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Biomedical subjects

S Szala

Publications and source records attributed to S Szala.

38 records · Page 3Linked to original sources

KDR promoter can transcriptionally target cytosine deaminase suicide gene to cancer cells of nonendothelial origin.

The KDR/flk-1 gene promoter is considered to be endothelial cell-specific. We show its activity in two cancer cell lines of non-endothelial origin: in murine L1 sarcoma and OVP-10 human ovarian carcinoma cell lines. KDR promoter-driven cytosine deaminase gene can be efficiently expressed in these cells leading to sensitization to 5-fluorocytosine, as demonstrated both in vitro and in vivo. Our results indicated that KDR promoter activity is not endothelial cell-exclusive and that this promoter can also be used to obtain specific expression of therapeutic genes in certain cancer cells.

3T3 Cells↗

Selective augmentation of radiation effects by 5-fluorocytosine on murine B16(F10) melanoma cells transfected with cytosine deaminase gene.

We report that in vitro 5-fluorocytosine sensitizes B16(F10) melanoma cells to radiation damage when they are transfected with cytosine deaminase gene (CD). The greatest enhancement of radiation cytotoxicity was observed when B16(F10)/CD cells were incubated in medium with 500 microM 5-fluorocytosine for 3 hours, with incubation starting 1 hour after irradiation. 5-Fluorocytosine did not change radiosensitivity of parental, nontransfected cells. The isoeffective dose for CD-transfected cells treated with 5-fluorocytosine was reduced by 20% at a 2-Gy level of effect for nontransfected cells. We believe that the observed outcome is related to 5-fluorouracil generated by CD and subsequent 5-fluorouracil anabolites. Our results support the development of in vivo models for tumor radiosensitization using the CD gene/5-fluorocytosine system.

Animals↗