title: Gene therapy for prostate cancer using the cytosine deaminase/uracil phosphoribosyltransferase suicide system.
abstract: BACKGROUND
  Cytosine deaminase (CD) activates prodrug 5-FC to 5-FU and is used for suicide gene therapy (the CD/5-FC system). E. coli uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that directly converts 5-FU into 5-fluorouridine monophosphate and improves the antitumoral effect of 5-FU. This study demonstrates the effectiveness of transduction of the UPRT gene in addition to CD/5-FC cancer suicide gene therapy.
  
  
  METHODS
  We investigated a combined suicide gene transduction therapy for human hormone independent prostate cancer cell line DU145 using two separate adenovirus vectors expressing the E. coli CD and E. coli UPRT genes and systemic 5-FC administration (the CD+UPRT/5-FC system).
  
  
  RESULTS
  Cells transfected with AdCA-UPRT showed approximately 57 times lower IC50 to 5-FU compared with those transfected with AdCA-LacZ. Furthermore, cells transfected with AdCA-CD and AdCA-UPRT proved to be more sensitive to 5-FC compared with those transfected with AdCA-CD. Intratumoral injection of AdCA-CD and AdCA-UPRT drastically suppressed the growth of tumors which had generated from DU145 cells inoculated into athymic (nude) mice compared with those injected with AdCA-LacZ or AdCA-LacZ and AdCA-CD.
  
  
  CONCLUSIONS
  These results suggest that the CD+UPRT/5-FC system could be a powerful factor in human prostate cancer suicide gene therapy.
authors.affiliation: Department of Urology, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Miyagi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Koshida
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Katoh
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.forename: Masayuki
authors.initials: M
authors.lastname: Egawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002460:Cell Line; D043525:Cytosine Deaminase; D005472:Fluorouracil / Q000494:pharmacology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009700:Nucleoside Deaminases / Q000235:genetics*; D010430:Pentosyltransferases / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000628:therapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil