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首页> 外文期刊>Cancer Cell >Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation; Role of oxygenation, angiopoietin-1, and matrix metalloproteinases.
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Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation; Role of oxygenation, angiopoietin-1, and matrix metalloproteinases.

机译：通过VEGFR2阻断的血管正常化动力学决定着脑肿瘤对放射的反应。氧化作用，血管生成素1和基质金属蛋白酶的作用。

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摘要

The recent landmark Phase III clinical trial with a VEGF-specific antibody suggests that antiangiogenic therapy must be combined with cytotoxic therapy for the treatment of solid tumors. However, there are no guidelines for optimal scheduling of these therapies. Here we show that VEGFR2 blockade creates a "normalization window"-a period during which combined radiation therapy gives the best outcome. This window is characterized by an increase in tumor oxygenation, which is known to enhance radiation response. During the normalization window, but not before or after it, VEGFR2 blockade increases pericyte coverage of brain tumor vessels via upregulation of Ang1 and degrades their pathologically thick basement membrane via MMP activation.
机译：最近使用VEGF特异性抗体进行的具有里程碑意义的III期临床试验表明，抗血管生成疗法必须与细胞毒性疗法相结合才能治疗实体瘤。但是，没有针对这些疗法的最佳时间表的指南。在这里，我们显示出VEGFR2阻断产生了“正常化窗口”，在此期间联合放疗可获得最佳结果。该窗口的特征在于肿瘤氧合的增加，已知这可以增强放射反应。在归一化窗口期间，但不是在归一化窗口之前或之后，VEGFR2阻断通过Ang1的上调增加脑肿瘤血管的周细胞覆盖，并通过MMP激活降解其病理性厚的基底膜。

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