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)

Gangliosides isolated from 5 cases of normal liver tissues, 11 cases of liver cirrhosis and 5 cases of hepatocellular carcinoma were compared in their concentrations and compositions. Quantitative analysis revealed no significant change of ganglioside levels between normal and cirrhotic liver tissues or hepatocellular carcinoma. There was also no significant difference (p greater than 0.05) between cirrhotic liver tissues and hepatocellular carcinoma. Two dimensional thin-layer chromatography of the total ganglioside preparations of liver tissues from both liver cirrhosis and hepatocellular carcinoma showed proliferation of GM2, GD3, GD1 and at least two unidentified components, named provisionally spots Nos. 1 and 2 in the present report, and loss of GM3. Sialidase treatment and thin-layer chromatography showed the components of these spots to be sialidase-labile monosialogangliosides and distinctly different from GD3 which was described elsewhere.
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PMID:Ganglioside variations in human liver cirrhosis and hepatocellular carcinoma as shown by two-dimensional thin-layer chromatography. 285 12

gamma-Glutamyltransferase from human hepatoma and the surrounding non-neoplastic liver tissue was purified by immunoaffinity column chromatography and characterized with regard to molecular weight, isoelectric point (pI), amino acid composition, hexosamine content and affinity for various lectins. Both enzymes showed the same molecular weight (the heavy subunit 64 000; the light subunit 26 000) and pIs (3.7-3.9) on SDS-polyacrylamide gel electrophoresis and isoelectric focusing in polyacrylamide gel, respectively. After neuraminidase treatment, the pIs for both enzymes shifted to a more alkaline pH (pI 5.7). Both enzyme preparations exhibited similar amino acid compositions; however, the glucosamine content of the hepatoma enzyme was 362 nmol/mg protein, about 3-fold higher than that of the enzyme isolated protein from the non-neoplastic tissue. Binding of the two enzymes to lectins revealed that less of the hepatoma enzyme bound to Sepharose-conjugated wheat germ agglutinin, erythroagglutinating phytohemagglutinin and Ricinus communis agglutinin. These results suggest that the two enzymes possess similar peptide moieties and degree of sialylation, but differ with respect to other aspects of their heterosaccharide moieties.
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PMID:Comparison of the peptide and saccharide moieties of gamma-glutamyltransferase isolated from neoplastic and non-neoplastic human liver tissue. 286 19

gamma-Glutamyltransferase was purified to apparent homogeneity from human adult liver, fetal liver and hepatoma by deoxycholate extraction, immunoaffinity chromatography, papain digestion, phenyl-Sepharose chromatography and preparative polyacrylamide gel electrophoresis. The purified enzyme from all three sources had an apparent Mr of 82 000 by Sephadex G-150 gel filtration and on dodecyl sulphate/polyacrylamide gel electrophoresis two nonidentical subunits of Mr 57 000 and 23 000 were obtained. The pI of all three forms was 3.85 and after neuraminidase treatment they each gave at least five bands with pI values ranging over 5.9-6.6. Sialic acid content was 188 (adult liver), 182 (fetal liver) and 188 (hepatoma) nmol/mg protein. Total neutral sugar content was 702 (adult and fetal liver) and 700 (hepatoma) nmol/mg protein. The hexosamine content of the enzyme from all the three sources was the same (354 nmol/mg protein) and galactosamine was absent. Partially purified hydrophobic and hydrophilic forms of gamma-glutamyltransferase from all the three sources were precipitated by Concanavalin A, Ricinus communis agglutinin and wheat germ agglutinin. These results show that gamma-glutamyltransferase from human adult liver, fetal liver and hepatoma are structurally similar and that the elevated levels found in fetuses and hepatoma are only a quantitative increase and are not due to a new isoenzyme.
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PMID:Comparative structural and lectin-binding studies on gamma-glutamyltransferase from human adult liver, fetal liver and primary hepatoma. 286 57

