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)

Intracellular levels of cyclic AMP (cAMP), adenylate cyclase, and cAMP-phosphodiesterase activities at lag-period, exponential and stationary growth phases of hepatoma 22a were determined. It was shown that the transition of tumour cells from the lag-period to the exponential phase of growth was accompanied by the two-fold decrease of intracellular cAMP level on account of drastic activation of cAMP phosphodiesterase. Subsequently the cAMP level lowered more slowly until the cells entered the stationary phase of growth. In view of the fact that the adenylate cyclase activity failed to change at different growth phases of hepatoma 22a, it seems very proballe that the rise of cAMP phosphodiesterase activity could be a signal for the exit of tumour cells from the lag-period and their entrance into the mitotic cycle.
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PMID:[Concentration and metabolism of cyclic AMP during the early stages of hepatoma 22a growth]. 19 92

Histochemical investigation shows that ATPase activity is located intensively on the surface of cell contacts in hepatoma cells grown in confluent monolayer culture. Dibutyryl cyclic AMP and theophylline-treated hepatoma cells which exhibit contact-inhibited growth show the absence of localization of intense ATPase activity at cell-cell contacts. However, after removal of these additives the activity fully recovers to the intense level of control cells, when the release of cells from contact inhibition of growth occurs. Cultured hepatic parenchymal cells in monolayer have little or no ATPase activity at their surface immediately after contacts are established, and again after growth to a confluent state. In a different type of hepatoma cell which is less malignant and forms a small tissue mass or island, cell surface ATPase activity at cell-cell contacts in an island is very weak or scarcely detected even when cells are not treated with dibutyryl cyclic AMP and theophylline.
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PMID:Surface ATPase activity at cell-cell contacts in hepatic parenchymal cells and in cAMP-treated hepatoma cells in monolayer culture. 20 55

Adenosine deaminase and adenosine kinase have been measured in rat liver, 12 transplantable hepatomas, regenerating, foetal and neonatal liver, adult and neonatal rat kidney and 2 transplantable kidney tumours. Adenosine, deaminase activity, relative to the normal liver value, was elevated 2-4 fold in hepatomas of rapid growth rate, was in the normal range in more slowly growing hepatomas and in regernerating liver, and was low in foetal and neonatal liver. Adenosine kinase activity was decreased, relative to rat liver values, in all the hepatomas; activity of this enzyme gave a negative correlation with tumour growth rate. Kinetic properties of the two enzymes were examined in partially purified preparations. Adenosine deaminases from both liver and rapidly growing hepatoma 3924A were subject to weak product inhibition by inosine. Adenosine kinase from liver and hepatoma 3924A was inhibited by the reaction products ADP and AMP, and the enzyme was also subject to excess substrate inhibition by concentrations of ATP in excess of 1 mM. In rat hepatoma cell lines growing in culture, the toxicity of adenosine correlated inversely with the ratio of adenosine deaminase activity to adenosine kinase activity. Chromatographic measurements showed that hepatoma cells incorporated less extracellular adenosine into their adenine nucleotide pools than did isolated liver cells. These results indicate that increased adenosine deaminase activity and decreased adenosine kinase activity may confer a selective advantage upon the cancer cell.
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PMID:Adenosine deaminase and adenosine kinase in rat hepatomas and kidney tumours. 20 96

High activities of L-threonine and l-serine dehydratases were maintained in spontaneous hepatoma of mice strain CBA as distinct from transplantable hepatoma. The initial rate [v] versus substrate concentration [S]0 curves had complex shapes for the enzymes from the liver tissue of healthy animals (especially after extraction of the enzymes by means of buffers with low concentration of K+). Kinetic patterns of l-threonine and L-serine dehydratases from hepatoma were distinct from those of normal mice liver tissue. The shape of [v] versus [S]0 plots was altered in response to AMP (1.10(-3) M). Contrary to the enzymes from normal tissue, dehydratases from hepatoma did not alter the shape of [v] versus [S]0 curves in response to AMP. The enzymes from hepatoma were apparently desensitized with respect to their possible allosteric effector. Threonine dehydratases of normal mice liver were also dissimilar as compared with the enzymes from hepatoma in the affinity of the apoenzyme to pyridoxal 5'-phosphate. This affinity was 3-fold lower for threonine dehydratase from hepatoma as compared with the enzyme from liver tissue.
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PMID:[Characteristics of L-threonine- and L-serine dehydratases from mouse liver and spontaneous hepatomas]. 20 90

