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)

Unlike other beta-class eukaryotic DNA polymerases, the enzyme purified from the Novikoff hepatoma is inhibited by both sulfhydryl blocking agents N-ethylmaleimide (NEM) and p-hydroxymercuribenzoate (pHMB). The degree of sensitivity varies depending on the enzyme purity, pH of the reaction, and the presence of sulfhydryl reducing agents. Novikoff beta-polymerase activity is unaffected by the presence of 2-mercaptoethanol (2-Me) or dithiothreitol (DTT); however, the combination of 2-mercaptoethanol and NEM or pHMB acts to reverse the inhibition of the sulfhydryl blocking agent. The reversal of inhibition involves more than just a titration of NEM with 2-mercaptoethanol since a) the combination of these two reagents actually stimulates the DNA polymerase, and b) dithiothreitol did not reverse the inhibition. Binding of the polymerase to DNA did not affect the enzyme sensitivity to NEM.
Nucleic Acids Res 1976 Sep
PMID:Novikoff hepatoma deoxyribonucleic acid polymerase. Sensitivity of the beta-polymerase to sulfhydryl blocking agents. 0 24

The objective of this investigation was to throw light on the biological behavior and metabolic regulation of hepatic enzymes of the nonoxidative branch of the pentose phosphate pathway. The activities of transaldolase (EC 2.2.1.2) and trasketolase (EC 2.2.1.1) Were compared in biological conditions that involve modulation of gene expression such as in starvation, in differentiation, after partial hepatectomy, and in a spectrum of hepatomas of different growth rates. The enzyme activities were determined under optimal kinetic conditions by spectrophotometric methods in the 100,000 X g supernatant fluids prepared from tissue homogenates. The kinetic properties of transaldolase and transketolase were similar in normal liver and in rapidly growing hepatoma 3924A. For transaldolase, apparent Km values of 0.13 mM (normal liver) and 0.17 mM (hepatoma) were observed for erythrose 4-phosphate and of 0.30 to 0.35 mM for fructose 6-phosphate. The pH optima in liver and hepatoma were at approximately 6.9 to 7.2. For the transketolase substrates, ribose 5-phosphate and xylulose 5-phosphate, the apparent Km values were 0.3 and 0.5 mM, respectively, in both liver and hepatoma. A broad pH optimum around 7.6 was observed in both tissues. In organ distribution studies, enzyme activities were measured in liver, intestinal mucosa, thymus, kidney, spleen, brain, adipose tissue, lung, heart, and skeletal muscle. Taking the specific activity of liver as 100%, transaldolase activity was the highest in intestinal mucosa (316%) and in thymus (219%); it was the lowest in heart (53%) and in skeletal muscle (21%). Transketolase activity was highest in kidney (155%) and lowest in heart (26%) and skeletal muscle (23%). Starvation decreased transaldolase and transketolase activities in 6 days to 69 and 74%, respectively, of those of the liver of the normal, fed rat. This was in the same range as the decrease in the protein concentration (66%y. In the liver tumors, transaldolase activity was increased 1.5- to 3.4-fold over the activities observed in normal control rat liver. Transketolase activity showed no relationship to tumor proliferation rate. In the regenerating liver at 24 hr after partial hepatectomy, the activity of both pentose phosphate pathway enzymes was in the same range as that of the sham-operated controls. In differentiation at the postnatal age of 5, 12, 23, and 32 days, hepatic transaldolase activities were 33, 44, 55, and 72%, respectively, of the activities observed in the 60-day-old, adult male rat. During the same period, transketolase activ-ties were 18, 21, 26, and 55% of the activities observed in liver of adult rat. The demonstration of increased transaldolase activity in hepatomas, irrespective of the degree of tumor malignancy, differentiation, or growth rate, suggests that the reprogramming of gene expression in malignant transformation is linked with an increase in the expression of this pentose phosphate pathway enzyme...
Cancer Res 1976 Sep
PMID:Behavior of transaldolase (EC 2.2.1.2) and transketolase (EC 2.2.1.1) Activities in normal, neoplastic, differentiating, and regenerating liver. 1 80

