Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma
Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma
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DOI：
10.1158/1078-0432.ccr-04-0194
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发表时间：
2004-07-01
影响因子：
11.5
通讯作者：
Bikfalvi, A
中科院分区：
文献类型：
--
作者：
Bello, L;Lucini, V;Bikfalvi, A
目的：我们研究了不同抑制剂的联合给药对胶质瘤血管生成、迁移和增殖的活性产生胶质瘤生长的长期抑制的能力。（PF-4/CTF、环VEGI）或同时影响血管生成和侵袭的抑制剂结果：当联合给药时，这些药物对胶质瘤生长的抑制作用与所用抑制剂的类型无关。组合施用比单独施用单一抑制剂更有效，并且用显著较低量的蛋白质达到强的治疗反应。最强的抑制被观察到时，人类PEX和PF-4/DLR，这两个影响胶质瘤血管生成和入侵的单独mechanisms，combined.Conclusions：这支持了这一概念，即长期胶质瘤生长抑制可以通过同时交付的分子，靶向肿瘤和内皮细胞，并通过单独的机制发挥作用。
Purpose: We investigated the ability of the combinatorial administration of different inhibitors with activities on glioma angiogenesis, migration, and proliferation to produce a prolonged inhibition of glioma growth.Experimental Design: We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF, cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX, PF-4/DLR).Results: When administered in combination, these drugs produced a prolonged and increased inhibition of glioma growth independently from the type of inhibitor used. The combinatory administration was more effective than the administration of a single inhibitor alone, and a strong therapeutic response was reached with a significantly lower amount of protein. The strongest inhibition was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis and invasion by separate mechanisms, were combined.Conclusions: This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.