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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of hexokinase between bound and soluble forms was studied by digitonin fractionation of Zajdela hepatoma ascites cells maintained under various metabolic conditions. Addition of glucose to Zajdela cells respiring on endogenous substrates induces an immediate inhibition of respiration by 50-60% ( Crabtree effect), and a production of acid due to glycolysis. Acid production decreases abruptly after 60s to 50% of the initial rate. The ATP/ADP ratio is not altered by the addition of glucose or by different rates of glycolysis. The uncoupling agent carbonyl cyanide m-chlorophenylhydrazone decreases the ATP/ADP ratio by 10-fold in cells respiring on endogenous substrate, but has little effect on cells oxidizing glucose. Rapid fractionation of the cells under these various metabolic conditions revealed no change in the distribution of hexokinase. Approx. 75% of hexokinase is bound in all cases, in contrast with lactate dehydrogenase, 95% of which was in the soluble form. Longer-term incubations (to 20 min) revealed only slight (10-15%) increases in soluble hexokinase in cells incubated with glucose. Various metabolic inhibitors had little additional affect on the subcellular distribution of hexokinase. Thus a rapid release of hexokinase from mitochondrial membrane is not a mechanism by which glycolysis is regulated in rapidly growing Zajdela hepatoma.
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PMID:Altered metabolic states do not change the intracellular distribution of hexokinase in Zajdela hepatoma ascites cells. 672 51

A brief treatment of H35 hepatoma cells with lysolecithin resulted in a cell population which is permeable to low-molecular weight charged molecules that cannot normally cross the plasma membrane. These include deoxynucleotide and nucleotide triphosphates, folyl and methotrexate polyglutamates, and trypan blue. As a result dTTP can be incorporated into the DNA of the permeable cells, providing the required nucleotides and deoxynucleotides are added to the medium. This result, combined with only a slight observed loss (20-25%) in total cell protein, lactate dehydrogenase (EC 1.1.1.27) activity and tyrosine aminotransferase (EC 2.6.1.5) activity, demonstrated that permeation of the cells does not extensively disrupt membrane integrity. Further support for this view comes from the fact that the permeable cells could seal when placed in enriched medium. The process of sealing was inhibited by cycloheximide and tunicamycin. The sealed cells, whose surfaces appeared identical to those of untreated cells by scanning electron microscopy, were fully capable of cell division when exposed to serum. Values for several other parameters, including dexamethasone-dependent tyrosine aminotransferase induction, thymidine incorporation into DNA, leucine incorporation into protein and folate coenzyme transport, supported the conclusion that sealed cells and untreated H35 cells have identical properties. Based on the characteristics of the permeable and sealed H35 cells, a discussion of the experimental potential of these preparations for studying macromolecular synthesis, investigating enzymes in situ and depleting cells of folate coenzymes is presented.
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PMID:Reversibly permeable hepatoma cells in culture. 717 28

Mouse teratocarcinoma cells (OTT6050) deficient for thymidine kinase were fused with rat hepatoma cells ( Fu5AH ) deficient for hypoxanthine phosphoribosyltransferase using inactivated Sendai virus. The hybrid cells were selected and cultured in the presence of HAT medium. A clonally established hybrid cell line ( As3 ), which in addition to its mouse genome contains several rat chromosomes, expresses rat specific enzyme variants and produces large primarily undifferentiated tumors, with some hepatoma characteristics in athymic nude mice. To reveal the in vivo developmental potential of these cells and to determine whether, under different experimental conditions, they are capable of participating in tissue differentiation, the As3 cells were injected into mouse blastocysts from the C57BL/6 strain. The experimental blastocysts were then transferred into the uteri of pseudopregnant foster mothers to allow further development. From a total of 212 blastocysts transplanted, 61 fetuses developed and were analysed for As3 contributions between the 10th and 18th day of gestation. Four fetuses at day 18 showed hybrid cell participation in their livers and a few organs of only endo-mesodermal origin, as judged from the presence of rat-specific enzyme variants. The enzymes were organ-specifically expressed (e.g., lactate dehydrogenase) or appeared newly during in situ differentiation while being absent in the original hybrid cells (e.g., glycerol-3-phosphate dehydrogenase). During short in vitro culture of the chimaeric organs, it was possible to select for the hybrid cells which reverted to an enzyme pattern simiar to but not identical with the As3 cell line and different to that observed in situ.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue preference and differentiation of malignant rat x mouse hybrid cells in chimaeric mouse fetuses. 718 53

