Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5,6-Dihydro-5-azacytidine hydrochloride, a chemically stable, soluble analog of 5-azacytidine, has cytostatic activity against mouse leukemic L1210 cells grown in culture, but concentrations on the order of 10 micronM, 10-fold higher, than the parent drug, are necessary to inhibit cell growth. The addition of either cytidine or uridine protected against growth inhibition by 5-azacytidine and 5,6-dihydro-5-azacytidine, whereas thymidine potentiated the cytostatic action of both drugs. Deoxycytidine also enhanced the action of 5-azacytidine but had no effect with the reduced analog. Cell suspensions of L1210 cells were able to phosphorylate 5-azacytidine and, to a lesser extent, 5,6-dihydro-5-azacytidine. In cell-free extracts in the presence of ATP and Mg2+, both drugs were converted to nucleotides but at less than 5% the rate of cytidine. As a substrate for mouse kidney cytidine deaminase, the apparent Km value for 5,6-dihydro-5-azacytidine (33 micronM) is of the same order of magnitude as that for cytidine (37 micronM) but less than that for 5-azacytidine (2.1 X 10(3) micronM). The Vm for deamination of the reduced analog is one-tenth that for 5-azacytidine. 3,4,5,6-Tetrahydrouridine, a potent inhibitor of cytidine deaminase, is more effective in blocking deamination of 5-azacytidine than 5,6-dihydro-5-azacytidine.
Cancer Res 1977 Jul
PMID:Comparative studies of the cytostatic action and metabolism of 5-azacytidine and 5,6-dihydro-5-azacytidine. 6 84

In 13 out of 26 patients with urinary bladder carcinomas in various stages of malignancy, the ATP-ase activity of circulating lymphocytes was found significantly elevated. A decline in the ATP-ase activity was demonstrated in 14 of 17 patients re-investigated after treatment, while the activity remained unchanged in 2 and rose in 1 patient. No correlation between the clinical tumour stage and the lymphocyte ATP-ase activity was found, but the activity was closely correlated to the histological grade of malignancy. In 11 of the 17 patients the clinical effect of the treatment was closely correlated to a decline in ATP-ase activity. Determination of lymphocyte ATP-ase activity is suggested as an additional and simple help in the diagnosis of bladder carcinoma and in the follow-up control after treatment of patients with this disease.
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PMID:ATP-ase activity of lymphocytes from patients with carcinomas of the urinary bladder. 12 45

Human adult lung fragments removed from macroscopically undamaged and anthracosis exempted zones of lungs of 20 pneumonectomies made for cancer, were tested for 25 enzymic activities. The location and intensities of these enzymic activities were different in the lung tissue components; The bronchial epithelia contained highly active LDH, MDH, SDH, NADH-TR and NADPH-TR, glucose-6-phosphate dehydrogenase, active hydroxyproline-2-epimerase, alkaline phosphatase. Ca2+-activated ATP-ase, and beta-galactosidase. Bronchial and vascular muscles presented intense activities of LDH, MDH and SDH of alkalinephosphatase, AMP-ase and Ca2+-activated ATP-ase, as well as of beta-galactosidase. The alveolar walls presented high activities of SDH, MDH and LDH, of alkaline and acid phosphatases, of beta-galactosidase and of Tween-40 and 60-esterases, of HEP, cytochrome-oxidase and peroxidase. The free alveolar macrophages were active for LDH, MDH, SDH, NADH-TR and NADPH-TR, G1-6-ph-DH, acid and alkaline phosphatase, cytochrome-oxidase and peroxidase, HEP, AMP-ase and Mg2+-activated ATP-ase, Tween-esterases, naphthol-ASD-acetate esterase, and beta-galactosidase. The endothelia contained high activities of alkaline phosphatase, of AMP-ase and Mg2+-activated ATPase, of LDH, MDH and SDH, and of beta-galactosidase. In bronchial lymphoid nodules it was the LDH, MDH, SDH, cytochrome-oxidase and peroxidase, HEP, alkaline phosphatase and AMP-ase, Tween-60-esterase and beta-galactosidase that were active. The interlobular areas of the lung presented intense activities of SDH, MDH, LDH, HEP and cytochrome-oxidase. The activities of the other tested enzymes were weaker or absent in the adult human lung components, the same as those of aminopeptidases which were present only in some free alveolar macrophages. The discussion of some relationships between these enzymic actitivies and the morphology of the human adult lung tissue asserted that the latter could not be considered as a "normal" tissue but as one overstrained by the components of blood and polluted air.
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PMID:Histoenzymology of the lung. I. Enzyme activities of the lung tissue of acult humans; relationships between structure and functions. 14 Mar 14

