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 identification of biological "markers" indicating distinctively different functions between preneoplastic and neoplastic as compared with normal cells has been a subject of intensive investigation, especially as additional technology becomes available. Although no distinct single biochemical marker is ubiquitous to the process of neoplasia or even to a single histogenetic type of neoplasm, a variety of histogenetic types of neoplasms in the human and experimental animals exhibit an extreme degree of marker or phenotypic heterogeneity. Particularly well studied are markers which occurred during the process of hepatocarcinogenesis in the rodent as well as in its final product, the hepatoma. Although phenotypic heterogeneity is characteristic of hepatocellular carcinomas in both the rat and mouse, some degree of predominant marker pattern(s) has become apparent. In multistage hepatocarcinogenesis in the rat a frequent but not completely ubiquitous marker is the enzyme gamma-glutamyltranspeptidase. In the mouse, although such markers have not been as extensively studied as in the rat, glucose 6-phosphatase is a predominant but not exclusive histochemical marker. Many preneoplastic lesions occurring during the stage of promotion exhibit reduced levels of enzymes of oxidative xenobiotic metabolism, but this pattern is not ubiquitous. Studies on the transcription of specific genes in mouse liver as well as preneoplastic and neoplastic lesions in this tissue further demonstrate the phenotypic heterogeneity characteristic of differentiated hepatocellular carcinomas. In general, current evidence supports the two theses that no single biologic marker or set of markers is uniquely characteristic of the preneoplastical and/or neoplastic phenotype and marker or phenotypic heterogeneity is by far the rule rather than the exception in hepatocarcinogenesis in the rodent and quite possibly in all histogenetic types of neoplasms in mammals.
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PMID:Biological markers characterizing the development of preneoplastic and neoplastic lesions in rodent liver. 288 60

A solid phase enzyme-linked immunosorbent assay for human immunoreactive gamma-glutamyltranspeptidase(gamma-GTP) was developed. The working range by this assay was from 1 ng to 100 ng. Serum immunoreactive gamma-GTP was significantly elevated in patient with hepatocellular carcinoma and moderate elevation was found in liver cirrhosis. On the other hand, in sera of patients with non neoplastic disease, including acute hepatitis, chronic hepatitis, fatty liver, hemangioma, the immunoreactive gamma-GTP was not significantly elevated. No correlation was found between the serum levels of gamma-GTP determined by enzymatic assay and enzyme-linked immunosorbent assay. In the tissues of hepatocellular carcinoma and metastatic liver tumor, the immunoreactive gamma-GTP contents were also elevated, which were well correlated with the enzyme contents in sera. When immunohistochemical study was carried out, the immunoreactive gamma-GTP was detected diffusely not only in the cell membrane and bile canaliculi but also in the cytoplasm of cancer cell. These results suggest that the hepatoma tissues contain an immunologically active, but enzymatically inactive form of gamma-GTP enzyme.
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PMID:[Measurement of human serum and liver tissue immunoreactive gamma-glutamyl transpeptidase in patients with various liver diseases]. 289 51

Tumorigenicity and oncogene expression were examined in HepG2 derived cells, a human hepatoma cell line. HepG2 cells and a single cell clonal HepG2 line, HLD2-6, were equally tumorigenic when injected s.c. into athymic nude mice. Cyclophosphamide pretreatment of both cell lines (500 micrograms cyclophosphamide/ml/two cell cycles) had no effect on tumor incidence or latency (P greater than 0.05). Tumors were nonencapsulated, highly invasive adenocarcinomas and were positive for gamma-glutamyltranspeptidase activity and bile production. Plasma from tumor-bearing mice was positive for human alpha-fetoprotein and negative for hepatitis B virus surface antigen as measured by radioimmunoassay. Two cell lines reestablished into tissue culture from HLD2-6 derived tumors had unaltered cell cycle times. Detailed in vitro translation analysis of RNA isolated from HLD2-6 derived cells and tumors were extremely similar to the translation products of RNA isolated from a normal human liver sample except for a Mr 53,000 polypeptide with an apparent charge shift. c-myc specific transcripts, when compared to a normal human liver sample, were increased in all HLD2-6 cell lines and tumors derived from HLD2-6 cells. This increase in c-myc expression could not be explained by gene amplification or hepatitis B virus integration. N-ras specific transcripts were not elevated in HLD2-6 cells grown in tissue culture but there was a selective increase of the 5.5-kilobase N-ras transcript in HLD2-6 derived tumors grown in nude mice. This increased 5.5-kilobase transcript did not remain elevated if the tumors were reestablished into tissue culture, suggesting some interaction with the host animal. c-Ha-ras expression could not be detected in any HLD2-6 derived tumor or cell line.
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PMID:Tumorigenicity and transcriptional modulation of c-myc and N-ras oncogenes in a human hepatoma cell line. 299 77

