UMLS:C0019204 - FACTA Search

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

Cytosolic pyruvate kinase fractions A and B obtained by salting out procedure from normal rat liver and Morris hepatoma 7777, purified by affinity chromatography on Blue Sepharose CL-6B, have shown similar electrophoretic patterns in polyacrylamide gel at pH 8.3 to previously studied pyruvate kinase extracts from chromatin of cell nuclei. Three variants (alpha 1, beta 1, gamma 1) from normal rat liver pyruvate kinase fraction A (type L) had the greatest electrophoretic mobility, showed sigmoidal kinetics in relation to 2-phosphoenolpyruvate (PEP), and sensitivity to ATP and fructose 1,6-diphosphate (FDP). The fraction A dominated over normal liver fraction B (type M2), which in electrophoresis showed a slower gamma 2 variant, similar to the fraction A of hepatoma. All variants from fractions B of normal liver and A of hepatoma had linear kinetics and were sensitive to ATP but not to FDP. The greatest differences showed pyruvate kinase fraction B from Morris hepatoma. Its all variants alpha 2, beta 2, gamma 3 were cathodic and had linear kinetics in relation to PEP. They all were insensitive to normal signal molecules (ATP and FDP). The gamma 3 alkaline variant acquired sensitivity to inhibition by L-cysteine. Showing several-fold higher activity, much greater affinity to the main substrate, and a lack of sensitivity to feed-back inhibition by ATP, it was responsible for a high rate of aerobic glycolysis and diminution of the Pasteur effect in metabolic studies. It was probably encoded during oncogene activation and plays a special role in different metabolic strategies of tumour cells.
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PMID:Electrophoretic pattern of cytosolic pyruvate kinase fractions A and B (type L and M2) from normal rat liver and Morris hepatoma 7777. 854 55

To discover a new phospholipase C (PLC) related to cell growth, we screened a cDNA library prepared from regenerating rat liver. A novel PLC (PLC delta 4) encoding a polypeptide of 770 amino acids with structural similarity to PLC delta-type isozymes was isolated. PLC delta 4 mRNA is expressed more remarkably in regenerating liver than in normal resting liver. It is also distributed abundantly in tumor cells such as hepatoma and src-transformed cells. Furthermore, its expression can be induced markedly by serum treatment and reaches a maximum at 8 h. Western blot analysis and immunocytochemical staining showed that PLC delta 4 is dominantly present in nucleus. Nuclear PLC delta 4 dramatically increases at the transition from G1- to S-phase, and the high content continues to the end of M-phase. PLC delta 4 almost disappears when cells re-enter the next G1-phase. On the other hand, the contents of PLC beta 1, PLC gamma 1, and PLC delta 1 do not change significantly during the cell cycle. These results suggest that PLC delta 4 is expressed in nucleus in response to mitogenic stimulation and plays important roles in cell growth as one of the early genes expressed during the transition from G1- to S-phase in the cell cycle.
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PMID:A new phospholipase C delta 4 is induced at S-phase of the cell cycle and appears in the nucleus. 855 May 86