Ultracytochemical investigation of ATP-ase activity was carried out in parietal cells of the mucosa and in cancer cells of human stomach carcinoma possessing a similar ultrastructure. In parietal cells the reaction product of ATP-ase was observed on the membranes of microvilli of intracellular canaliculi, on the membranes delineating the lateral intercellular space, on the basal plasmolemma and in the nucleoli. The reaction product was absent on the membranes of tubuvesicles and on the apical surface of the plasmalemma. In cancer cells the reaction product was found on the membranes of the microvilli of the intracellular canaliculi, basal plasmolemma and in the nucleoli. Comparative examination of ATP-ase activity in these cells implies that at least the part of the mechanism of hydrochloric acid secretion which is involved in the transfer of H+ and Cl- is retained in cancer cells. A steady decrease in hydrochlorid acid secretion observed in the stomach mucosa in cancer as well as in the tumour itself seems to be associated with other mechanisms.
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PMID:[Ultracytochemical study of ATP-ase activity in mucosal parietal cells and in the cells of human adenocarcinoma of the stomach]. 15 Feb 95

Ether-permeabilized (nucleotide-permeable) Escherichia coli cells exhibited DNA excision repair when exposed to the following carcinogenic K-region epoxides: 7-methyl- and 7,12-dimethyl-benz[a]anthracene-5,6-oxide, chrysene-5,6-oxide and benzo[a]pyrene-4,5-oxide. This DNA excision repair was missing in uvr A and uvr B mutant cells. The K-region epoxide phenanthrene-9,10-oxide was ineffective in all E. coli strains tested. In contrast to the K-region epoxides which where found active only in wild type cells, 1,2,3,4-diepoxybutane and the 6,7-epoxides of the tumor promoter TPA (12-O-tetradecanoyl-phorbol-13-acetate) elicited DNA repair in uvrA, uvrB mutant cells as well. Enzymic activities catalyzing particular repair steps were identified by determining a) repair polymerization and b) size reduction of denatured DNA. A) An easily quantifiable effect in E. coli wild type cells was epoxide-induced repair polymerization. None of the K-region epoxides tested stimulated DNA repair synthesis in uvrA, uvrB mutant cells, indicating that the uvrA-, uvrB-controlled UV-endonuclease initiated excision repair by cleaving epoxide-damaged DNA. 1,2,3,4-Diepoxybutane and the TPA-6,7-oxides induced DNA repair polymerization in uvr-deficient cells, although to a lesser extent than in wild type cells, suggesting the involvement of uvr-independent incision steps. None of the epoxides induced repair polymerization in a mutant (polA107) lacking the 5'--3'exonucleolytic activity of DNA polymerase I (exonuclease VI). The absence of any repair polymerization in the polA107 mutant indicates that the exonuclease VI plays a central role in removing epoxide-damaged nucleotides. As evidenced by greatly reduced levels of repair polymerization measured in polA1 cells, DNA polymerase I was the main polymerizing enzyme. b) As a consequence of treatment with 7-methyl-benz[a]anthracene-5,6-oxide, DNA from wild type cells, contrary to uvrA mutant cells, showed size reduction after denaturation and sedimentation in alkaline sucrose gradients. This is explained by repair-specific endonucleolytic cleavage of damaged DNA. The incision required the presence of ATP indicating that functional UV-endonuclease needs ATP as a cofactor.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1978 Sep 28
PMID:Carcinogen-induced DNA repair in nucleotide-permeable Escherichia coli cells. Analysis of DNA repair induced by carcinogenic K-region epoxides and 1,2,3,4-diepoxybutane. 15 97

