Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Adenylate cyclase in plasma membranes from rat liver was stimulated by prostaglandin E1, and to a lesser extent by prostaglandin E2. Prostaglandin F1alpha and A1 did not stimulate the cyclase. The prostaglandin E1-mediated activation was found to require GTP when the substrate ATP concentration was reduced from 3 mM to 0.3 mM in the reaction mixture. Adenylate cyclase of the plasma membranes from rat ascites hepatomas AH-130 and AH-7974 was not stimulated by prostaglandin E1 in the presence or the absence of GTP, although the basal activity of adenylate cyclase as well as its stimulation by GTP alone were similar to normal liver plasma membranes. 2. Liver plasma membranes were found to have two specific binders for [3H] prostaglandin E1 with dissociation constants of 17.6-10(-9) M and 13.6-10(8) M (37 degrees C) and one specific binder for [3H]prostaglandin F2alpha with a dissociation constant of 2.31-10(8) M (37 degrees C). The specific binders for prostaglandin E1 could not be detected in the hepatoma plasma membranes. 3. Binding of [3H] prostaglandin E1 to the liver plasma membranes was exchange by, GTP dGPT, GDP, ATP and GMP-P(N)P, but not by GMP, CGMP, DTTP, UTP or CTP. The increase in the binding of [3H] prostaglandin E1 was found to be due to the increased affinity of the specific binders to prostaglandin F2alpha was not affected by GTP. 4. GTP alone was found to increase V of adenylate cyclase of liver plasma membranes, while GTP plus prostaglandin E1 was found to decrease Km of adenylate cyclase in addition to the increase of V to a further extent.
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PMID:Prostaglandin receptor-adenylate cyclase system in plasma membranes of rat liver and ascites hepatomas, and the effect of GTP upon it. 18 13

The subcellular and submitochondrial localization of CTP:phosphatidate cytidylyltransferase is altered in the Morris 7777 hepatoma. Mitochondria in this poorly differentiated tumor are the principal sites of CDP-diacylglycerol synthesis, in contrast to normal rat liver where the endoplasmic reticulum is most active. This enzyme activity was increased 17-fold in the outer mitochondrial membrane, and a 22% increase was noted in the inner mitochondrial membrane of the 7777 hepatoma as compared with the corresponding fractions from normal rat liver. Increased mitochondrial CTP:phosphatidate cytidylyltransferase was present in six other Morris hepatomas, but it was not found in fetal rat liver mitochondria, suggesting that rapid growth alone is not responsible for the difference. Evidence is presented which indicates that mitochondrial lipid degradation is similar in normal liver and the 7777 hepatoma, in vitro. The increased activity of CTP: phosphatidate cytidylytransferase is thought to be responsible in part for the moderately increased diphosphatidylglycerol content of 7777 hepatoma mitochondria.
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PMID:Altered subcellular and submitochondrial localization of CTP:phosphatidate cytidylyltransferase in the Morris 7777 hepatoma. 20 10

Interaction between the de novo and salvage pathways of pyrimidine metabolism was studied in a line of rat hepatoma cells by co-labelling with [14C]-uridine and [3H]orotate. A difference in the ratio of 14C/3H between CTP and UTP in acid-soluble nucleotide pool was reflected in the corresponding ratios in CMP and UMP in RNA, with uridine labelling cytidine nucleotides relatively more effectively than orotate. These results are not compatible with the concept of a single UTP pool, and a new model for pyrimidine anabolic pathways, based on compartmentation of de novo from salvage pathways, is proposed.
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PMID:Evidence for compartmentation of uridine nucleotide pools in rat hepatoma cells. 57 61

The effects of nutritional variables on the processing of exogenous precursors into RNA was examined. General nutritional deprivation, or asparagine depletion, led to significant changes in the absolute pool sizes, especially of ATP, UTP and CTP. Fluctuations were found depending on the elapsed time after the nutritional perturbations occurred, and the cell density of the cultures. Depletion of the medium by 28 h of growth, or 1 h of guinea pig asparaginase action, led to considerable inhibition of the conversion of exogenous uridine to CTP by the cells. A series of experiments indicated that in 6C3HED lymphoma cells the uridine nucleotide pool which provided the immediate precursors to RNA (denoted UTP-NA) behaves as a small compartment in rapid equilibrium with exogenously supplied nucleosides. The resemblance to the compartmentation model described by Plagemann (Plagemann, P.G.W. (1972) J. Cell Biol. 52, 131-146 and (1971) J. Cell. Physiol. 77, 241-258) for rat hepatoma cells was close. The UTP-NA pool of the 6C3HED cells constitutes no more than 5% of the cellular UTP pool and is relatively slow in equilibrating with the general cell pool. Correction of the rates of incorporation of isotope into RNA by using some function of the whole cell UTP specific activity to normalize the pool effects, was shown to be invalid.
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PMID:Nutritional effects on precursor uptake and compartmentalization of intracellular pools in relation to RNA synthesis. 117 50

