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 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

The effects of four isomeric forms of aminophenols, ortho-, meta-, para-aminophenol and acetaminophen (o-, m-, p-AP and AAP, respectively) on liver and kidney carcinogenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested. Rats were given 0.1% EHEN (in their drinking water for 2 weeks) and then diet containing these compounds at concentrations of 0.8% for 49 weeks. Administration of o-AP and AAP significantly decreased the number and area of preneoplastic foci staining immunohistochemically for glutathione S-transferase placental type (GST-P) per unit area of liver section as compared with the values for rats given EHEN alone. o-AP and AAP also significantly decreased the incidence of hepatocellular carcinoma. In contrast, p-AP and AAP significantly increased quantitative values for kidney preneoplastic lesions and renal cell adenoma. It is suggested that the cytotoxic effects of these chemicals preferentially suppressed the proliferation of preneoplastic liver cells, but stimulated the mitotic activity of preneoplastic tubular lesions in the kidney.
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PMID:Reciprocal modifying effects of isomeric forms of aminophenol on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine. 362 66

We have used a rat glutathione S-transferase P (GST-P) complementary DNA as a probe to screen a human placenta complementary DNA library constructed in the lambda gt11 vector. One of the positive clones contained the complete coding region (630 base pair) and the entire 3'-noncoding region (78 base pair) of the putative human glutathione S-transferase pi (GST-pi) subunit mRNA. From the nucleotide sequence we deduced the complete amino acid sequence of the GST-pi subunit. It contained 209 amino acids with the relative molecular mass of Mr 23,224. Comparison of the amino acid sequences between GST-pi and GST-P subunits suggests that they are the corresponding enzymes in these species. GST-pi and GST-P both consist of 209 amino acids and differ in only 30 amino acids (85.6% homology). The difference in amino acid composition can explain the large difference in isoelectric point between GST-pi subunit (pI 5.5) and GST-P subunit (pI 6.9). The expression of GST-pi mRNA in some normal and cancerous tissues, including some hepatoma cell lines, hepatoma, and colon carcinoma specimens was determined using complementary DNA as a probe. The results indicate that the mode of the expression of GST-pi in humans is different from that of GST-P in rats.
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PMID:Structure and expression of a human class pi glutathione S-transferase messenger RNA. 366 69

The dose-dependent effects of three hepatocarcinogens were investigated by measuring the number and area of glutathione S-transferase placental form (GST-P)-positive foci and nodules appearing in the liver under short-term conditions (Experiment I) and evaluating the incidence of hepatocellular carcinoma after long-term chronic administration (Experiment II). For these purposes, three different doses of 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethy-laminoazobenzene (3'-Me-DAB), and DL-ethionine (ethionine) were given to male F344 rats for 6 weeks after a single injection of diethylnitrosamine (DENA) in Experiment I or for 104 weeks without initiation by DENA in Experiment II. In Experiment I, the induction of GST-P-positive foci and nodules by 2-AAF and 3'-Me-DAB was clearly dose-dependent. In contrast, ethionine showed enhancing effects inducing GST-P-positive foci and nodules only in groups given the highest dose level. Similarly, in Experiment II, induction of hepatocellular carcinomas by 2-AAF and 3'-Me-DAB was clearly dose-dependent, whereas liver neoplasms were only induced by the highest dose level of ethionine. These results indicate that degree of induction of GST-P positive foci and nodules in a short-term in vivo test for liver carcinogens corresponds with the incidences of hepatocellular carcinomas revealed in a long-term in vivo assay.
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PMID:Comparative effects of carcinogens on the induction of placental glutathione S-transferase-positive liver nodules in a short-term assay and of hepatocellular carcinomas in a long-term assay. 383 82

