system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Coculture Techniques, Colonic Neoplasms, Cytosine Deaminase, Escherichia coli, Escherichia coli Proteins, Extracellular Fluid, Female, Fluorouracil, Genetic Therapy, Mice, Mice, Nude, Plasmids, Prodrugs, Rats, Thymidylate Synthase, Xenograft Model Antitumor Assays.
user
Does extracellular expression of cytosine deaminase result in increased 5-FU production for enhanced enzyme/prodrug therapy? Context: The cytosine deaminase/5-fluorocytosine (CD/5-FC), strategy for cancer gene therapy shows considerable promise in experimental models but, because CD is a cytosolic enzyme, intracellular production of 5-fluorouracil (5-FU) causes the demise of the transduced cells before cytotoxic concentrations of' 5-FU can be achieved within the extracellular milieu. A soluble secreted form of CD was constructed and evaluated compared to intracellular CD in vitro and in vivo. The secreted form of CD temporarily spared transduced cells and enhanced accumulation of extracellular 5-FU. Cytosolic CD produced rapid inhibition of thymidylate synthase and cell death before significant extracellular concentrations of 5-FU developed. Finally, tumors expressing the secreted form of CD had an improved response to 5-FC treatment compared to tumors expressing intracellular CD.
assistant
Further evaluation of extracellular expression of CD for enzyme/prodrug therapy may provide improvements in this commonly studied gene therapy strategy. Final Decision: yes