Adenylate cyclase can be resolved into at least two proteins, a thermolabile, N-ethylmaleimide-sensitive component and a second protein (or proteins) that is more stable to either of these treatments. Neither component by itself catalyzes the formation of cyclic AMP using MgATP as substrate. However, mixture of the two reconstitutes MgATP-dependent fluoride- and guanyl-5'-yl imidodiphosphate (Gpp(NH)p)-stimulatable adenylate cyclase activity. The more stable component can be resolved from the first in various tissues or cultured cells by treatment of membrnes or detergent extracts with heat or N-ethylmaleimide. The two proteins have also been resolved genetically in two clonal cell lines that are deficient in adenylate cyclase activity. An adenylate cyclase-deficient variant of the S49 lymphoma cell (AC-) contains only the thermolabile activity, while the activity of the more stable protein is found in a complementary hepatoma cell line (HC-1). In addition, AC-S49 cell plasma membranes contain MnATP-dependent adenylate cyclase activity. The protein that catalyzes this reaction appears to be the same as that which can combine with the thermostable component to reconstitute Mg2+-dependent enzyme activity because both activities co-fractionate by gel exclusion chromatography and sucrose density gradient centrifugation, both activities have identical denaturation kinetics at 30 degrees C, and both activities are stabilized at 30 degrees C and labilized at 0 degree C by various nucleotides and divalent cations with similar specificity. It is thus hypothesized that the thermolabile factor is the catalytic subunit of the physiological adenylate cyclase and that the Mn2+-dependent activity is a nonphysiological expression of the catalytic protein. The thermostable moiety of the enzyme, which is proposed to serve a regulatory function, appears to consist of two functional components, based upon differential thermal lability of its ability to reconstitute hormone-, NaF-, or Gpp(NH)p-stimulated adenylate cyclase activity. These components have not, however, been physically separated. The thermolabile and thermostable components can interact in detergent solution or in a suitable membrane. Mixing of the detergent-solubilized regulatory component with AC-membranes that contain only the catalytic protein and beta-adrenergic receptors reconstitutes catecholamine-stimulatable adenylate cyclase activity; however, addition of the catalytic protein to membranes that contain receptor and the regulatory component yields MgATP-dependent enzymatic activity that is unresponsive to hormone.
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PMID:Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme. 21 Jan 83

The treatment of Hepa-2 cells, a permanent mouse hepatoma cell line, for 72 h with hydrocortisone (10(-6) M), N6,O2-dibutyryl cyclic AMP (10(-3) M), or 8-bromocyclic AMP (10(-3) M) results in a 2-,3- or 4-fold increase, respectively, in rates of synthesis and secretion of mouse serum albumin. Simultaneous treatment with hydrocortisone and N6,O2-dibutyryl cyclic AMP results in a 10-fold stimulation in these parameters, an effect that is significantly more than additive for the two compounds tested. The number of albumin mRNA sequences, determined by hybridization of total cell RNA to albumin complementary DNA, was increased in direct proportion to the increases in albumin synthesis in all experiments. The relative rate of albumin synthesis approaches in vivo levels in cells treated simultaneously with hydrocortisone and N6,O2-dibutyryl cyclic AMP. We propose that these factors may be necessary to maintain the maximal level of differentiated function in the continuous culture of Hepa-2 cells.
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PMID:Coordinated modulation of albumin synthesis and mRNA levels in cultured hepatoma cells by hydrocortisone and cyclic AMP analogs. 22 17

Plasma and 24-hour urinary cyclic AMP and cyclic GMP levels were determined by saturation analysis in specimens from normal subjects and from 101 patients with tumours of the gastrointestinal tract, breast, lung, bladder or prostate, or with cirrhosis of the liver. Relative to 46 control subjects, plasma cyclic GMP concentrations were significantly elevated in seven patients with gastric tumours, 20 patients with cancer of the breast, six patients with lung cancer, and 12 patients with cirrhosis of the liver. Urinary cyclic GMP/creatinine ratios were significantly increased in cirrhotic patients and in the lung and oesophageal cancer groups. In no cancer group were increases in plasma or urine cyclic GMP levels sufficiently consistent to be of value in the diagnosis of human malignant disease. Changes in extracellular fluid cyclic nucleotide levels in the cirrhotic group were very similar to those that have been reported for primary hepatoma patients.
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PMID:Plasma and urine cyclic nucleotide levels in malignant disease and cirrhosis of the liver. 23 Feb 5

Adenylate cyclase can be resolved into at least two protein components, neither of which by itself catalyzes the formation of cyclic AMP with Mg-ATP as substrate. Mixture of the two reconstitutes Mg-ATP-dependent, fluoride- and Gpp(NH)p-stimulable activity. One, a heat-labile, N-ethylmaleimide-sensitive protein of molecular weight 190,000 can catalyze cyclic AMP formation with Mn-ATP as substrate, and is therefore proposed to be the catalytic moiety of the adenylate cyclase complex. The other protein (or proteins) is more resistant to heating or N-ethylmaleimide, and is proposed to confer upon the catalyst the ability to ultilize Mg-ATP as substrate. It is also required for the regulation of that activity by guanine nucleotides, hormones, and probably fluoride ion. The catalytic protein is found in a phenotypically adenylate cyclase-deficient (AC-) variant of S49 lymphoma cells. The thermostable regulatory protein can be resolved from the catalyst by heat treatment or N-ethylmaleimide treatment of plasma membranes of wild-type S49 cells, rat or rabbit liver, or avian erythrocytes, and is also found in a phenotypically adenylate cyclase-deficient hepatoma cell line. Mixture of AC- S49 membranes, which contain the beta-adrenergic receptor, with a crude detergent-solubilized preparation of the regulatory protein reconstitutes hormone-stimulable adenylate cyclase activity. Binding of the regulatory protein to the membranes is a time- and temperature-dependent process that requires an activating ligand of the adenylate cyclase system [fluoride, Gpp(NH)p].
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PMID:Identification and partial characterization of some components of hormone-stimulated adenylate cyclase. 23 86

The behavior of the activity of arginyl-tRNA synthetase (L-arginine : tRNAArg Ligase(AMP-forming), EC 6.1.1.19) was determined in extracts of rat liver: normal adult, normal proliferating (from developing and from partially hepatectomized rats), and neoplastic (hepatomas of different growth rates) and in extracts of rat kidney cortex and transplantable kidney tumors. The Km values for arginine, ATP, and tRNA of the enzyme of the rapidly growing hepatoma 3924A were the same as those of the enzyme from the liver of control rats. The pH optima of the control and neoplastic livers were in the same range of 7.25-8.0. Taking the hepatic specific activity for arginyl-tRNA synthetase as 100%, deep layer of gut, thymus and testis had higher activity; renal cortex and spleen had the same activity; and skeletal muscle, brain, heart, lung, superficial layer of gut and adipose tissue had lower activity. In a wide spectrum of hepatomas of different growth rates, a significant increase of 1.4-2.4-fold in arginyl-tRNA synthetase activity was observed when compared with that of liver of control normal rats. This elevation in enzyme activity in hepatomas appears to be specific to neoplasia, since it is unaltered in regenerating and low in differentiating liver. The increase in arginyl-tRNA synthetase in the liver tumors appears to be transformation-linked, since the activity was increased in all hepatomas, even in the slowest growing ones. Furthermore, the increase in enzyme activity was not limited to hepatic neoplasms, since a rise was also observed in transplantable rat kidney tumors. Thus, the reprogramming of gene expression in neoplastic tissue entails an increase in arginine-tRNA synthetase activity.
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PMID:Neoplastic transformation-linked alterations in arginyl-tRNA synthetase activity. 42 64

Endotoxin-stimulated glucocorticoid-antagonizing factor (GAF) was assayed by its specific inhibition of hydrocortisone-induced synthesis of phosphoenolpyruvate carboxykinase. Defined induction of phosphoenolpyruvate carboxykinase synthesis in hydrocortisone-treated rat hepatoma cells permitted reliable quantitation of GAF and analysis of the mechanism of cortisol antagonism. GAF was present maximally in serum 2 hours after endotoxin challenge in mice; however, GAF production could be suppressed by pretreating mice with indomethacin or cortisol. Endotoxin-tolerant mice were also nonresponsive to endotoxin-stimulated GAF production. Gel filtration on Sephadex G-200 resolved four regions of glucocorticoid-antagonizing activity in serum from endotoxin-poisoned mice, two of which were not present in normal serum. Cortisol antagonism by GAF resembled that of insulin; however, insulin differed from GAF in its ability to antagonize dibutyryl cyclic AMP. Unlike insulin, endotoxin-induced serum glucocorticoid-antagonizing activity was heat-labile at 70 degrees C. GAF antagonism of hydrocortisone was partially reversible but did not act in a competitive manner. Production of hepatoma growth inhibitory activity and glucocorticoid-antagonizing activity in serum were closely associated, indicating a common methanism for their generation.
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PMID:The use of Reuber hepatoma cells for the study of a lipopolysaccharide-induced macrophage factor: glucocorticoid-antagonizing factor. 45 33


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