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

Hyperplastic growth and expression of gamma-glutamyl transpeptidase were induced in adult rat hepatocytes using a model of chemical hepatocarcinogenesis. The hyperplastic response was maximal at 10 weeks after initiation of the model, at which time some 20-25% of the cross-sectional area of liver sections showed hepatocyte expression of gamma-glutamyl transpeptidase. The altered growth patterns appeared to be independent of carcinoma development since at 12 months after initiation only one of 10 animals showed evidence of hepatocellular carcinoma. A 43,000 dalton protein of isoelectric point 6.9 was solubilized by DNASE I from nuclei derived from livers at 10 weeks after initiation of the regime. This protein was scarcely detectable in the nuclei of control livers or in control and treated livers at other times after initiation of the regime. These observations suggest that alterations to a prominent nonhistone protein associated with the transcriptionally active fraction of chromatin occurred during hyperplastic growth of hepatocytes induced by chemical carcinogens.
 ...
PMID:An analysis of nuclear and chromatin proteins in rat livers exhibiting hyperplastic growth induced by chemical carcinogens. 285 63

Short-term treatment of rats with hepatocarcinogens elicits a consistent pattern of phenotypic changes in hepatic drug metabolizing enzymes, the most striking of which is a marked increase in microsomal epoxide hydrolase (EH) activity. The antihistaminic drug methapyrilene induces a high incidence of hepatocellular carcinoma in F-344 rats. The studies reported here were designed to assess the effects of methapyrilene on hepatic EH activity, cytochrome P-450-dependent mixed-function oxidase activities, liver morphology, and liver-derived serum enzymes. Male F-344 rats were treated with three daily oral doses of methapyrilene-HCl, up to 300 mg/kg/day, and were sacrificed 48 hr after the last dose. Hepatic microsomal EH and cytosolic DT-diaphorase activities were increased in a dose-related fashion, to 420 and 230% of control, respectively. Cytochrome P-450 content and benzphetamine-N-demethylase and ethoxycoumarin-O-deethylase activities were concomitantly decreased to 35-50% of control. Serum gamma-glutamyl transpeptidase and alanine aminotransferase activities were elevated 22- to 27-fold, and serum bile acids to 36-fold by treatment with methapyrilene. Periportal lesions, characterized by inflammation, nuclear and nucleolar enlargement, bile duct hyperplasia, and hepatocellular necrosis, were observed following methapyrilene administration. The severity of the periportal lesion correlated with elevations in the serum chemistry parameters. The increases noted in microsomal EH activity supports the suggestion that this enzyme may be a useful biochemical marker for exposure to hepatocarcinogens.
 ...
PMID:Effects of methapyrilene on rat hepatic xenobiotic metabolizing enzymes and liver morphology. 285 28

Although primary hepatoma is not very frequent in alcoholics, the incidence of hepatoma in cases of hepatitis B infection combined with heavy alcohol drinking is high. In the present study, the effects of chronic alcohol administration on the development of chemical-induced hepatic cancer in rats were analyzed. In 70% hepatectomized Wistar strain male rats, a single dose (1 mg per 100 gm body weight) of diethylnitrosamine was injected intraperitoneally. Eight weeks after the injection, 20% alcohol-10% sucrose solution (diethylnitrosamine-alcohol group), 0.1% sodium phenobarbital solution (diethylnitrosamine-phenobarbital group), 10% sucrose solution (diethylnitrosamine-sucrose group) or tap water (diethylnitrosamine-alone group) was given as drinking water for 32 weeks. The numbers of visible nodules per liver were significantly greater in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups compared to the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups. The numbers of enzyme-altered foci which were positive to gamma-glutamyl transpeptidase staining per square centimeter of liver section were also greater in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups than in the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups, although the numbers of nodules and enzyme-altered foci were significantly larger in the diethylnitrosamine-phenobarbital group than in the diethylnitrosamine-alcohol group. The enzyme-altered foci areas calculated by gamma-glutamyl transpeptidase staining were significantly larger in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups than in the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups. Histologically, visible nodules observed in diethylnitrosamine-phenobarbital and diethylnitrosamine-alcohol groups showed characteristic features of neoplastic nodules. These results indicate that alcohol has a promoter action on the development of chemically induced hepatic cancer like phenobarbital.
 ...
PMID:Effects of ethanol on experimental hepatocarcinogenesis. 286 66

By different experimental approaches in culture, we obtained convergent responses to 13 cis-retinoic acid (RA) in rat liver epithelial cell lines. We showed that the degree of transformation of the cells which had already been spontaneously transformed in culture, could be enhanced, since the capacity of these cells both to grow in soft agar and to express gamma-glutamyl transpeptidase increased markedly. We also showed that RA acted synergistically with a promoter, 12-tetradecanoyl-phorbol-13-acetate (TPA), as regards the promoter's property of blocking the metabolic cooperation between cells. RA did not, however, trigger cell transformation in the lines which had not yet been transformed, and unlike TPA, did not by itself inhibit intercellular communications. On the other hand, in our in vivo experiments, it appeared that RA, by slowing down the growth of a transplanted rat hepatoma, might have a slightly protective effect against tumour development.
 ...
PMID:Effects of retinoic acid on the transformation and metabolic cooperation of rat liver cells in vitro, and on the growth of hepatoma cells in vivo. 287 Aug 21

