Biomedical subjects
TS Lawrence
Publications and source records attributed to TS Lawrence.
Fluoropyrimidine-Radiation Interactions in Cells and Tumors.
The fluoropyrimidines (fluorodeoxyuridine [FdUrd] and fluorouracil [5-FU] are potent radiation sensitizers. This article summarizes recent data concerning potential mechanisms of fluoropyrimidine-radiation interactions at the cellular and tumoral level. Evidence now suggests cells can be radiosensitized when exposed to the fluoropyrimidines either before or after radiation but by different mechanisms. Sensitization is not explained by redistribution of cells into a sensitive phase of the cell cycle. Rather, cells that are exposed to FdUrd before radiation progress in S phase in the presence of fluoropyrimidines and are radiosensitized. Radiation can also increase the anabolism of 5-FU into the toxic metabolite and decrease drug clearance from the tumor. These laboratory data may aid in the design of clinical trials combining radiation and fluoropyrimidines.
Clinical Results of the Combination of Radiation and Fluoropyrimidines in the Treatment of Intrahepatic Cancer.
Radiation therapy has played a minor role in the conventional management of patients with unresectable primary hepatobiliary malignancies and liver metastases. This can be attributed to normal tissue toxicity, which has limited the dose of radiation that can be safely administered, and imaging limitations, which have prevented focal irradiation of involved regions. Trials of whole-liver irradiation with and without 5-fluorouracil (5-FU) or fluorodeoxyuridine (fur) suggest that the addition of fluoropyrimidines results in a slight increase in the median survival without an increase in radiation-induced liver disease (RILD). The development of three-dimensional radiotherapy techniques has now allowed high-dose focal irradiation to be safely delivered, which, when combined with hepatic arterial fur, produces a much higher rate of response and, in some cases, prolonged survival particularly for patients with primary hepatobiliary cancers. Further investigations into the optimal methods of combining the fluoropyrimidines and radiation to permit higher doses of both agents to be delivered as well as methods of protecting the normal liver are expected to yield significant improvement in the outcome of treatment for patients with intrahepatic malignancies.
Fluoropyrimidines as Radiation Sensitizers.
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Clinical Experience With Three-Dimensional Treatment Planning.
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