Proliferation of preexisting bile ducts, ductular metaplasia of hepatocytes and proliferation and differentiation of liver stem cells are discussed in the pathogenesis of neoductular structures in the liver. Under the condition of experimental bile duct obstruction and in extrahepatic bile duct stenosis neoductular structures are first the result of proliferation and sprouting of preexisting ducts and cholangioles. Especially in later stages of cholestasis but also in other chronic progredient liver diseases such as chronic alcoholic liver disease and chronic active hepatitis periportal hepatocytes may show a phenotypic shift towards ductular epithelia. In postnatal liver diseases hepatocytes first express keratin 7 and later keratin 19 during ductular transdifferentiation. This is in contrast to embryonal cholangiogenesis. In alpha-1-antitrypsin-deficiency, hemochromatosis, Wilson's disease, and chronic active hepatitis B cellular deposites typically located in hepatocytes such as alpha-1-AT, siderin, copper, HBs-Ag, and HBc-Ag can also be found in neoductular cells close to hepatocytes. These deposites seem to be retained during the ductular transdifferentiation of hepatocytes. Expression of bile duct-type integrin subtypes and TGF beta 1 in neoductular cells are involved in the changing parenchymal/mesenchymal interplay during neoductogenesis, resulting in periductular basal membrane and periductular fibrosis. In FNH the ductular transdifferentiation of hepatocytes is integrated in the histogenesis of micronodules and portal tract equivalents of these tumor-like lesions. Ductular structures in hepatoblastomas and especially in combined hepatocellular and cholangiocarcinomas (CHCC) may reflect the common embryologic derivation of hepatocytes and biliary epithelia. Non-neoplastic liver tissue in resection specimens of our CHCC showed a lower rate of cirrhosis, and a significantly higher Ki 67-LI of neoductular cells compared to liver tissue in resection specimens of HCC and liver metastases. 3 of 10 CHCC had developed in alpha-1-AT-deficiency, in which this protease-inhibitor was predominantly retained in periportal hepatocytes. These findings in non-neoplastic tumor-bearing liver tissue suggest that CHCC include a special histogenic type of primary liver carcinoma which in analogy to some experimental liver tumors might develop from periportal parenchymal cells.
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PMID:[Hepatic neoductules]. 860 Jun 93

We compared (i) the enhancer/promoter (mCMV promoter) from the murine cytomegalovirus (CMV) major immediate early gene,(ii) the enhancer/promoter from human CMV major immediate early gene, containing a short promoter (h1CMV) or a long stretch of 5' untranslated region (UTR) from the gene promoter (h2CMV) and (iii) the simian virus 40 (SV40) enhancer/early region promoter (SV2) for their ability to direct foreign gene expression in transiently transfected mammalian cell lines. Two series of recombinant plasmids containing the different viral promoters fused to the cat reporter gene and 3'-UTR for processing of transcripts from either the SV40 early region or the rabbit Beta 1-globin-encoding gene (Glb) were also analyzed for their effect on transient gene expression. The mCMV was the most active in dihydrofolate reductase-deficient Chinese hamster ovary (CHOdhfr-) cells and BALB/3T3 clone A31 mouse embryo cells. The h2CMV was more active than the other promoters in Bowes human melanoma cells and in Vero African green monkey kidney cells. In human hepatoma (Hep G2) cells, similar levels of CAT synthesis were observed with the h2CMV- and the mCMV-based vectors. In Hep G2 and Bowes cells, 3'-UTR from the SV40 early region resulted in consistently higher levels of cat expression, as compared to the rabbit beta 1-Glb gene, while the converse was true in BALB/3T3 clone A31 and Vero cells. SV40 early region and rabbit beta1-Glb gene 3'-UTR resulted in similar cat expression in CHOdhfr- cells.
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PMID:Efficiency of different viral promoters in directing gene expression in mammalian cells: effect of 3'-untranslated sequences. 865 43

We have previously documented a dramatic elevation in the activity of alpha 2,6-sialytransferase towards Gal beta 1,4GlcNAc (EC 2.4.99.1) (alpha 2,6ST) in CaCo-2 cells maintained in culture for several days after confluence to elicit a high degree of enterocytic differentiation phenotype. Northern analysis performed with a probe complementary to a region of human alpha 2,6ST mRNA common to all known transcripts demonstrated that the expression of alpha 2,6ST mRNA in CaCo-2 cells increased with the degree with the degree of differentiation. When probes complementary to 5'-untranslated exons (Y + Z or X) previously identified in transcripts isolated from human placenta and from several human lymphoblastoid cell lines were used, no hybridization signal with mRNA of CaCo-2 cells was found, as reported for the mRNA of hepatoma cell line HepG2 (Wang XC, Vertino A, Eddy RL, Byers MG, Jani-Sait SN, Shows TB, Lau JTY (1993) J Biol Chem 268: 4355-61). These results support the notion that the major alpha 2,6ST transcript of CaCo-2 cells was the hepatoma isoform or a new one, so far unreported. Consistent with the differentiation-dependent increase in alpha 2,6ST-mRNA expression, an elevation of the reactivity with Sambucus nigra agglutinin of differentiated CaCo-2 cell-surface was observed, indicating an enhanced alpha 2,6-sialylation of membrane glycoconjugates.
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PMID:Differentiation -dependent expression of human beta-galactoside alpha 2,6-sialyltransferase mRNA in colon carcinoma CaCo-2 cells. 878 82

