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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. |



| 血管生成是大量的血管源性的因子通過信號(hào)傳導(dǎo)通路調(diào)節(jié)的。血管內(nèi)皮生長因子和notch信號(hào)可能是調(diào)節(jié)胚胎期血管生成和腫瘤血管生成的兩個(gè)最重要的機(jī)制。在臨床病例中,有效的阻礙血管內(nèi)皮生長因子通路能阻礙腫瘤血管生成和成長。在許多癌癥病人的第三期治療中加入抗血管內(nèi)皮生長因子的治療已經(jīng)獲得成功。最新研究表明notch信號(hào)通路通過抑制內(nèi)皮末端細(xì)胞的形成來減少血管的生成,同時(shí),阻止notch信號(hào)能顯著的增加非多產(chǎn)性的血管生成,同時(shí)減少血管生成因子敏感性的和有血管生成因子抗性腫瘤細(xì)胞的生長。血管生成因子和notch信號(hào)通路在脈管系統(tǒng)的多處相互影響。血管生成因子的信號(hào)能夠誘導(dǎo)notch的信號(hào)同時(shí)notch的信號(hào)能夠調(diào)節(jié)血管生成因子的信號(hào)通路。Notch和血管生成因子是血管生成的陰陽兩面了。在臨床上通過阻礙notch和血管內(nèi)皮生長因子的協(xié)同治療來阻礙腫瘤的生長。因此,notch路徑的靶位雖然還在早期階段,但是有可能會(huì)為臨床治療提供新方案。 |

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