Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of the studies on pharmacokinetics of fluorinated pyrimidines have been precisely reported. In mice bearing Ehrlich ascites carcinoma, 5-FU showed highest concentration in the lung and kidney immediately after i.v. administration of 5-FU, and in the liver, it showed rather lower concentration but for a longer period. 5-FU in blood was transferred into ascites fluid rapidly, and thus, the level of 5-FU in ascites fluid became higher than that in blood. FT is a masked compound of 5-FU, having a tetrahydrofuryl group. Drug metabolizing enzyme, natural degradation, and thymidine phosphorylase are considered to be responsible for the molecular conversion of FT into 5-FU. In order to increase the level of drug metabolizing enzyme, P450 in the liver of tumor bearers, of which P450 level was extremely lower as compared to normal individuals, phenobarbital was very effective from our previous experiment. Clinically, phenobarbital 200mg/day for 3 successive days was administered in prior to FT, and a better response was obtained than FT alone. Prevention from degradation of 5-FU in the liver by uracil kept higher level of 5-FU in blood. HCFU and 5'DFUR are also masked form of 5-FU and are converted to 5-FU in the liver.
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PMID:[Pharmacokinetic studies on fluorinated pyrimidine in cancer cell and tissue]. 155 91

Age-related changes in the activity of thymidine- and adenosine-metabolizing enzymes were studied in healthy females and those with breast cancer aged 46-70 years. A significant increase in activity of thymidine kinase, adenosine deaminase and 5'-nucleotidase and a decrease in that of thymidine phosphorylase were registered in blood serum of breast cancer patients of all age brackets. Adenosine deaminase activity in blood serum and lymphocytes of breast cancer patients was found to significantly change after surgery. A direct correlation was established between pretreatment thymidine phosphorylase activity and histological type of tumor, on the one hand and results of chemotherapy, on the other. The applicability of enzyme level assay for evaluating response to pre- and postoperative medication was studied.
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PMID:[Activity of the enzymes of DNA metabolism in the blood of patients with breast cancer]. 215 96

5-fluorouracil (5-FU) concentrations in peripheral blood, portal blood, normal and cancer tissues were evaluated in 26 patients with colorectal cancer after SF-SP administration (800 mg/day for 10 days). Thymidine phosphorylase activity in cancer tissues was also evaluated. 5-FU concentration in cancer tissues was significantly higher than that in other three specimens, and much higher than 0.05 microgram/g which was reported to be the minimum effective concentration. 5-FU concentration in portal blood was lower than MEC (0.05 microgram/ml). As for the relationship with the pathological features of cancer, the protruding lesions showed a higher 5-FU concentration than the ulcerative ones, and the lesions invaded only to submucosa or proper muscle showed a higher concentration than others. 5-FU concentration ratio in cancer tissues per in peripheral blood (T/B ratio) was related to thymidine phosphorylase activity. The higher was the thymidine phosphorylase activity, the greater T/B ratio. The results suggest that the tumor with higher thymidine phosphorylase activity might have a more pronounced anticancer efficacy of 5-FU.
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PMID:[Studies on 5-FU concentration and thymidine phosphorylase activity in tissues of patients with colorectal cancer after SF-SP administration]. 226 Aug 69

The C-1300 neuroblastoma tumor which arises spontaneously in the A/J mouse has been maintained in this mouse strain. Two different cell populations have been recognized in cultured C-1300 mouse neuroblastoma (MNB): (1) round, "neuroblast-like" cells, growing in suspension (poorly attached), that have a highly malignant behavior when injected into the A/J mouse (T1 cells); and (2) flat, "epithelioid" cells that attach well to surfaces and show low malignancy towards the inoculated animals (T2 cells). The specific activities of the pyrimidine metabolizing enzymes thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and thymidine kinase (TK) were examined in both MNB cell lines by a new radiochromatographic method. Enzymatic activities of TP and DPD in the cytosols of T2 (weakly malignant) cells were up to 15 times higher than those of T1 (strongly malignant) cells, whereas the mean TP/DPD activity ratio was 16 in either cell line. TP and DPD activity levels increased with time of growth in culture in T2 cells while no such increase was seen in the T1 cells. Maximal TK activity was similar in both cell lines but dropped more rapidly in the T2 cells as cell densities increased. The enzymatic activity levels of TP and DPD but not of TK correlated inversely with neoplastic expression of MNB cells. The observed patterns of pyrimidine metabolizing enzymes in MNB cells could result in an increased thymidine pool in T1 cells whenever TK activity is suppressed, whereas such conditions would favor the generation of thymine in the T2 cells.
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PMID:Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells. 271 95

