title: Oncolytic viral therapy by bladder instillation using an E1A, E1B double-restricted adenovirus in an orthotopic bladder cancer model.
abstract: OBJECTIVE
  To investigate the therapeutic effect of AxdAdB-3, a double-restricted oncolytic adenovirus harboring a mutant E1A and an E1B-55KD deletion, on human bladder cancer cell lines and the SCID mouse model of orthotopic bladder cancer.
  
  
  METHODS
  The cytopathic effects of AxdAdB-3 were evaluated in several cell lines (YTS-1, YTS-3, T24, J82, 5637) derived from human bladder or ureteral cancer and in a normal bladder mucosa-derived cell line (HCV29) with AxCAlacZ (control) or AxE1AdB (E1B-55KD-defective adenovirus) or dl922-947 (E1A-mutated adenovirus). The efficacy of bladder instillation therapy with AxdAdB-3 for orthotopic bladder cancer of SCID mice was investigated. The oncolytic effects were monitored by ultrasound examination.
  
  
  RESULTS
  AxdAdB-3 caused the oncolysis of bladder cancer cell lines in vitro, and it was more cytopathic than AxE1AdB or dl922-947 in the cancer cell lines. AxdAdB-3 was not cytotoxic against HCV29. Direct instillation of AxdAdB-3 into the bladder of the orthotopic model inhibited tumor growth, leading to significantly prolonged survival.
  
  
  CONCLUSIONS
  Oncolytic viral therapy delivered by instillation of AxdAdB-3 is a promising tool for treating bladder cancer.
authors.affiliation: Division of Urology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. wang@uro.med.tohoku.ac.jp
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Makoto
authors.initials: M
authors.lastname: Satoh
authors.forename: Hisashi
authors.initials: H
authors.lastname: Abe
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamura
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Shigeto
authors.initials: S
authors.lastname: Ishidoya
authors.forename: Seiichi
authors.initials: S
authors.lastname: Saito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000283:Administration, Intravesical; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D050130:Oncolytic Virotherapy / Q000379:methods*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*