CMP-N-acetylneuraminic acid: glycoprotein sialyltransferase activities were assayed in microsomal fractions from chicken liver and hepatoma, induced by the leukosis virus strain Mc-29, using asialofetuin as the substrate acceptor of N-acetylneuraminic acid. The effect of some nucleotides and metal ions on the enzyme activity was investigated. Kinetic studies revealed that the Km values toward asialofetuin at a saturation concentrations of CMP-N-acetylneuraminic acid for both liver and hepatoma enzymes are very closed, while V value was lower for the tumor enzyme. The liver and hepatoma enzymes have no exogenous Mn cations requirement and are inhibited by CTP, CMP and ATP. CMP was shown to act as a competitive inhibitor with an apparent Ki of 0.24 mM for the liver and 0.16 mM for hepatoma enzyme, respectively.
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PMID:Partial characterization of microsomal sialyltransferase from chicken liver and hepatoma Mc-29: I. Effect of nucleotides and metal ions. 208 38

The combination of 3 types of antipyrimidines was studied in AS-30D hepatoma cells in suspension culture and in the rat in vivo. Cellular UTP and CTP pools can be depleted most effectively by combining an inhibitor of de novo UMP synthesis with sugar analogs diverting UMP to UDP-sugar analogs. The following UMP-trapping sugar analogs were employed: D-galactosamine, D-galactosone, D-glucosone, and D-glucosamine. These D-galactose and D-glucose analogs intensified the depletion of UTP and CTP pools induced by the following inhibitors of de novo UMP synthesis: acivicin, PALA, lapachol, pyrazofurin, and 6-azauridine. The sugar analogs, in the absence of inhibitors of the de novo pathway, enhanced the rate of de novo UMP synthesis several-fold, as indicated by incorporation of 14CO2 into intermediates and products of the pathway and by the expansion of the acid-soluble uracil nucleotide pool. Reduction of UTP and CTP contents to less than 5 and 15% of control, respectively, by D-galactosamine and PALA resulted in a decrease of the rate of RNA synthesis to 19% of control as calculated from the changes in specific activities of [14C]CTP and of [14C]cytidine in RNA after labeling with [14C]uridine. Hepatoma cells released uridine and cytidine into the extracellular fluid. This release was reduced to one third in UTP-deficient cells, indicating that pyrimidine nucleoside excretion is regulated by pyrimidine nucleotide levels, possibly by UTP and CTP regulation of uridine kinase. Determination of the rates of de novo pyrimidine synthesis, of the formation of RNA pyrimidines, and of pyrimidine nucleoside excretion indicates that de novo synthesis provides only about 67% of the pyrimidines required for the consuming processes. The difference, as well as the dilution of labeled pyrimidine nucleotide pools under conditions of a blocked de novo pathway, suggests a considerable salvage of pyrimidine nucleosides derived from RNA. This salvage of pyrimidines may be intracellular and/or by an excretion and re-uptake process. Depletion of UTP and CTP pools, induced in hepatoma cells by D-galactosamine and 6-azauridine, leads to growth inhibition in suspension culture; this inhibition becomes irreversible in an increasing percentage of cells, killing all cells after 20 hr of UTP deficiency. The enhanced uptake of 5-fluorouridine by UTP-deficient cells was associated with an increase of FUMP incorporation into RNA up to 4-fold and with stronger inhibition of cell growth.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Uridylate-trapping sugar analogs in combination with inhibitors of uridylate synthesis de novo and 5-fluorouridine. 241 94

Using the well differentiated rat hepatoma Fao we have studied the regulation of phosphoenolpyruvate carboxykinase (PEPCK) mRNA by insulin and glucose and compared these results to glucose production as estimated by glucose release into the medium. Fao cells possess an active gluconeogenic pathway and, when grown in glucose-free medium, release glucose for over 8 h. Addition of the cAMP analog, 8-(4-chlorophenyl-thio) cAMP (8-CTP-cAMP) or increasing the concentration of dihydroxyacetone and oxaloacetate results in an increase in glucose release which can be suppressed by insulin at concentrations between 1 and 100 nM. These effect of cAMP and insulin are associated with parallel changes in the level of mRNAPEPCK. Insulin treatment reduces mRNAPEPCK levels in these cells by 80%; this effect is transient reaching a maximum at 2-4 h. Addition of glucose to cells grown in glucose-free (G-) medium produces a decrease in mRNAPEPCK which is similar in magnitude and kinetics to that produced by insulin. Conversely, when cells grown in normal medium are placed in G- medium mRNAPEPCK levels triple over a period of 8 h, then return toward the basal value. Cells grown in G- medium or in G- medium plus 10nM insulin for 1 yr exhibit only slightly increased levels of mRNAPEPCK and respond to both 8-CTP-cAMP, and insulin, although the response to 8-CTP-cAMP is slightly blunted. These data indicate that glucose and insulin can play independent roles in regulation of PEPCK gene expression, and that these regulatory effects are usually transient.
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PMID:Acute and chronic regulation of phosphoenolpyruvate carboxykinase mRNA by insulin and glucose. 254 57

