Subject(s)
Apoptosis , Cardiac Output, Low/prevention & control , Glutamic Acid/genetics , Lysine/genetics , Myocardium/enzymology , Neovascularization, Physiologic , Proto-Oncogene Proteins c-akt/metabolism , Animals , Blood Pressure , Cardiac Output, Low/chemically induced , Cardiac Output, Low/pathology , Cardiac Output, Low/physiopathology , Coronary Circulation , Gene Expression Regulation , Mice , Myocardium/pathology , Myocytes, Cardiac/pathology , Proto-Oncogene Proteins c-akt/chemistry , Proto-Oncogene Proteins c-akt/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
This paper summarizes preliminary results of combining suicide gene strategy (E. coli cytosine deaminase gene--CD) with immunotherapy (murine interleukin-4 gene) for treatment of experimental B16(F10) melanomas implanted into C57Bl/6 mice. The best therapeutic results, inhibition of tumor growth and prolonged survival time of treated vs. control mice, were obtained when plasmid expression vectors containing therapeutic genes were transferred into mice via DDAB/DOPE cationic liposome carrier on the third or fourth day following inoculation of mice with cancer cells. Extension of survival time has been noted in the case of two-gene therapy (as compared with one-gene therapy) of tumors which originated from cells transfected in vitro with CD gene and which were subsequently injected in vivo with IL-4-secreting cells. However, no improvement of therapeutic effect was obtained in case of mice treated with a combination of two genes transferred intratumorally with DDAB/DOPE cationic liposomes as compared to mice treated with a single gene only.