In the rat, asialoorosomucoid and rat dimeric immunoglobulin A are both taken up by hepatocytes via receptor-mediated endocytosis. The fate of these two proteins, however, differs significantly. Rat dimeric IgA is taken up into smooth vesicles, transported to the bile canaliculus and secreted intact into the bile, whereas asialoglycoproteins are internalized via coated vesicles and transported to lysosomes for degradation. Recently, several studies both in the rat and in cultured human hepatoma cells have suggested that the receptor for asialoglycoproteins may play a role in the hepatic uptake and processing of human polymeric IgA. Using receptor-binding techniques, we have provided quantitative data for the competition of human monomeric, polymeric and secretory IgA with asialoorosomucoid for its receptor on liver plasma membrane preparations from rat, monkey and man. Some IgA molecules required desialylation with neuraminidase to enhance markedly their efficacy for asialoorosomucoid inhibition. Quantitatively, human IgA molecules showed an affinity for the ASOR receptor similar to that for asialoceruloplasmin. Rat dimeric IgA does not compete for this binding site. We conclude that human IgA can compete with ligands for the asialoglycoprotein receptor of rat, monkey and human liver. This receptor may provide an alternative pathway for the hepatic processing of IgA and IgA immune complexes when secretory component-mediated uptake is not available as in the monkey and man, particularly under pathological conditions where serum IgA concentrations accumulate to abnormally high levels.
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PMID:Hepatic asialoglycoprotein receptor-mediated binding of human polymeric immunoglobulin A. 291 27

During the first stage of infection, the paramyxovirus Sendai virus attaches to host cells by recognizing specific receptors on the cell surface. Productive virus-cell interactions result in membrane fusion between the viral envelope and the cell surface membrane. It has recently been shown that the ganglioside GD1a and its more complex homologs GT1b and GQ1b are cell surface receptors for Sendai virus. We report in this paper that the temperature-sensitive mutant ts271 of the Enders strain of Sendai virus lacks the viral attachment protein HN and the biological activities of hemagglutination and sialidase activity associated with it when the virus is grown at 38 degrees C. This HN- virus was unable to infect or agglutinate conventional host cells that contained receptor gangliosides and were readily infected by the parental wild-type virus. The HN- virus did, however, attach to and infect Hep G2 cells, a line of hepatoma cells that retains the asialoglycoprotein receptor (ASGP-R) upon continuous culture. This receptor is a mammalian lectin that recognizes galactose- or N-acetylgalactosamine-terminated proteins. In accordance with the known properties of this receptor, infection by the HN- virus was abolished by treatment of Hep G2 cells with sialidase, by the presence of Ca2+ chelators, and by competition with N-acetylgalactosamine, asialoorosomucoid, and antibody to the receptor. F, the only glycoprotein on the HN- virus, was shown to compete with the galactose-terminated protein asialoorosomucoid for the ASGP-R. The ability of the HN- virus to cause cell-cell fusion of Hep G2 cells indicated that attachment of this virus to the ASGP-R still permitted viral entry by its usual mode--i.e., membrane fusion at the cell surface. These results open up the possibility that enveloped viruses, which contain glycosylated proteins or lipids, may make use of naturally occurring lectins in addition to their normal receptors as a means of attachment to host cells.
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PMID:An alternative route of infection for viruses: entry by means of the asialoglycoprotein receptor of a Sendai virus mutant lacking its attachment protein. 298 37

To define the basis of the heterogeneity of angiotensinogen, we have characterized the immunoreactivity of high molecular weight (HMW) and low molecular weight (LMW) plasma angiotensinogen, the angiotensinogen precursor synthesized by cell-free translation, and angiotensinogen secreted by human hepatoma (Hep G2) cells. Angiotensinogen precursor synthesized by rabbit reticulocyte lysate primed with RNA prepared from liver or Hep G2 cells was compared with angiotensinogen secreted by Hep G2 cells by using immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). So as to assess the contribution of N-glycosylation of angiotensinogen, Hep G2 cells were incubated in the presence of tunicamycin. Glycosylation of secreted angiotensinogen was further characterized by using chromatography on concanavalin A-Sepharose, digestion with neuraminidase, and treatment with trifluoromethane sulfonic acid. In Sephadex G-200 column chromatography, HMW plasma angiotensinogen eluted just after the column void volume and was clearly separated from LMW angiotensinogen which eluted just before bovine serum albumin. Both HMW and LMW plasma angiotensinogen were shown to bind to monoclonal and polyclonal antibodies raised against pure LMW angiotensinogen. Only one angiotensinogen precursor (mol wt 50,000) was identified by cell-free translation which, after cleavage by renin, was reduced to mol wt 45,600. Angiotensinogen secreted by Hep G2 cells showed electrophoretic heterogeneity (mol wt 53,100-65,400). Tunicamycin-treated Hep G2 cells secreted five discrete forms of angiotensinogen, a predominant form of mol wt 46,200, with other forms (mol wt 46,800, 48,100, 49,200, and 49,600) representing 10% of secreted angiotensinogen. All five forms showed a similar reduction in molecular weight after cleavage by renin. The predominant 46,200-mol wt protein represented nonglycosylated angiotensinogen in that, after cleavage by renin, it had an electrophoretic mobility (mol wt 45,600) identical to the desangiotensin I-angiotensinogen resulting from renin cleavage of the angiotensinogen precursor. The other higher molecular weight forms of angiotensinogen secreted by tunicamycin-treated Hep G2 cells were shown to represent O-glycosylated angiotensinogen in that they were reduced to 46,200 mol wt by treatment with trifluoromethane sulfonic acid. Dexamethasone (10(-7) and 10(-6)M) stimulated angiotensinogen secretion by Hep G2 cells two- to fourfold, both in the absence and presence of tunicamycin. However, a small stimulatory effect of mestranol (10(-7) M) was evident only in the presence of tunicamycin. Neither dexamethasone nor mestranol influenced the electrophoretic pattern (SDS-PAGE) of angiotensinogen secreted by Hep G2 cells. However, when incubation media were chromatographed on Sephadex G-200 with subsequent immunoprecipitation of the column fractions, both dexamethasone and mestranol were shown to stimulate the secretion of HMW angiotensinogen (eluting just after the column void volume) which, on SDS-PAGE, migrated in a position identical to LMW angiotensinogen. From these studies, we conclude that all forms of human angiotensinogen are derived from a single precursor. The heterogeneity of secreted angiotensinogen represents differences in posttranslational processing of angiotensinogen. This processing includes both N- and O-glycosylation, and also the formation of HMW complexes (HMW angiotensinogen) through association either with other angiotensinogen molecules or with some other protein(s) whose secretion by hepatocytes is stimulated by glucocorticoids and estrogens.
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PMID:Characterization of precursor and secreted forms of human angiotensinogen. 298 36

