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 two-year-old boy with a malignant tumor of the brain (medulloblastoma) excreted large amounts of thymine and uracil in his urine. The excretion was related to progress and regress of the disease, and reached a maximum of 3.0 mol of thymine per mole of creatinine and 2.6 mol of uracil per mole of creatinine. The excretion by 20 apparently normal children was less than 0.01 mol/mol of creatinine for each of the two pyrimidines. Three children with brain tumors, two with leukemias, and one with neuroblastoma were also studied; two of them had a moderate increase in urinary pyrimidine excretion, but only up to 0.07 mol/mol of creatinine. The activity of dihydrouracil dehydrogenase (NADP+) (EC 1.3.1.2) in cultured fibroblasts from the patient was somewhat lower than in control fibroblasts. The tumor was considered to be the likely cause of the increased excretion of pyrimidines, but an impaired degradation of pyrimidines in the liver could not be ruled out.
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PMID:Urinary excretion of thymine and uracil in a two-year-old child with a malignant tumor of the brain. 28 71

In a 10-year old girl with a telangiectasic osteosarcoma of the proximal right tibia, sequential bone scintigraphy with 99mTc-DPD showed the tumor as an atypical photopenic lesion in the osseous phase. Considering conventional radiographs, angiographic features and histologic aspects, possible explanations for this unusual finding are discussed.
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PMID:[Atypical scintigraphic appearance of an osteosarcoma. An explanation using x-ray and histologic findings]. 164 56

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

Seventeen patients with advanced breast cancer were imaged with a specially collimated gamma camera to study tumor uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) before and during therapy. Fourteen patients (82%) showed increased FDG accumulation in metastatic tumors, 6/8 (75%) of axillary, supra or infraclavicular metastatic lymph nodes were detectable. In one of these cases, FDG imaging was the first method to identify axillary metastasis causing nerve compression. Also, pulmonary and liver metastases could be imaged with FDG; both in two patients. The intra individual variability in uptake was considerable in bone metastases, and some lesions remained FDG negative: 99mTc-DPD was superior in detecting bone disease. Bone metastases of the osteolytic or mixed type were better visualized than sclerotic ones. Ten patients were reimaged later to assess the effect of therapy on FDG uptake. Increased uptake was associated with clinical progression, while unchanged or diminished uptake did not predict the course of disease as reliably. This study indicates that FDG can be used to image breast cancer metastases. FDG may be valuable in monitoring treatment response, but positron emission tomography (PET) would probably be more appropriate than planar imaging for this purpose.
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PMID:[18F]fluorodeoxyglucose scintigraphy in diagnosis and follow up of treatment in advanced breast cancer. 292 Jul 39

In order to study the interactions between UFT and anticoagulants, the plasma and tissue concentrations of 5-FU, uracil and FT-207 were examined in patients with lung cancer. Higher plasma concentrations of 5-FU and uracil were observed in the patients who were given warfarin and ticlopidine beforehand, whereas the concentrations of FT-207 were almost the same in the patients who were given anticoagulants as in those who were not. This may be interpreted as an inhibition of dihydrouracil dehydrogenase, the common metabolizing enzyme of 5-FU and uracil, by anticoagulants. With regard to the tissue concentrations, higher levels of 5-FU and uracil in the tumor and lymph nodes were obtained after anticoagulants were given beforehand. Concentrations of FT-207 in these tissues, however, were almost the same in the patients who were given anticoagulants as in those who were not. We thus concluded that an increase of 5-FU in tumor cells and lymph nodes can be achieved after elevating the plasma concentrations of ordinary oral doses of UFT by using anticoagulation therapy beforehand.
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PMID:Interactions between UFT and anticoagulants in lung cancer patients. 313 66

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

Bromovinyldeoxyuridine (BVDU) is a highly potent and selective antiherpetic agent which offers great potential for the treatment of severe herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) infections in cancer patients. BVDU inhibits the replication of HSV-1 and VZV at a concentration as low as 1-10 ng/ml; and the proliferation of tumor cells transformed with the HSV-1 thymidine kinase gene is even inhibited by BVDU concentrations lower than 1 ng/ml. Moreover, BVDU is inhibitory to Epstein-Barr virus replication in vitro at a concentration of 0.02 micrograms/ml. Due to the action of pyrimidine nucleoside phosphorylases, BVDU is rapidly degraded to the free pyrimidine base bromovinyluracil (BVU). In contrast to BVDU, which is cleared from the bloodstream within 2-3 hours, BVU persists in the plasma for at least 24 hours. During this period BVU can be converted again to BVDU upon administration of deoxythymidine, deoxyuridine or any other deoxyribonucleoside capable of transferring its deoxyribosyl moiety onto BVU. BVU owes its long persistence in the bloodstream to the fact that it does not act as substrate for dihydrothymine dehydrogenase, the enzyme that catalyzes the first step in the catabolic pathway of pyrimidines. On the contrary, BVU acts as an efficient inhibitor of this enzyme and thereby prevents the degradation of fluorouracil (FU), a well-known anticancer agent. As a consequence, BVDU via BVU enhances the antitumor activity of FU, as has been demonstrated in the murine P388 leukemia model. Thus, BVDU may be useful in anticancer chemotherapy from several viewpoints, e.g. for treatment of intercurrent herpesvirus infections, and, in combination with FU, for treatment of those malignant diseases that are amenable to FU therapy.
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PMID:Potential of bromovinyldeoxyuridine in anticancer chemotherapy. 375 35

