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

A system for study and measurement of the attachment in vitro of exogenous polyribosomes to membranes has been presented. Its main features are use of low temperature, post-microsomal supernatant, pyrophosphate and citric acid to remove ribosomes from the surface of rough endoplasmic reticulum, and a method for quantitative separation of unattached from membrane-associated polyribosomes. The following were found. (1) Rough endoplasmic reticulum, from which ribosomes had been removed by treatment with pyrophosphate and citrate, bound over 50% of added polyribosomes, whereas the untreated (or control) rough and smooth endoplasmic reticulum and the smooth endoplasmic reticulum treated with pyrophosphate-citrate did not bind polyribosomes. (2) The polyribosome-binding capacity of rough endoplasmic reticulum stripped of its ribosomes decayed upon storage of the membranes at 0-4 degrees C. The half-life of this decay was about 6 days whereas that of the polyribosome-binding capacity of hepatoma stripped rough endoplasmic reticulum was about 1.5 days. (3) Preparations of stripped rough endoplasmic reticulum after reassociation with polyribosomes in vitro were quite similar to preparations of native rough endoplasmic reticulum as viewed with the electron microscope. Evidence is presented to support the contention that association of polyribosomes with membranes was the result of polyribosomal reattachment to the membranes rather than trapping of the polyribosomes between vesicles of the membranes.
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PMID:Polyribosomal attachment to rat liver and hepatoma endoplasmic reticulum in vitro. A method for its study. 433 91

Exposed thiol groups do not appear to be related to the binding of (32)P-labelled polyribosomes to stripped rough endoplasmic reticulum in vitro. Treating stripped rough endoplasmic reticulum with GSSG did not diminish binding of polyribosomes, suggesting that binding in vitro has no correlation with the inhibition of protein synthesis in vitro reported by Kosower et al. (1971). Thiol reagents, which are known to dissociate ribosomes, did not significantly decrease binding of (32)P-labelled polyribosomes to stripped rough endoplasmic reticulum. Denaturing the protein of (32)P-labelled polyribosomes or stripped rough endoplasmic reticulum of liver or hepatoma with heat, trichloroacetic acid, or HClO(4) did not alter the binding in vitro. Therefore, the practice of measuring the binding of (32)P-labelled polyribosomes to stripped rough endoplasmic reticulum in vitro (Shires et al., 1971b) is an unsuitable indicator of biological significance in the intact cell.
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PMID:Binding of rat liver and hepatoma polyribosomes to stripped rough endoplasmic reticulum in vitro. Biological or an artifact? 434 80

Cytoplasmic changes were investigated in livers of rats at various intervals up to 50 weeks during primary induction of hepatoma by thioacetamide feeding.Microsomal Glucose-6-phosphatase and ATPase activities were shown to decrease progressively with increased period of thioacetamide feeding the fall in activities being more pronounced during the first 15 weeks.Hormonal induction of tryptophan pyrrolase and tyrosine transaminase activities was shown to undergo a significant decrease of 65% and 55% respectively at the end of 50 weeks feeding.The substrate induced tryptophan pyrrolase activity was decreased to 50% during the 50 weeks period whereas the substrate induced tyrosine transaminase activity gradually increased to 200%. The latter is attributable to differences in the optimal induction dose of tyrosine in normal and carcinogen fed rats.The m-RNA template lifetime for tryptophan pyrrolase was shown to be exceeding 24 hours in normal rats as against that of 13 hours in rats fed with carcinogen for 30 weeks. On the other hand the m-RNA template lifetime for tyrosine transaminase was 3 hours in control rats while it was 7 hours in the carcinogen fed rats.The observed changes were shown to occur long before the onset of malignant transformation.The alterations in terms of decreased Glucose-6-phosphatase and substrate induced tryptophan pyrrolase activities were shown to be reversible when the carcinogen was withdrawn from the diet after 30 weeks of feeding.The significance of these observations is discussed in relation to damage to endoplasmic reticulum during hepatocarcinogenesis.
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PMID:Cytoplasmic changes during thioacetamide induced hepatocarcinogenesis in rats. 439 24

As previously described, a cell surface-associated adhesive factor (AF) was separated from differentiated rat ascites hepatoma AH136B cells (forming cell islands in vivo) and highly purified by chromatography. AF synthesis by the cells was investigated by means of ultrastructural immunoperoxidase cytochemistry. Its synthesis and localization in vivo were observed in the perinuclear spaces, the rough endoplasmic reticulum, the Golgi apparatus, the smooth-membranous vesicles, and the contact region of basolateral cell surfaces of the cells in the islands, and also in the intercellular spaces. No AF synthesis was detectable in the nucleus, the free ribosomes, the mitochondria or the apical non-contacting cell surfaces. Similar features of AF synthesis and localization were also induced by dissociated AH136B cells in vitro. Upon adhesion of such recovered cells, AF was also localized at the contact surface of the adjacent cells, but not at the non-contacting free surface.
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PMID:An immunoelectron microscopic study on the distribution of a cell surface-associated adhesive glycoprotein synthesized by rat ascites hepatoma cells. 608 10

