Calcitonin-Specific Transcription and Splicing Targets Gene-Directed Enzyme Prodrug Therapy to Medullary Thyroid Carcinoma Cells
作者： Marinella Messina , Denise M. T. Yu , Gerald W. Both , Peter L. Molloy , Bruce G. Robinson
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摘要: Recurrent and metastatic medullary thyroid carcinoma (MTC) remains difficult to treat due its limited responsiveness chemotherapy, radiotherapy, imaging. To investigate an alternative therapeutic approach, we examined the feasibility of targeting gene-directed enzyme/prodrug therapy delivered by adenoviral vectors MTC. We previously described a modified human calcitonin (CT)/CT gene-related peptide promoter that produced increased expression while maintaining specificity for MTC cells. In this study, introduced additional level using cell-specific splicing whether selectivity was enhanced when both features were combined in single transcription unit. Two replication-defective adenoviruses constructed expressed Escherichia coli purine nucleoside phosphorylase (PNP) gene under transcriptional control T2 (Ad.T2-PNP) or i...
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