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)

A prospective study of the initial liver laboratory tests was carried out in the following patients: 55 patients with alcoholic liver disease, 53 with cholangitis, 41 with hepatocellular carcinoma, 65 with acute viral hepatitis, and 49 with hepatitis-B surface antigen-positive chronic active hepatitis. There was considerable overlap in the levels of the serum gamma-glutamyl transpeptidase (GT) and alkaline phosphatase (AP) among the five groups. However, the ratio of GT to AP was significantly higher in the group with alcoholic liver disease than in any of the other four groups. When the ratio was higher than 1.4, the diagnostic efficiency for distinguishing the alcohol group from the other four groups was 78% (the normal upper limit for GT and AP being 35 and 115 U/1, respectively). A possible explanation for this higher ratio in alcoholic liver disease is suggested. We conclude that when the GT and AP is greater than 1.4, it is of greater diagnostic value than either variable alone in differentiating alcoholic from other liver diseases.
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PMID:The diagnostic value of the ratio of serum gamma-glutamyl transpeptidase to alkaline phosphatase in alcoholic liver disease. 612 89

Earlier, we demonstrated that feeding to rats a diet devoid of choline, a lipotropic factor, markedly enhances hepatoma induction by several chemical carcinogens, and that the diet acts as a strong promoter of the evolution of initiated cells to foci of altered hepatocytes. The ability of several factors to modulate the action of the choline-devoid (CD) diet as a promoter was investigated by quantitating the foci of gamma-glutamyl transpeptidase-positive hepatocytes developed in rats exposed to a single injection of diethylnitrosamine. Addition to the diet of phenobarbital (PHB) resulted in a promoting action stronger than those of the CD diet or of PHB alone. Two other barbiturates, amobarbital (AMB) and pentobarbital (PTB) exerted an effect similar to that of PHB, while barbituric acid (BA) had no effect. In other studies, lowering the fat content of the CD diet reduced its efficacy as a promotor, while the addition of a hypolipidemic agent, BR931, 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxy-ethyl)acetamide, completely abolished the promoting action of the CD diet. In rats not exposed to carcinogen, feeding the CD diet caused a marked enhancement of liver DNA synthesis and of cell proliferation. Inclusion of PHB, PTB or AMB in the CD diet inhibited these effects, while BA exerted no inhibition. The increased rate of DNA synthesis and cell proliferation in the liver were not affected by the level of fat in the CD diet. These results suggest that beside a stimulation of liver cell proliferation, other factor(s) determine the efficacy with which a CD diet exerts its promoting action.
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PMID:Modulation of tumor promotion in liver carcinogenesis. 613 7

A sensitive enzyme immunoassay method for rat gamma-glutamyl transpeptidase was developed that was able to quantitate between 5 to 500 ng of the enzyme. The enzyme contents of fetal liver, adult liver, hyperplastic nodules, and various tissues including hepatoma were determined. Normal rat liver contained very little enzyme, while fetal liver and hepatoma tissue contained high levels. The gamma-glutamyl transpeptidase content of the liver was assayed during the process of 3'-methyl 4-dimethyl-aminoazobenzene-induced hepatocarcinogenesis. The content was increased at an early stage, then decreased, and again increased at the stage when hepatoma developed. The change of the enzyme content determined by an enzyme immunoassay was highly consistent with that determined by enzymatic assay. This indicates that the increased activity of the enzyme as previously reported was accompanied by an increased immunoreactive enzyme protein. Immunohistochemical studies on the hyperplastic nodule revealed the presence of gamma-glutamyl transpeptidase in the hepatocyte membrane.
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PMID:gamma-Glutamyl transpeptidase of rat liver and hepatoma tissues: an enzyme immunoassay and immunostaining studies. 614 74

