Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma

被引:35
作者
Bello, L
Lucini, V
Costa, F
Pluderi, M
Giussani, C
Acerbi, F
Carrabba, G
Pannacci, M
Caronzolo, D
Grosso, S
Shinkaruk, S
Colleoni, F
Canron, X
Tomei, G
Deleris, G
Bikfalvi, A
机构
[1] Univ Milan, Osped Maggiore Policlin, Ist Ricovero & Cura Carattere Sci, Dept Neurol Sci, I-20122 Milan, Italy
[2] Univ Milan, Dept Pharmacol, Milan, Italy
[3] Univ Bordeaux 1, INSERM, Unit EMI 0113, Mol Angiogenesis Lab, Talence, France
[4] Univ Victor Segalen Bordeaux 2, INSERM, U577, Grp Chim Bioorgan, Bordeaux, France
关键词
D O I
10.1158/1078-0432.CCR-04-0194
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:4527 / 4537
页数:11
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