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)

beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked oligosaccharides and forms a bisecting GlcNAc structure. Although the biological meaning of the bisecting GlcNAc structure remains unclear, it is known that the attachment of a bisecting GlcNAc inhibits further processing of oligosaccharides by other glycosyltransferases. To investigate whether or not structural changes of oligosaccharides affect secretion and gene expression of hepatitis B virus (HBV), we introduced the GnT-III gene into a human hepatoma cell line, HB611, which secreted HBV-related proteins into the medium. Positive transfectants were cloned by hygromycin resistant selection. Three clones have high activities of GnT-III and secreted lower levels of HBV-related proteins into the medium in comparison with other clones. These clones showed marked suppression of HBV-related mRNAs and an increased binding with E-PHA as judged by lectin blot. Expression of beta actin, alpha fetoprotein, albumin, and prealubmin was not correlated with GnT-III activity in all the seven clones. Treatment of these cells with tunicamycin or swainsonine resulted in enhanced expression of HBV-related mRNA. These results indicate that some glycoproteins whose oligosaccharide structures are changed by over-expression of GnT-III suppress HBV gene expression.
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PMID:Transfection of N-acetylglucosaminyltransferase III gene suppresses expression of hepatitis B virus in a human hepatoma cell line, HB611. 749 30

A monoclonal antibody (mAb 33.4) is described which inhibits the adhesion and spreading of an adherent cell line (A-cells), established from Morris hepatoma 7777 and isolated hepatocytes on collagen IV but not on laminin, fibronectin, and vitronectin. mAb 33.4 retains its immunological activity after immobilization and covalent cross-linking to Protein G-Sepharose and is therefore a suitable tool for the preparative equimolar purification of two proteins with M(r) of 130 and 190 kDa from detergent-solubilized membrane fractions by immunoaffinity chromatography. The 190-kDa protein was identified as rat alpha 1-integrin subunit by N-terminal amino acid sequencing, while the 130-kDa protein was specifically stained by a beta 1-integrin subunit-specific antiserum. In immunoblot analysis mAb 33.4 recognized the 190-kDa band, suggesting that it is specific for the rat alpha 1-integrin subunit. The epitope recognized by mAb 33.4 is conformation-dependent because the staining in immunoblots was very strong if the SDS-PAGE was performed in the absence of reducing agents. The expression of alpha 1 beta 1-integrin in sinusoidal hepatocyte membrane domains of liver sections is shown by mAb 33.4 and antisera raised against the rat alpha 1- and beta 1-integrin subunits.
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PMID:Cell-collagen adhesion is inhibited by monoclonal antibody 33.4 against the rat alpha 1-integrin subunit. 751 46

The serum levels of beta 1 integrin (microgram/ml) were significantly higher in the patients with chronic persistent hepatitis (2.59 +/- 0.04), chronic active hepatitis (3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Serum levels of beta 3 integrin (microgram/ml) were significantly higher in the patients with chronic active hepatitis (10.48 +/- 1.22), liver cirrhosis (13.55 +/- 1.54) and hepatocellular carcinoma (14.1 +/- 1.77) when compared with normal subjects (5.51 +/- 0.52). A positive correlation was found between serum levels of beta 1 and beta 3 integrins (p < 0.001). A strong positive correlation was observed between serum levels of beta 1 integrin and histologic features, particularly in the degree of hepatic fibrosis, while no correlation was found between serum levels of beta 3 integrin and hepatic fibrosis. Immunohistochemical studies revealed that the beta 1 integrin was present on the plasma membranes of hepatocytes and sinusoidal lining cells in the normal liver, and was increased in fibrotic areas, and on the plasma membranes of hepatocytes and sinusoidal lining cells of the chronic liver disease. However, no positive staining for beta 3 integrin was observed in fibrotic area. The serum level of beta 1 integrin in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.
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PMID:Serum levels of integrins in chronic liver diseases. 753 15

Changes in cytokines, intercellular cell-matrix adhesion molecules and integrins may influenced tumor cell invasion and metastases. This study described the distribution, pattern and intensity of cytokine TGFa, adhesion molecules CD 34 and CD 44 and integrins a2, a3, CD 29 (beta 1 chain) and CD 61 (beta 3 chain) in hepatocellular carcinoma (HCC), metastatic liver tumors and hepatic cirrhosis. Fresh snap-frozen tissue from 20 cases of HCC, 5 metastatic adenocarcinomas and 10 cirrhotic livers was studied immunohistochemically using available antibodies. The most intense staining of TGFa was found in metastatic adenocarcinoma, following by regenerating hepatocytes in cirrhotic liver and well differentiated HCC. Insignificant differences in activity of CD 34 in various pathologies, up-regulation of CD 44 in poorly differentiated HCC and down-regulation in metastatic tumors were found. All integrins studied showed down-regulation in poorly differentiated HCC, relatively high activity of a2, a3 and beta 1 in metastatic tumors and the presence of all integrins in cirrhotic liver.
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PMID:Differential expression of transforming growth factor alpha, adhesions molecules and integrins in primary, metastatic liver tumors and in liver cirrhosis. 753 39