The growth of rat ascites hepatoma cells (AH 66) in vitro was inhibited and the amount of alpha-fetoprotein (AFP) in the culture medium was increased in the presence of dibutyryl adenosine 3'-5' cyclic monophosphate (DBc-AMP). Electronmicroscopically, AH 66 cells that had been incubated with DBc-AMP showed an increase in polysomes on rough endoplasmic reticulum (RER), and some mitochondria appeared to be completely surrounded by RER. AFP in untreated cells was found to be localized on ribosomes of RER, free ribosomes and occasionally also on microvilli of cell membranes by electronmicroscopic and immunohistochemical analysis. After DBc-AMP treatment, increased staining of AFP was identified on ribosomes of RER and microvilli of cell membranes as well as on nuclear membranes. These results suggest that DBc-AMP accelerates the production and release of AFP in cultured rat ascites hepatoma cells.
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PMID:Effects of dibutyryl adenosine 3'-5' cyclic monophosphate on the ultrastructure of rat ascites hepatoma cells and on the intracellular localization of alpha-fetoprotein. 608 27

Antibodies to purified nucleotide pyrophosphatase (NPPase) and dipeptidyl peptidase IV (DPP IV) were used to study the biogenesis of these rat liver plasma membrane glycoproteins in vivo. Following injection of tritiated leucine, the radioactivity in NPPase and DPP IV decayed at markedly different rates in the plasma membrane, with apparent half-lives of about 1 and 5 days, respectively. In short term experiments, labeling of total plasma membrane proteins was rapid and insensitive to colchicine, while labeling of both NPPase and DPP IV showed a lag of about 15 min, followed by colchcine-sensitive/cycloheximide-insensitive increases to half-maximal and maximal values at about 1 and 2 h, respectively. A peak of labeled DPP IV in rough microsomes at 15 min showed increased mobility on polyacrylamide gels and was largely inaccessible to antibodies in intact microsomes, consistent with its being an underglycosylated precursor, exposed on the cisternal side of the rough endoplasmic reticulum. In contrast, the behavior of unlabeled DPP IV in preparations of rough microsomes and Golgi was consistent with its being contributed by contaminating right-side-out plasma membrane vesicles. This conclusion was also necessary to fit the tracer kinetic data to a simple membrane-flow model, which gave precursor pools (1 microgram/g of liver) and fluxes (1 microgram/h/g of liver) for both DPP IV and NPPase which were about 3 orders of magnitude less than those for the synthesis of rat serum albumin. Thus, unlike hepatoma tissue culture cells (Doyle, D., Baumann, H., England, B., Friedman, E., Hou, E., and Tweto, J. (1978) J. Biol. Chem. 253, 967-973), normal rat liver does not contain large amounts of preformed intracellular plasma membrane precursors.
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PMID:Biogenesis of plasma membrane glycoproteins. Tracer kinetic study of two rat liver plasma membrane glycoproteins in vivo. 610 97

Data from studies of ascitic cells of Chang hepatoma have shown that acid phosphatase (ACPase) can be localized simultaneously within the trans portion of the Golgi apparatus and in tubules of the Golgi-endoplasmic reticulum-lysosome (GERL) system. Reaction products of thiamine pyrophosphatase (TPPase) were also present consistently within trans elements of the Golgi apparatus and within GERL tubules. These new findings indicate that a close physiological association may exist between the Golgi apparatus and GERL, a concept that is consistent with previous observations of fibroblasts. When horseradish peroxidase (PO) is injected intraperitoneally into ascites-bearing rats and the ascitic cells withdrawn at different time intervals, PO could be localized within vesicles and tubules in the GERL region but could not be detected within the Golgi apparatus. Bulk-phase endocytosis requires a long time and a high concentration of PO to occur. The presence of PO within GERL indicates that this organelle may play a role in transporting or processing of certain exogenous proteins.
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PMID:A cytochemical study of acid phosphatase, thiamine pyrophosphatase and horseradish peroxidase in the Golgi-GERL complex of hepatoma ascites cells. 613 85

