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Type IV collagenase inhibitor as an angiogenic inhibitor

IV 型胶原酶抑制剂作为血管生成抑制剂

基本信息

批准号：
04671425
负责人：
SHIMAMURA Mariko
金额：
$ 1.22万
依托单位：
THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671425/
关键词：
TYPE IV COLLAGENASE ENZYME INHIBITOR ANGIOGENIC INHIBITOR CAM METHOD 血管新生阻害

项目摘要

Angiogenesis, neovascularization, is an essential phenomenon not only in normal physiological process, but also in some disease states such as chronic inflammation and tumor formation. Many reports have shown the importance of angiogenesis for the progressive growth of solid tumors and the shedding of metastatic tumors from the primary sites. So the inhibition of angiogenesis may cause the suppression of tumor growth. Angiogenesis occurs via a copmlex cascade of events including activation of endothelial cells by angiogenic factor(s), degradation of the basement membrane by enzymes, migration, proliferation of capillary endothelial cells and tube formation by capillary endothelial cells. A variety of proteases have been implicated in angiogenesis, and collagenase and plasminogen activator have been suggested to play the important roles in degradation of the basement membrane. However, the dominant enzyme in angiogenesis in vivo has not been elucidated clearly. The clarification of the … More key enzymes in angiogenesis and their specific inhibitors may lead to search for potent inhibitors of angiogenesis, and may also lead to the regulation of tumor growth and metastasis through the inhibition of angiogenesis.Previously, we examined the effects of low molecular weight protease inhibitors on the angiogenesis of CAM to clarify the key enzyme during angiogenesis in vivo and found actinonin as a angiogenic inhibitor. We also examined theinhibitory mechanism of actinonin on angiogenesis, using capillary endothelial cells, and suggested that actinonin inhibited angiogenesis through the inhibition of type IV collagenase and that this enzyme was adominant enzyme in angiogenesis.In this study, we attempted to examine the correlation between the ability of the inhibition of type IV collagenase and angiogenesis inhibition, using actinonin and its derivatives, to determine whether this enzyme activity was important to angiogenesis. Both activities were correlative. We also examined the antitumor activity of actinonin. Actinonin inhibited the tumor uptake to the host. These results indicated that 1) type IV collagenase was a dominant enzyme in angiogenesis, 2) inhibition of type IV collagenase led to the angiogenesis inhibition and 3) type IV collagenase Less

血管生成，即新生血管形成，不仅是正常生理过程中必不可少的现象，也是慢性炎症、肿瘤形成等疾病过程中必不可少的现象。许多报道表明血管生成对于实体瘤的进行性生长和转移性肿瘤从原发部位脱落的重要性。因此，抑制血管生成可能导致抑制肿瘤生长。血管生成通过复杂级联事件发生，包括血管生成因子激活内皮细胞、酶降解基底膜、毛细血管内皮细胞迁移、增殖和毛细血管内皮细胞形成管。多种蛋白酶参与血管生成，胶原酶和纤溶酶原激活剂在基底膜降解中起重要作用。然而，在体内血管生成的优势酶尚未阐明清楚。的澄清 ...更多信息血管生成关键酶及其特异性抑制剂的研究有助于寻找有效的血管生成抑制剂，并可能通过抑制血管生成来调节肿瘤的生长和转移。我们还利用毛细血管内皮细胞研究了放线菌素对血管生成的抑制机制，并认为放线菌素通过抑制IV型胶原酶来抑制血管生成，而IV型胶原酶是血管生成中的优势酶。以确定这种酶活性是否对血管生成重要。这两项活动是相互关联的。我们还研究了放线菌素的抗肿瘤活性。放线菌素抑制肿瘤对宿主的摄取。这些结果表明：1）IV型胶原酶是血管生成的优势酶，2）抑制IV型胶原酶导致血管生成抑制，3）IV型胶原酶较少