Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts Journal Article

  

Authors:	Kikuchi, E.; Menendez, S.; Ozu, C.; Ohori, M.; Cordon-Cardo, C.; Logg, C. R.; Kasahara, N.; Bochner, B. H.
Article Title:	Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts
Abstract:	We have developed unique replication-competent retroviral (RCR) vectors based on murine leukemia virus that provide improved efficiency of viral delivery, allow for long-term transgene expression and demonstrate an intrinsic selectivity for transduction of rapidly dividing tumor cells. The purpose of this study was to evaluate the in vivo transduction efficiency and the therapeutic efficacy of the RCR vector mediated delivery of Escherichia coli purine nucleoside phosphorylase (PNP) in combination with fludarabine phosphate for bladder cancer. We constructed vectors containing green fluorescent protein (GFP) gene (ACE)-GFP) or PNP gene (ACE-PNP). KU-19-19 bladder tumors exhibited 28.3±16.1, 46.6±5.8 and 93.7±7.8% of GFP expression on 14, 18 and 26 days after intratumoral injection of ACE-GFP, respectively. GFP expression could not be observed in normal tissues surrounding the injected tumors. No detectable polymerase chain reaction products of GFP gene could be observed in any distant organs. Intratumoral injection of ACE-PNP, followed by systemically administered fludarabine phosphate, significantly inhibited the growth of pre-established KU-19-19 tumors. Our results indicate that RCR vectors are a potentially efficient gene delivery method and that the RCR vector mediated PNP gene transfer and fludarabine phosphate treatment might be a novel and potentially therapeutic modality for bladder cancer. © 2007 Nature Publishing Group All rights reserved.
Keywords:	controlled study; human cell; nonhuman; systemic therapy; combined modality therapy; dna replication; polymerase chain reaction; mouse; animals; mice; gene expression; antimetabolites, antineoplastic; green fluorescent protein; animal experiment; animal model; cytotoxicity; tumor xenograft; tumor cells, cultured; urinary bladder neoplasms; mice, inbred balb c; gene transfer; viral gene delivery system; genetic transduction; genetic vectors; transduction, genetic; cancer inhibition; mice, nude; escherichia coli; gene therapy; retrovirus vector; transplantation, heterologous; green fluorescent proteins; drug metabolism; tumor growth; bladder carcinoma; retrovirus; transgenics; gene transfer techniques; prodrugs; cancer gene therapy; retroviral vector; suicide gene; in vivo culture; purine-nucleoside phosphorylase; murine leukemia virus; purine nucleoside phosphorylase; leukemia virus, murine; fludarabine phosphate; vidarabine phosphate
Journal Title:	Cancer Gene Therapy
Volume:	14
Issue:	3
ISSN:	0929-1903
Publisher:	Nature Publishing Group
Date Published:	2007-08-01
Start Page:	279
End Page:	286
Language:	English
DOI:	10.1038/sj.cgt.7701013
PUBMED:	17218950
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33847043563&partnerID=40&md5=6e2909ea3784b7532184b51f0d3d8941
Notes:	--- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: CGTHE" - "Source: Scopus"

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