The biosynthesis and post-translational processing of the insulin-like growth factor II (IGF-II) receptor has been studied in H-35 hepatoma cells using a specific polyclonal anti-receptor immunoglobulin preparation. Cells were pulse-labeled with [35S]methionine followed by incubation with excess unlabeled methionine (chase). Gel electrophoresis of the immunoadsorbed receptors shows that the receptor is first synthesized as a 245-kDa precursor which is transformed to the mature 250-kDa form with a half-time of about 2 h. The 245-kDa precursor could also be labeled biosynthetically with [3H]mannose, only one-half of which was ultimately found associated with the 250-kDa product. Neuraminidase converts the 250-kDa receptor species to a 245-kDa form. Whereas the 250-kDa receptor is insensitive to detectable cleavage by endoglycosidase H, digestion of the 245-kDa species with this enzyme produces a 232-kDa form. A similar 232-kDa receptor species accumulates in H-35 cells incubated with tunicamycin (2 micrograms/ml). This tunicamycin-induced aglyco-receptor is not further processed to the 250-kDa form. Monensin (50 nM) blocks receptor processing at the 245-kDa stage. Endoglycosidase H treatment of the monensin-induced 245-kDa species indicates that this is a mixture of partially processed precursors having equivalent Mr. No evidence was obtained for the presence of O-linked oligosaccharides on the IGF-II receptor. The IGF-II binding activity of the three different biosynthetic forms of the receptor was assessed by affinity cross-linking of 125I-IGF-II to the receptors using disuccinimidyl suberate. Both the mature 250-kDa receptor and the neuraminidase-digested 245-kDa form specifically bound 125-I-IGF-II. However, the 232-kDa aglyco-receptor had no detectable IGF-II binding activity using this method. In summary, these studies show: 1) that the H-35 cell IGF-II receptor is synthesized first as a 245-kDa precursor having 4-6 high-mannose oligosaccharide side chains, 2) processing of the receptor oligosaccharides by mannose removal and terminal sialylation converts the 245-kDa precursor to the 250-kDa mature product which has been previously identified as the functional receptor in the plasma membrane, 3) the apparent molecular mass of the receptor in the absence of N-glycosylation is 232-kDa, and 4) glycosylation of the IGF-II receptor is required for the acquisition of IGF-II binding activity.
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PMID:Biosynthesis and processing of the type II insulin-like growth factor receptor in H-35 hepatoma cells. 299 8

