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)

The ascites form of a chemically induced guinea pig hepatoma, line-10, was resistant to killing in vitro by xenogeneic antibody and guinea pig complement. Pretreatment of line-10 cells with certain proteolytic enzymes rendered tham susceptible to the killing action of antibody and guinea pig complement. The effects of enzyme pretreatment were dependent on enzyme concentration, temperature, and could be blocked by addition of competitive or non-competitive inhibitors. The effect of the enzyme treatment could reversed by incubating the treated cells at 37 degrees C (but not at 0 degrees C), in the absence of the enzyme. Effective enzymes included ficin, bromelain, pronase, elastase, papain, trypsin, collagenase, lipases type I and type VI, and the neuraminidase preparation isolated from Clostridium perfringens. The activity of the lipase preparations and the neuraminidase preparation isolated from Clostridium perfringens appeared to be caused by proteolytic enzyme contamination. Enzyme preparations that proved ineffecitve in rendering the line-10 cells sensitive to killing by antibody and guinea pig complement included DNase, RNase, beta-glucuronidase type 6A or type B10, hyaluronidase type V or type VI, and pectinesterase.
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PMID:Lysis of tumor cells by antibody and complement. VI. Enhanced killing of enzyme-pretreated tumor cells. 17 70

During lipolysis of chylomicron triacylglycerol by lipoprotein lipase, arachidonic acid (AA) esters are hydrolyzed at a slower rate than the predominant 16-18 carbon fatty acid esters. The further metabolism of the AA that is hereby enriched in the chylomicron remnant acylglycerols has not been investigated. In the present study, we examined the low density lipoprotein (LDL) dependent and independent metabolism of [14C]AA present in chylomicron remnants in the human hepatoma cell line Hep G2. Mesenteric duct cannulated rats were fed [14C]AA and [3H]cholesterol in corn oil, and the chyle obtained was injected intravenously into hepatectomized rats to form chylomicron remnants labeled with [14C]AA in the triacylglycerol (TG) and with 3H in the cholesteryl ester portion. The remnants were then incubated with Hep G2 cells. The uptake of [14C]AA within 2-4 h was similar to that of [3H]cholesteryl ester. After uptake into the cells, [14C]AA was preferentially incorporated into phospholipids, a high proportion being found in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol. [14C]AA and [3H]cholesteryl ester uptake were influenced to similar extents by factors unknown to regulate the LDL receptor and by an anti-LDL receptor antibody. Addition of compactin thus increased the uptake of [14C]AA by 50% in 4 h and mevalonolactone decreased the uptake by 86%. Using an anti-LDL receptor antibody, 25.0% of [3H]cholesterol/cholesteryl ester and 37.7% of [14C]AA binding to the cells at 4 degrees C were blocked. There was no lipolysis of [14C]TG or [14C]diacylglycerol by lipase secreted into the medium during incubations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein receptor mediated metabolism of [14C]arachidonic acid labeled chylomicron remnants by Hep G2 cells. 133 5

A pancreatic carcinoma and liver metastases associated with marked elevation of the serum alpha-fetoprotein (AFP) level were resected from a 57-year-old man. On microscopic examination, the tumor cells showed a predominantly acinar arrangement, with tubular and trabecular structures; in some foci it had features of a medullary pattern. Alpha-fetoprotein, lipase, trypsin, chymotrypsin, and alpha 1-antitrypsin were strongly demonstrated in tumor tissue by immunohistochemical techniques. A biochemical analysis of AFP on affinity sepharose columns revealed that the AFP derived from the tumor tissues was similar to that of hepatocellular carcinoma. Ultrastructural study showed that most of the tumor cells had abundant rough endoplastic reticulum and numerous zymogen granules. No squamoid corpuscles, neuroendocrine granules, bile production, or bile canaliculi were recognized. These findings suggest that this unique tumor originated from acinar cells.
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PMID:Alpha-fetoprotein-producing acinar cell carcinoma of the pancreas. 137 64

Serum low-density lipoprotein (LDL) concentration is a major determinant of susceptibility to the development of atherosclerosis. A major component of the protein moiety of LDL and its precursor very-low-density lipoprotein is apolipoprotein B (apo B). The human hepatoma cell line, Hep G2, was used as a model for the investigation of mechanisms which control hepatic secretion of the apo B and lipid components of lipoproteins. Using a sensitive immunoradiometric assay for apo B developed in this laboratory, we showed that bovine serum albumin inhibited and glucose, and fatty acids enhanced the rate of accumulation of apo B in the culture medium of Hep G2 cells. However, these substances did not necessarily affect LDL lipids in the same way as apo B. This finding appeared to be due to Hep G2 cells expressing lipase activities which led to triacylglycerol and phospholipid hydrolysis and lipid reuptake. Reuptake of apo B also occurred, but its rate of accumulation in the culture medium suggested it was a closer reflection of its true secretory rate.
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PMID:Lipoprotein secretion by the human hepatoma cell line Hep G2: differential rates of accumulation of apolipoprotein B and lipoprotein lipids in tissue culture media in response to albumin, glucose and oleate. 195 47

