Characterization of dihydropyrimidine dehydrogenase in human colorectal tumours

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Regulation of dihydropyrimidine dehydrogenase in colorectal cancer.

Dihydropyrimidine dehydrogenase (DPD) is responsible for degradation of the pyrimidines uracil and thymine and the inactivation of the chemotherapeutic agent 5-fluorouracil. DPD activity is highly variable in cancer populations, and this variation may influence the antitumor efficacy of 5-fluorouracil. However, little is known about the regulation of DPD mRNA expression in any tissues. Using a ...

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Although dihydropyrimidine dehydrogenase has been purified to varying degrees from several species, very little is known about the human enzyme. The importance of this enzyme has recently been shown with cancer chemotherapy, particularly in patients with genetic deficiency of this enzyme. In the present study, this enzyme was purified 7800-fold to homogeneity from human liver by introducing sev...

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Relationship between intratumoral dihydropyrimidine dehydrogenase activity and gene expression in human colorectal cancer.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for 5-fluorouracil catabolism. In this study, both the enzymatic activity and mRNA level of DPD were estimated in the tumor tissue and adjacent normal mucosa of 51 patients with colorectal cancer. Although no significant difference in enzymatic activity was observed between tumor tissue and normal mucosa (70.4 and 70.7 pmol/min/m...

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Familial Deficiency of Dihydropyrimidine Dehydrogenase

Severe neurotoxicity due to 5-fluorouracil (FUra) has previously been described in a patient with familial pyrimidinemia. We now report the biochemical basis for both the pyrimidinemia and neurotoxicity in a patient we have recently studied. After administration of a "test" dose of FUra (25 mg/m2, 600 gCi 16-3HJFUra by intravenous bolus) to a patient who had previously developed neurotoxicity a...

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Structural organization of the human dihydropyrimidine dehydrogenase gene.

Deficiency of the pyrimidine catabolic enzyme, dihydropyrimidine dehydrogenase (DPD), has been shown to be responsible for a pharmacogenetic syndrome in which administration of 5-fluorouracil is associated with severe and potentially life-threatening toxicity. Following the recent availability of the cDNA for DPD, there were initial reports of several molecular defects (point mutations, deletio...

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ژورنال

عنوان ژورنال: British Journal of Cancer

سال: 1998

ISSN: 0007-0920,1532-1827

DOI: 10.1038/bjc.1998.73