1. A factor, which amplifies the inductions of several liver enzymes by glucocorticoid, was partially purified from Proteus mirabilis from rat intestine. The factor (amplifier) was completely inactivated by alpha-glucosidase, but not by other glycoside hydrolases, proteases, nucleases or phosphatases tested; it was also hydrolysed by HCl with liberation of reducing sugars. Thus the oligosaccharide in this factor seems to be essential for the amplification. 2. In adrenalectomized rats the amplifier increased the inductions of several liver enzymes, such as tyrosine aminotransferase and leucine aminotransferase, by glucocorticoid. But it did not amplify the induction of tyrosine aminotransferase by glucagon or insulin or the activities of enzymes that are not induced by glucocorticoid. The amplifier by itself did not have any glucocorticoid-like action in adrenalectomized rat. These results show that the amplifier specifically increases the inductions of liver enzymes by glucocorticoid. 3. Since similar amplification was also observed in isolated perfused liver and cultured hepatoma cells in vitro, the amplifier seems to act directly on the target organ or cells.
Eur J Biochem 1977 Sep
PMID:A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. 1. Purification, properties and biological action. 2 Oct 83

The activities of gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (A-p), and leucine aminopeptidase (LAP) were examined in 18 cases of hepatomas. The activity of gamma-GTP was most remarkable in the hepatoma consisting of small to medium-sized tumor cells showing the least atypism. The enzyme activity found in the type composed of large tumor cells resembled that of normal liver and was considered to be the most mature form of the neoplasm. This enzyme was not found in the immature type composed of small typical tumor cells. A-P activity was seen in only a few cases of hepatoma; conspicuous in one case showing immature features and sporadically in one case with florid histological pattern. The activity of this enzyme could not be confirmed in the type demonstrating marked gamma-GTP activity. LAP activity was noted in the majority of cases, especially marked in the medium-sized tumor cells, but there was hardly any connection between this enzyme and histological type. In general, the cases demonstrating positive gamma-GTP activity tended to show LAP activity. Although the activity of gamma-GTP and that of A-p usually showed an inverse relation, all three enzymes demonstrated almost equal activity in the type showing a florid histological pattern.
Acta Pathol Jpn 1977 Sep
PMID:Enzyme histochemical study on hepatoma--the relation between enzyme activity and histological type. 2 15

In certain lines of hepatoma tissue culture (HTC) cells, glutamine synthetase (EC 6.3.1.2) specific activity is increased 2.5- to 3-fold by the addition of glucocorticoids to the growth media. Actinomycin D blocks both the induction and deinduction of glutamine synthetase by glucocorticoids, suggesting a requirement of RNA synthesis for both processes. Using an antiserum raised against purified rat liver glutamine synthetase, we have precipitated radiolabeled glutamine synthetase from HTC cells. Electrophoresis of the immunoprecipitates on sodium didecyl sulfate-acrylamide gels isolates the subunit of glutamine synthetase and permits the radioactivity in the glutamine synthetase band to be quantitated. Using this technique, we have investigated the effect of dexamethasone, a synthetic glucocorticoid, on the rates of synthesis and degradation of glutamine synthetase. Dexamethasone (10(-7) M) increases the rate of synthesis of glutamine synthetase 2- to 3-fold but has no effect on the rate of glutamine synthetase degradation. The rates of total cell protein synthesis and degradation are not significantly affected by dexamethasone. The presence of actinomycin D at the time of removal of dexamethasone from induced cells prevents the fall in the induced rate of synthesis of glutamine synthetase normally seen when the inhibitor is removed from the culture medium. The regulation of glutamine synthetase by dexamethasone has been compared to the regulation of another dexamethasone-inducible enzyme in HTC cells, tyrosine aminotransferase, and been found to be similar in all parameters studied.
J Biol Chem 1978 Sep 10
PMID:Regulation of glutamine synthetase by dexamethasone in hepatoma tissue culture cells. 2 25

