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-

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671268/
• 关键词: Matrix Metalloproteinase; VEGF; Angiogenesis; Cytokine; Chemoprevention; Hepatocellular carcinoma; Angiogenetic therapy; chemoprevention

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肿瘤相关的肝细胞癌（HCC）血管生成。在这项特殊的研究中，血管生成相关基质金属蛋白酶（MMPs）、血管内皮生长因子（VEGF）和血管生成相关细胞因子网络被重点关注。在二乙基亚硝胺诱导的大鼠HCC模型检查中，观察到MMP-2和MT1-MMP的表达增强，这些位点的相容性以及MMP-9在HCC侵袭性病变中的表达增强，并观察到其纤维化和癌变。在临床病例中，有趣的是，在经导管动脉栓塞后的HCC活细胞中观察到MMP-7的表达增强，怀疑其参与了MMP-3的增殖，7与上述结果相似。此外，MT1 -MMP似乎是HCC的关键因素。值得注意的是，在VEGF与MMPs的相关性中，经常观察到VEGF与MMP-9的相容性。在临床病例中，IFN-γ的降低和IL-8的升高在癌变前后具有特征性。体外研究还表明，I-ICV尤其与血管生成密切相关。在基础研究中，MMP抑制剂和血管内皮增生抑制剂对HCC具有肿瘤休眠、肿瘤缩小和化学预防作用。抗血管生成疗法的临床应用备受期待。

项目成果

Y.Ishii, Y.Nakasato, T.Aoki.: "New Strategy for Hepatocellular Carcinoma For Clinical Application of Matrix Metalloproteinase Inhibitor"Microcirculation. Vol.7. 391-396 (2001)

Y.Ishii、Y.Nakasato、T.Aoki.：“基质金属蛋白酶抑制剂临床应用的肝细胞癌新策略”微循环。

Y.Ishii, Y.Nakasato, T.Aoki: "New Strategy for Hepatocellular Carcinoma For Clinical Application of Matrix Metalloproteinase Inhibitor"Microcirculation. Vol.7. 391-396 (2001)

Y.Ishii、Y.Nakasato、T.Aoki：“基质金属蛋白酶抑制剂临床应用的肝细胞癌新策略”微循环。

Y. Ishii, Y Nakasato, and T. Aoki.: "New strategy for Hepatocellular Carcinoma ・For Clinical Application of Matrix Metalloproteinase Inhibitor・"Microcirculation. Vol.7. 391-396 (2001)

Y. Ishii、Y Nakasato、T. Aoki.：“肝细胞癌的新策略·基质金属蛋白酶抑制剂的临床应用·”《微循环》第 7 卷（2001 年）。