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有读书笔记有附件Tumor vascular changes mediated by inhibition of oncogenic signaling

热3 管理员 添加于 2009-8-4 19:38 | 2867 次阅读 | 0 个评论

  •  作 者

    Qayum N, Muschel RJ, Im JH, Balathasan L, Koch CJ, Patel S, McKenna WG, Bernhard EJ

  •  摘 要

    Many inhibitors of the epidermal growth factor receptor (EGFR)-RAS-phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway are in clinical use or under development for cancer therapy. Here, we show that treatment of mice bearing human tumor xenografts with inhibitors that block EGFR, RAS, PI3K, or AKT resulted in prolonged and durable enhancement of tumor vascular flow, perfusion, and decreased tumor hypoxia. The vessels in the treated tumors had decreased tortuosity and increased internodal length accounting for the functional alterations. Inhibition of tumor growth cannot account for these results, as the drugs were given at doses that did not alter tumor growth. The tumor cell itself was an essential target, as HT1080 tumors that lack EGFR did not respond to an EGFR inhibitor but did respond with vascular alterations to RAS or PI3K inhibition. We extended these observations to spontaneously arising tumors in MMTV-neu mice. These tumors also responded to PI3K inhibition with decreased tumor hypoxia, increased vascular flow, and morphologic alterations of their vessels, including increased vascular maturity and acquisition of pericyte markers. These changes are similar to the vascular normalization that has been described after the antiangiogenic treatment of xenografts. One difficulty in the use of vascular normalization as a therapeutic strategy has been its limited duration. In contrast, blocking tumor cell RAS-PI3K-AKT signaling led to persistent vascular changes that might be incorporated into clinical strategies based on improvement of vascular flow or decreased hypoxia. These results indicate that vascular alterations must be considered as a consequence of signaling inhibition in cancer therapy.

  •  详细资料

    • 文献种类:期刊
    • 期刊名称: Cancer Research
    • 期刊缩写: Cancer Res
    • 期卷页: 2009年  第69卷 第15期 6347-6354页
    • 地址: Gray Institute for Radiation Oncology and Biology, Oxford University, Oxford, United Kingdom
    • ISBN: 1538-7445
    • 备注:PMID:19622766

  •  标 签

    生物研究进展 

  • 相关链接 DOI URL 

  •  附 件

    PDF附件全文下载 

  •  管理员 的文献笔记  订阅

    英国一项最新研究显示，利用药物改善恶性肿瘤中的血管状况，可以起到“软化”肿瘤的作用，这有助于随后实施放射疗法杀死癌细胞。

    英国牛津大学3日发布新闻公报说，一般来讲，恶性肿瘤中的血管状况不好，会影响血液对癌细胞的供氧量。该校研究人员通过动物实验发现，通过药物改善恶性肿瘤中的血管状况，可以增加肿瘤中的含氧量，使得其对放射疗法更为敏感，同时，也有利于治疗药物被送达癌细胞。

    研究人员说，人们可能会以为改善肿瘤中的血管状况会帮助癌细胞生长，但实验显示这恰恰为放射疗法做了“软化”癌细胞的准备，从而能更有效地治疗癌症。

    相关报告发表在新一期美国《癌症研究》杂志上。

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