Pyrimidine nucleoside monophosphate kinase [deoxycytidine monophosphate:adenosine triphosphate (dCMP:ATP) phosphotransferase. EC 2.7.4.14] has been purified from rat Novikoff ascites hepatoma and rat liver, each to a single major band appearing on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Differences exist in regard to efficiency and regulation of enzymatic activities. The Km values of the tumor kinase for cytidine monophosphate (CMP) (0.0053 +/- 0.0008 MM) and dCMP (0.715 +/- 0.068 MM) are approximately one-fourth the Km values of the rat liver kinase, for CMP (0.030 +/- 0.007 MM) and dCMP (2.77 +/- 0.39 MM). The tumor dCMP kinase exhibits a lower Km for ATP (0.134 +/- 0.008 MM) than the rat liver kinase (0.68 +/- 0.09 mM). Moreover, the dCMP:CMP kinase activity ratio for the tumor enzyme is 1.12, while that for the rat liver enzyme is 0.45. The uridine monophosphate:CMP kinase activity ratio for the tumor enzyme is 1.93, while that for the rat liver enzyme is 2.68. Lower concentrations of dithiothreitol are required for 50% reactivation of the tumor dCMP kinase (1.00 mM) and CMP kinase (0.10 mM) than rat liver dCMP kinase (2.20 mM) and CMP kinase (0.57 mM). Thus, the kinase from Novikoff hepatoma exhibits properties of increased efficiency and relaxed regulation of activity which render it more suitable for a tumor, in which active DNA synthesis is ongoing.
Cancer Res 1976 Jul
PMID:Differences between pyrimidine nucleoside monophosphate kinase from rat Novikoff ascites hepatoma and rat liver. 17 2

Activities of a broad spectrum of enzymes were studied histochemically in renal adenocarcinomas induced in young male F344 rats by chronic dietary administration of the carcinogen N(4'-fluoro-4-biphenylyl)acetamide. Enzymes included were: dehydrogenases of glucose-6-phosphate, lactate, succinate, malate, and alpha-glycerophosphate; peroxidase (catalase); glucose-6-phosphatase; alkaline and acid phosphatase; Mg2+ ATPase; 5'-nucleotidase; and aminopeptidase. Levels of enzyme activity were estimated visually and scored from 0 (not detectable) to a maximum of 5 (intense). Comparison of estimated activity for each enzyme was made between small neoplastic nodules (stage III tumors) and large adenocarcinomas (stage IV tumors) and between tumors and portions of normal proximal tubules in parenchyma of kidneys from untreated control rats. The results, which revealed nearly identical levels of activity for most enzymes in both stages III and IV tumors, suggested similar metabolic and biologic behavior of these lesions. However, when data for tumors were compared with data for normal proximal tubules, striking differences were observed consistent with: 1) a marked shift of energy metabolism from oxidative to glycolytic production of ATP, with a corresponding reduction in mitochondrial respiration; and 2) simplification of plasma membrane specializations that were possibly associated with a reduction or loss of transport function. These findings were compared with other histochemical, biochemical, and ultrastructural studies of renal adenocarcinomas in rats and man.
J Natl Cancer Inst 1976 Oct
PMID:Adenocarcinoma of the kidney. II. Enzyme histochemistry of renal adenocarcinomas induced in rats by N-(4'-fluoro-4-biphenylyl)acetamide. 18 77

