
ISHII Yuji
金额：
$ 2.11万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

本研究的目的是控制肝细胞癌（HCC）的肿瘤相关血管生成，在这项特殊研究中，重点关注血管生成相关的基质金属蛋白酶（MMP）、血管内皮生长因子（VEGF）和血管生成相关的细胞因子网络。在使用二乙基亚硝胺诱导的大鼠 HCC 模型的检查中，MMP-2 和 MT1-MMP 的表达增强，这些位点的相容性和增强在临床病例中，经导管动脉栓塞后，在 HCC 活细胞中观察到 MMP-9 的表达及其纤维化和癌变，有趣的是，MMP-7 的表达可能与 MMP-3 的增殖有关。 ,7 除了与上述相似的结果外，MT1-MMP 似乎是 HCC 的关键因素，值得注意的是 VEGF 和 MMP 的相容性。在临床病例中，经常观察到癌变前后IFN-γ的减少和IL-8的增加，体外研究也表明I-ICV与血管生成尤其密切相关。在基础研究中，MMP抑制剂和血管内皮增殖抑制剂显示出对HCC的肿瘤休眠、肿瘤缩小和化学预防作用，抗血管生成治疗的临床应用备受期待。