Avastin enhances photodynamic therapy treatment of Kaposi's sarcoma in a mouse tumor model.
The goal of the current study was to determine if the antiangiogenic drug Avastin would improve the effectiveness of Photodynamic Therapy (PDT) in a xenograft model of Kaposi's sarcoma (KS). Human KS-Imm tumors transplanted in nude mice were treated with Photofrin-mediated PDT. Expression parameters of proangiogenic molecules were documented and the tumoricidal effectiveness of PDT combined with the VEGF inhibitor Avastin was determined. PDT induced increased expression of HIF-1alpha, VEGF, PGE2, TNF-alpha, and IL-1beta within treated KS tumor tissue. Significant overexpression of KS cell derived human VEGF and to a lesser extent overexpression of host cell derived mouse VEGF were detected within treated tumors. Combining PDT with Avastin resulted in a significant increase in the long-term responsiveness of treated KS tumors when compared to individual treatments. These results demonstrate for the first time that Avastin can improve PDT treatment effectiveness and suggest that VEGF inhibitors may ameliorate the clinical efficacy of PDT.
Saban Research Institute, University of Southern California, Los Angeles, CA 90027, USA.
Angela
A
Ferrario
Charles J
CJ
Gomer
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007375:Interleukin-1; D017319:Photosensitizing Agents; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D017323:Dihematoporphyrin Ether; D015232:Dinoprostone