<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Dickerson, Erin B</style></author><author><style face="normal" font="default" size="100%">Akhtar, Nasim</style></author><author><style face="normal" font="default" size="100%">Steinberg, Howard</style></author><author><style face="normal" font="default" size="100%">Wang, Zun-Yi</style></author><author><style face="normal" font="default" size="100%">Lindstrom, Mary J</style></author><author><style face="normal" font="default" size="100%">Padilla, Marcia L</style></author><author><style face="normal" font="default" size="100%">Auerbach, Robert</style></author><author><style face="normal" font="default" size="100%">Helfand, S C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Enhancement of the antiangiogenic activity of interleukin-12 by peptide targeted delivery of the cytokine to alphavbeta3 integrin.</style></title><secondary-title><style face="normal" font="default" size="100%">Molecular cancer research : MCR</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Mol. Cancer Res.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Angiogenesis Inhibitors</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">CHO Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Cloning, Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Cricetinae</style></keyword><keyword><style  face="normal" font="default" size="100%">Flow Cytometry</style></keyword><keyword><style  face="normal" font="default" size="100%">Integrin alphaVbeta3</style></keyword><keyword><style  face="normal" font="default" size="100%">Interferon-gamma</style></keyword><keyword><style  face="normal" font="default" size="100%">Interleukin-12</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred BALB C</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred DBA</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Knockout</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Transgenic</style></keyword><keyword><style  face="normal" font="default" size="100%">Necrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Neoplasm Transplantation</style></keyword><keyword><style  face="normal" font="default" size="100%">Neovascularization, Pathologic</style></keyword><keyword><style  face="normal" font="default" size="100%">Oligopeptides</style></keyword><keyword><style  face="normal" font="default" size="100%">Peptides</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmids</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Engineering</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Isoforms</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Interleukin</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Interleukin-12</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombinant Fusion Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombinant Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Time Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Transfection</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2004</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2004 Dec</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">2</style></volume><pages><style face="normal" font="default" size="100%">663-73</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">We engineered a fusion protein, mrIL-12vp [mouse recombinant interleukin (IL)-12 linked to vascular peptide], linking the vascular homing peptide CDCRGDCFC (RGD-4C), a ligand for alphavbeta3 integrin, to mrIL-12 to target IL-12 directly to tumor neovasculature. The fusion protein stimulated IFN-gamma production in vitro and in vivo, indicating its biological activity was consistent with mrIL-12. Immunofluorescence techniques showed mrIL-12vp specifically bound to alphavbeta3 integrin-positive cells but not to alphavbeta3 integrin-negative cells. In corneal angiogenesis assays using BALB/c mice treated with either 0.5 microg/mouse/d of mrIL-12vp or mrIL-12 delivered by subcutaneous continuous infusion, mrIL-12vp inhibited corneal neovascularization by 67% compared with only a slight reduction (13%) in angiogenesis in the mrIL-12-treated animals (P = 0.008). IL-12 receptor knockout mice given mrIL-12vp showed a marked decrease in the area of corneal neovascularization compared with mice treated with mrIL-12. These results indicate that mrIL-12vp inhibits angiogenesis through IL-12-dependent and IL-12-independent mechanisms, and its augmented antiangiogenic activity may be due to suppression of endothelial cell signaling pathways by the RGD-4C portion of the fusion protein. Mice injected with NXS2 neuroblastoma cells and treated with mrIL-12vp showed significant suppression of tumor growth compared with mice treated with mrIL-12 (P = 0.03). Mice did not show signs of IL-12 toxicity when treated with mrIL-12vp, although hepatic necrosis was present in mrIL-12-treated mice. Localization of IL-12 to neovasculature significantly enhances the antiangiogenic effect, augments antitumor activity, and decreases toxicity of IL-12, offering a promising strategy for expanding development of IL-12 for treatment of cancer patients.</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/15634755?dopt=Abstract</style></custom1></record></records></xml>