title: Potentiated antitumor effects of interleukin 12 and matrix metalloproteinase inhibitor batimastat against B16F10 melanoma in mice.
abstract: The application of antiangiogenic agents in cancer therapy has been studied extensively. Combination of agents with antiangiogenic properties could possibly enhance antitumor effects. Interleukin 12 is a cytokine with potent antitumor activity mediated also via antiangiogenic mechanisms. These effects are attributed to IFN-gamma production stimulated by IL-12. Since IFN-gamma has been reported to augment antitumor effects when combined with one of the metalloproteinase inhibitors--batimastat (BB-94), we have examined a combined treatment with IL-12 and BB-94 in a murine melanoma model. The administration of both agents showed potentiated antitumor activity. Furthermore, we have shown in a tumor-induced angiogenesis model that the combined application of IL-12 and batimastat inhibits the formation of new blood vessels to a greater extent than either agent alone. Our observations show that antiangiogenic effects are at least partly responsible for the enhanced antitumor effects of the combined treatment with IL-12 and BB-94.
authors.affiliation: Department of Immunology, Medical University of Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Dabrowska
authors.forename: A
authors.initials: A
authors.lastname: Giermasz
authors.forename: M
authors.initials: M
authors.lastname: Marczak
authors.forename: J
authors.initials: J
authors.lastname: Gołab
authors.forename: M
authors.initials: M
authors.lastname: Jakóbisiak
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004357:Drug Synergism; D018664:Interleukin-12 / Q000494:pharmacology / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D013876:Thiophenes; D018664:Interleukin-12; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases