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)

The total activity of superoxide dismutase and glutathione peroxidase and the tissue content of Cu,Zn-superoxide dismutase, glutathione, and lipoperoxides in the gastric mucosa were determined in patients with chronic liver disease and in healthy controls. The mean levels of Cu,Zn-superoxide dismutase in liver cirrhosis and in hepatocellular carcinoma with cirrhosis were significantly reduced compared to controls (32.0 +/- 4.4, and 35.8 +/- 2.2, vs 44.6 +/- 2.2 ng/mg protein, p < 0.01). Mucosal levels of glutathione were significantly lower in chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma with cirrhosis than in controls (9.7 +/- 2.1, 8.9 +/- 2.3, and 11.0 +/- 3.4, vs 23.6 +/- 4.7 nmol/mg protein, p < 0.05). However, there were no significant differences between chronic liver disease and controls in the activity of gastric superoxide dismutase and glutathione peroxidase. Gastric lipoperoxide concentrations were significantly higher in chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma with cirrhosis than in controls (0.56 +/- 0.07, 0.50 +/- 0.12, 0.50 +/- 0.05 vs 0.18 +/- 0.03 nmol/mg protein, p < 0.05). These results suggest that the concentrations of gastric mucosal antioxidants were decreased in chronic liver disease, and that these changes may be responsible for the higher frequency of gastric mucosal lesions observed in patients with chronic liver disease.
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PMID:Superoxide dismutase and glutathione in the gastric mucosa of patients with chronic liver disease. 133 97

Deviations of the enzyme activity, immunoreactivity and messenger ribonucleic acid (mRNA) levels of glutathione peroxidase (GSH-PO) in 3'-methyl-4-dimethylaminoazobenzene- induced hepatocellular carcinoma of the rat were investigated. Enzyme activities of GSH-PO were significantly lower in hepatocellular carcinomas than those in the normal control rat liver. Immunohistochemically, GSH-PO was strongly localized in normal hepatocytes, but was only faintly stained in hepatocellular carcinoma cells. Heterogeneous staining patterns of GSH-PO were observed among individual cancer cells. In Northern blot analysis, GSH-PO mRNA in the cancer tissue was decreased to two thirds of the level in normal hepatocytes. It was suggested that suppressed expression of GSH-PO in carcinogen-induced hepatocellular carcinomas occurred at the level of mRNA transcription.
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PMID:Suppression of messenger ribonucleic acid for glutathione peroxidase in chemically induced rat hepatocellular carcinoma and its biological significance. 171 59

We have compared some mechanisms involved in the defense against doxorubicin-induced free radical damage in rat hepatoma and glioblastoma cell lines and their doxorubicin-resistant variants presenting an overexpression of the multidrug resistance gene. Immediate in vivo production of malondialdehyde was minor and was not different in sensitive and resistant cells. Alpha-tocopherol was undetectable in all cell lines. Glutathione levels were not different in sensitive and resistant cells and these levels did not vary upon doxorubicin treatment. Resistant cells exhibited either a 50% decrease (hepatoma) or a 25% increase (glioblastoma) of glutathione-S-transferase activity. Glutathione reductase presented no important change upon acquisition of resistance. In contrast, selenium-dependent glutathione peroxidase activity was consistently 2-6-fold increased in the resistant cells, which suggests a magnification of protection mechanisms against hydroxyle radical formation from H2O2 in resistant cells. Depletion of glutathione levels by buthionine sulfoximine sensitized hepatoma resistant cells to doxorubicin, but had no effect on doxorubicin cytotoxicity to glioblastoma cells.
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PMID:Development of mechanisms of protection against oxidative stress in doxorubicin-resistant rat tumoral cells in culture. 196 16

Recently old rats were found to be much more susceptible than young rats to the hepatocarcinogenic effect of a 55-59-week treatment with the peroxisome proliferator nafenopin (NAF) (B. Kraupp-Grasl, W. Huber, H. Taper, and R. Schulte-Hermann, Cancer Res., 51: 666-671, 1991). In the present study indicators of oxidative stress were measured in the livers of the same animals (male Wistar). NAF enhanced peroxisomal beta-oxidation 10-12-fold and reduced glutathione peroxidase activity by 40-50%. Indicators of lipid peroxidation like thiobarbituric acid reactive substances and malondialdehyde were both decreased by one-third and two-thirds, respectively. Of the oxidation-sensitive polyunsaturated fatty acids linoleic acid and docosahexaenoic acid were decreased by 40% and two-thirds, respectively, but the particularly sensitive arachidonic acid remained unchanged. Taken together these data suggest that NAF did not significantly enhance lipid peroxidation in the present experiment. All NAF effects were of the same magnitude in the old and young animals. Therefore, the considerably stronger induction of hepatocarcinoma by NAF in the old animals was not associated with evidence of enhanced oxidative stress. These findings are consistent with the hypothesis that NAF acts hepatocarcinogenically by promotion of tumor development from preneoplastic lesions occurring spontaneously with age.
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PMID:Role of oxidative stress in age dependent hepatocarcinogenesis by the peroxisome proliferator nafenopin in the rat. 200 63

