title: Oncolytic virotherapy for prostate cancer by E1A, E1B mutant adenovirus.
abstract: OBJECTIVE
  To report our therapeutic results in prostate cancer using double-mutated adenovirus AxdAdB-3, which has a mutation of E1A and deletion of E1B 55KD. Advanced prostate cancer can harbor multiple genetic alterations, including p53 and Rb/E2F/p16, and is often refractory to hormonal ablation. Virotherapy has been used to target these genetic abnormalities using mutant oncolytic adenovirus for the management of other cancers.
  
  
  METHODS
  The cytopathic effects of AxdAdB-3 were examined in human prostate carcinoma cell lines (DU145, PC3, and LNCaP) and human normal prostate-derived cell lines (PrEC and PrSC) with AxE1AdB and dl922-947 by crystal violet staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The therapeutic efficacy of AxdAdB-3 for the treatment of prostate cancer was investigated in an orthotopic prostate cancer model established with DU145 in severe combined immunodeficiency (SCID) mice.
  
  
  RESULTS
  AxdAdB-3 induced potent cytopathic effects in the prostate cancer cell lines tested. AxdAdB-3 showed no cytotoxicity in the normal prostate-derived cell lines PrEC and PrSC. In vivo, AxdAdB-3 showed apparent antitumor effect in the orthotopic prostate cancer model and significantly improved survival.
  
  
  CONCLUSIONS
  These results suggest that AxdAdB-3 could be a promising tool for virotherapy against prostate cancer in patients with disease resistant to hormonal therapy.
authors.affiliation: Division of Urology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Satoh
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Shigeto
authors.initials: S
authors.lastname: Ishidoya
authors.forename: Hisashi
authors.initials: H
authors.lastname: Abe
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003588:Cytopathogenic Effect, Viral; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D050130:Oncolytic Virotherapy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy*; D011991:Receptors, Virus / Q000032:analysis
chemical_list: D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus