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CYTOTOXICITY OF ADENOVIRAL-MEDIATED CYTOSINE DEAMINASE PLUS 5-FLUOROCYTOSINE GENE THERAPY IS SUPERIOR TO THYMIDINE KINASE PLUS ACYCLOVIR IN A HUMAN RENAL CELL CARCINOMA MODEL

1999; Lippincott Williams & Wilkins; Volume: 162; Issue: 3 Part 1 Linguagem: Inglês

10.1097/00005392-199909010-00096

1527-3792

Toshiro Shirakawa, Thomas A. Gardner, Song-Chu Ko, Neil H. Bander, Savio L‐Y. Woo, Akinobu Gotoh, Sadao Kamidono, Leland W.K. Chung, Chinghai Kao,

Renal cell carcinoma treatment

No AccessJournal of UrologyInvestigative Urology1 Sep 1999CYTOTOXICITY OF ADENOVIRAL-MEDIATED CYTOSINE DEAMINASE PLUS 5-FLUOROCYTOSINE GENE THERAPY IS SUPERIOR TO THYMIDINE KINASE PLUS ACYCLOVIR IN A HUMAN RENAL CELL CARCINOMA MODEL TOSHIRO SHIRAKAWA, THOMAS A. GARDNER, SONG-CHU KO, NEIL BANDER, SAVIO WOO, AKINOBU GOTOH, SADAO KAMIDONO, LELAND W.K. CHUNG, and CHINGHAI KAO TOSHIRO SHIRAKAWATOSHIRO SHIRAKAWA More articles by this author , THOMAS A. GARDNERTHOMAS A. GARDNER More articles by this author , SONG-CHU KOSONG-CHU KO More articles by this author , NEIL BANDERNEIL BANDER More articles by this author , SAVIO WOOSAVIO WOO More articles by this author , AKINOBU GOTOHAKINOBU GOTOH More articles by this author , SADAO KAMIDONOSADAO KAMIDONO More articles by this author , LELAND W.K. CHUNGLELAND W.K. CHUNG More articles by this author , and CHINGHAI KAOCHINGHAI KAO More articles by this author View All Author Informationhttps://doi.org/10.1097/00005392-199909010-00096AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: An estimated 11,600 Americans will die of renal cell carcinoma in 1998. The lack of effective chemotherapy or radiotherapy requires the investigation of novel treatment modalities. We compared two forms of toxic gene therapy, cytosine deaminase (CD) plus 5-fluorocytosine (5-FC) and thymidine kinase (TK) plus acyclovir (ACV), in pre-clinical models of human renal cell carcinoma. Materials and Methods: Replication-deficient recombinant adenoviral vectors containing the Rous sarcoma virus promoter driving CD (Ad-RSV-CD) or TK (Ad-RSV-TK) gene expression were constructed and tested for in vitro cell-killing assays at various viral multiplicity of infection (MOI) and in vivo for growth inhibition of a human renal cell carcinoma, SK-RC-29 models. Subcutaneous tumors of SK-RC-29 were examined by electron microscopy for presence of intercellular gap junctions. Levels of expression of the gap junctional associated connexin 43 protein in SK-RC-29, 31, 38, 42, 52 human RCC cell lines were examined by western immunoblotting. Results: In vitro cell-killing assay comparing Ad-RSV-CD/5F-C and Ad-RSV-TK/ACV at a wide range of MOI (2.5 to 20) revealed superior cell-kill by Ad-RSV-CD/5-FC over Ad-RSV-TK/ACV. Consistent with these results, we observed that Ad-RSV-CD/5-FC but not Ad-RSV-TK/ACV demonstrated a significant in vivo tumor growth inhibition. 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Google Scholar From the Molecular Urology and Therapeutics Program, Department of Urology, University of Virginia Health Sciences Center, Charlottesville, Virginia, the Department of Urology, New York Hospital-Cornell Medical Center, the Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York, and the Department of Urology, Kobe University School of Medicine, Kobe, Japan(Gardner) Requests for reprints: Molecular Urology and Therapeutics Program, Department of Urology, Indiana University, 535 Barnhill Drive, Suite 420, Indianapolis, IN 46202-5289.Supported by the American Foundation of Urologic Diseases (IM-Clone Scholar), NIH Training Grant 5-T32-DK07642, the Ades family, and NIH R29-CA74042 and DOD-DAMD17-98-1-8643 grants.© 1999 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 162Issue 3 Part 1September 1999Page: 949-954 Advertisement Copyright & Permissions© 1999 by American Urological Association, Inc.MetricsAuthor Information TOSHIRO SHIRAKAWA More articles by this author THOMAS A. GARDNER More articles by this author SONG-CHU KO More articles by this author NEIL BANDER More articles by this author SAVIO WOO More articles by this author AKINOBU GOTOH More articles by this author SADAO KAMIDONO More articles by this author LELAND W.K. CHUNG More articles by this author CHINGHAI KAO More articles by this author Expand All Advertisement PDF DownloadLoading ...