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)

Gamma-Glutamyltransferase (GGT), formerly called gamma-glutamyltranspeptidase, is predominantly a membrane-bound enzyme. The estimation of enzyme activity in serum is useful in monitoring hepatobiliary complaints. The electrophoresis with surfactant (Triton X-100) developed by the authors demonstrates five distinct bands of enzyme activity in the serum from patients with hepatitis. These bands are called isoenzyme GGT1 to 5 from anode to cathode, respectively. Four isoenzymes GGT2 to 5, except GGT1 are demonstrated in normal adult serum. The affinity electrophoresis is more variable to identify the hepatoma associated isoenzyme, namely HA-GGT. Concanavalin A used in the method has no affinity with HA-GGT and this isoenzyme is separated from GGT2. The diagnostic sensitivity and specificity for the measurement of HA-GGT were 58% and 83%, respectively.
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PMID:[Gamma Glutamyltransferase]. 760 73

Liver DNA specimens from woodchucks kept in captivity, 10 naturally infected with hepatitis virus (WHV) and five WHV-free, were examined for the presence of carcinogen-DNA adducts by 32P-postlabeling. The number of adducts was significantly higher in WHV carriers than in uninfected animals, and the total amounts of adducts per 10(9) nucleotides were also considerably enhanced by WHV infection, when using both butanol extraction (22.2 +/- 7.1 vs. 12.6 +/- 2.8, means +/- S.D.) and nuclease P1 enrichment (8.5 +/- 5.9 vs. 2.8 +/- 1.7). Two individual adducts were also significantly higher in WHV carriers. No significant variation occurred as related to age, sex or time length of captivity. These findings are consistent with our previous studies supporting an enhanced metabolism of chemical hepatocarcinogens in both human and woodchuck hepadnavirus infections. Several significant and remarkable correlations were pointed out by relating DNA adduct data to more than 30 virological, histopathological and metabolic parameters which had been previously evaluated in the same animals. For instance, numbers and/or levels of adducts were positively related to the amounts of virus present in hepatocytes, to cell damage (gamma-glutamyltranspeptidase activity), to the severity of the liver histopathological picture, and to monooxygenase activities, while they were inversely related to cellular glutathione concentrations and to detoxification of the direct-acting mutagen 4-nitroquinoline 1-oxide. The major adduct significantly correlated with the metabolic activation of the aromatic amine 2-aminofluorene and of the heterocyclic amines 3-amino-1-methyl-5H-pyrido(4,3)indole (Trp-P-2) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ), whereas another adduct significantly correlated with the metabolic activation of the mycotoxin aflatoxin B1. Thus, the enhanced metabolism of chemical hepatocarcinogens and the increased formation of carcinogen-DNA adducts in the liver of WHV carriers appear to represent one of the mechanisms contributing to the association between chronic hepadnavirus infection and development of primary hepatocellular carcinoma.
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PMID:Enhanced levels of DNA adducts in the liver of woodchucks infected with hepatitis virus. 767 44

We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for serum ornithine carbamoyltransferase (OCT) protein, and examined serum OCT concentrations in patients with various liver diseases. OCT concentrations were markedly elevated in cases of hepatic encephalopathy, 'acute on chronic', and those with the acute phase of acute hepatitis, moderately in chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis, and slightly in those with a fatty liver. High percentages (92-98%) of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma had higher than normal concentrations of serum OCT protein. There was a close correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and moderate correlations with those of mitochondrial AST, glutamate dehydrogenase and gamma-glutamyltranspeptidase. The OCT/ALT ratio was higher in patients with liver cirrhosis than in those with chronic hepatitis (p < 0.001), and was still higher in cases of hepatocellular carcinoma (p < 0.05). In 2 patients with 'acute on chronic' disease, OCT concentrations decreased similarly with or more rapidly than AST or ALT activities after admission. In 2 patients with hepatic encephalopathy, the OCT concentrations changed similarly with AST and ALT activities. This OCT ELISA system will aid in diagnosing various liver diseases and in the follow-up of the patients, and the OCT/ALT ratio may serve for a differential diagnosis of liver diseases.
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PMID:Clinical evaluation of serum ornithine carbamoyltransferase by enzyme-linked immunosorbent assay in patients with liver diseases. 778 67

