Combined effects of angiostatin and ionizing radiation in antitumour therapy
Combined effects of angiostatin and ionizing radiation in antitumour therapy
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DOI：
10.1038/28412
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发表时间：
1998-07-16
期刊：
影响因子：
64.8
通讯作者：
Weichselbaum, RR
中科院分区：
文献类型：
--
作者：
Mauceri, HJ;Hanna, NN;Weichselbaum, RR
血管生成，即从原有血管中形成新的毛细血管，是肿瘤进展的必要条件（1-5）。血管抑制素是一种纤溶酶原(6)的蛋白水解片段，首次从荷瘤小鼠(7)的血清和尿液中分离出来，抑制血管生成，从而抑制原发性(8)和转移性（7,9,10）肿瘤的生长。放射治疗在许多人类癌症的治疗中很重要，但由于肿瘤细胞的放射抵抗，通常不成功（11,12）。在这里，我们结合放疗和血管抑制素来靶向肿瘤血管，这些血管在基因上是稳定的，因此不太可能产生耐药性（13-15）。结果显示电离辐射和血管抑制素对四种不同肿瘤类型的抗肿瘤相互作用，在放射治疗中使用的辐射剂量。该组合对正常组织的毒性没有增加。体外研究表明，辐射和血管抑制素对内皮细胞有联合的细胞毒性作用，但对肿瘤细胞没有作用。在体内的研究表明，这些药物，联合起来，针对肿瘤血管系统。我们的结果为电离辐射联合血管抑制素提高肿瘤根除而不增加有害影响提供了支持。
Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumour progression(1-5). Angiostatin, a proteolytic fragment of plasminogen(6) that was first isolated from the serum and urine of tumour-bearing mice(7), inhibits angiogenesis and thereby growth of primary(8) and metastatic(7,9,10) tumours. Radiotherapy is important in the treatment of many human cancers, but is often unsuccessful because of tumour cell radiation resistance(11,12). Here we combine radiation with angiostatin to target tumour vasculature that is genetically stable and therefore less likely to develop resistance(13-15). The results show an antitumour interaction between ionizing radiation and angiostatin for four distinct tumour types, at doses of radiation that are used in radiotherapy. The combination produced no increase in toxicity towards normal tissue. In vitro studies show that radiation and angiostatin have combined cytotoxic effects on endothelial cells, but not tumour cells. In vivo studies show that these agents, in combination, target the tumour vasculature. Our results provide support for combining ionizing radiation with angiostatin to improve tumour eradication without increasing deleterious effects.