Chemical analysis of ascitic fluid may be helpful in determining the underlying disease. We discuss the diagnostic accuracy of the common and newer chemical parameters (protein, LDH, lactate, glucose, cholesterol, triglycerides, phospholipids, fibronectin, albumin gradient [value of serum minus value of ascites], ferritin, tumor markers, immunomodulators, leukocytes, bacterial and cytologic examinations). We also review the pathogenesis and clinical findings of the most frequent ascites forms (benign hepatic, infective, malignant ascites, ascites associated with liver metastases or hepatocellular carcinoma, cardiac and pancreatic ascites) and the most important diagnosis criteria. In the malignant ascites a high cholesterol, a narrow albumin gradient or a high ferritin value have high diagnostic accuracy, but diagnosis is by the finding of malignant cells. For the diagnosis of infective ascites, bacteriology is mandatory even though the results are negative in most cases, particularly in spontaneous bacterial peritonitis where diagnosis has to be established clinically, by a low pH or by a high leukocyte count. Benign hepatic ascites is diagnosed by demonstrating an underlying chronic liver disease and laboratory examinations of the peritoneal fluid to exclude other causes. The laboratory tests in ascites associated with liver metastases or with hepatocellular carcinoma were similar to those in benign hepatic ascites and the two ascites forms must be separated by other clinical and technical findings. Pancreatic ascites can easily be distinguished from the other forms by the high amylase and lipase content.
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PMID:[Laboratory chemical analysis in ascites]. 203 10

The culture fluid of Hep G2 human hepatoma cells contains triglyceridase activity resistant to high-salt concentrations. The lipase binds to Sepharose-heparin columns from which it can be eluted by 0.8 to 0.9 M NaCl. The nature of this lipase was studied using antibodies raised against "liver" lipases from human and rat origin. The anti-rat liver lipase inhibits both the postheparin human and rat plasma enzyme while the anti-human liver lipase has no effect on the rat enzyme. The lipase of the Hep G2 cultures showed affinity to the antibodies raised against rat as well as human "liver" lipase as shown by inhibition experiments. These results show that Hep G2 cells secrete "liver" lipase and that there seems to exist a structural homology between the lipases from rat and human origin.
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PMID:Human hepatoma (Hep G2) cultures contain salt-resistant triglyceridase ("liver lipase"). 241 21

Monoclonal antibodies against human alpha-fetoprotein (AFP) were obtained by the hybridoma technique and studied with regard to their reactivities with the human hepatoma cell lines PLC/PRF/5 and KN, and a spontaneously immortalized cell line derived from fetal liver, NuE, all of which synthesize AFP. One of the monoclonal antibodies, 19F12 (IgG2b) became bound to free AFP which was used as the immunogen with an affinity constant of 3.4 X 10(8) M-1. This value was not much higher than those of two other antibodies, 19B1 (IgG1) and 9D12 (IgG2b). However, only antibody 19F12 showed definite reactivity with AFP-producing cells in analysis using flow cytometry. Immunofluorescence microscopy showed that antibody 19F12 detected AFP over the surface of NuE and PLC/PRF/5 cells with a uniform distribution, whereas definite reactivities of antibodies 19B1 and 9D12 to these cells were not detected. These antibodies did not show the specific binding to a non-AFP-producing human lung cancer cell line, PC-9, or to human peripheral blood lymphocytes. The binding ability of 19F12 to hepatoma cells was shown in both viable and fixed cells. Addition of free AFP inhibited the binding of antibody 19F12 to PLC/PRF/5 cells in a concentration-dependent manner. The specific reactivity of 19F12 to human AFP was also confirmed by immunostaining of a tissue section of human cancer proved to be AFP positive with AFP-specific antisera. In two-dimensional polyacrylamide gel electrophoresis of the antigen (from membrane fraction of PLC/PRF/5 cells)-antibody (19F12) complex, spots derived from the antibody and a spot (pI 4.7, Mr 65,000) corresponding in pI and molecular weight to AFP were detected. Western blot analysis showed that material in the membrane fraction of PLC/PRF/5 cells recognized by antibody 19F12 has the same molecular weight as human AFP derived from placenta. In a study of reactivities to PLC/PRF/5 cells treated with various enzymes, the reactivity of this antibody decreased when cells were treated with protease and trypsin and increased when lipase was used. The binding of 19F12 to AFP was not inhibited by concanavalin A. The antibody 19F12 appeared to recognize an epitope that is considered to be part of the peptide area of AFP. These results indicate that the reactivity, the amount of bound antibodies, and the distribution of monoclonal antibodies on antigen-producing cells vary, respectively, even though these antibodies were produced using the same antigen as an immunogen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Detection of membrane-bound alpha-fetoprotein in human hepatoma cell lines by monoclonal antibody 19F12. 246 75