Glutathione S-transferases play a central role in drug detoxification and have been implicated in the sensitivity of tumour cells to anticancer drugs. In this study, glutathione S-transferase (GST) isozyme expression in normal and tumour tissue from human lung, colon, stomach, breast, kidney and liver tissue has been quantified using sensitive and subunit specific radioimmunoassays (RIA), together with Western blot analysis and measurement of substrate metabolism. Glutathione S-transferase pi was the predominant GST in the majority of the tumours examined. The concentration of this enzyme was increased significantly in tumour tissue relative to normal lung, colon, and stomach tissue. A strong correlation was observed (r = 0.77, P less than 0.01) between GST activity and GST pi levels in those tumour samples. The concentrations of the alpha class GST, the predominant isoenzymes in normal stomach, kidney and liver, decreased dramatically in tumour tissue from these organs. Western blot analysis revealed the presence of novel polypeptides that cross-reacted with antisera raised against alpha and mu class GST. Our data demonstrates that although GST pi is the predominant GST isoenzyme in many tumours, significant levels of the other GST subunits are also present and collectively can represent a significant proportion of the GST content. Therefore the properties of all the GST isoenzymes need consideration when assessing the role of these proteins in drug resistance. Selenium-dependent glutathione peroxidase, an enzyme activity also implicated in the mode of action of certain antitumour agents, was also studied and shown to be the predominant glutathione-dependent peroxidase in all tumours except the hepatoma.
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PMID:Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. 231 Nov 89

Cellular copper metabolism and the mechanism of resistance to copper toxicity were investigated using a wild type hepatoma cell line (HAC) and a copper-resistant cell line (HAC600) that accumulates copper and has a highly elevated level of metallothionein (MT). Of the enzymes involved in reactive oxygen metabolism, only glutathionine peroxidase was elevated (3-4-fold) in resistant cells, suggestive of an increase in the cellular flux of hydrogen peroxide. A majority of the cytoplasmic copper (greater than 60%) was isolated from both cell lines as a GSH complex. Kinetic studies of 67Cu uptake showed that GSH bound 67Cu before the metal was complexed by MT. Depletion of cellular GSH with buthionine sulfoximine inhibited the incorporation of 67Cu into MT by greater than 50%. These results support a model of copper metabolism in which the metal is complexed by GSH soon after entering the cell. The complexed metal is then transferred to MT where it is stored. This study also indicates that resistance to metal toxicity in copper-resistant hepatoma cells is due to increases in both cellular GSH and MT. Furthermore, it is suggested that elevated levels of GSH peroxidase allows cells to more efficiently accommodate an increased cellular hydrogen peroxide flux that may occur as a consequence of elevated levels of cytoplasmic copper.
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PMID:The role of glutathione in copper metabolism and toxicity. 256 91

Twelve adults with hepatocellular carcinoma (HCC) and 8 individuals with histologically normal liver, were measured for serum selenium concentration and glutathione peroxidase (GSH-Px) of liver tissue. It was found a reduced serum selenium and liver GSH-Px in patients with HCC. Serum selenium concentration and the enzyme activity were positively correlated (p less than 0.01). The increased risk of carcinoma in selenium deficiency may be partially due to a reduced activity of GSH-Px, one of the most important scavenger enzymes of oxygen toxic radicals.
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PMID:Reduction of liver glutathione peroxidase activity and deficiency of serum selenium in patients with hepatocellular carcinoma. 302 33

The importance of some glutathione metabolic pathways was examined in two highly dedifferentiated hepatomas, Yoshida AH-130 and Morris 3924 A hepatomas, and in normal liver in relation to their role against oxidative stress. The cytosol prepared from Yoshida hepatoma cells decreased the peroxidation rate in normal liver microsomes and mitochondria, but this antioxidant property was not displayed by Morris hepatoma. Glutathione peroxidase and glutathione-S-transferases activities were extremely low in both hepatomas; glutathione reductase activity values were about half the normal liver values. The large decrease in glutathione peroxidase and glutathione-S-transferases suggests that in these two tumors only small amounts of GSH can be used in reduction or conjugation reactions, such as the reduction of hydrogen peroxide and lipid hydroperoxides or the conjugation of GSH with the end products of lipoperoxidation, aldehydes or ketones. The hypothesis of a more efficient GSSG reduction in hepatomas, due to the low glutathione peroxidase/glutathione reductase activity ratio, is also discussed. The described changes in glutathione related enzymes do not seem to have any correlation with the protective effect against the lipoperoxidative processes displayed by some tumors since these enzymatic activities were similar in both hepatomas whereas only Yoshida hepatoma showed antioxidant properties.
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PMID:Analysis of glutathione-dependent enzyme activities in two different rat hepatomas and in normal liver in relation to their role in resistance to oxidative stress. 323 5

Fischer F-344 male rats, fed a choline-devoid diet that leads to a highly reproducible sequence of biochemical and biological changes with an ultimate development of hepatocellular carcinoma, show elevated levels of glutathione in the liver at 3, 6 and 8 days. Several enzymes related to the metabolism of free radicals, including superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and DT-diaphorase show neither increased nor decreased activity as measured between 12 h and 8 days on the diet. Thus, of several known cellular components related to the possible scavenger of free radicals in the liver, only glutathione responded to the feeding of the CD diet. It is tentatively concluded that a decrease in the levels of possible scavengers for free radicals is not a major basis for the nuclear and mitochondrial lipid peroxidation seen early in rats fed a choline-devoid diet.
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PMID:Glutathione and enzymes related to free radical metabolism in liver of rats fed a choline-devoid low-methionine diet. 339 Aug 3

The human hepatoma cell line Hep 3B, which has the hepatitis B virus genome, shows over 80% decrease of copper/zinc superoxide dismutase activity, over 90% decrease of manganese superoxide dismutase activity, over 70% decrease of catalase activity, absence of glutathione peroxidase and glutathione S-transferase activities, over 270-fold increase of ferritin content and 25-fold increase of total iron compared to normal autopsy liver. These conditions of low antioxidant enzyme activities and iron overload are those which support the accumulation of oxygen free-radicals and DNA damage commonly considered to be carcinogenic mechanisms.
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PMID:Antioxidant systems in tumour cells: the levels of antioxidant enzymes, ferritin, and total iron in a human hepatoma cell line. 350 92


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