Role of Thymidine Phosphorylase in Biomodulation of Fluoropyrimidines

Authors: Morita T.; Matsuzaki A.; Suzuki K.; Tokue A.

Source: Current Pharmaceutical Biotechnology, Volume 2, Number 3, September 2001 , pp. 257-267(12)

Publisher: Bentham Science Publishers

Abstract:

Thymidine phosphorylase (TP) is a key enzyme in the activating pathway of 5DFUR and capecitabine. On the other hand, TP is identical to platelet-derived endothelial cell growth factor (PD-ECGF) which is known to be an angiogenic factor. Recent studies show TP expression is increased in various malignancies compared with the surrounding normal tissues. These reports demonstrate that elevated TP expression indicates a predisposition for aggressive disease and / or poor prognosis. Therefore, it is a reasonable strategy to target TP in cancer treatment by using fluoropyrimidines including 5-fluorouracil (5FU), 5DFUR and capecitabine. TP-mediated biomodulation of fluoropyrimidines to enhance their anti-tumor effects has been investigated. TP up-regulators including cytokines, anti-tumor drugs and X-ray irradiation significantly increase cytotoxicity of fluoropyrimidines. Also, transfection of TP cDNA significantly enhances cytotoxicity of fluoropyrimidines. Biomodulation of fluoropyrimidines is clinically successful in treating some malignancies. We report a review on roles of TP in biomodulation of fluoropyrimidines.

Keywords: thymidine phosphorylase; fluoropyrimidines; dfur; capecitabine; fibroblasr growth factor bfgf; endothelial growth factor vegf; tp expression; fluropyrimidine cytotoxicity; tp cdna transfection; biomodulation; dilhydropyrimidine dehydrogenase

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201013378662

Publication date: 2001-09-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

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• By this author: Morita T. ;  Matsuzaki A. ;  Suzuki K. ;  Tokue A.

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