Administration of 2-acetylaminofluorene to rats for 12 weeks induces hyperplastic nodules (HPNs) and later well-differentiated hepatocellular carcinomas (HCCs) in the liver. Total cellular proteins from normal liver, HPN, and HCC were analyzed by two-dimensional gel electrophoresis with a high resolution. Several hundred polypeptides were well resolved as seen by Coomassie blue staining, forming a reproducible and characteristic pattern for each tissue. The polypeptide patterns were very similar among normal liver, HPN, and HCC. Especially the proteins of HPN and HCC were almost indistinguishable. These neoplastic lesions, however, were clearly different from control liver in that a new spot p35-6.6 (designated by molecular weight X 10(-3) and pl) appeared, and five polypeptides, p57-6.9, p57-6.7, p26-6.9, p26-6.6, p26-6.4, increased dramatically in amount as compared with normal liver. These last three spots were found to be a new type of glutathione S-transferase as judged from the specific binding to the antibody. The same changes in polypeptide pattern were found in HCCs induced by other chemical carcinogens, diethylnitrosamine and 3'-methyl-4-dimethylaminoazobenzene, but not in regenerating and neonatal livers. Fetal liver showed a rather different pattern than adult liver, but only p26-6.6 was increased among the spots characteristic of HPN and HCC. Protein phosphorylation was also examined for these cells by incubating tissue slices with 32PO4. After alkali treatment of the gels to eliminate serines phosphorylation, several dozens of phosphoproteins were clearly detected. The patterns of the labeled spots were again very similar among control liver, HPN, and HCC. Only the intensity of a spot designated p57-6.6 increased markedly in both HPN and HCC. This spot was further resolved by an expanded pH gradient into four distinct spots, the major one of which contained phosphothreonine. Similar changes in phosphorylation were noted in hepatomas induced by diethylnitrosamine and 3'-methyl-4-dimethylaminoazobenzene but not in regenerating, fetal, and neonatal livers. These changes are discussed in terms of gene expression relevant to malignant transformation of hepatic cells.
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PMID:Changes in polypeptide pattern of rat liver cells during chemical hepatocarcinogenesis. 396 45

Several naturally occurring porphyrins and porphyrins used in photodynamic therapy inhibit glutathione S-transferase isoenzymes either purified from rat liver or lung or in cytosol from normal and from cancerous (Morris 7288C hepatoma) liver. Although differences occur in the type and amount of transferases in normal and cancerous liver and in the liver of rats bearing an extrahepatic tumour, these enzymes are potential binding sites for porphyrins. Porphyrin structure is an important factor in determining the affinity of binding, as shown by the relative inhibitory effectiveness. Of the dicarboxylic porphyrins in the mixture used clinically, OO'-diacetylhaematoporphyrin and monohydroxyethylmonovinyldeuteroporphyrin are more effective inhibitors than haematoporphyrin and protoporphyrin IX. Of the naturally occurring porphyrins the order of effectiveness is protoporphyrin IX (dicarboxylic) greater than coproporphyrin (tetracarboxylic) greater than uroporphyrin (octacarboxylic) and type I greater than type III isomers of both uroporphyrin and coproporphyrin, and the synthetic tetra-meso-phenylporphinetetrasulphonate is a better inhibitor (apparent Ki = 250 nM) than coproporphyrin, which contains a comparable number of negative charges. In addition, iron-porphyrin chelates are more effective inhibitors of the transferases, with 25-fold decrease in Ki value, than the free porphyrins. These results indicate that one means whereby porphyrins accumulate in tissues is the occupation of intracellular binding sites, such as the transferases. Since porphyrins inhibit the activity of these important detoxifying enzymes, there will be metabolic consequences to the cell.
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PMID:Interactions with glutathione S-transferases of porphyrins used in photodynamic therapy and naturally occurring porphyrins. 405 30

Qualitative and quantitative changes in glutathione S-transferase (GSH-T) were studied in human hepatocellular carcinoma. GSH-T specific activity (mumoles per min per mg protein) was variably reduced in hepatocellular carcinoma. Similar changes were seen in "cationic" GSH-T (ligandin) concentration determined by radioimmunoassay. Immunohistochemical studies with antihuman liver ligandin suggest that positive staining was more frequently found in well-differentiated tumors. The relative activities of "cationic," "neutral," and "anionic" transferases (pI greater than 7.5) activity ranged from virtually absent to near normal values. "Neutral" (pI 6 to 6.5) and "anionic" (pI less than 5.4) species were present more often in tumors than in normal liver. In two cases, normal liver tissue and tumor were obtained from the same patient. In one, only quantitative differences were present, while in the other "cationic" and "neutral" GSH-Ts were present in the normal liver tissue while both "cationic" and "anionic" species were found in the tumor. Our studies indicate that qualitative as well as quantitative changes of GSH-T occur in human hepatocellular carcinoma.
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PMID:Glutathione S-transferase in human hepatocellular carcinoma. 618 52

