Antitumoral and antimetastatic effect of antiangiogenic plasmids in B16 @entity320 : Higher efficiency of the recombinant disintegrin domain of XXXX .

@entity39244 @entity9842 @entity5 @entity19 @entity3 @entity72859 @entity320
BACKGROUND: Despite the discovery of novel inhibitors of @entity5 angiogenesis, protein-based antiangiogenic @entity5 therapy suffers some limitations that antiangiogenic gene therapy could overcome. We investigated whether intra-tumoral electrotransfer of three angiogenic plasmids could inhibit @entity5 growth and @entity3 . METHODS: Plasmids encoding recombinant disintegrin domain of @entity72859 (RDD), @entity39244 ( @entity39244 ), and the soluble isoform of the VEGF receptor 1 ( @entity9842 ) were injected into B16F10 @entity320 -bearing C57BL/6 @entity19 followed by electroporation. @entity5 volume was measured daily using a digital caliper. @entity3 was monitored by in vivo bioluminescence after surgical removal of the primary luciferase-encoding B16F10 @entity5 5 days after intra-tumoral electrotransfer. Markers of vascularization and cell proliferation were quantified by immunohistochemistry. RESULTS: Intra-tumoral electrotransfer of the antiangiogenic plasmids induced a significant inhibition of @entity5 growth, doubling of mean survival time and long-term survivors (   40% vs 0% in control). When the @entity5 was removed by surgery after intra-tumoral plasmid electrotransfer, a significant decrease in @entity5 @entity3 was observed leading to long-term @entity5 -free survival especially after treatment with pRDD plasmid (84% vs 0% in control). Unlike pTSP-1 and psFlt-1, pRDD significantly decreased cell proliferation in B16F10 @entity5 which express avb3 and a5b1 integrins. No effect of antiangiogenic plasmid electrotransfer on normal skin blood flow was detected. CONCLUSION: The intra-tumoral electrotransfer of the three antiangiogenic plasmids is a promising method for the treatment of @entity320 . The plasmid encoding RDD seems to be particularly effective due to its direct antitumoral activity combined with angiogenesis suppression, and its marked inhibition of @entity3 .
