PMID- 9694160
OWN - NLM
STAT- MEDLINE
DCOM- 19981023
LR  - 20220309
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 9
IP  - 11
DP  - 1998 Jul 20
TI  - In vivo gene therapy for prostate cancer: preclinical evaluation of two different 
      enzyme-directed prodrug therapy systems delivered by identical adenovirus 
      vectors.
PG  - 1617-26
AB  - Advanced prostate cancer is invariably lethal once it becomes androgen 
      independent (AI). With the aim of developing a new treatment we have used the 
      human androgen-independent prostate cancer cell line, PC-3, to evaluate the 
      effectiveness of two enzyme-directed prodrug therapy (EPT) systems as a novel 
      means for promoting tumor cell destruction in vivo. We have confined our study to 
      the use of a PSA promoter, in a preliminary attempt to achieve prostate 
      specificity. The two EPT systems used were the HSVTK/GCV and PNP/6MPDR systems. 
      These were chosen for their differential dependence on DNA replication for their 
      mechanism of action. In the present work, either the HSVTK or PNP gene, each 
      controlled by a PSA promoter fragment, was delivered by an E1-, 
      replication-deficient human adenovirus (Ad5) into PC-3 tumors growing 
      subcutaneously in BALB/c nude mice. Tumors were injected with a single dose of 
      recombinant Ad5 and mice were treated intraperitoneally with the appropriate 
      prodrug, twice daily, for 6 days thereafter. The growth of established PC-3 
      tumors was significantly suppressed and host survival increased with a single 
      course of HSVTK/GCV or PNP/6MPDR treatment. HSVTK/GCV-treated PC-3 tumor growth 
      was 80% less than that of control treatments on day 33, while PNP/6MPDR-treated 
      tumor growth was approximately 75% less than that of control treatments on day 
      52. Survival data showed that 20% of HSVTK/GCV- or PNP/6MPDR-treated animals 
      lived >45 and >448 days, respectively, longer than control animals. These results 
      demonstrate that both HSVTK/GCV and PNP/6MPDR therapies interrupt the growth of 
      an aggressive human prostate cancer cell line in vivo.
FAU - Martiniello-Wilks, R
AU  - Martiniello-Wilks R
AD  - Oncology Research Centre, Prince of Wales Hospital, Randwick, NSW, Australia.
FAU - Garcia-Aragon, J
AU  - Garcia-Aragon J
FAU - Daja, M M
AU  - Daja MM
FAU - Russell, P
AU  - Russell P
FAU - Both, G W
AU  - Both GW
FAU - Molloy, P L
AU  - Molloy PL
FAU - Lockett, L J
AU  - Lockett LJ
FAU - Russell, P J
AU  - Russell PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Prodrugs)
RN  - EC 2.4.2.1 (Purine-Nucleoside Phosphorylase)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Adenocarcinoma/*therapy
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Escherichia coli/enzymology
MH  - Ganciclovir/pharmacology
MH  - *Genetic Therapy
MH  - Genetic Vectors
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Prodrugs/*pharmacology
MH  - Prostatic Neoplasms/*therapy
MH  - Purine-Nucleoside Phosphorylase/*genetics/metabolism
MH  - Simplexvirus/enzymology
MH  - Thymidine Kinase/*genetics/metabolism
MH  - Tumor Cells, Cultured
EDAT- 1998/08/07 00:00
MHDA- 1998/08/07 00:01
CRDT- 1998/08/07 00:00
PHST- 1998/08/07 00:00 [pubmed]
PHST- 1998/08/07 00:01 [medline]
PHST- 1998/08/07 00:00 [entrez]
AID - 10.1089/hum.1998.9.11-1617 [doi]
PST - ppublish
SO  - Hum Gene Ther. 1998 Jul 20;9(11):1617-26. doi: 10.1089/hum.1998.9.11-1617.