Objectives: The aim of the study was to determine the clinical importance of the determination of thymidylate synthase (TS) and thymidine kinase (TK) - the two rate limiting enzymes of thymidylate biosynthesis - in human colorectal cancers. We intended to find correlation between the activity of the enzymes and prognosis of the disease. Moreover we analyzed if the activity of TS, the most important molecular target of 5-fluorouracil might be helpful in the prediction of the chemosensitivity of tumors against 5-fluorouracil. Materials and methods: Enzyme activities were determined from the tumor and normal tissue of 47 colorectal cancer patients. TS and that of TK activities were determined by radioenzymatic methods applying deoxy-[5-3H]-uridine-5mono-phosphate (Amersham) and [2-lAC] thymidine as substrates. Results: Both enzymes of thymidylate biosynthesis increased significantly in the colorectal tumors compared to the normal tissues. In the case of TS very high individual differences (0.2-16.0 pmol dTMP/min/mg protein), were found between the patients. There was no correlation between the activity of the enzymes and Duke's stage, although the highest TS value was demonstrated in patients with Dukes stage D. Significant relationship was demonstrated between the survival of the patients and TS activity of the tumors. In the low activity group only 13% of the patients died during the observation period , 87% were alive more than 3 years, however, in the high activity group 50% of the patients died within 2 years. Conclusions: TS is an important prognostic factor of the survival in patients with colorectal cancers, moreover together with TK they are useful to predict the chemosensitivity of patients against 5-fluorouracil.
|Number of pages||6|
|Publication status||Published - Dec 1 1997|
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