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 effects of oral fructose on hepatocarcinogenesis were investigated with cytomorphological, cytochemical and stereological methods. Carcinogenesis was induced in male Sprague-Dawley rats by application of N-nitrosomorpholine (NNM) for 7 weeks. Afterwards, the animals received fructose in the drinking water (120 g/l) and food ad libitum (group I) or tap water and food ad libitum (group II). The incidence of hepatocellular carcinoma in rats treated with NNM plus fructose was 46% as compared to 24% in animals receiving NNM alone (P less than 0.05). There was no difference in the incidences of other malignancies between the groups (group I: 32.1%, group II: 32.0%). Morphometric evaluation of preneoplastic liver lesions indicated the enhancing effect of the fructose treatment several months before malignant tumors appeared. As early as 6 weeks after treatment the hepatic parenchyma occupied by focal lesions was increased from 6.7% in the animals which had received NNM alone to 8.5% (P less than 0.05) in animals having received NNM plus fructose. This increase was predominantly caused by an increase in glycogen storing foci (P less than 0.0005). In addition, the fructose treatment caused a histochemically detectable increase in the activity of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase in both the hepatocytes of the focal lesions and the surrounding parenchyma. In the NNM plus fructose group the activity of the glucose-6-phosphatase in the foci was frequently approximately equal to the activity in the parenchyma of untreated controls. The striking increase in the activity of this enzyme in the surrounding hepatocytes, however, still sharply demarcated the lesions. The potential mechanisms by which fructose enhances hepatocarcinogenesis are discussed.
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PMID:Enhancement of hepatocarcinogenesis in rats by dietary fructose. 256 39

Activities of key carbohydrate-metabolizing enzymes in biopsied human tissues of hepatocellular carcinoma and related conditions were determined by established methods. Among the enzymes analyzed, fetal-type liver enzymes (low-Km hexokinase, glucose 6-phosphate dehydrogenase, and pyruvate kinase-M2) showed increased activities, and adult-type liver enzymes [glucose 6-phosphatase, fructose 1,6-bisphosphatase, high-Km hexokinase (or glucokinase), and pyruvate kinase-L] showed decreased activities, resulting in undifferentiated enzyme patterns not only in fetal livers and hepatocellular carcinomas but also in livers of acute and chronic hepatitis and liver cirrhosis with or without tumors. Hepatocellular carcinomas showed a general tendency of having greater enzyme deviations than hepatitic and cirrhotic livers. The extent of the enzyme deviation in hepatocellular carcinomas varied considerably from one enzyme to another for each tumor tissue as compared with that in the benign liver diseases. Thus, the phenotypic heterogeneity was important for discriminating between the neoplastic and inflammatory changes in differentiation markers. The enzyme patterns of tumors and their corresponding host cirrhotic livers were unrelated, suggesting that the cirrhotic liver has a significance as preneoplastic state only in terms of having a high incidence of evolving hepatocellular carcinoma.
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PMID:Profiles of carbohydrate-metabolizing enzymes in human hepatocellular carcinomas and preneoplastic livers. 282 76

Segregation of the X-linked mink markers alpha-galactosidase (GLA), phosphoglycerate kinase-1 (PGK1), hypoxanthine phosphoribosyltransferase (HPRT), and glucose-6-phosphate dehydrogenase (G6PD) was analyzed in hybrids of gamma-irradiated mink fibroblasts and Chinese hamster cells and in hybrids of nonirradiated mink fibroblasts and mouse hepatoma cells. Based on this analysis, the order of the four genes is GLA-PGK1-HPRT-G6PD on the mink X chromosome. Cytogenetic analysis of five mink x Chinese hamster hybrid clones containing mink GLA, PGK1, and HPRT, but lacking G6PD, tentatively localized mink G6PD to Xq15.22----qter and also confirmed the gene order as GLA-PGK1-HPRT-G6PD-qter. Comparison of this order with its counterpart in man and the mouse, as well as an analysis of the G-band patterns of their X chromosomes, demonstrated putative similarities between mink and man and differences in the mouse. These differences may be due to a different rate of X-chromosomal rearrangement in mammalian evolution.
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PMID:Subchromosomal localization and order of GLA, PGK1, HPRT, and G6PD loci on the X chromosome of the American mink (Mustela vison). 284 37

