TWO ENDOGENOUS ANTIANGIOGENIC INHIBITORS, ENDOSTATIN AND ANGIOSTATIN, DEMONSTRATE BIPHASIC CURVES IN THEIR ANTITUMOR PROFILES
TWO ENDOGENOUS ANTIANGIOGENIC INHIBITORS, ENDOSTATIN AND ANGIOSTATIN, DEMONSTRATE BIPHASIC CURVES IN THEIR ANTITUMOR PROFILES
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DOI：
10.2203/dose-response.10-020.javaherian
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发表时间：
2011-01-01
期刊：
影响因子：
2.5
通讯作者：
Hlatky, Lynn
中科院分区：
文献类型：
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作者：
Javaherian, Kashi;Lee, Tong-Young;Hlatky, Lynn
血管生成是指从原有的血管中生长出来的血管。1971年，福克曼提出，通过切断肿瘤的血液供应，它们就会挨饿，从而导致它们的死亡。几年前，单抗阿瓦斯丁成为FDA批准的第一个用于治疗癌症患者的抗血管生成生物。另外两个抗血管生成的内源性蛋白质片段十多年前在福克曼的实验室中被分离出来。在这里，我们提供一个简短的数据回顾，证明血管抑素和内皮抑素显示出双相抗肿瘤剂量-反应。这种行为在大量抗血管生成药物中是常见的，高剂量率下抗血管生成药物的有效性降低可能是由于抑制了携带该药物进入肿瘤周围关键区域的新血管的生长。
Angiogenesis refers to growth of blood vessels from pre-existing ones. In 1971, Folkman proposed that by choking off the blood supply to tumors, they are starved, leading to their demise. A few years ago, the monoclonal antibody Avastin became the first antiangiogenic biological approved by FDA, for treatment of cancer patients. Two other antiangiogenic endogenous protein fragments were isolated in Folkman's laboratory more than a decade ago. Here, we present a short review of data demonstrating that angiostatin and endostatin display a biphasic antitumor dose-response. This behavior is common among a large number of antiangiogenic agents and the reduced effectiveness of antiangiogenic agents at high dose rates may be due to suppression of growth of new vessels carrying the agent into the critical region around the tumor.