title: Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice.
abstract: BACKGROUND
  Clinical trials have indicated that preclinical results obtained with human tumor xenografts in mouse models may overstate the potential of adenovirus (Ad)-mediated oncolytic therapies. We have previously demonstrated that the replication of human Ads depends on cyclin E dysregulation or overexpression in cancer cells. ED-1 cell derived from mouse lung adenocarcinomas triggered by transgenic overexpression of human cyclin E may be applied to investigate the antitumor efficacy of oncolytic Ads.
  
  
  METHODS
  Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies.
  
  
  RESULTS
  Murine ED-1 cells were permissive for human Ad replication and Ad-cycE repressed ED-1 tumor growth in immunocompetent FVB mice. ED-1 cells destroyed by oncolytic Ads in tumors were encircled in capsule-like structures, while cells outside the capsules were not infected and survived the treatment.
  
  
  CONCLUSIONS
  Ad-cycE can target cyclin E overexpression in cancer cells and repress tumor growth in syngeneic mouse models. The capsule structures formed after Ad intratumoral injection may prevent viral particles from spreading to the entire tumor.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. paisin.paisin@gmail.com.
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Cheng
authors.affiliation: James Graham Brown Cancer Center, University of Louisville Medical School, 505 South Hancock Street, CTR Building, Room 306, Louisville, KY, 40202, USA. x0rao001@louisville.edu.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Rao
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. slwech01@exchange.louisville.edu.|Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA. slwech01@exchange.louisville.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Wechman
authors.affiliation: Department of Diagnostic Radiology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. x0li0027@exchange.louisville.edu.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. mcmasters@louisville.edu.|Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA. mcmasters@louisville.edu.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.affiliation: James Graham Brown Cancer Center, University of Louisville Medical School, 505 South Hancock Street, CTR Building, Room 306, Louisville, KY, 40202, USA. hszhou01@louisville.edu.|Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA. hszhou01@louisville.edu.|Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. hszhou01@louisville.edu.
authors.forename: Heshan Sam
authors.initials: HS
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019927:Cyclin E / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D064596:Isografts; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses; D023041:Xenograft Model Antitumor Assays
chemical_list: D019927:Cyclin E