Rats fed a choline-deficient diet develop foci of enzyme-altered hepatocytes with subsequent formation of hepatic tumors. They also develop fatty livers, because choline is needed for hepatic secretion of lipoproteins. We have previously reported that 1,2-sn-diradylglycerol accumulates in the livers of rats fed a choline-deficient diet for 1-27 weeks, and that protein kinase C activity in the hepatic plasma membrane is elevated during that time (da Costa et al., J. Biol. Chem., 268, 2100-2105, 1993). In the present study, we examined the changes that occur in rat liver at 52 weeks of choline deficiency and determined whether these changes were reversible when choline was returned to the diet of the deficient animals for 1 or 16 weeks. At 52 weeks, non-tumor liver samples from the experimental animals had increased 1,2-sn-diradylglycerol concentrations in the lipid droplets compared with control animals. Plasma membrane 1,2-sn-diradylglycerol levels in the liver did not differ between the two groups, but an age-related increase in membrane 1,2-sn-diradylglycerol concentrations was observed. Unsaturated free fatty acids, another activator of protein kinase C, accumulated in the deficient livers. Protein kinase C activity associated with the plasma membrane remained significantly elevated at 52 weeks in deficient livers. Hepatic foci expressing gamma-glutamyltranspeptidase were detected only in the deficient rats (0.83% of liver volume) and 15% of these rats had hepatocellular carcinoma at 1 year on the diet. At 53 weeks (1 week after choline was returned to the deficient group), 1,2-sn-diradylglycerol concentrations in the lipid droplets and hepatic free fatty acids had dropped to control levels. By 68 weeks (16 weeks of re-feeding choline), the membrane protein kinase C activity had returned to normal. At this time, 14% of the experimental animals had hepatocellular carcinoma. We suggest that choline deficiency altered the protein kinase C-mediated signal transduction within liver and this contributed to hepatic carcinogenesis in these animals.
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PMID:Effects of prolonged (1 year) choline deficiency and subsequent re-feeding of choline on 1,2-sn-diradylglycerol, fatty acids and protein kinase C in rat liver. 785 65

gamma-Glutamyl transpeptidase (GGT) is an enzyme encoded by multiple mRNAs (mRNAI to mRNAIV) that, in the rat, are transcribed from a single copy gene in a tissue-specific manner. In the liver, GGT expression is up-regulated in transformed cells, and this induction is the most widely used marker of liver cell transformation. We characterized the GGT mRNA species expressed in the liver (mRNAIII), and we report that this mRNA differs from the other GGT mRNA species by a 275-base alternate 5'-end sequence. Its transcription occurs on a specific promoter (promoter III) that maps on the GGT gene upstream of the two promoters coding for the GGT mRNAI and mRNAII. In hepatoma cells, mRNAIII expression is related to the differentiation state of the cells. We have shown that, in Reuber H-35-derived cell lines, the GGT mRNAIII is transcribed in cells that express a differentiated phenotype (Fao), but not in the dedifferentiated C2 and H5 variants. Moreover, we observed a reexpression of the GGT mRNAIII species in the C2 Rev7 variant, which has reverted from C2 toward a differentiated hepatocyte phenotype. In the proximal promoter III region, we identified a sequence that strongly enhances transcriptional activity in Fao and C2 Rev7 cells, but not in the dedifferentiated C2 variant. This motif interacts with nuclear proteins belonging to the NF-1 and NF-Y families that govern GGT promoter III expression in differentiated hepatoma cells.
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PMID:Functional characterization of the rat gamma-glutamyl transpeptidase promoter that is expressed and regulated in the liver and hepatoma cells. 791 Aug 21

Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, gamma-glutamyltranspeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second-generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. 798 43

Sodium butyrate was used to enhance biosynthesis rates of recombinant human gamma-glutamyl transferase (GGT) expressed under the control of the SV40 or the cytomegalovirus immediate early promoter, respectively, in transfected V79 and CHO Chinese hamster cell lines. Maximal induction of GGT specific activity in butyrate-treated cells ranged from 3 to 5-fold and resulted from a strong increase in the GGT mRNA ratio. We also observed that maximal transcription level in V79 cells occurred within 12 hr of treatment, whilst the cell proliferation was transiently arrested. Despite its processing requirements, induced GGT exhibited unchanged catalytic and physico-chemical features relative to human serum or hepatoma enzyme, thus appearing as an excellent model for further studies on human GGT.
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PMID:Induction of recombinant human gamma-glutamyl transferase by sodium butyrate in transfected V79 and CHO Chinese hamster cells. 809 85