To understand the function of thyroid hormone nuclear receptors (TRs) in human hepatocellular carcinoma cells (HCC), we characterized the hormone binding and transactivational activity of TRs in a HCC cell line, J7. TR alpha 1 (J7-TR alpha 1) and TR beta 1 (J7-TR beta 1) complementary DNAs were cloned from this cell line, and the binding activity to the hormone response elements (TREs) and to the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3) of the expressed TR proteins were evaluated. J7-TR alpha 1 and J7-TR beta 1 bound to TREs similarly as the TRs isolated from other tissues. However, J7-TR alpha 1 did not bind to T3, and J7-TR beta 1 bound to T3 with only about 10% the affinity of the wild-type TR beta 1. Sequencing of the complementary DNAs shows a single Met259Ile mutation in J7-TR alpha 1 and Met334Val in J7-TR beta 1. Using reporters containing TREs, we found that J7-TR alpha 1 and J7-TR beta 1 had virtually lost their transactivational activity. Moreover, these two mutants inhibited the transactivational activity of the wild-type TRs by a dominant negative effect not only on the transfected TRs, but also on endogenous TRs in other two HCC cell lines, SK-Hep-1 and HepG2. The potency of the dominant negative effect of these two mutants inversely correlated with the expression level of endogenous TRs. The present studies identified two novel naturally occurring TR mutants that have potent dominant negative action. The identification of both the alpha and beta dominant negative mutants in J7 made this cell line a useful model system to further understand the molecular mechanism of the dominant negative action of TR mutants.
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PMID:Identification of naturally occurring dominant negative mutants of thyroid hormone alpha 1 and beta 1 receptors in a human hepatocellular carcinoma cell line. 882 58

Protein kinase C mu (PKC mu) displays unusual structural features like a pleckstrin homology domain and an amino-terminal hydrophobic region with a putative leader peptide and transmembrane sequence. As a discrete location often is a direct clue to the potential biological function of a kinase, antibodies directed against unique amino- and carboxy-terminal domains of PKC mu were used to localize the protein within intracellular compartments in immunofluorescence and subcellular fractionation studies. Confocal laser scanning microscopy showed colocalization of PKC mu with the resident Golgi marker protein beta 1,4 galactosyltransferase in PKC mu transfectants and in the human hepatocellular carcinoma cell line HepG2, expressing endogenous PKC mu. Long-term treatment of cells with brefeldin A, which disintegrates the Golgi apparatus, disrupted PKC mu-specific staining. Cosegregation of PKC mu with beta 1,4 galactosyltransferase, but not with the endosomal marker rab5, upon density gradient fractionation and Western blot analysis of HepG2 cell extracts, provides independent evidence for a Golgi localization of PKC mu. Moreover, cellular sulfate uptake and Golgi-specific glycosaminoglycan sulfation was enhanced in PKC mu transfectants. Together, these data suggest that PKC mu is a resident protein kinase of the core Golgi compartment and is involved in basal transport processes.
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PMID:Protein kinase C mu is located at the Golgi compartment. 883 Jul 70

