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Synergistic antitumoral effect of IL-12 gene cotransfected with antiangiogenic genes for angiostatin, endostatin, and saxatilin.

Abstract
Previously, it was reported that the cotransfection of angiostatin K1-3, endostatin, and saxatilin genes using cationic liposomes significantly inhibited tumor progression. IL-12 is a well-known immune modulator that promotes Th1-type antitumor immune responses and also induces antiangiogenic effects. In this study, we have examined the antitumoral function of the IL-12 gene cotransfected with antiangiogenic genes for angiostatin K1-3, endostatin, and saxatilin by O,O'-dimyristyl-N-lysyl glutamate (DMKE) cationic liposomes in a mouse tumor model. According to our results, the administration of the IL-12 gene or the genes for angiostatin K1-3, endostatin, and saxatilin exhibited effective inhibition of B16BL6 melanoma growth in mice. In particular, intravenous administration of the IL-12 gene along with intratumoral administration of the three antiangiogenic genes synergistically inhibited the B16BL6 tumor growth. These results suggest that systemically expressed IL-12 enhances antitumoral efficacy of locally expressed antiangiogenic proteins.
AuthorsHong Sung Kim, Hwa Yeon Jeong, Yeon Kyung Lee, Keun Sik Kim, Yong Serk Park
JournalOncology research (Oncol Res) Vol. 21 Issue 4 Pg. 209-16 ( 2013) ISSN: 1555-3906 [Electronic] United States
PMID24762227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dipeptides
  • Disintegrins
  • Endostatins
  • Liposomes
  • O,O'-dimyristyl-N-lysyl glutamate
  • saxatilin
  • Interleukin-12
  • Angiostatins
  • DNA
Topics
  • Angiostatins (biosynthesis, genetics)
  • Animals
  • Cell Growth Processes (genetics)
  • DNA (administration & dosage, chemistry, genetics)
  • Dipeptides (administration & dosage, chemistry)
  • Disintegrins (biosynthesis, genetics)
  • Endostatins (biosynthesis, genetics)
  • Female
  • Gene Expression
  • Genetic Therapy (methods)
  • Interleukin-12 (biosynthesis, genetics)
  • Liposomes (administration & dosage, chemistry)
  • Melanoma, Experimental (blood supply, genetics, pathology, therapy)
  • Mice
  • Mice, Inbred C57BL
  • Plasmids (administration & dosage, chemistry, genetics)
  • Transfection (methods)

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