Biochemical impairments in spleen immunocompetent cells (T- and B-lymphocytes) were revealed in host (C3HA mice) of transplantable and ortoaminoazotoluol-induced hepatomas in the course of their growth. As soon as hepatoma emerged (chemical carcinogenesis), the activity of adenosine deaminase and purine nucleoside phosphorylase in T- and B-lymphocytes were found to be reduced 2-6 and 7-10-fold, respectively in parallel with the impairment of their immune system. These alterations were accompanied by the increase in concentrations of dGTP in T-lymphocytes (5.4-fold) and of dATP in B-lymphocytes (4-fold) as well as with the inhibition of DNA synthesis, predominantly in T-lymphocytes. In both T- and B-lymphocytes, the dCTP pool was decreased. In the spleen, T- and B-lymphocytes of mice carrying transplantable 22 hepatoma 22 by the moment of its maximal growth (5th day), the DNA synthesis was inhibited as revealed by the reduction of (a) thymidine kinase activity, (b) rate of the labeled thymidine incorporation into DNA, and (c) intracellular dTTP and dCTP concentrations. In latter periods (from 8th day up to the moment of death), drastic stimulation of DNA synthesis in spleen T- and B-lymphocytes was observed irrespective of the impairments in the immune function and the decrease of the adenosine deaminase activity. In the course of growth of both transplantable and induced solid hepatomas in host spleen T- lymphocytes, the activity of the CTP-dependent thymidine kinase isoenzyme increased, coinciding in time with the activation of antigen-specific T-suppressors in the same organ.
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PMID:[Changes in DNA and purine nucleotide synthesis in lymphoid cells and sensitivity to glucocorticoids associated with the impairment of differentiation and immune function in mice during tumor growth. Spleen T- and B-lymphocytes]. 308 34

In thymocytes of C3HA mice carrying the transplantable and ortoaminoazotoluene induced hepatomas at the time of their intense growth a drastic decrease in adenosine deaminase activity set in and 3-4-fold augmentation of intracellular concentration of dATP and dGTP, potential inhibitors of ribonucleoside diphosphate reductase was observed, leading to the reduction of the DNA synthesis. The latter event was evidenced by a suppressed 14C-thymidine incorporation into thymocytes DNA in vitro, decreased thymidine kinase activity, intracellular dTTP and depletion of dCTP pools. Only in the terminal period of hepatocarcinogenesis (12 months) a 4-fold increase in the corticosterone serum concentration was observed. As for the mice carrying transplantable 22a hepatoma, serum hormone levels augmented 4-fold as early as 24 h after tumor implantation and thereafter kept increased two fold. An elevated activity of terminal deoxynucleotidyl transferase in mouse thymocytes has been shown to be characteristic of the late periods of tumor growth reflecting the arrest of the immature cortical thymocyte differentiation. By the time hepatomas emerged in the course of hepatocarcinogenesis in spleen T and B lymphocytes a significant drop in the activity of adenosine deaminase (3-4-fold) and purine nucleoside phosphorylase (2-8-fold) was noted--the events directly correlated with the weakening of cell immune functions. The disorders described were accompanied by the accumulation of dGTP in spleen T lymphocytes, dATP in B lymphocytes and inhibition of DNA synthesis, predominantly in T lymphocytes. In the latter instance the pool of dCTP was found to be depleted. In spleen T and B lymphocytes of mice carrying solid 22a hepatoma when the peak of its growth was reached (day 5) the rate of DNA synthesis dropped. Later on (from day 8 to the animal death), however, in spite of the suppression of immune function and the decrease in adenosine deaminase activity a drastic stimulation of DNA synthesis in spleen T and B lymphocytes was observed. The increase in spleen T suppressor activity in the course of intense growth of the both types of hepatomas coincided in the time with the stimulation of the CTP-dependent thymidine kinase isoenzyme activity in total T lymphocyte population of the same organ.
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PMID:Some biochemical mechanisms underlying the impairment of T and B cell immunity in C3HA mice during hepatoma growth. 349 9

A rapid, specific, and sensitive method has been developed for the determination of ribonucleoside and deoxyribonucleoside triphosphates in Novikoff hepatoma cells. A simple three-step procedure was used. Extraction of the biological material with 5% cold trichloroacetic acid (TCA); elimination of TCA by ethilic ether wash and concentration of the sample by lyophilization; and separation of CTP, dCTP, ATP, dATP, UTP, dTTP, GTP, dGTP and their quantitation by anionic-exchange high-performance liquid chromatography under isocratic conditions. All the compounds were identified by comparing their retention times with those of pure compounds, by cochromatography with single pure ribonucleoside triphosphates (NTPs) or deoxyribonucleoside triphosphates (dNTPs), and by comparing the 280 nm:254 nm spectral ratios of the peaks with those of known NTP and dNTP standards. The specific activity of all the above mentioned nucleotides also was determined in Novikoff hepatoma cells labeled with [32P]orthophosphate.
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PMID:Determination of ribonucleoside triphosphates and deoxyribonucleoside triphosphates in Novikoff hepatoma cells by high-performance liquid chromatography. 356 56


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