Some aspects of carbohydrate metabolism were investigated in three non-malignant, glycogen storing, cell lines derived from a primary culture of rat hepatocytes, and in the Morris hepatoma 3924 cells. The three cell lines show biochemical alterations which are, to a large extent, similar to those found in the hepatoma cells: increased activity of glycolytic enzymes and decreased activity of gluconeogenetic enzymes. An increase of glucose-6-phosphate dehydrogenase activity is also found. The three cell lines, as the Morris hepatoma cells, actively convert glucose into lactate under the in vitro conditions of culture. Fructose is not taken up as quickly as glucose and galactose is not metabolized. As compared with normal hepatocytes, the three cell lines have altered metabolism and growth behaviour. They largely resemble the preneoplastic cells appearing in rat liver at the early stages of experimental carcinogenesis.
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PMID:Study of carbohydrate metabolism in glycogen storing cell lines derived from cultured rat hepatocytes. 298 18

The X-chromosome-linked glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP+ oxidoreductase, EC 1.1.1.49) of humans and other mammals consists of a subunit with a molecular weight of about 58,000. The enzyme plays a key role in the generation of NADPH, particularly in matured erythrocytes, and the genetic deficiency of the enzyme is associated with chronic and drug- or food-induced hemolytic anemia in humans. The enzyme was purified to homogeneity from human erythrocytes. The complete amino acid sequence of the subunit, consisting of 531 amino acid residues, was determined by automated and manual Edman degradation of tryptic, chymotryptic, thermolytic, and cyanogen bromide peptides obtained from the enzyme. Based on the amino acid sequence data thus obtained, a 41-mer oligonucleotide with unique sequence was prepared. Two cDNA libraries constructed in phage lambda gt11--i.e., a human liver cDNA library and a human hepatoma Li-7 cDNA library--were screened with the synthetic nucleotide probe. Two positive clones, lambda G6PD-19 and lambda G6PD-25, were obtained from the hepatoma library. lambda G6PD-19 contained an insertion of 2.0 kilobase pairs (kbp), and encoded 204 amino acid residues that were completely compatible with the COOH-terminal portion of the enzyme. The insertion of the clone had a 3' noncoding region of 1.36 kbp. The other clone, lambda G6PD-25, had an insertion of 1.8 kbp and encoded 362 amino acid residues of G6PD. Southern blot analysis of DNA samples obtained from cells with and without the human X chromosome indicated that the cDNA hybridizes with a sequence in the X chromosome.
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PMID:Human glucose-6-phosphate dehydrogenase: primary structure and cDNA cloning. 301 56

Monoclonal antibodies that immunoprecipitate human monoamine oxidase (MAO) A or human MAO B, but not the corresponding mouse enzymes, were used to assay for the presence of immunoprecipitable MAO A or MAO B (presumably coded by the respective human genes) in mouse-human hybrid somatic cell lines containing small numbers of human chromosomes. The results were as follow: Extracts of a human lymphoblastoid x mouse hepatoma hybrid line that retained the human X chromosome contained immunoprecipitable MAO B, while a similar hybrid line that contained the same human chromosomes, except for the human X, did not. Extracts of a human fibroblast x mouse neuroblastoma hybrid cell line, whose human chromosomal material consisted solely of the X, contained both immunoprecipitable MAO A and MAO B. Extracts of a related hybrid line, whose human chromosomal material consisted solely of an autonomous fragment and a fragment translocated to a mouse chromosome, contained immunoprecipitable MAO A. However, the level of immunoprecipitable MAO B activity in extracts of this hybrid was low or undetectable. Among extracts of 33 human fibroblast x mouse hepatoma hybrids that had been selected for expression of the X-linked human enzyme HPRT, 60% contained immunoprecipitable MAO B. This figure was comparable to the 58% that expressed the X-linked human isozyme for glucose-6-phosphate dehydrogenase (G6PD). When 11 of these hybrid lines, which contained immunoprecipitable MAO B and human HPRT, were selected for loss of HPRT, all lost immunoprecipitable MAO B in addition to HPRT. These data demonstrate that genes controlling the expression of MAO A and MAO B, which can be immunoprecipitated with the human-specific monoclonal antibodies, are located on the human X chromosome. Properties of the immunological epitopes recognized by the monoclonal antibodies suggest that the X-linked genes detected in this study are probably structural genes for the enzymes.
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PMID:Assignment of genes for human monoamine oxidases A and B to the X chromosome. 354 Mar 17

Fusion of hypoxanthine phosphoribosyltransferase (HPRT)(-) rat hepatoma cells with HPRT(+) human fibroblasts yielded hybrid clones that grew in HAT selective medium and contained all the rat chromosomes and one to nine human chromosomes. Among the retained chromosomes was the human X chromosome. In all clones backselected in medium containing 8-azaguanine, human X chromosome was absent. Electrophoretic analysis revealed that, without exception, hybrid clones growing in HAT medium had an active HPRT enzyme, either human or rat, or both. When these clones were backselected in 8-azaguanine, they did not show HPRT enzyme activity. Hybrids that contained the human X chromosome also had human glucose-6-phosphate dehydrogenase. The observed reexpression of rat HPRT in hybrid cells derived from HPRT(-) rat cells suggests that a genetic factor from the human cell determined the expression of the rat structural gene for HPRT.
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PMID:Reexpression of the rat hypoxanthine phosphoribosyltransferase gene in rat-human hybrids. 435 57