Serum alpha-fetoprotein (AFP) is a glycoprotein of which the sugar chain is considered to show structural changes with malignancies. Microheterogeneity of the serum AFP carbohydrate structure was studied in samples from 35 patients with benign and malignant diseases. Sera were digested directly, extensively, and sequentially with sialidase. beta-galactosidase and beta-N-acetylhexosaminidase. Before and after digestion, sera were examined by means of lectin affinity electrophoresis using eight lectins. Relationships between AFP carbohydrate structures and liver diseases were elucidated by the lectin-reactive profiles and the effect of glycosidase digestion. More than 94% of the AFP carbohydrate structures found in patients with benign and malignant liver diseases were biantennary complex-type oligosaccharides. Changes in the AFP carbohydrate structures at the early stage of hepatocellular carcinoma revealed the addition of alpha 1-->6 fucose to the reducing terminal N-acetylglucosamine and monosialylated AFPs. In both advanced hepatocellular carcinoma and AFP producing extrahepatic malignancies, AFP carbohydrate structures were characterized as the further addition of beta 1-->4 N-acetylglucosamine and heterogeneity in the galactose and N-acetylglucosamine residues. Sequential glycosidase digestion and lectin affinity electrophoresis is useful for analysing the carbohydrate structures of serum glycoprotein.
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PMID:Comparison of carbohydrate structures of serum alpha-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis. 889 7

A human hepatocellular carcinoma cell line, SMMC-7721, was treated with all-trans-retinoic acid (RA) and phorbol 12-myristate 13-acetate (PMA) to induce its differentiation and proliferation respectively. A biantennary sugar chain fluorescently labelled with 2-aminopyridine (PA), GlcNAc beta 1-2Man alpha 1-6(GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, was used to detect the activity of beta-1,4-galactosyltransferase on the cell surface by HPLC. The results show that the activity of beta-1,4-galactosyltransferase on the cell surface increases when the cell is treated with RA, but decreases when it is treated with PMA, whereas the activities of the whole cell remain stable during the treatments.
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PMID:Effect of all-trans-retinoic acid and phorbol 12-myristate 13-acetate on the activity of human hepatocellular carcinoma cell-surface beta-1,4-galactosyltransferase. 897 76

The effects of coculture and conditioned medium of rat hepatoma Reuber H-35 cells on the subsequent in vitro development and hatching of mouse 2-cell embryos were examined. The hatching of embryos obtained from CD-1 mice was accelerated by coculture with Reuber H-35 cells in the presence of 3 mg/ml BSA. The promoting effect on complete hatching from zona pellucida was evident even in cell-conditioned medium containing 60 micrograms/ml BSA. In the presence of 60 micrograms/ml BSA, more than 20% of embryos completely hatched, whereas none hatched in the control culture. The promoting activity was also found in both the M(r) < 10,000 and the M(r) > 10,000 subfractions of the conditioned medium separated by ultrafiltration. The cell number per blastocyst was increased to 1.1- to 1.3 times the control by culturing embryos from the 2-cell stage with the conditioned medium or its subfractions. The effective target of promoting factors for complete hatching was after the morula stage, and blastocysts hatched completely even when incubated in conditioned medium for 6 h. Inhibitors of DNA polymerase alpha, protein synthesis, and protein kinase partially reduced (40-90% inhibition) the promoting effect of the conditioned medium. On the other hand, protease inhibitors showed no effect. In a caseinolytic assay, protease activity was undetectable in the conditioned medium. Incubating the 125I-labeled proteins derived from the M(r) > 10,000 fraction with blastocysts revealed that at least 9 proteins with apparent molecular masses of 76, 60, 49, 38, 34, 31, 24, 22, and 18 kDa specifically bound to or accumulated in the embryos. Moreover, reverse-transcriptase polymerase chain reaction showed that Reuber H-35 cells expressed mRNAs for epidermal growth factor, transforming growth factors alpha and beta 1, and stem cell factor. These results indicated that embryonic development and the process of zona hatching was accelerated by factors synthesized by Reuber H-35 cells. This and other studies demonstrated that Reuber H-35 cells exert positive (later than 2-cell stage) and negative (at 2-cell stage) effects upon the development of mouse embryos at different embryonic stages. These factors will serve as valuable tools to clarify the proliferating and differentiating mechanisms of the preimplantation embryo.
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PMID:Rat hepatoma Reuber H-35 cells produce factors that promote the hatching of mouse embryos cultured in vitro. 909 89

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