Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin.
Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin.
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发表时间：
1998-12
期刊：
影响因子：
11.2
通讯作者：
David H. Gorski;H. Mauceri;Rabih M. Salloum;Stephen Gately;Samuel Hellman;Michael A. Beckett;
中科院分区：
文献类型：
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作者：
David H. Gorski;H. Mauceri;Rabih M. Salloum;Stephen Gately;Samuel Hellman;Michael A. Beckett;
血管抑素是纤溶酶原的蛋白水解片段，通过抑制血管生成抑制原发性和转移性肿瘤的生长。当与电离辐射（IR）联合使用时，血管抑素表现出有效的抗肿瘤协同作用，主要是由抑制肿瘤微血管引起的。我们在这里报告的时间相互作用的血管抑素和IR在刘易斯肺癌（LLC）肿瘤生长在同基因小鼠的后肢。初始平均体积为510 +/- 151 mm 3的肿瘤仅用IR治疗（第0天和第1天20戈伊x 2次给药），血管抑素单药（25 mg/kg/天，每日两次），或如下所述的两者的组合：（0 - 13天）;（B）IR加血管抑素（0和1天）;和（c）IR，随后在IR完成后的第二天开始血管抑素，此后每天给药（2 - 13天）。到第14天，未处理的对照小鼠中的肿瘤已生长至6110 +/-582mm3，而在用以下处理的小鼠中：（a）单独IR，肿瘤已生长至2854 +/-338mm3（与单独IR相比P 0.05）;（c）IR加短程血管抑素，肿瘤达到1032 +/- 78 mm 3（与单独IR相比P < 0.001）。这些结果表明，实验性放射治疗的疗效是通过短暂的伴随暴露的肿瘤血管生成抑制素增强。
Angiostatin, a proteolytic fragment of plasminogen, inhibits the growth of primary and metastatic tumors by suppressing angiogenesis. When used in combination with ionizing radiation (IR), angiostatin demonstrates potent antitumor synergism, largely caused by inhibition of the tumor microvasculature. We report here the temporal interaction of angiostatin and IR in Lewis lung carcinoma (LLC) tumors growing in the hind limbs of syngeneic mice. Tumors with an initial mean volume of 510 +/- 151 mm3 were treated with IR alone (20 Gy x 2 doses on days 0 and 1), angiostatin alone (25 mg/kg/day divided twice daily) on days 0 through 13, or a combination of the two as follows: (a) IR plus angiostatin (days 0 through 13); (b) IR plus angiostatin (days 0 and 1); and (c) IR followed by angiostatin beginning on the day after IR completion and given daily thereafter (days 2 through 13). By day 14, tumors in untreated control mice had grown to 6110 +/- 582 mm3, whereas in mice treated with: (a) IR alone, tumors had grown to 2854 +/- 338 mm3 (P 0.05 compared with IR alone); and (c) IR plus short-course angiostatin, tumors reached 1032 +/- 78 mm3 (P < 0.001 compared with IR alone). These findings demonstrate that the efficacy of experimental radiation therapy is potentiated by brief concomitant exposure of the tumor vasculature to angiostatin.