The enhancing or inhibitory action of the hepatotoxic agents, carbon tetrachloride (CCl4) and azathioprine (AZP), on the evolution of hyperplastic liver nodule (HN) and hepatocellular carcinoma (HCC) in diethylnitrosamine (DEN)- and N-2-fluorenylacetamide (FAA)-treated rats (control group) was tested. The area of gamma-glutamyl transpeptidase(gamma-GTP)-positive HN and/or foci in the eighth week was remarkably small in rats fed on a diet containing FAA and AZP (the AZP group), but was quite large in rats fed a diet containing FAA in addition to repeated CCl4 injections (the CCl4 group). HCC was first detected in the 21st week and the incidence of HCC within the 36 weeks of the experiment was very high in the CCl4 group. However, no tumor, including HCC, was detected in the AZP group during this observation period. No essential differences in the biochemical characteristics of HCC between the control group and the CCl4 group were observed with respect to several enzyme activities. The increased activity of liver aniline hydroxylase observed 12 hr after the administration of FAA, AZP, or DEN decreased when AZP was administered simultaneously with FAA to rats treated with DEN in advance. The mechanisms of the enhancing of inhibitory effect observed are discussed with special reference to the drug-drug interactions.
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PMID:Effect of azathioprine and carbon tetrachloride on induction of hyperplastic liver nodule and hepatocellular carcinoma by diethylnitrosamine and N-2-fluorenylacetamide in rats. 614 75

By making use of the structural change of the sugar chains of liver gamma-glutamyl transpeptidase associated with malignant transformation, a new method has been developed to distinguish human serum gamma-glutamyl transpeptidase associated with primary hepatoma from that of non-hepatoma patients. In principle, the method consists of affinity chromatography of the desialylated serum enzyme on a Phaseolus vulgaris erythroagglutinating lectin agarose column.
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PMID:Application of a Phaseolus vulgaris erythroagglutinating lectin agarose column for the specific detection of human hepatoma gamma-glutamyl transpeptidase in serum. 614 47

The biosynthesis of gamma-glutamyl transpeptidase was investigated in hepatoma tissue culture cells. Pulse-chase experiments using [35S]methionine labeling have shown that the two glycosylated subunits of the enzyme (Mr = 58,000 and 29,000) derive from a single glycosylated precursor (Mr = 79,000 at early times). Only one polypeptide chain was immunoprecipitated from cell-free translation products and was shown to correspond to the nonglycosylated precursor (Mr = 64,000). Treatment with endoglycosidase H was used to probe for the transfer of the proteins from the endoplasmic reticulum to the Golgi and demonstrated: (i) that the precursor is at least partially cleaved in the endoplasmic reticulum; (ii) that part of the precursor is transferred to the Golgi where the processing of the oligosaccharide chains takes place. None of the precursor forms were detected at the surface of the cell where the mature enzyme was found. Tunicamycin, an inhibitor of protein glycosylation, did not prevent the proteolytic processing of the enzyme, but delayed the appearance of the mature enzyme at the cell surface. Monensin, which is known to alter Golgi functions, significantly delayed the acquisition of complex type oligosaccharides and the appearance of the enzyme at the cell surface. It did not, however, alter the proteolytic processing of the precursor of gamma-glutamyl transpeptidase. Taken together, these results show that gamma-glutamyl transpeptidase is synthetized as a single precursor which is at least partially cleaved in the endoplasmic reticulum. Part of the precursor is transferred to the Golgi where its oligosaccharide chains are processed.
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PMID:Biosynthesis and processing of gamma-glutamyl transpeptidase in hepatoma tissue culture cells. 614 5

Serum gamma-glutamyl transpeptidase from patients with various hepatobiliary diseases was fractionated by polyacrylamide gradient gel slab electrophoresis to study the specific patterns of gamma-glutamyl transpeptidase fractions in hepatic cancer. On zymograms of normal serum gamma-glutamyl transpeptidase, a total of 10 fractions was observed. Additionally, fractions I', I" and II' were recognized in sera from hepatocellular carcinoma patients. Among these, fraction I', which migrated slightly, but significantly, slower than fraction I was the most specific; it was found in 55% of the hepatocellular carcinoma patients. Fractions I" and II' were also relatively specific, each was observed in about 29% of these patients. Fractions V to IX were observed in few hepatocellular carcinoma cases. Fraction I' is thought to be a hepatoma-related fraction, highly specific for the serum of hepatocellular carcinoma patients. Fractions I" and II' were also thought to be hepatoma-related fractions of gamma-glutamyl transpeptidase. We suggest that fractions I', I" and II' may be useful in the diagnosis of hepatocellular carcinoma.
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PMID:Electrophoretic fractionation of serum gamma-glutamyl transpeptidase in human hepatic cancer. 615 3