The biosynthesis of gamma-glutamyl transpeptidase was investigated in hepatoma tissue culture cells. Pulse-chase experiments using [35S]methionine labeling have shown that the two glycosylated subunits of the enzyme (Mr = 58,000 and 29,000) derive from a single glycosylated precursor (Mr = 79,000 at early times). Only one polypeptide chain was immunoprecipitated from cell-free translation products and was shown to correspond to the nonglycosylated precursor (Mr = 64,000). Treatment with endoglycosidase H was used to probe for the transfer of the proteins from the endoplasmic reticulum to the Golgi and demonstrated: (i) that the precursor is at least partially cleaved in the endoplasmic reticulum; (ii) that part of the precursor is transferred to the Golgi where the processing of the oligosaccharide chains takes place. None of the precursor forms were detected at the surface of the cell where the mature enzyme was found. Tunicamycin, an inhibitor of protein glycosylation, did not prevent the proteolytic processing of the enzyme, but delayed the appearance of the mature enzyme at the cell surface. Monensin, which is known to alter Golgi functions, significantly delayed the acquisition of complex type oligosaccharides and the appearance of the enzyme at the cell surface. It did not, however, alter the proteolytic processing of the precursor of gamma-glutamyl transpeptidase. Taken together, these results show that gamma-glutamyl transpeptidase is synthetized as a single precursor which is at least partially cleaved in the endoplasmic reticulum. Part of the precursor is transferred to the Golgi where its oligosaccharide chains are processed.
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PMID:Biosynthesis and processing of gamma-glutamyl transpeptidase in hepatoma tissue culture cells. 614 5

Recently several continuous cell lines (among these PLC/PRF/5 cells) producing hepatitis B surface antigen (HBsAg) were established from human hepatocellular carcinomas. The cultured cells provide the first opportunity to study HBsAg synthesis and secretion in vitro. HBsAg, but not HBcAg, was localized by the fluorescent antibody technique in the cytoplasm and on the surface of the cultured cells. Under the electron microscope, th PLC/PRF/5 cells displayed morphologic characteristics of both hepatocytes and hepatocellular carcinoma cells. However, 22-nm. spherical or filamentous HBsAg particles were not seen in the cells, although spherical HBsAg particles were observed in the supernatant culture media. Therefore, the indirect immunoperoxidase technique was used to demonstrate HBsAg at the ultrastructural level. Electron-dense reaction product was detected along the nuclear envelope, on rough-surfaced endoplasmic reticulum, and in cisternae of endoplasmic reticulum. These findings suggest that HBsAg is synthesized on rough-surfaced endoplasmic reticulum and transferred into endoplasmic cisternae for processing and secretion. This mode of HBsAg production is identical with that observed in hepatocytes of patients infected with hepatitis B virus. The absence of detectable intracellular HBsAg particles suggests that the cultured cells secrete the particles very rapidly or that they may have a defect in intracisternal packaging of HBsAg into particles.
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PMID:Ultrastructural analysis of hepatitis B surface antigen production in vitro. 618 89

1- Deoxynojirimycin is a specific inhibitor of glucosidases I and II, the first enzymes that process N-linked oligosaccharides after their transfer to polypeptides in the rough endoplasmic reticulum. In a pulse-chase experiment, 1- deoxynojirimycin greatly reduced the rate of secretion of alpha 1-antitrypsin and alpha 1-antichymotrypsin by human hepatoma HepG2 cells, but had marginal effects on secretion of the glycoproteins C3 and transferrin, or of albumin. As judged by equilibrium gradient centrifugation, 1- deoxynojirimycin caused alpha 1-antitrypsin and alpha 1-antichymotrypsin to accumulate in the rough endoplasmic reticulum. The oligosaccharides on cell-associated alpha 1-antitrypsin and alpha 1-antichymotrypsin synthesized in the presence of 1- deoxynojirimycin , remained sensitive to Endoglycosidase H and most likely had the structure Glu1- 3Man9GlcNAc2 . Tunicamycin, an antibiotic that inhibits addition of N-linked oligosaccharide units to glycoproteins, had a similar differential effect on secretion of these proteins. Swainsonine , an inhibitor of the Golgi enzyme alpha-mannosidase II, had no effect on the rates of protein secretion, although the proteins were in this case secreted with an abnormal N-linked, partially complex, oligosaccharide. We conclude that the movement of alpha 1-antitrypsin and alpha 1-antichymotrypsin from the rough endoplasmic reticulum to the Golgi requires that the N-linked oligosaccharides be processed to at least the Man9GlcNAc2 form; possibly this oligosaccharide forms part of the recognition site of a transport receptor for certain secretory proteins.
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PMID:Glucose removal from N-linked oligosaccharides is required for efficient maturation of certain secretory glycoproteins from the rough endoplasmic reticulum to the Golgi complex. 623 87


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