This program will continue the preclinical development of benzylacyclouridine (BAU) as an adjunct to fluorouracil therapy in model colon tumors. It will also extend initial isolation experiments on the transporter protein responsible for the facilitated diffusion of nucleosides. 5'-Amino analogs will be used to prepare selective affinity matrices and antibodies will be raised to the purified transporter protein. A new method is proposed for the selection of cell populations that uniquely are deficient in nucleoside transport to study the frequency and nature of controls on this essential mechanism neoplastic cell lines. A series of new compounds that may be covalent or high affinity inhibitors of transport will be prepared to assist in this process and as possible adjuncts to current therapeutic regimens by regulation of nucleoside accessibility in tumors. Also under development are genetic techniques employing a nucleoside transport defective clone as a recipient for DNA transfection preparatory to characterization of the gene(s) responsible for facilitated diffusion.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Experimental Therapeutics Subcommittee 1 (ET)
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Yale University
Schools of Medicine
New Haven
United States
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Pizzorno, G; Handschumacher, R E (1995) Effect of clinically modeled regimens on the growth response and development of resistance in human colon carcinoma cell lines. Biochem Pharmacol 49:559-65
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Pizzorno, G; Sun, Z; Handschumacher, R E (1995) Aberrant cell cycle inhibition pattern in human colon carcinoma cell lines after exposure to 5-fluorouracil. Biochem Pharmacol 49:553-7
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