Accession Number : ADA433972


Title :   Genetic Radiotherapy of Prostate Cancer


Descriptive Note : Final rept., 1 Dec 2001-30 Nov 2004


Corporate Author : ALABAMA UNIV IN BIRMINGHAM


Personal Author(s) : Buchsbaum, Donald J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a433972.pdf


Report Date : Dec 2004


Pagination or Media Count : 105


Abstract : The goal to achieve a high intra-tumoral concentration of 5-fluoro-uracil (5-FU) via molecular chemotherapy employing adenoviral (Ad) vectors encoding the genes for somatostatin receptor subtype 2(SSTr2) and cytosine deaminase (CD) which converts the prodrug 5-fluoro-cytosine (5-FC) to 5-FU under control of the cyclo-oxygenase-2 (Cox-2) tumor-specific promoter was achieved. We evaluated novel two-gene Ad vectors: (1) a native fiber Ad (AdCMVCDCMVSSTr2) and (2) Ad under control of the Cox-2 promoter expressing CD and SSTr2. The vectors were tested for SSTr2 and CD expression employing membrane receptor binding in vitro with 125/somatostatin and 99m/Tc-P2045 that binds to SSTr2, conversion of 5-FC to 5-FU, and cytotoxicity against Ad infected cells in the presence of 5-FC. The vectors were evaluated in vivo for SSTr2 expression and CD expression. Efforts to produce RGD modified vectors expressing CD and SSTr2 under control of the Cox-2L promoter were not successful. We identified chimeric Ad5/3 virus with the Cox-2L promoter driving CD and SSTr2 to have therapeutic efficacy against prostate cancer xenografts, and identified that Ad virus expressing CDUPRT was more efficacious than CD in combination with 5-FC and radiation therapy.


Descriptors :   *ADENOVIRUSES , *DISEASE VECTORS , *RADIOTHERAPY , *PROSTATE CANCER , *GENE THERAPY , MOLECULES , ENZYMES , IN VITRO ANALYSIS , IN VIVO ANALYSIS , RECEPTOR SITES(PHYSIOLOGY) , CHEMOTHERAPY , CYTOSINE , URACILS , TRANSCRIPTION(GENETICS)


Subject Categories : Medicine and Medical Research
      Radiobiology
      Microbiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE