Nitric Oxide Gene Therapy for Prostate Cancer
Annual rept. 1 Oct 1998-30 Sep 1999
WILLIAM BEAUMONT HOSPITAL ROYAL OAK MI
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Traditional therapies for advanced prostate cancer are unable to cure a majority of patients. One approach to therapy is over-production of inducible nitric oxide synthase iNOS within the tumor by injecting replication defective adenovirus containing the DNA sequences for iNOS into prostate tumors. The adenovims gene transfer technology is readily applicable and an iNOS, with CMV promoter, containing adenovirus Ad5-CMV- iNOS has been constructed and tested in our laboratory. The production of nitric oxide in DU-l45 prostate cancer cells growing in vitro after infection with Ad5-CMV-iNOS has been determine. Maximum NO release rate occurred when cells were infected at multiplicity of infection MOI 15 and after 24 to 36 hours incubation. Direct cell killing commenced within 3 days after infection and occurred at MOI greater than 5. In the second phase of the project DU-145 and PC-3 cells will be grown as xenograft tumors in nude mice, infected by injection with Ad5-CMV-iNOS, and analyzed for nitric oxide, superoxide, peroxynitrite, and hydrogen peroxide production, cytotoxicity, and radiation sensitization. These results will help determine the best approach to applying iNOS gene therapy to the treatment of prostate cancer in human patients.
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