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Six cell lines differing in histological origin were studied regarding the growth inhibitory effect of fluoropyrimidines in relation to their metabolism. The human colon carcinoma cell line WiDr was most sensitive to 5-fluorouracil (FUra) (50% growth inhibitory concentration, 0.7 microM) and to its analogue 5'deoxy-5-fluorouridine (5'dFUR) (50% growth(More)
A phase I trial and pharmacokinetic study of 5-aza-2'-deoxycytidine (5-aza-dCyd) were conducted in 21 patients with advanced solid tumors. The drug was given as three 1-h infusions, separated by intervals of 7 h. Treatment was repeated every 3-6 weeks. Forty-six cycles of 5-aza-dCyd were administered at 7 dose levels ranging from 25 to 100 mg/m2 in three(More)
The effect of high-dose uridine on body temperatures of rabbits and man has been studied in relation to plasma concentrations of uridine and its catabolite uracil. Uridine induced fever in both rabbits and man. High-dose cytidine had no influence on body temperature in rabbits. Plasma concentrations of uridine were between 1 and 1.5 mM at 30 min after an iv(More)
The reduction of the tetrazolium salt MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) to a blue-black formazan product by living but not by dead cells can be used to measure chemosensitivity of tumor cells. The main advantages of the MTT assay are its simplicity, rapidity, and the fact that the results are read automatically with a(More)
Administration of high-dose uridine or cytidine (3500 mg/kg) resulted in severe hypothermia of 6-10 degrees C in mice. This effect of uridine was observed in three different mouse strains, C57B1/6, Balb/c, and Swiss. A high-dose of uridine also caused hypothermia in Wistar rats. Co-infusion of uridine with benzylacyclouridine, an inhibitor of uridine(More)
The effect of delayed uridine administration on the in vitro growth inhibitory effects of 5-fluorouracil (5FU) and on the in vivo antitumour activity and toxicity was studied. In vitro growth inhibition of the human intestinal cell lines WiDr and Intestine 407 by 3 microM 5FU could be reversed by 1.0 mM uridine; the effect was more pronounced with WiDr(More)
OBJECTIVE To compare the performance of human papillomavirus (HPV) assays with conventional Pap cytology for cervical cancer (CC) screening in Mexico. METHODS Pap smears, self-collected vaginal specimens (SS) for HPV testing, and clinician-collected cervical specimens (CS) for HPV testing were obtained from 7868 women, aged 15-85 years old, attending CC(More)
DUP 785 (NSC 368390; Brequinar sodium) is a new inhibitor of pyrimidine de novo biosynthesis with antitumor activity against several experimental tumors. DUP 785 inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, blocking the conversion of dihydroorotate to orotate. We examined the influence of exposure time to DUP 785 on its growth-inhibitory(More)
The clinical effects and pharmacokinetics of high-dose uridine were determined in seven patients with advanced-stage cancer and in one healthy volunteer. Uridine was also examined for its effect on 5-fluorouracil toxicity in two patients. Uridine was administered as a 1-hr i.v. infusion at doses of 1 to 12 g/sq m. Plasma and urine samples were analyzed for(More)
Deoxycytidine kinase (dCK) and deaminase (dCDA) are both key enzymes in the activation and inactivation, respectively, of several deoxycytidine antimetabolites. We determined the total dCK and dCDA activities using standard assays, in 28 human solid tumours grown as xenografts in nude mice, and four corresponding cell lines. dCK activities in colon tumours(More)