The lacto-N-neotetraose-containing lipooligosaccharide (LOS) present on the surface of most Neisseria gonorrhoeae organisms may serve many important functions in gonococcal pathogenesis. This surface glycolipid contains the cross-reactive epitope to human paragloboside and can be sialylated by gonococci grown in the presence of CMP-N-acetylneuraminic acid. Another possible role for this glycolipid could be to mimic human asialocarbohydrates and act as a ligand for asialoglycoprotein receptors contained on numerous human cells. The most noted of this large family of receptors is that expressed on the surface of hepatic cells. In a model cell system, using the hepatoma tissue culture cell line HepG2, we wanted to investigate if the presence of this asialoglycoprotein receptor influenced the adherence and/or invasion of gonococci expressing the lacto-N-neotetraose structure. Piliated variants of the gonococcal wild-type strain 1291 and its isogeneic LOS mutant 1291E were used in adherence-invasion assays. This gonococcal strain is somewhat unusual in that it expresses large amounts of predominantly one species of LOS, thus reducing the complexity of interpreting the data. The data from these assays suggested that the Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc carbohydrate structure on the wild-type LOS affected the adherence-invasion of gonococci into the HepG2 cells. In studies to determine whether the major hepatic asialoglycoprotein receptor was involved in these interactions, we found that the HepG2 cells contained two receptors which bound gonococcal LOS. One of these was the asialoglycoprotein receptor, and the data concerning this receptor will be reported elsewhere. The data on the second receptor are reported here. Purified, 125I-labeled gonococcal LOS was used to identify specific high-affinity LOS-binding sites. These binding experiments revealed one major binding site corresponding to a protein with a molecular mass of 70 kDa (p70). Several lines of evidence in this study suggested that the oligosaccharide region of LOS played an important role in LOS binding to the p70 of HepG2 cells. In addition, we show that this human LOS receptor has some similarities to the gonococcal Opa proteins.
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PMID:A lipooligosaccharide-binding site on HepG2 cells similar to the gonococcal opacity-associated surface protein Opa. 753 7

We report here data on the galactosyltransferase activity in serum, liver and Zajdela ascitic hempatoma cells and about the rate of galactose attachment to appropriate acceptors by beta(1-4, beta(1-3) and alpha(1-3) linkages in liver and hepatoma cell homogenates. It was established that in serum of Zajdela bearing rats, in host liver and in Zajdela ascitic cells, galactosyltransferase activity towards ovomucoid was elevated in comparison with control serum and liver. The activity towards low molecular acceptor (N-acetylglucosamine) in liver and hepatoma was nearly the same. The predominant isomer synthesized in both tissues was beta 1-4-galactose-N-acetylglucosamine. When asialofetuin was used as acceptor the activity of alpha(1-3) galactosyltransferase was measured. In Zajdela ascitic hepatoma cells alpha(1-3) galactosyltransferase activity was 3 times higher than that in liver. The elevated ability of the tumor cells to attach galactose residues with alpha(1-3) linkage to Gal beta 1-4GlcNAc-R sequence should be considered as a characteristic feature of these malignant cells.
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PMID:Comparative studies on the uridine-5'-diphosphate-galactose: glycoprotein galactosyltransferase activity in rat liver and Zajdela ascitic hepatoma. 754 Sep 47

A characteristic defect occurs in rat and human hepatocellular carcinoma (HCC) resulting in a loss of function of the vitamin K-dependent enzyme gamma-glutamyl-carboxylase in the tumor but not in the underlying liver. This causes the secretion of elevated levels of the immature or des-gamma-carboxylated form of prothrombin, which is used as a marker of HCC. We investigated whether, using the defined conditions of growing HCC cell lines in tissue culture, addition of the naturally occurring vitamins K1 or K2 or the synthetic vitamin K3 could influence the secretion of immature prothrombin. We found that vitamins K1, K2 and K3 all suppressed the secretion of immature prothrombin into the tissue culture medium. Vitamins K2 and K3 were also found to inhibit growth of the HCC cell line, in an apparently nontoxic and reversible manner. The influence of the vitamins K on the expression of some genes related to vitamin K action was examined and compared with that of another growth inhibitor, TGF beta 1 protein. The vitamins K were found to increase the expression of prothrombin and carboxylase messenger RNA and c-myc messenger RNA, but had no effects on the expression of TGF beta 1 messenger RNA. By contrast, TGF beta 1 increased TGF beta 1 messenger RNA levels, but had no effects on the other genes, suggesting a different pathway. The previously studied vitamin K3-mediated inhibition of growth was antagonized by the addition of catalase to the culture medium, but the inhibitory effects of vitamin K2 were not antagonized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The growth inhibitory effects of vitamins K and their actions on gene expression. 765 95