Effects of a 7-day treatment with the maturational agents DMF and sodium butyrate on enzymes of pyrimidine metabolism, growth rate and cell maturation were assessed in 5 human tumor cell lines, ARH-77 (myeloma), K-562 (chronic myeloid leukemia), KG-1 (myeloid leukemia), HL-60 (promyelocytic leukemia) and RWLy-1 (non-Hodgkin's lymphoma). DMF lengthened the doubling times of all five cell lines while sodium butyrate lengthened only those of K-562, HL-60 and RWLy-1. Full maturation was induced only in HL-60 by either agent and in K-562 by butyrate. Exposure resulted in a decreased activity of the anabolic enzyme orotate phosphoribosyltransferase (EC 2.4.2.10) and increased activities of the catabolic enzymes thymidine phosphorylase (EC 2.4.2.4) and dihydrouracil dehydrogenase (EC 1.3.1.2). Changes in the amphibolic enzyme, uridine phosphorylase (EC 2.4.2.3) did not follow any apparent pattern. This study indicates that the pattern of pyrimidine metabolism differs between the differentiated and slowly growing, and undifferentiated rapidly growing counterpart of several human tumors, suggesting that enzymes of pyrimidine metabolism can be used as markers for cellular growth and/or maturity.
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PMID:Effects of N,N-dimethylformamide and sodium butyrate on enzymes of pyrimidine metabolism in cultured human tumor cells. 368 65

Biosynthesis of pyrimidine nucleotides was intensified in proliferating tissues. Age-dependent alterations in activities of thymidine kinase and thymidine phosphorylase were found in healthy persons of 17-70 years old. Distinct increase in activity of thymidine kinase was observed in patients with gastric ulcer but the activity was decreased with ageing. Alterations in the ratio between anabolic and catabolic reactions involving thymidine were studied also in patients with gastric tumor depending on age.
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PMID:[Age-related characteristics of thymidine metabolism in healthy subjects and in patients with stomach ulcer and cancer]. 381 Dec 86

5-fluorouracil analogs investigated in this study include a combination of uracil and Ftorafur (UFT), Ethyl (+/-)-t-butoxy-5-fluoro-hexahydro-2, 4-dioxopyrimidine r-5-carboxylate (TAC-278), and 5'-deoxy-5-fluorouridine (5'-DFUR). In a total of 45 patients with gastric cancer, tumor tissue level of 5-fluorouracil (5-FU) was determined at 2, 4, 6, 8, and 12 hours following the oral administration of drug, using a resected stomach specimen as material. As a result, it was demonstrated that oral administration of 200 mg/m2 of UFT maintained above 0.05 microgram/g (minimum inhibitory concentration: MIC) of 5-FU in tumor tissues over 12 hours in 11 of 13 patients. On the contrary, 133 mg/m2 of TAC-278, and 200 mg/m2 or 300 mg/m2 of 5'-DFUR (which is activated by thymidine phosphorylase in man) did not produce an effective 5-FU concentration in tumor tissues. Serum 5-FU level was high in order of TAC-278, UFT, and 5'-DFUR. Clinical response rates obtained with UFT (200 mg/m2 twice a day), or TAC-278 (133-200 mg/m2, 3 times daily) were 27.5% (49 of 178 cases), and 8.3% (3 of 36 cases, by Koyama et al.), respectively. Fisher's direct probability test revealed that there was a significant difference (p less than 0.05) between them in the response rate. It was considered that the measurement of concentration of anticancer drugs in tumor tissues might provide us useful information for the designing of chemotherapy of gastric cancer.
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PMID:Studies on the designing of chemotherapy for gastric cancer in man, based on the tumor tissue concentration of anticancer agents. 621 37