Computerized dynamic gamma camera scintigraphy was performed with [18F]2-fluoro-2-deoxy-D-glucose [( 18F]FDG) on 10 patients with different cancers; tumor perfusion was evaluated in four patients with 99mTc-DPD. All tumors were visible in the [18F]FDG scans with tumor-to-tissue image contrast ratios of 1.2-11.7. Tumor perfusion exceeded that of the surrounding normal tissue in three of the four patients studied. Tumor-to-normal tissue [18F]FDG ratios were plotted as a function of the time. Two types of curves emerged: curves showing a linear increase in the ratio and curves showing a constant value for the ratio. These studies show that [18F]FDG can be used for clinical tumor imaging with a gamma camera, and that there appears to be biological differences in tumor uptake of [18F]FDG.
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PMID:Scintigraphy with [18F]2-fluoro-2-deoxy-D-glucose of cancer patients. 377 Dec 40

Pharmacokinetic studies of 5-FU in normal and Sarcoma 180-bearing mice were performed, and the following results obtained: When the administered dose of 5-FU was increased, it was found that there was an increase in the half-life and AUC (area under the concentration curve) and a lower rate of plasma clearance. When the drug was administered at equal doses of 40 mg/kg, the rate of clearance was high in the order of p.o. greater than continuous infusion greater than i.v. bolus. When Sarcoma 180-bearing mice were injected with CCl4 to induce liver dysfunction and subsequently administered 5-FU, the AUCs of 5-FU in the plasma and tumor tissue were increased by 2 and 1.3 times, respectively, as compared with non-treated mice. The Vmax (nmol/mg protein/min) of DHU (dihydrouracil dehydrogenase) in the liver homogenate from normal mice was 1.18 and found to be 0.70 in CCl4-treated mice. In conclusion, the pharmacokinetics of 5-FU were found to be dependent on the dose, infusion time, administration route and liver function, which seem to be correlated with the capacity of the catabolic enzyme, DHU.
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PMID:[Dose, administration time and route and hepatic function-dependent metabolism of 5-FU in mice]. 378 59

In contrast to thymine and 5-fluorouracil (FUra) which were cleared from the bloodstream within 2-4 h after their i.p. administration (200 mumol/kg) to rat, (E)-5-(2-bromovinyl)uracil (BVUra) maintained a concentration of 50-70 microM for at least 6 h and was still present in the plasma 24 h after its administration. In vitro experiments with rat liver extracts indicated that BVUra was not a substrate but an inhibitor for the reductive step in pyrimidine degradation catalyzed by dihydrothymine dehydrogenase. Kinetic and dialysis experiments suggested that BVUra was an irreversible inhibitor of this enzyme. The binding of BVUra to the enzyme depended on the presence of reduced nicotinamide adenine dinucleotide phosphate in the reaction mixture. Dihydrothymine dehydrogenase activity was also inhibited in the dialysed 105,000 X g supernatant fraction of livers from rats that had previously been treated with BVUra. Such inhibitory effects also occurred in vivo; previous administration of BVUra increased the plasma half-lives of thymine and FUra by 10- and 5-fold and their area under the curve by 9- and 8-fold, respectively. The effect of BVUra on the antitumor activity of FUra was evaluated in DBA/2 mice inoculated with 10(6) P388 leukemia cells. The mean survival times for the control and FUra-treated mice (5 mg/kg at 1, 3, 5, and 7 days after tumor cell inoculation) were 9.7 and 12.4 days, respectively. When BVUra (200 mumol/kg) was administered 1 h before each injection of FUra, the mean survival time was extended to 17.1 days. BVUra alone did not affect the mean survival time. When the dose of FUra was increased to 20 mg/kg, the mean survival time was 15.3 days; upon a preceding injection of BVUra the mean survival time decreased to 9.2 days. The latter effect probably resulted from an increased toxicity of FUra. Similar results were obtained if FUra was replaced by 5-fluoro-2'-deoxyuridine and BVUra by (E)-5-(2-bromovinyl)-2'-deoxyuridine. The enhancement of both the antitumor and toxic effects of FUra by BVUra were most probably due to an inhibition of FUra degradation, since, like in rats, BVUra increased the plasma half-life of FUra in DBA/2 mice. Hence BVUra appears to be an interesting compound, increasing the potency of FUra by decreasing its degradation.
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PMID:Effect of (E)-5-(2-bromovinyl)uracil on the catabolism and antitumor activity of 5-fluorouracil in rats and leukemic mice. 394 86


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