Insulin molecules were covalently attached to detergent-solubilized Sendai virus envelope glycoproteins (HN and F polypeptides) by the use of the crosslinking reagent succinimidyl 4-(p-maleimidophenyl)butyrate (SMPB). Reconstitution of modified viral glycoproteins (carrying covalently attached insulin) together with unmodified viral glycoproteins resulted in the formation of "fusogenic" viral envelopes bearing insulin molecules. Reconstitution of such fusogenic viral envelopes in the presence of ricin A or simian virus 40 (SV40) DNA resulted in the formation of viral envelopes bearing insulin molecules and loaded with ricin A or SV40 DNA. Such viral envelopes were able to bind to hepatoma tissue culture cells (HTCC) from which Sendai virus receptors were removed by treatment with neuraminidase. Incubation of viral envelopes loaded with ricin A with virus receptor-depleted HTCC resulted in fusion-mediated injection of the toxin, as inferred from inhibition of protein synthesis and decrease in cell viability of the microinjected cells. Fusion-mediated injection of SV40 DNA was inferred from the appearance of SV40 tumor antigen in microinjected cells. Binding and fusion of the loaded viral envelopes to neuraminidase-treated HTCC was mediated solely by the virus-associated insulin molecules. Addition of free insulin molecules inhibited binding of the viral envelopes and, consequently, the microinjection of ricin A and SV40 DNA.
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PMID:Targeting of loaded Sendai virus envelopes by covalently attached insulin molecules to virus receptor-depleted cells: fusion-mediated microinjection of ricin A and simian virus 40 DNA. 299 83

Monoclonal antibodies were used to define cell surface antigens which are present on rat hepatocytes but are absent from hepatoma cells. One monoclonal antibody, referred to as Be 9.2, recognizes a major component of purified rat liver plasma membranes with a Mr of 110 000. This antigen (gp110) was not found in the transplantable Morris hepatoma 9121 and 7777 nor on two cultured hepatoma cell lines. Isoelectric focussing showed that gp110 is a very acidic membrane component with an isoelectric point of 3.6 to 3.8. Treatment with neuraminidase reduced the Mr to 95 000. Gp110 while bound to the membrane was resistant to trypsin, but sensitive to papain. The tissue distribution of gp110 was examined by indirect immunofluorescence in frozen sections. The antigen was found on the bile canalicular domain of hepatocytes, the microvillous zone of enterocytes of the small intestinal villi, the luminal plasma membrane of acinar cells in the submaxillary and extraorbital gland and of epithelial cells of the vesicular gland. Gp110 could not be detected in the stomach, pancreas, large intestine, kidney, thymus, spleen, heart, lung, muscle cells and fibers and in the brain. Identical results were obtained by the use of an antiserum raised against purified gp110. They confirm the transformation-sensitive character of this glycoprotein. A possible identity with dipeptidyl peptidase IV and aminopeptidase M, which have similar molecular weights and are also present in rat liver on the bile canalicular domains, could be excluded. The results suggest that the loss of gp110 might be regarded as a marker for transformation or dedifferentiation of hepatocytes.
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PMID:Identification of a transformation-sensitive 110-kDa plasma membrane glycoprotein of rat hepatocytes. 300 50

The quantity of tumor-associated antigens carrying type 2 chain polylactosamines with four types of fucosyl determinants, LeX (X-hapten), poly-LeX, sialyl LeX, and LeY (Y-hapten), present in sera of patients with various malignant and non-malignant disorders, as well as the qualitative chemical properties of the carrier molecules in sera, have been investigated using four monoclonal antibodies, each of which defines one of these determinants. The following findings are of particular importance: the serum levels of LeX defined by antibody FH2 and poly-LeX defined by ACFH18 in patients with cancer were occasionally high (incidence about 10%); however, the majority of patients did not show elevated levels; the serum level of the antigen, defined by monoclonal antibody FH6 (termed sialyl LeX-i since this determinant is carried by i antigen), was significantly high in patients with cancers originating from organs from which adenocarcinomas often develop. For example, among various types of lung cancer, only adenocarcinoma but not squamous cell carcinoma, small cell carcinoma, or large cell carcinoma showed a high level of sialyl LeX-i antigen in sera. The incidence of high antigen levels in sera of patients with adenocarcinomas of lung was as high as 76% of the observed cases; the serum level of Ley (Y-hapten) was frequently high in patients with hepatoma (incidence, 34%); sialyl LeX-i antigen was separated on gel filtration as a glycoprotein with an average molecular weight greater than 10(6). It was characterized by its susceptibility to basehydrolysis, Pronase digestion, and sialidase and endo-beta-galactosidase treatment and is assumed to be a high molecular weight mucin-type glycoprotein; sialyl LeX-i antigen expressed in sera of patients with cancer was soluble in perchloric acid, while the same antigen in sera of patients with noncancerous diseases and normal subjects was mostly insoluble in perchloric acid. LeX, a poly-LeX, and essentially all LeY antigens in sera of patients with cancer were perchloric acid-insoluble.
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PMID:Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing fucosyl or sialyl-fucosyl type 2 chain polylactosamine. 300 96


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