Hepatocellular carcinoma (HC) is often difficult to distinguish from secondary liver neoplasia (SLN) by physical and imaging diagnostic procedures alone. To this aim we have extended and improved a laboratory approach based on a serum lactate dehydrogenase isoenzyme ratio (LD4:LD5) by adding the carcinoembryonic antigen: alpha-fetoprotein ratio, alkaline phosphatase, and serum iron concentrations to obtain a highly efficient discriminant function. In two successive cohorts, for a total of 102 patients, all histologically diagnosed, with a prevalence of HC vs SLN of 3:1, we correctly classified 96% of cases (100% of SLN cases). Subsequent verification with the jackknife reallocation statistical algorithm confirmed these results. In conclusion, this discriminant function based on simple laboratory assays of a few analytes is an important tool in solving a diagnostic dilemma in cases of liver neoplasia.
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PMID:Discriminant function based on serum analytes differentiates hepatocarcinoma from secondary liver neoplasia. 753 73

We have developed a new multienzyme control serum, Seraclear-HE, which was designed to function not only as an accuracy and precision control serum but also as an intermethod calibrator for unifying interlaboratory clinical enzyme data in terms of reference method values. Seraclear-HE contains as analytes the following enzymes of human origin only: aspartate aminotransferase (AST, EC 2.6.1.1) and lactate dehydrogenase (LD, EC 1.1.1.27) from erythrocytes; alanine aminotransferase (ALT, EC 2.6.1.2) from a hepatoma cell line; alkaline phosphatase (ALP, EC 3.1.3.1) from an amnion cell line; creatine kinase (CK, EC 2.7.3.2) from an embryo kidney cell line; gamma-glutamyltransferase (GGT, EC 2.3.2.2) from a macrophage cell line; and amylase (AMY, EC 3.2.1.1) from urine and saliva. The seven partly purified enzymes were lyophilized in partially delipidated human serum containing sucrose (50 g/L), pyridoxal 5'-phosphate (30 mmol/L), and other stabilizers. The material is stable for at least 2 years at temperatures < or = 10 degrees C. For two concentrations of this preparation, reference method values (mainly International Federation of Clinical Chemistry and Japan Society of Clinical Chemistry) obtained at both 30 degrees C and 37 degrees C are assigned.
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PMID:Multienzyme control serum (Seraclear-HE) containing human enzymes from established cell lines and other sources. 1: Preparation and properties. 753 43

gamma-Glutamyl hydrolase is a ubiquitous enzyme that has the capacity to cleave gamma-glutamyl bonds of cellular folyl- and antifolylpoly-gamma-glutamates. This study has revealed that the enzyme is secreted by primary cultures of rat hepatocytes and by H35 hepatoma cells. It was found that more than 99% of the total enzyme from H35 cells accumulated in the medium after 48 hr incubation with the serum-free medium. The cells were shown to remain intact during the secretion period since lactate dehydrogenase, dihydrofolate reductase and lysosomal hydrolases other than gamma-glutamyl hydrolase were retained within the cell. When PteGlu5 (folylGlu4) is used as a substrate the initial product is PteGlu (folate), and there is no appearance of intermediate chain length pteroyl polyglutamates. Therefore, the secreted and cellular gamma-glutamyl hydrolase from hepatoma cells appears to be an endopeptidase. Polyclonal antibodies to the poly-gamma-glutamate substrates of the enzyme were prepared and characterized. The antibodies recognize the structural differences between alpha- and gamma-glutamyl linkages but appear equally active with PteGlu5 and its analogs such as 4-NH2-10-CH3PteGlu5 and pABAGlu5. The affinity of the antibodies is related to the gamma-glutamyl structure since L-glutamic acid, folate or p-aminobenzoic acid are inactive with the antibodies. Furthermore, poly-gamma-glutamate has lower affinity for the antibodies than the poly-gamma-glutamate derivatives of PteGlu, 4-NH2-10-CH3PteGlu or pABA.
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PMID:The properties and function of gamma-glutamyl hydrolase and poly-gamma-glutamate. 768 89

A transformed human hepatoma cell line was examined to determine if it was an appropriate model system for studying the mechanism of action of two peroxisome proliferators that lower blood lipids. Cultures of HepG2 cells were exposed to four different concentrations of either the hypolipidemic drug, clofibric acid (CLO), or the adrenal steroid, dehydroepiandrosterone (DHEA). Activities of two peroxisomal enzymes, palmitoyl-CoA oxidase and catalase, and two mitochondrial enzymes, carnitine palmitoyl-CoA transferase and succinate-INT-reductase, were measured in CLO- and DHEA-treated cells. In general, as the concentration of these hypolipidemic agents increased from 0 to 1000 microM, the specific activities of peroxisomal palmitoyl-CoA oxidase and catalase increased, and mitochondrial carnitine palmitoyl-CoA transferase and succinate-INT-reductase decreased. The activity of lactate dehydrogenase was significantly higher in the medium of cultures exposed to the 500 and 1000 microM concentration of DHEA compared with the control cultures, indicating the cytotoxic effects of this steroid at millimolar levels in vitro. In summary, the peroxisomal proliferators, DHEA and CLO, inversely altered peroxisomal and mitochondrial beta-oxidation in HepG2 cultures, but not to the extent reported for rat hepatocytes in vitro. In vitro concentrations of DHEA greater than 500 microM adversely affected the viability of HepG2 cells. The results of this study suggest that beta-oxidation in this human hepatoma cell line may not be as sensitive to hypolipidemic agents as are primary cultures of rat hepatocytes.
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PMID:Inverse relationship between peroxisomal and mitochondrial beta-oxidation in HepG2 cells treated with dehydroepiandrosterone and clofibric acid. 770 Aug 86

