Read e-book online New Drugs, Concepts and Results in Cancer Chemotherapy PDF

By John S. Holcenberg, Henry P. Wu (auth.), F. M. Muggia (eds.)

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It would seem logical that increasing intracellular FdUMP levels would lead to a decrease in the activity of thymidylate synthase, causing a depletion in dTTP pools. 5 11M dipyridamole [5]. Thus, the data suggest that the depletion of dTTP pools was not the primary mechanism of 5FU toxicity in these cells and that the increase of 5FU toxicity caused by dipyridamole was not due to a further depletion of dTTP. Although dipyridamole did significantly impair the uptake of thymidine and uridine [5,41-43], this was not the crucial mechanism by which dipyridamole increased its cytotoxicity against HCT 116 cells.

With the exploitation of further discoveries, one might be able to design effective chemotherapeutic regimens using dipyridamole, and ultimately, dipyridamole might become as important in cancer treatment as many chemotherapeutic agents are today. Acknowledgments We would like to thank Seem a Goel for drawing figures 2, 4, and 5. This work was supported by the Alberta Heritage Trust Fund for Medical Research, and it was conducted in part by the Clayton Foundation for Research -California Division.

Chabner BA and Myers CEo Clinical pharmacology of cancer chemotherapy. In: Cancer Principles and Practice of Oncology, VD DeVita, S Hellman, and SA Rosenberg (eds). B. Lippincott, Philadelphia, 1989, pp. 349-395. 24. Ackland SP and Schilsky RL. High-dose methotrexate: a critical reappraisal. J Clin Oncol 5:2017-2031, 1987. 25. Allegra CJ, Hoang K, Yeh GC, Drake JC, and Baram J. Evidence for direct inhibition of de novo purine synthesis in human MCF-7 breast cells as a principal mode of metabolic inhibition by methotrexate.

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