Growth of cultured rat hepatoma cells in the presence of 5-bromodeoxyuridine results in a rapid inhibition of the synthesis of adrenal steroid-inducible tyrosine aminotransferase (EC 2.6.1.5) and slower decreases in the concentrations of lactate dehydrogenase (EC 1.1.1.27), alcohol dehydrogenase (EC.1.1.1.1), and glucose-6-phosphate dehydrogenase (EC 1.1.1.49). During the same period, neither overall cell growth nor the concentrations of malate dehydrogenase (EC 1.1.1.37), acid phosphatase (EC 3.1.3.2), or alanine aminotransferase (EC 2.6.1.2) were significantly decreased by the base analog. Addition of thymidine to the growth medium rapidly counteracts the inhibition of tyrosine aminotransferase synthesis but restores the normal concentrations of lactate-, alcohol-, and glucose-6-phosphate dehydrogenases much more slowly. Growth of the cells for only one generation in the presence of bromodeoxyuridine, followed by the addition of thymidine, produces transient decreases in the concentrations of the three "late-responding" dehydrogenases, beginning 2-3 generations after exposure to the analog.It is concluded that the selective inhibitory effects of the analog could result from a mechanism in which bromodeoxyuridine is uniformly incorporated into cellular DNA, but inhibits the transcription of only certain genes into messenger RNA. A mathematical model is derived to account for the observed differences in the kinetics of the inhibition of synthesis of the gene products that are sensitive to the analog.
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PMID:Differential effect of 5-bromodeoxyuridine on the concentrations of specific enzymes in hepatoma cells in culture. 439 42

Two X-linked genes, specifying ornithine transcarbamoylase (OTC) and glucose-6-phosphate dehydrogenase (Glc-6-PD), are reversibly suppressed in certain derivatives of the rat H4-II-E hepatoma. Either gene can become reactivated spontaneously, and it is shown that both can be reactivated by azacytidine treatment. This gene reactivation has been investigated by enzyme assay and by the use of selective growth media ('ornithine-medium' to select for OTC, and medium containing diamide to select for Glc-6-PD). There is a clear tendency for both genes to be reactivated together, though either can become active alone. Since OTC is an enzyme of the urea-cycle, and Glc-6-PD is an enzyme of the hexose monophosphate shunt, and since these two pathways are normally under quite separate control, it would seem that the coupled regulation of the two genes in these hepatomas is abnormal. It is suggested that the suppression of the two genes resembles X-inactivation: in both cases, azacytidine treatment induces gene reactivation with a high frequency and results in different clones of cells expressing widely varying amounts of enzyme activity. The association between the re-expression of OTC and Glc-6-PD might indicate that some phenomenon like the position-effect is occurring.
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PMID:The associated reactivation of two X-linked genes. The spontaneous and azacytidine-induced reexpression of ornithine transcarbamoylase and glucose-6-phosphate dehydrogenase in a rat hepatoma. 608 29

The activities of key enzymes of glycolysis and of the glucose shunt as well as the capacity of lactic acid formation were determined in the high-speed tissue supernatant of the transplantable Albert hepatoma of mouse [originally produced by oral application of chrysoidin (2,4-diaminoazobenzene) on C57 Black mice]. Furthermore, the particle-bound hexokinase activity was determined. The following results were obtained: In the hepatoma the activities of aldolase, pyruvate kinase and lactic dehydrogenase are hardly altered compared with normal liver. The activities of hexokinase and phosphofructokinase are increased 2,5-fold, those of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase 2-fold. The capacity for lactic acid formation from glucose is 7 times as high in the hepatoma supernatant. Strong differences emerge from the liver-to-hepatoma relationship in terms of intracellular distribution of the hexokinase (total homogenate 1 : 5, supernatant 1 : 2,5 and particle-bound hexokinase activity 1 : 18). A summarizing consideration of all the results obtained so far for the Albert hepatoma shows that this malignoma departss in several biochemical parameters from the "Molecular Correlation Concept" maintained by Weber, providing more evidence for the individuality of tumors.
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PMID:[Activities of several enzymes of glycolysis and of the glucose shunt in the Albert hepatoma of mouse (author's transl)]. 625 66


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