At a nontoxic dose (50 microM), the two potent uridine phosphorylase inhibitors, benzylacyclouridine and benzyloxybenzylacyclouridine (BBAU), potentiated 5-fluoro-2'-deoxyuridine (FdUrd) growth inhibition of human pancreatic carcinoma (DAN) and, to a lesser extent, human lung carcinoma (LX-1) cells in culture. BBAU was more effective than benzylacyclouridine. BBAU (50 microM) enhanced the cytocidal effect of FdUrd (1 microM, 3 hr) on DAN grown on soft agar from 75 to 88%. In antithymocyte serum-immunosuppressed mice bearing DAN, the mean tumor weight in animals treated with FdUrd (50 mg/kg/day for 2 days) was 11% less than that of untreated controls. When BBAU (10 mg/kg/day for 2 days) was coadministered, the mean tumor weight at Day 10 was 78% less than untreated controls, with no apparent host toxicity, clearly demonstrating the potentiation of the antitumor effects of FdUrd by BBAU. The fact that DAN responded better than LX-1 to benzylacyclouridine and BBAU could be due, in part, to the lower relative activity of thymidine phosphorylase to uridine phosphorylase in DAN compared to LX-1. The activities of other enzymes involved in FdUrd metabolism, thymidine kinase, uridine kinase, orotate phosphoribosyltransferase, 5'-nucleotidase, and dihydrouracil dehydrogenase, did not differ between the two cell lines.
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PMID:Potentiation of 5-fluoro-2'-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine. 623 86

It has been reported that 5'-DFUR is converted to 5-FU by uridine phosphorylase in experimental animal tumors. The conversion of thymidine, uridine and 5'-DFUR as substrates was studied in tumor and normal tissues of human and animals. A further series of studies was performed using 1-(2'-deoxy-beta-D-glucopyranosyl) thymine (GPT), a specific inhibitor of uridine phosphorylase. We found that this conversion in human tumors was catalyzed not by uridine phosphorylase but by thymidine phosphorylase. It was also confirmed that the enzyme activities in various human cancers were significantly several times higher than those in adjacent normal tissues. We succeeded in tried and isolating thymidine phosphorylase in a fairly pure form, from which enzyme Km values were calculated. After administration of 5'-DFUR intravenously or orally to patents, tissue and blood samples were collected by biopsy or surgical operation to determine the 5-FU level. The 5-FU levels were always higher in tumor tissues than in the blood or in normal tissues. Finally effective clinical efficacy was demonstrated by oral administration of 5'-DFUR.
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PMID:[5'-Deoxy-5-fluorouridine enzymatic activation from the masked compound to 5-fluorouracil in human malignant tissues]. 623 13

Enzymatic conversion of tegafur was studied using a thymidine phosphorylase preparation purified from human liver cancer. Tegafur dissolved in water slowly decomposed to 5-FU upon storage at 37 degrees C and this conversion was further activated with an addition of a thymidine phosphorylase preparation. Analysis of Tegafur and 5-FU was performed on a high performance liquid chromatograph. The Km value was in agreement with Michaelis-Menten Kinetics and 2.44 X 10(-2) M without thymidine phosphorylase preparation. When the preparation was added, it was 2.53 X 10(-4) M and 1.75 X 10(-3) M, respectively. Determination of 5-FU concentrations in blood, normal and tumor tissues following a long term administration of Tegafur was performed. The highest concentration of 5-FU was detected in tumor tissue followed by normal tissue and blood, suggesting a human liver thymidine phosphorylase was capable of converting Tegafur to 5-FU more actively in tumor tissue than in normal tissue.
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PMID:[Enzymatic conversion of tegafur in human tumor tissue]. 640 7


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