Ascites hepatoma cells grown in Wistar rats were incubated anaerobically in the absence of glucose or in the presence of both glucose and D(+)glucosamine, or monoiodoacetate, or NADH, which interfered with glycolysis at different steps and with different mechanisms: Under all these conditions the incorporation of amino acids into the proteins of hepatoma cells was severely reduced without any clear relationship to the degree of inhibition of glycolysis. The postmitochondrial supernatants showed defective incorporation only when obtained from cells incubated in the absence of glucose or in the presence of monolodoacetate; inhibition of glycolysis by glucosamine and NADH did not seem to affect the subcellular basis for protein synthesis. When present, the defect of the cell sap (monoiodoacetate and absence of glucose) and to disaggregation and reduced functional capacity of the polysomes (absence of glucose). The results suggested that the effects of the inhibition of glycolysis on protein synthesis and on the integrity of the protein-synthesizing machinery--which were primarily due to the depletion of the energy stores--might have been modified by the particular mechanism of action of the inhibitor and by the way low levels of ATP were reached in the cell.
J Natl Cancer Inst 1977 Mar
PMID:Inhibition of glycolysis and interference with protein synthesis in hepatoma cells. 19 Apr 11

The reduction of uridine 5'-diphosphate (UDP) and uridine 5'-triphosphate (UTP) has been studied in normal adult rat liver, the Dunning hepatoma, and Morris 5123D and 7793 hepatomas. A new paper chromatographic method that separates and quantitates all the major products of the reduction and hydrolysis or other reactions of the substrate has been devised. All of the above tissues were able to reduce UDP and UTP at relatively slow rates ranging from 0.25 nmole of deoxycompound formed (deoxyuridine 5'-triphosphate) per mg protein per hr for liver to 3.5 nmoles deoxyuridine 5'-triphosphate for the Morris 7793 hepatoma when UTP was the substrate. In general, UTP was a better substrate than UDP. The method may also be used to measure cytidine 5'-diphosphate (CDP) reduction, and under the same conditions, the reduction of CDP proceeded at about 6 times the rate of UTP reduction in the Dunning hepatoma. Like CDP reduction, the reduction of UTP was strongly modulated by ATP. Reduction of UTP was insignificant with no ATP or 1.5 micronmoles ATP added to the reaction mixture and was maximal with 0.25 micronmole. The reduction of UTP was inhibited by deoxyuridine 5'-monophosphate, deoxythymidine 5'-triphosphate, deoxycytidine 5'-triphosphate, and deoxyribose 1'-phosphate. The effects of deoxyadenosine 5'-triphosphate varied, depending on its concentration in the reaction medium and whether UDP or UTP was a substrate. However, hydroxyurea did not inhibit reduction of UDP or UTP at concentrations that strongly inhibited CPD reduction. All of the tissues were able to hydrolyze [alpha-32P]deoxyuridine 5'-triphosphate readily to the diphosphate and monophosphate. It is suggested that the enzyme that reduces UTP or UDP may be different in these tissues from the enzyme that reduces CDP.
Cancer Res 1977 Jun
PMID:The reduction of uridine 5'-diphosphate and uridine 5'-triphosphate in some transplantable rat hepatomas. 19 67

In hepatomas of various malignancy contrary to normal and regenerating liver tissue a considerable part of hexokinase (HK) activity was bound with mitochondria. The HK activity, estimated in nuclei, microsomes and apparently in cytoplasma membranes, was due to contamination with mitochondrial fraction. High specific activity of HK in mitochondria of tumors might be responsible for the increased glycolysis, when these organelle preparations were added to the soluble fraction of cells. The HK of tumors was extracted from the preparations by alternative pathways. Reversible binding of some part of the enzyme with mitochondria was regulated by concentration of metabolites (ATP and G6P) similarly to the bound HK from normal tissues (brain, retina). At the same time the other part of unregulated HK activity (isozyme I only) was found in hepatomas to be intercalated into lipoprotein membranes; it was not controlled by metabolites.
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PMID:[Subcellular distribution of hexokinase in hepatoma and its electrophoretic properties]. 19 17


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