In diethylnitrosamine-initiated rats, administration of clofibrate for 32 weeks induced neoplastic lesions and hepatocellular carcinoma. In contrast to conventional carcinogens, clofibrate effected a marked decrease in the activity of gamma-glutamyltranspeptidase. Ornithine was selectively channeled into polyamine synthesis with concomitant repression of the urea cycle and the transamination pathway. These histological and biochemical studies suggest that clofibrate acts as a promoting agent in hepatocarcinogenesis.
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PMID:Hypolipidemic drug clofibrate promotes hepatic tumor. 324 Mar 12

Characteristic and patterns of gamma-glutamyltranspeptidase (GGT) expression were studied in four rat and three human hepatoma cell lines. Phenotypic diversity of GGT expression was demonstrated by the following findings. (a) GGT specific activity increased rapidly in three of four rat lines during the first 72 hr after subculture. (b) GGT activity was detected in the fourth rat cell line only from 96 to 120 hr after subculture. (c) In late log or stationary cultures, each of the four rat lines assumed a unique and characteristic level of GGT specific activity. (d) The intracellular GGT distribution pattern was markedly varied in rat and human cell lines. (e) GGT activity was confined to isolated cell clusters in one human line in vitro and one rat line both in vivo and in vitro. And (f) there was poor correlation between GGT specific activity and several liver-associated and hepatoma-associated properties. In contrast to evidence of diversity in GGT expression, GGT was shown to be a nonsecreted protein in all four rat cell lines. The constitutive or autogenous nature of the GGT phenotype in rat hepatoma cells was demonstrated by the retention of the GGT-positive and GGT-negative phenotypes of two strains grown in mixed culture; the lack of change in GGT activity when cells were cultured on different substrata, in different media, or in media containing hormones (insulin, dexamethasone, triiodothyronine, or glucagon); and the assumption of nearly constant levels of GGT specific activity in late log or stationary cultures. The results suggest that GGT activity is expressed in hepatomas as a result of disturbed differentiation and that this expression is not necessarily linked to cell proliferation.
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PMID:Phenotypic diversity of gamma-glutamyltranspeptidase activity and protein secretion in hepatoma cell lines. 612 Jul 61

In inbred Wistar rats bearing transplantable hepatoma induced by aflatoxin B1 tissue porphyrins and the level of the serum gamma-glutamyltranspeptidase (GGTP) were studied. A liver reaction in carriers of transplants was ascertained, that was expressed especially by an increase in porphyrins, mainly the protoporphyrin fraction, and by morphological changes. The content of porphyrins in lung metastases was higher than in hepatomas and livers. The level of serum GGTP was higher in females up to the 40th passage, and up to the 90th passage higher in males. Hormonal conditioning of the early AFB1-hepatoma passages is supported by a lower level of serum GGTP in females and higher in males, and the liver and tumor porphyrins in animals previously castrated in comparison with uncastrated rats. Comparative data of the quantity and quality of porphyrins in different rat tissues with primary and transplantable AFB1-hepatomas demonstrate that systemic metabolic disorders of porphyrins are greater in rats with primary than in the case of transplantable tumors.
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PMID:The particular traits of carcinogenesis induced in Wistar rats by aflatoxin B1. IV. Porphyrins and the activity of gamma-glutamyltranspeptidase in Wistar rats bearing transplantable hepatoma. 613 86