Immunohistochemical localization of gamma-glutamyl transpeptidase (gamma-GTP) in rat liver during 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) hepatocarcinogenesis was investigated and compared with sites of gamma-GTP activity. Immunohistochemically, gamma-GTP was stained in the apical border of proliferating oval cells during the early stages of azo-dye carcinogen feeding. After 7 weeks, multiple hyperplastic nodules appeared in which gamma-GTP was localized in the bile canaliculi. In hepatoma tissues, positive staining for gamma-GTP was observed in the bile canaliculi-like spaces, on the cell membrane, and sometimes in the cytoplasm of malignant cells. Enzyme histochemical staining showed gamma-GTP activity to be present in almost the same areas as the immunoreactive gamma-GTP. However, some areas adjacent to hepatoma tissue showed immunohistochemically reactive protein but no enzyme activity. Immunoreactive gamma-GTP was present in all locations at which enzyme activity was seen. The present data suggest that an altered form of gamma-GTP might be present in tissues during 3'-Me-DAB hepatocarcinogenesis.
 ...
PMID:gamma-Glutamyl transpeptidase in rat liver during 3'-Me-DAB hepatocarcinogenesis: immunohistochemical and enzyme histochemical study. 287 49

Monoclonal antibodies have been raised against rat kidney gamma-glutamyl transpeptidase (GGT). All five antibodies immunoprecipitate enzyme activity from solubilized kidney brush-border membranes, but not from hepatocellular carcinoma membranes. Three of the antibodies react immunohistochemically with brush-border membranes in sections of adult rat kidney, but none of the antibodies cross-react with sections of guinea-pig, mouse or marmoset kidney or with untreated or carcinogen-treated rat liver. The antibodies do not recognize GGT in foetal-rat kidney and react poorly with kidney from 2-year-old rat. They do react with tubules trapped within mesenchymal kidney tumours induced by dimethylnitrosamine, but epithelial tumours, which are GGT-positive (although much less so than normal kidney), are not immunoreactive.
 ...
PMID:Monoclonal antibodies against rat kidney gamma-glutamyl transpeptidase show species and tissue specificity. 287 35

Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities and their subcellular distributions were compared in human hepatic cancer and embryonal tissues. The activity of GPDA in cancer tissues was significantly higher than that found in healthy liver, though there were no significant differences between fetal and adult livers. The placenta, however, had the highest GPDA activity. The activity of gamma-GTP, on the other hand, was increased significantly not only in cancer tissues but also in live tissues adjacent to the tumor, and it was higher in the fetal liver but much lower in the placenta. Subcellular distribution of GPDA was also different from that of gamma-GTP in cancer tissues, especially after postmortem changes. These results suggest the possibility that GPDA has carcinoembryonic characters similar to gamma-GTP, but the mechanisms, whereby serum activities of these two enzymes were increased in hepatocellular carcinoma patients, are different from each other.
 ...
PMID:Glycylproline dipeptidyl aminopeptidase and gamma-glutamyl transpeptidase in human hepatic cancer and embryonal tissues. 288 5

The effect of ethanol on protein synthesis in the C2 rat hepatoma cell line was analyzed by two-dimensional gel electrophoresis after the labeling with [35S]methionine of cells that were untreated or had been treated with 180 mM ethanol. In this cell line, this concentration of ethanol is known to induce gamma-glutamyl transpeptidase, a marker of alcoholism in man (Barouki et al., Hepatology 1983; 3: 323-329). In the present work we demonstrate that ethanol, besides causing a slight decrease in overall protein synthesis (less than 25%), primarily regulates the expression of two unique proteins among 1500 labeled products that were analyzed: one of these was induced and did not correspond to gamma-glutamyl transpeptidase, and one was repressed after 20 h of ethanol treatment. We conclude that the set of hepatic proteins altered by ethanol is likely to be very limited in number, which reflects the specificity of alcohol action on protein synthesis in the C2 cell line.
 ...
PMID:Specific modulation by ethanol of the protein synthesis pattern in the C2 rat hepatoma cell line. 289 91

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.
 ...
PMID:Enzyme-altered liver cell foci in woodchucks infected with woodchuck hepatitis virus. 289 65

Human hepatoma cell (Hep G2) gamma-glutamyl transpeptidase (gamma-GT), a 120 ka single-chain glycoprotein, is much larger than the expected precursor of the dimeric enzyme in other human tissues. However, the Hep G2 gamma-GT mRNA encodes a 63 kDa peptide, similar to that of rat gamma-GT mRNA product and to the predicted, unglycosylated precursor of the enzyme in human tissues. Translation in presence of dog pancreas microsomes results in processing of the 63 kDa to an 80 kDa core-glycosylated species which is subsequently cleaved to 58 and 22 kDa subunits resembling those in other human tissues. The unusually large Mr of gamma-GT in Hep G2 would thus seem to be due to further glycosylation and processing in the Golgi. A deficiency of the processing protease is the most likely reason for the persistence of the single-chain form of gamma-GT in Hep G2 cells.
 ...
PMID:In vitro translation and processing of human hepatoma cell (Hep G2) gamma-glutamyl transpeptidase. 290 Jun 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>