Regulation of nitric oxide signalling by thrombospondin 1: implications for anti-angiogenic therapies.

Regulation of nitric oxide signalling by thrombospondin 1: implications for anti-angiogenic therapies.
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DOI:
10.1038/nrc2561
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发表时间:
2009-03
期刊:
Nature reviews. Cancer
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除了长期调节血管生成,血管生成生长因子信号通过一氧化氮(NO)急性控制血流和止血。抑制这一途径可能是目前用于癌症治疗的血管内皮生长因子拮抗剂导致高血压和血栓形成前副作用的原因。第一个确定的内源性血管生成抑制剂,血栓反应蛋白-1,也通过拮抗NO信号控制组织灌注、止血和放射敏感性。我们研究这些和其他新出现的血栓反应蛋白-1在癌症中的作用。阐明内源性和治疗性血管生成抑制剂如何调节血管NO信号可以促进更多选择性抑制剂的开发。
In addition to long term regulation of angiogenesis, angiogenic growth factor signaling through nitric oxide (NO) acutely controls blood flow and hemostasis. Inhibition of this pathway may account for the hypertensive and prothrombotic side effects of vascular endothelial growth factor antagonists currently used for cancer treatment. The first identified endogenous angiogenesis inhibitor, thrombospondin-1, also controls tissue perfusion, hemostasis, and radiosensitivity by antagonizing NO signaling. We examine the role of these and other emerging activities of thrombospondin-1 in cancer. Clarifying how endogenous and therapeutic angiogenesis inhibitors regulate vascular NO signaling could facilitate development of more selective inhibitors.
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