Flow cytometric analysis of the ploidy of normal and neoplastic hepatocyte nuclei obtained from adult woodchucks, a model of human hepadnavirus-induced hepatocellular carcinoma, was performed. All 36 samples of nuclei from non-neoplastic liver from woodchuck hepatitis virus-infected or uninfected liver were diploid, indicating that age-related nuclear polyploidization does not occur in this species, unlike other rodents. Individual or multiple hepatic neoplasms were obtained from each of 14 woodchuck hepatitis virus-infected woodchucks. Nineteen samples of hepatocellular carcinoma and eight adenomas were examined. Aneuploid nuclei were detected in 10 of the hepatocellular carcinomas and three of the adenoma samples. Similar DNA indexes, ranging from 1.11 to 1.22, were found in 7 of the 10 aneuploid HCCs and all 3 aneuploid adenomas. Nine of the 19 hepatocellular carcinoma samples and 5 of the 8 adenomas were diploid. Four of the diploid hepatocellular carcinomas had increased proportions of tetraploid nuclei. The presence of aneuploid nuclei was not related to histological appearance of the neoplasms or serum gamma-glutamyltranspeptidase levels. Because none of the hepatocellular carcinomas metastasized, the presence of aneuploidy could not be related to biological behavior. We determined the proportion of uninucleate and binucleate hepatocytes in hepatocellular carcinoma and nonneoplastic liver. Approximately 7% of hepatocytes were binucleate in nonneoplastic liver from woodchuck hepatitis virus-infected and uninfected liver. Only 2% of malignant hepatocytes were binucleate. The results of this study indicate that aneuploidy is a common change in hepatic neoplasms from woodchuck hepatitis virus-infected woodchucks.
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PMID:Nuclear ploidy of normal and neoplastic hepatocytes from woodchuck hepatitis virus-infected and uninfected woodchucks. 817 28

gamma-Glutamyl transpeptidase (GGT) is normally absent from adult rat hepatocytes but is induced by a range of xenobiotics, including carcinogens and chemoprotective agents. As many as six mRNA species for this enzyme have been described in both rat and mouse, with various degrees of tissue specificity. These originate from one gene and have separate promoters within alternative 5' untranslated sequences. By using a cDNA-derived sequence specific for GGT mRNA III to screen a rat genomic library, a clone that contains the promoter region for this mRNA was isolated and characterized. The transcriptional start site lay some 3.5 kb upstream from that already characterized for mRNA II in rat kidney. Luciferase activity was obtained after transfection of rat hepatoma-derived cell lines with constructs containing the putative promoter III fused to a luc reporter. Although this promoter lacks a TATA box, a sequence close to the start site that binds the transcription factor TFIID in vitro was identified. By using PCR techniques, mRNA III (homologous to both mouse III and IV) and an mRNA (IV) with homology to VI in mouse were found in ethoxyquin- and aflatoxin B1-treated rat liver and kidney as well as in a hepatoma-derived cell line. No evidence was found for a product homologous to mRNA from promoter V described in the mouse.
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PMID:Characterization of a promoter for gamma-glutamyl transpeptidase activated in rat liver in response to aflatoxin B1 and ethoxyquin. 851 14

Expression of cancerous isoenzymes in various malignant tumors has been extensively studied using different biochemical techniques. Cancerous alkaline phosphatase (ALP) isoenzymes, such as placental ALP and variant ALP, are detected from sera of patients with various malignant diseases. Variant ALP is a specific tumor marker for hepatocellular carcinoma (HCC). The positive rate of each ALP isoenzyme is, however, low except for a high positivity of placental ALP in seminoma. Novel gamma-glutamyltranspeptidase (gamma-GTP) isoenzyme is specifically found in about 60% of the sera from patients with HCC but in only 3% of those from patients with benign liver diseases, suggesting a high specificity for HCC. Thus, cancerous isoenzymes are available for diagnosis of various malignant tumors.
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PMID:[Isoenzyme]. 869 1


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