The mechanism for the stimulation of hepatic lipase secretion by heparin was studied in cultured Fu5AH rat hepatoma cells. Quantitative immunoprecipitation followed by electrophoresis and fluorography were used to isolate and quantitate the radioactive enzyme; hepatic lipase protein mass was quantitated by ELISA. Addition of heparin to the medium resulted in a 2-fold increase in lipase secretion rate, whereas cell-surface-associated and intracellular lipase decreased by 76 and 20%, respectively. Rates of synthesis of hepatic lipase measured by incorporation of Trans 35S-label into enzyme protein were not different in control or heparin-treated dishes. In pulse-chase studies, it was estimated that the degradation rate constants for control and heparin-treated cultures were 0.51 +/- 0.09 and 0.14 +/- 0.13 h-1 for control and heparin-treated cultures, respectively. 52% of the synthesized enzyme was degraded in control cultures; addition of heparin to the culture medium reduced this figure to 11% of the synthetic rate. Equilibrium binding data of highly purified 125I-hepatic lipase to Fu5AH cells at 4 degrees C demonstrate the presence of a class of high-affinity binding sites. At 37 degrees C, cell-surface-bound 125I-hepatic lipase is internalized and either degraded or recycled to the medium. The half-intracellular residence times of hepatic lipase were 55 and 31 min in control and heparin-treated cultures, respectively. Radioactivity incorporated in the 55.4 kDa high-mannose-containing lipase and the mature 57.6 kDa species was measured as a means of locating the enzyme in the secretory pathway before or beyond the medial Golgi. The disappearance of the 55.4 kDa species from the cell is similar in control and heparin-treated cultures with half-intracellular residence times of 29 and 25 min, respectively. In contrast, the amount of radiolabeled 57.6 kDa species in control cells remained constant from 15 min to 2 h, whereas it decreased by 79% in heparin-treated cells. The above data demonstrate that the increase in hepatic lipase secretion is due to a decreased degradation rate with no change in synthetic rate and that heparin primarily affected the residence time of hepatic lipase in the medial Golgi-plasma membrane region.
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PMID:Heparin decreases the degradation rate of hepatic lipase in Fu5AH rat hepatoma cells. A model for hepatic lipase efflux from hepatocytes. 266 15

By immunoscreening of a human cDNA expression library and hybridization of colonies, four partially overlapping cDNA clones of human hepatic triglyceride lipase (HTGL) mRNA were isolated. The clones included the complete coding sequence, the 3'- and at least part of the 5'-untranslated region. The length of the composite HTGL cDNA segment (1.7 kb) was consistent with the size of the mRNA identified in an established human hepatoma cell line. DNA-sequence analysis of cDNAs of partially unspliced mRNAs, and of cloned genomic DNA indicated that the HTGL coding sequence comprises at least six exons. As predicted from the cDNA, the unprocessed HTGL protein has a molecular weight of 56, three potential glycosylation sites, and a signal peptide of 23 amino acids. Sequence comparison with cDNA of other lipases, including rat hepatic lipase, revealed 30%-75% protein-sequence homology. The data establish that HTGL is a secretory protein produced in the hepatocyte, and that its synthesis can be continued in permanent cell lines of hepatoma origin. Our studies also showed that HTGL is another member of a lipase gene family which has interfacial binding sites and possibly other functional domains in common.
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PMID:Human hepatic triglyceride lipase: cDNA cloning, amino acid sequence and expression in a cultured cell line. 282 41

Hepatic triglyceride lipase (H-TGL) was isolated from human postheparin plasma by column chromatography on heparin-Sepharose and phenyl-Sepharose and immunoaffinity chromatography with monoclonal antibodies. The purified enzyme had an apparent molecular weight of 65,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an amino-terminal sequence of Leu-Gly-Gln-Ser-Leu-Lys-Pro-Glu. Partial amino acid sequences of seven cyanogen bromide peptides were obtained. A human hepatoma cDNA library was screened with synthetic oligonucleotides derived from the partial protein sequence. The cloned H-TGL cDNA of 1569 nucleotides predicts a mature protein of 477 amino acids plus a leader sequence of 22 amino acids. Blot hybridization analysis of poly(A)+ mRNA with a putative H-TGL cDNA clone gave a single hybridizing band of 1.7 kilobases. The protein contains four consensus N-glycosylation sequences based on the cDNA sequence. Comparison of the enzyme sequence with that of other lipases reveals highly conserved sequences in regions of putative lipid and heparin binding. The carboxyl terminus of H-TGL contains a highly basic sequence which is not reported to be present in rat H-TGL or other members of the lipase gene family.
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PMID:Isolation and cDNA sequence of human postheparin plasma hepatic triglyceride lipase. 283 10


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