Hybrids between mouse hepatoma cells (which secrete several serum proteins) and mouse or rat fibroblasts (which do not secrete these proteins) produce transferrin and the third component of complement (C3) like the parental hepatoma cells, while they do not secrete either albumin or alpha-fetoprotein (AFP). This lack of albumin and AFP secretion is probably due to a lack of synthesis, rather than to a simple defect in secretion. The cessation of albumin and AFP production is not dependent upon the parental fibroblast nor upon the selection conditions; it is best explained by a shut-off synthesis and could thus reflect the existence of a regulatory mechanism. This would imply a difference between the control of albumin and AFP synthesis and that of transferrin and C3 synthesis. On the other hand, in agreement with Peterson and Weiss (1972), hybrids between rat hepatoma cells and mouse fibroblasts continue to product rat albumin. This suggests that the mouse hepatoma cells differ from the rat hepatoma cells in the way they control albumin production.
Cell 1975 Sep
PMID:The control of serum protein synthesis in hepatoma-fibroblast hybrids. 5 90

The alpha-fetoprotein (AFP) and albumin localization were studied in the cells of rat Zaidel's ascitic hepatoma. It was shown in the paraffine sections of the hepatoma cells fixed by mixture of 96 degrees ethanol with 1% glacial acetic acid that 9.3% of hepatoma cells contained AFP and 0.6% of the cells--serum albumin. Small quantities of the tumour cells had both of these proteins simultaneously. There was no definite regularity in the distribution of the AFP and albumin-containing cells in the tumour islands.
Biull Eksp Biol Med 1975 Sep
PMID:[Distribution of alpha-fetoprotein and albumin in paraffin sections of cells of Zaidel's ascitic hepatoma]. 5 59

Transplabtable Zajdela rat ascites hepatoma cells, previously considered "nonproducers," synthesize detectable amounts of intracellular alpha-fetoprotein (AFP) and fibrinogen, but fail to secret or release these serum proteins. Evidence for defective secretory mechanisms for serum proteins in these hepatoma cells (a) explains the failure to detect AFP in either the serum or ascitic fluid of rats bearing this hepatoma, (b) indicates that some hepatoma cells should be classified as "nonsecretors," rather than nonproducers of AFP, and (c) suggests that failure to detect AFP in some human and animal hepatomas in vivo and in vitro may also reflect failure of secretion rather than failure of intracellular synthesis.
Cancer Res 1976 Sep
PMID:Intracellular synthesis of alpha-fetoprotein and fibrinogen without secretion by Zajdela rat ascites hepatoma cells. 6 10

The clinical and biochemical findings in 207 Black patients with hepatocellular carcinoma are presented. A bruit over the liver was heard in 25% of the patients, a previously underemphasised sign. In 28 of the 30 biopsy-proven cases alpha-fetoprotein levels were elevated. Hepatitis B antigen was found in 41% of the patients.
S Afr Med J 1976 Sep 25
PMID:Clinical aspects of hepatocellular carcinoma in man. 6 8

In a previous study, we demonstrated three variants of human alphafetoprotein by crossed immunoelectrophoresis. In addition, we correlated the capacity of alpha-fetoprotein isolates from various hepatoma and fetal sources to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. We have now isolated alpha-fetoprotein from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient and from a homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver alphafetoprotein were found to be extremely potent, serum alphafetoprotein had intermediate potency, and ascitic fluid alpha-fetoprotein was the least potent. Analysis of these isolates by crossed immunoelectrophoresis confirmed the correlation between the proportion of HAFP-3 and the immunosuppressive potency of each isolate. In addition, analysis of these isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least six molecular variants were apparent. The proportion of one of these variants, termed HAFP-3a, in each isolate was correlated with the immunosupressive potency of the isolate. The sialic acid content of the various alpha-fetoprotein isolates did not vary significantly. Our data suggest that a postsynthetic modification of alphafetoprotein occurs, probably after secretion, which reduces immunosuppressive potency by converting the active electronegative species to an inactive electropositive form. This modification probably involves a charged moiety other than sialic acid on the molecule.
Proc Natl Acad Sci U S A 1977 Sep
PMID:A postsynthetic modification of human alpha-fetoprotein controls its immunosuppressive potency. 7 37


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