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• W2000913845 abstract "Neuroblastoma is derived from cells of neural crest origin and often expresses the transcription factor human achaete-scute homolog 1 (HASH1). The aim of this study was to selectively kill neuroblastoma cells by expressing the suicide gene E. coli purine nucleoside phosphorylase (PNP) under the control of the Mash1 promoter, the murine homolog of HASH1.The E. coli PNP gene regulated by the Mash1 promoter was cloned into an expression vector and transfected into neuroblastoma and non-neuroblastoma cell lines. After addition of the prodrug M2-fluoroadenine 9-beta-D-arabinofuranoside (F-araA) the cell-specific toxicity was examined. To optimize the cell specific activity, different sizes of the Mash1 promoter were analyzed in neuroblastoma cell lines and compared with the activity in non-neuroblastoma cells.Estimated as the percentages of CMV enhancer-promoter, the activity was significantly higher in the neuroblastoma cells, ranging from 17 to 58% when the shortest and the most active promoter was measured. The non-neuroblastoma cells yielded only 1-6% of the CMV promoter activity. When the shortest Mash1 promoter was combined with the E. coli PNP gene the cytotoxicity was 65% in the neuroblastoma cells with low cell death in the non-neuroblastoma cell lines, relative to the cytotoxicity where the E.coli PNP gene was regulated by the strong but non-specific CMV enhancer-promoter.We show here that the Mash1 promoter regulating the PNP gene confers a cell-type selective toxicity in neuroblastoma cell lines. These results indicate the feasibility to use the Mash1 promoter for regulating E.coli PNP expression in gene-directed enzyme prodrug therapy (GDEPT) of neuroblastoma." @default.
• W2000913845 created "2016-06-24" @default.
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• W2000913845 date "2004-01-01" @default.
• W2000913845 modified "2023-10-13" @default.
• W2000913845 title "Neuroblastoma-specific cytotoxicity mediated by theMash1-promoter andE. coli purine nucleoside phosphorylase" @default.
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• W2000913845 doi "https://doi.org/10.1002/pbc.20163" @default.
• W2000913845 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15390277" @default.
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