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| Angiogenesis is regulated by a number of angiogenic factors through many signalling pathways. The VEGF pathway and Notch signalling are perhaps two of the most important mechanisms in regulation of embryonic vascular development and tumour angiogenesis. Blockade of the VEGF pathway effectively inhibits tumour angiogenesis and growth in preclinical models. The successes in phase III trials have added anti-VEGF agents to standard cancer therapy in several major cancers. A recent flurry of findings indicate that DLL4/Notch signalling decreases angiogenesis by suppressing endothelial tip cell formation; importantly, blockade of DLL4/Notch signalling strikingly increases non-productive angiogenesis but significantly reduces the growth of VEGF-sensitive and VEGF-resistant tumours. The VEGF pathway interplays at several levels with DLL4/Notch signalling in vasculature. VEGF induces DLL4/Notch signalling while DLL4/Notch signalling modulates the VEGF pathway. DLL4 and VEGF emerge to be the yin and yang of angiogenesis. Combination therapy by blocking DLL4/Notch and VEGF pathways synergistically inhibits tumour growth in preclinical models. Thus, targeting the DLL4/Notch pathway, though still at an early stage, may lead to exciting new therapies for clinical application. |
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2楼2013-04-07 17:49:52
3楼2013-04-07 17:50:49
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yin198716: 金币+15, 翻译EPI+1 2013-04-25 22:49:38
yin198716: 金币+15, 翻译EPI+1 2013-04-25 22:49:38
| 血管生成是大量的血管源性的因子通过信号传导通路调节的。血管内皮生长因子和notch信号可能是调节胚胎期血管生成和肿瘤血管生成的两个最重要的机制。在临床病例中，有效的阻碍血管内皮生长因子通路能阻碍肿瘤血管生成和成长。在许多癌症病人的第三期治疗中加入抗血管内皮生长因子的治疗已经获得成功。最新研究表明notch信号通路通过抑制内皮末端细胞的形成来减少血管的生成，同时，阻止notch信号能显著的增加非多产性的血管生成，同时减少血管生成因子敏感性的和有血管生成因子抗性肿瘤细胞的生长。血管生成因子和notch信号通路在脉管系统的多处相互影响。血管生成因子的信号能够诱导notch的信号同时notch的信号能够调节血管生成因子的信号通路。Notch和血管生成因子是血管生成的阴阳两面了。在临床上通过阻碍notch和血管内皮生长因子的协同治疗来阻碍肿瘤的生长。因此，notch路径的靶位虽然还在早期阶段，但是有可能会为临床治疗提供新方案。 |
4楼2013-04-08 20:15:34