Assay conditions of human liver glutathione S-transferase and its activity in human serum from liver disease patients were investigated. One mmol/l reduced glutathione, and 1 mmol/l-1-chloro-2,4-dinitrobenzene, pH 6.5, were used for the measurement, because of the very low non-enzymatic conjugation. Glutathione S-transferase activity was inhibited by bilirubin, but this inhibition was counteracted by the presence of a low concentration of albumin. The normal human serum glutathione S-transferase activity was 5.2 +/- 2.4 I.U./l (mean +/- S.D.), and was not influenced by any differences of age, sex or leukocyte count. A significant increase in serum enzyme activity was noted in cases of acute hepatitis with GPT exceeding 200 I.U./l, primary hepatoma and metastatic liver cancer. Some of the cases with fulminant hepatitis showed extremely high values. The degree of correlation between serum glutathione S-transferase and GOT or GPT was high in acute hepatitis, with GOT or GPT exceeding 200 I.U./l, in fulminant hepatitis, primary hepatoma and gall stones, while in chronic hepatitis and liver cirrhosis it was low. In cases of acute hepatitis and fulminant hepatitis, the disappearance of serum glutathione S-transferase from the blood was much faster than that of GOT and GPT. Serum glutathione S-transferase measurements will provide new and unique information for the diagnosis of acute liver diseases.
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PMID:Serum glutathione S-transferase activity in liver diseases. 625 85

Specific enzyme immunoassays for cationic and anionic glutathione S-transferases were established using the specific antibodies which were purified by antigen-bound adsorbent column chromatography. The enzyme immunoassay for cationic glutathione S-transferase had high specificity to cationic enzyme, but showed no cross reactivity with anionic one, and vice versa. The recovery of cationic glutathione S-transferase by the enzyme immunoassay was 94.7%, and coefficient of variation for within day and day-to-day precision were 7.8-10.4% and 8.5-12.5%, respectively. The enzyme immunoassay for anionic glutathione S-transferase also had a good recovery and precision. Using these enzyme immunoassays for glutathione S-transferases, sera of various patients were analyzed. Serum cationic glutathione S-transferase was increased in patients with hepatitis and hepatoma, and anionic glutathione S-transferase in serum was increased in patients with liver cirrhosis.
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PMID:Differential determination of cationic and anionic glutathione S-transferases by enzyme immunoassay. 637 45

A 39-kDa protein copurifies with the low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) and inhibits the binding and/or cellular uptake of ligands by this receptor. We recently utilized glutathione S-transferase (GST)-39-kDa fusion protein constructs to demonstrate that constructs encoding amino-terminal residues 1-114 and carboxy-terminal residues 115-319 of the 39-kDa protein independently bind to purified LRP and to LRP on hepatoma cells with similar affinities as the full-length GST-39-kDa protein (Kd approximately 8-10 nM). These regions, however, inhibit ligand binding to LRP differently: GST/1-114 inhibits both tissue-type plasminogen activator (t-PA) and alpha 2-macroglobulin-methylamine (alpha 2M*) binding whereas GST/115-319 only potently inhibits t-PA binding. Four domains, containing residues 18-24 and 100-107 within amino-terminal constructs and residues 200-225 and 311-319 within carboxy-terminal constructs, are required for inhibition of ligand binding. In the present study, we generated additional 39-kDa protein constructs to precisely define residues within each domain required for inhibition of t-PA and alpha 2M* binding to LRP. The potential importance of these residues in mediating direct binding both to purified LRP and to LRP on hepatoma cells was examined. Within amino-terminal residues 1-114, alanine 103 and leucine 104 are required for inhibition of t-PA and alpha 2M* binding. These residues, however, are not required for binding either to purified LRP or to LRP on hepatoma cells. Within domain 18-24, arginine 21 is required for inhibition of t-PA and alpha 2M* binding as well as for the direct binding of amino-terminal constructs to LRP. Within carboxy-terminal domains 200-225 and 311-319, leucine 222 and leucine 319 are both required for inhibition of t-PA binding. Deletion of leucine 319 changes the ligand specificity from inhibition of t-PA binding to inhibition of alpha 2M* binding. Thus, leucine 319 is not required for direct binding to LRP whereas leucine 222 is required for high-affinity binding to LRP.
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PMID:Sites within the 39-kDa protein important for regulating ligand binding to the low-density lipoprotein receptor-related protein. 753 37


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