The patient was a 60-year-old Japanese male. He complained of epigastralgia and right chest pain of 4 month's duration, and general malaise, nausea and vomiting of 2 month's duration. Physical examination revealed on the right third rib a tender mass with a diameter of 2 cm and hepatomegaly with a multi-nodular surface and red palms. There were no signs of carcinoid syndrome, such as cutaneous flushing. Laboratory examinations disclosed certain biochemical alterations; alkaline phosphatase 810 IU/l, gamma-glutamyl transpeptidase (gamma-GTP) 2090 IU/l, carcinoembryonic antigen (CEA) 23.5 ng/ml and alpha-fetoprotein (AFP) 6,800 ng/ml. Both HBs-Ag and HBs-Ab were negative. The patient died in a uremic state, with rapid increases of jaundice and ascites. Autopsy revealed gastric carcinoid with extensive metastases to the liver and the bone marrow. Tumor cells showed argyrophilia but not argentaffinity. Immunofluorescence specific for AFP was positive in the hepatocytes, particularly those adjacent to the metastatic tumor cells but not in the tumor cells, either primary or secondary. 79 cases reported in Japan of serum AFP-positive malignant tumor other than hepatocellular carcinoma and certain other malignancies of germ cell origin are reviewed and discussed.
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PMID:Serum alpha-fetoprotein-positive gastric carcinoid with liver metastasis. 616 67

Hepatoma cells isolated from rats after administration of a carcinogen, diethylnitrosamine, and propagated in culture, contained a genetically stable cytoskeletal abnormality resembling Mallory bodies. These juxtanuclear aggregates of intermediate-sized filaments were maintained in carcinomas produced in nude mice after inoculation of uncloned mass cultures and a cloned subculture. Paraffin and frozen sections of these tumors revealed acentric nuclei and a glassy hyalin-type cytoplasmic lesion which stained pink with hematoxylin-eosin and blue with Mallory's aniline blue stain. The cells in culture and in the tumor sections were strongly positive for gamma-glutamyl transpeptidase. Cryostat sections examined by indirect immunofluorescence microscopy with antisera to purified bovine hoof prekeratin, desmosome-associated tonofilaments from bovine muzzle, and murine vimentin, as well as transmission electron microscopy revealed the presence of juxtanuclear aggregates of intermediate-sized filaments. All characteristics previously reported for the tissue culture cell line were stably maintained in the tumor tissue. These results suggest that the Mallory body-containing cells frequently observed in man in alcoholic hepatitis and other degenerative liver diseases could, under appropriate environmental "promoting" conditions, be precursor cells in focal hepatocellular carcinoma formation.
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PMID:Mallory body-like abnormalities in carcinomas induced by cultured transformed rat liver cells. 627 81

Effects of carbon tetrachloride (CCl4) and azathioprine (AZP) on the evolution of hyperplastic liver nodules and foci and hepatocellular carcinoma (HCC) were tested in short- and long-term in vivo experiments. In diethylnitrosamine (DEN)-treated rats, which were fed a N-2-fluorenylacetamide (FAA)-containing diet and additionally treated with repeated CCl4 injections, gamma-glutamyl transpeptidase (gamma-GTP)-positive hyperplastic nodules were markedly developed in the 8th week of the experiment. However, their number and area in liver sections were remarkably small in DEN-treated rats fed a diet containing both FAA and AZP. Increased area of gamma-GTP-positive foci was also observed in the 12th week in DEN-injected rats fed a choline-devoid died alone or treated with repeated doses of CCl4 alone. Hepatocellular carcinoma in DEN-injected rats treated with both FAA and CCl4 was first detected in the 21st week, and the incidence up to the 36th week was very high. However, no hepatocellular carcinoma developed in DEN-injected rats treated with both FAA and AZP. The increased activity of liver aniline hydroxylase observed 12 h after the administration of FAA, AZP or DEN alone was not observed when AZP was administered simultaneously with FAA to DEN-injected rats. The mechanisms of the effects of CCl4 and AZP on hepatocarcinogenesis are discussed with special reference to drug interaction.
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PMID:Effects of carbon tetrachloride and azathioprine on diethylnitrosamine and N-2-fluorenylacetamide-induced hyperplastic liver nodule and hepatocellular carcinoma. 652 46


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