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  • Title: Effect of electroporation-mediated diphtheria toxin A expression on PSA positive human prostate xenograft tumors in SCID mice.
    Author: Goepfert C, Gazdhar A, Frey FJ, Frey BM.
    Journal: Prostate; 2011 Jun 01; 71(8):872-80. PubMed ID: 21456069.
    Abstract:
    BACKGROUND: Current therapies to treat prostate cancer are often limited. Since it has been shown that very low concentrations of diphtheria toxin A (DT-A) result in abrogation of protein synthesis and apoptosis of cells, DT-A might serve as an efficient killer in cancer gene therapy. For this purpose we investigated in a quantitative manner using a stereological approach the apoptotic effect of DT-A in androgen receptor (AR) and prostate specific antigen (PSA) expressing cells after tumor formation in both flanks of SCID mice. METHODS: First, DT-A plasmid transfection was evaluated, using the lipid formulation DMRIE-C in C4-2 prostate cancer xenografts. After detection of an overall high rate of apoptosis by DMRIE-C alone, plasmid delivery was performed in a second study by electroporation. Finally this method was used to specifically target the AR and PSA expressing cell line C4-2 using pDT-A driven by a prostate specific promoter and enhancer (PSE/PSA). PC-3 cells, being AR and PSA negative, served as controls. RESULTS: The experiments revealed evidence of a reduced growth rate of AR and PSA expressing C4-2 cells in vitro and in vivo compared to the AR and PSA negative prostate cancer cell line PC-3. The electroporation technology favored the response compared to DMRIE-C. CONCLUSION: These results suggest that the local delivery of DT-A plasmid by electroporation might present a favorable factor to treat prostate cancer.
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