We have previously described a variant form of the integrin beta 1 subunit (beta 1B)1 characterized by an altered sequence at the cytoplasmic domain. Using polyclonal antibodies to a synthetic peptide corresponding to the unique sequence of the beta 1B, we analyzed the expression of this molecule in human tissues and cultured cells. Western blot analysis showed that the beta 1B is expressed in skin and liver and, in lower amounts, in skeletal and cardiac muscles. The protein was not detectable in brain, kidney, and smooth muscle. In vitro cultured keratinocytes and hepatoma cells are positive, but fibroblasts, endothelial cells, and smooth muscle cells are negative. An astrocytoma cell line derived from immortalized fetal astrocytes was found to express beta 1B. In these cells beta 1B represent integral of 30% of the beta 1 and form heterodimers with alpha 1 and alpha 5 subunits. To investigate the functional properties of beta 1B, the full-length cDNA coding for this molecule was transfected into CHO cells. Stable transfectants were selected and the beta 1B was identified by a mAb that discriminate between the transfected human protein and the endogenous hamster beta 1A. Immunoprecipitation experiments indicated that the beta 1B was exported at the cell surface in association with the endogenous hamster alpha subunits. The alpha 5/beta 1B complex bound to a fibronectin-affinity matrix and was specifically released by RGD-containing peptides. Thus beta 1B and beta 1A are similar as far as the alpha/beta association and fibronectin binding are concerned. The two proteins differ, however, in their subcellular localization. Immunofluorescence studies indicated, in fact, that beta 1B, in contrast to beta 1A, does not localize in focal adhesions. The restricted tissue distribution and the distinct subcellular localization, suggest that beta 1B has unique functional properties.
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PMID:Expression and functional analysis of a cytoplasmic domain variant of the beta 1 integrin subunit. 768 33

This study analyzed new cell lineage markers for the differential diagnosis between hepatocellular carcinoma (HCC) and cholangiocarcinoma (ChC), as well as the potential pathways of cell-cell and cell-extracellular matrix interactions of neoplastic liver cells during tumor spread and invasion, by comparing the expression of (VLA) integrins, vitronectin receptor, and neural cell adhesion molecule in normal, inflamed, and neoplastic human liver biopsies. All cases of liver cell adenoma and well-differentiated HCC expressed the same set of integrins as observed in normal liver tissue, i.e., VLA-alpha 1 and VLA-beta 1. Poorly differentiated HCC also expressed VLA-alpha 1 and VLA-beta 1, but in addition de-novo expressed VLA-alpha 2, VLA-alpha 3, VLA-alpha 6 and vitronectin receptor. All cases of well-differentiated ChC expressed an identical integrin immunoprofile as observed in normal bile duct epithelium, i.e., VLA-alpha 2, VLA-alpha 3, VLA-alpha 6, VLA-beta 4 and vitronectin receptor, whereas poorly differentiated ChC showed a markedly decreased expression of these integrin subunits. VLA-alpha 1 was constantly absent from all cases of ChC, whereas VLA-beta 4 was never expressed by HCC. Neural cell adhesion molecule, exclusively expressed by proliferating reactive bile ductules in cholestatic and regenerating liver, was constantly absent from both malignant neoplasms. In conclusion, the integrin make up of various liver tumors closely follows that of their normal counterparts. Differences in integrin receptor expression vary according to the cellular origin of the tumors and are associated with a poor differentiation. Our findings suggest that immunohistochemical staining for VLA-alpha 1 and VLA-beta 4 integrin subunits, which highlight the cellular phenotype of the two neoplasms, might be a helpful tool in the differential diagnosis between HCC and ChC.
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PMID:Integrins as differential cell lineage markers of primary liver tumors. 768 97

Human serum alpha-fetoprotein (AFP) is elevated in not only hepatocellular carcinoma (HCC) but also benign liver diseases. AFP produced in HCC and benign liver diseases was separated into several isoforms corresponding to different sugar chain structures by several types of lectin affinity electrophoresis, and the HCC-specific AFP isoform was discriminated from those of benign liver diseases. Because a small amount of HCC-specific AFP isoform was detected in cord serum AFP, the whole sugar chain structures of human cord serum AFP were determined, as follows: Neu5Ac alpha 2-->Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6(Neu5Ac alpha 2 -->6Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->3)Man beta 1-->4R1 and R2, Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6(Neu5Ac alpha 2-->6Gal beta 1 -->4GlcNAc beta 1-->2Man alpha 1-->3)Man beta 1-->4R1 and R2, and Neu5Ac alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6(Neu5Ac alpha 2 -->6Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->3)Man beta 1-->4R1 and R2 in the ratio of 81.6:8.9:9.5. R1 and R2 denote GlcNAc beta 1-->4GlcNAcOT (subscript OT represents an NaB3H4-reduced oligosaccharide) and GlcNAc beta 1-->4(Fuc alpha 1-->6)GlcNAcOT, respectively, and the ratio between R1 and R2 in the respective fractions was approximately 19:1. In contrast, the sugar chain structure of HCC highly specific AFP isoform was found to comprise a monosialyl-biantennary sugar chain with additional fucosylation of the proximal N-acetylglucosamine. Fucosylation of AFP produced in fetal liver increased in inverse proportion to the gestation period, in weeks, indicating that fucosylation of AFP in HCC may be related to the dedifferentiation of human hepatocytes through malignant transformation.
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PMID:Sugar chains of human cord serum alpha-fetoprotein: characteristics of N-linked sugar chains of glycoproteins produced in human liver and hepatocellular carcinomas. 768 46

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