The accumulation process of copper (Cu) in the liver and the following metabolic disorder of Cu were examined in LEC rats, a mutant strain which accumulates Cu with age and shows spontaneous acute hepatitis and/or hepatoma. Cu concentration in the liver of female rats was approximately 220 micrograms/g liver at 2 weeks of age, decreased to 100 micrograms/g liver at 4-6 weeks, and then started to increase with age linearly to the highest concentration of 250 micrograms/g liver at 16 weeks. Although the Cu level expressed by concentration (microgram/g liver) decreased during weaning, it increased linearly with age when it was expressed by content (mg/liver), indicating a constant and preferential accumulation of Cu in the liver. Cu concentration stopped increasing at 16 weeks in the liver, followed by a sudden decrease to 1/2 the highest level. Biological markers (serum lactate dehydrogenase and glutamic-oxaloacetic transaminase activities) for liver damage started to increase, together with the appearance of signs of jaundice, when Cu attained the highest concentration. Distributions of Cu and zinc (Zn) in the supernatant fraction of the liver indicated that both metals were mostly distributed to metallothionein (MT) and, to a small extent, to superoxide dismutase on a gel filtration column throughout the course of the experiments. Serum Cu concentration started to increase in a form of ceruloplasmin, together with serum marker enzyme activities for liver damage. Cu concentration in the kidneys also started to increase after the increase of serum Cu. The results indicate that Cu accumulates in the form of MT in the liver of LEC rats to a maximum level of approximately 250 micrograms/g liver, and then decreases suddenly with the onset of acute hepatitis. The maximum level seems to be related to the capacity of MT synthesis, and acute hepatitis is assumed to occur when Cu accumulates beyond the capacity. Serum Cu started to increase, from the abnormally low level, when the metal accumulated beyond the capacity of MT synthesis in the liver, and it was partly reabsorbed by the kidneys and the rest was excreted into urine. Changes in iron and zinc levels were determined and discussed in relation to those of Cu.
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PMID:Copper metabolism leading to and following acute hepatitis in LEC rats. 771 95

A hitherto unreported lactate dehydrogenase (LD) isoenzyme, which migrates electrophoretically to the relative position between LD2 and LD3 has been identified in the electropheratogram in 7 of 7 (100%) cultured hepatoma cell lines with various degrees of differentiation and is thus given the name LD2-3. LD2-3 seems to be specific for hepatoma cells because this atypical isoenzyme can not be detected in other tumor cell lines. In addition, the hepatoma cell lines also show a distinct pattern of LD isoenzyme and the isoenzyme pattern varies with the degree of differentiation. Hence, the expression pattern of LD isoenzyme phenotypes may provide a good marker for the investigation of human hepatoma cell differentiation.
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PMID:Detection of a novel lactate dehydrogenase isozyme and an apparent differentiation-associated shift in isozyme profile in hepatoma cell lines. 781 40

Liver cells, isolated from male Sprague-Dawley rats and established in primary culture, were treated with a dose of 180 pmol aflatoxin B1 (AFB1) for 2 hr. Reticuloendothelial nonparenchymal cells (NPC) metabolized a total of 28% of the AFB1. In contrast, parenchymal epithelial cells or hepatocytes (HC) were highly efficient in conjugating AFB1 to water-soluble products (50-70% of the dose) but also bound a large proportion (27%) of the toxin to cellular macromolecules. In comparison to NPC, HC bound 90-fold more AFB1 per cell. Cytotoxicity in primary cultures was evaluated by changes in membrane integrity (lactate dehydrogenase release), inhibition of glutathione-S-transferase activity and cell monolayer morphology over a range of AFB1 doses. No response was detected in NPC, whereas HC exhibited dose-related cytotoxic responses to AFB1. In rat liver both cell types form AFB1-DNA adducts in a dose-dependent fashion and yet only epithelial cell carcinomas have been observed in whole animal studies. The possibility that cell-specific AFB1 cytotoxicity produces a promotional stimulus for hepatocellular carcinoma is discussed.
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PMID:Metabolism and cytotoxicity of aflatoxin B1 in cultured rat hepatocytes and nonparenchymal cells: implications for tumorigenesis. 797 99


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