A comparative study using hydrazinolysis has revealed that the oligosaccharide pattern of gamma-glutamyltranspeptidase purified from rat AH-66 hepatoma cells is very different from that of the enzyme from rat liver. Studies of oligosaccharides in each fraction have clarified the structural basis of the difference found in the sugar chains of the two enzymes. The sugar chains of the liver enzyme were all acidic, while 28% of those of the hepatoma enzyme were neutral, the latter being composed of high-man-nose-type and complex-type sugar chains. Three prominent structural differences were found in the acidic sugar chains of the two enzymes: (a) the sugar chains of the liver enzyme have complete outer chains, Gal beta 1 leads to 4GlcNAc beta 1 leads to, while many of those of the hepatoma enzyme have incomplete outer chains without galactose (Gal); (b) the Gal beta 1 leads to 4GlcNAc beta 1 leads to Gal beta 1 leads to 4GlcNAc beta 1 leads to group is found in the sugar chains of the liver enzyme but not in those of the hepatoma enzyme; (c) more than 40% of the sugar chains of the hepatoma enzyme contain bisect N-acetylglucosamine (GlcNAc) residue which is not found in those of the liver enzyme. Furthermore, the total number of asparagine-linked sugar chains in one molecule of hepatoma enzyme was about 4 times that found in one molecule of liver enzyme.
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PMID:Comparative study of the sugar chains of gamma-glutamyltranspeptidases purified from rat liver and rat AH-66 hepatoma cells. 613 77

Gamma glutamyltransferase (GGT) is a membrane-bound enzyme that is involved in glutathione metabolism and aminoacids uptake. GGT activity is stimulated by a number of hormones and pharmacological agents in certain animal tissues. In rat liver, adrenalectomy causes a 2-fold decrease in GGT activity and hydrocortisone treatment of adrenalectomized animals specifically stimulates this enzyme activity. In a highly differentiated hepatoma cell line, Fao, GGT activity is similar to rat liver and is under glucocorticoids control. These hormones specifically stimulate GGT activity (2- to 3-fold). Translation and transcription inhibitors prevent the hormonal effect. The stimulation of GGT activity is therefore probably due to an increase in GGT mRNA synthesis. The results reported suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of both the glucocorticoid effects on differentiated cells as well as the modulation of membrane-bound enzymes biosynthesis.
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PMID:The hormonal induction of gamma glutamyltransferase in rat liver and in a hepatoma cell line. 613 63

Studies were made on the effects of butylated hydroxyanisole (BHA), ethoxyquin (EQ) and acetaminophen (AAP) on the induction of neoplastic lesions in the liver and kidney of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, EQ or AAP were significantly less than in rats given EHEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. No liver lesions were found in any animals given BHA, EQ or AAP orally without EHEN. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma were significantly increased in groups given BHA, EQ or AAP. The results clearly demonstrated that BHA, EQ and AAP inhibited the development of gamma-GT+ foci, HN and HCC, whereas they enhanced the appearance of preneoplastic and neoplastic lesions in the kidney.
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PMID:Modifying effects of butylated hydroxyanisole, ethoxyquin and acetaminophen on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine. 614 74

Studies were made on the effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium L-ascorbate (SA), ethoxyquin (EQ) and acetaminophen (AAF) on the induction of neoplastic lesions in the liver, kidney or urinary bladder of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN), diethylnitrosamine (DEN) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, BHT, EQ or AAP, but not SA, were significantly less than in rats given EHEN or DEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma in the group given EHEN were significantly increased in groups given BHA, EQ or AAP administration. For assesing the influence of BHA and BHT on urinary bladder carcinogenesis, rats received BHA or BHT after treatment with BBN. The incidences and the number per unit length of basement membrane of papilloma and carcinomas were significantly increased in rats given BHA. BHT also showed significant increase but values were less than with BHA. These results clearly demonstrated that BHA, BHT, EQ and AAP inhibit the development of gamma-GT+ foci, or HN and HCC, whereas BHA, EQ and AAP enhance the appearance of preneoplastic and neoplastic lesions in the kidney, BHA and BHT also enhancing urinary bladder carcinogenesis.
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PMID:Modification of carcinogenesis by antioxidants and other compounds. 614 34


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