title: Effect of electroporation-mediated diphtheria toxin A expression on PSA positive human prostate xenograft tumors in SCID mice.
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.
  
  
  CONCLUSIONS
  These results suggest that the local delivery of DT-A plasmid by electroporation might present a favorable factor to treat prostate cancer.
authors: Department of Nephrology and Hypertension, University of Berne, Berne, Switzerland.
authors: Christine
authors: C
authors: Goepfert
authors: Amiq
authors: A
authors: Gazdhar
authors: Felix J
authors: FJ
authors: Frey
authors: Brigitte M
authors: BM
authors: Frey
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004167:Diphtheria Toxin / Q000008:administration & dosage*; D018274:Electroporation; D006801:Humans; D008055:Lipids; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010446:Peptide Fragments / Q000008:administration & dosage*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: C410798:AR protein, human; D004167:Diphtheria Toxin; D008055:Lipids; D010446:Peptide Fragments; D000644:Quaternary Ammonium Compounds; D011944:Receptors, Androgen; C029795:diphtheria toxin fragment A; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; D017430:Prostate-Specific Antigen