Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Hepatocytes were isolated from human fetal liver in order to analyze the direct effects of growth factors and hormones on human hepatocyte proliferation and function. Mechanical fragmentation and then dissociation of fetal liver tissue with a collagenase/dispase mixture resulted in high yield and viability of hepatocytes. Hepatocytes were selected in arginine-free, ornithine-supplemented medium and defined by morphology, albumin production and ornithine uptake into cellular protein. A screen of over twenty growth factors, hormones, mitogenic agents and crude organ and cell extracts for effect on the stimulation of hepatocyte growth revealed that EGF, insulin, dexamethasone, and factors concentrated in bovine neural extract and hepatoma cell-conditioned medium supported attachment, maintenance and growth of hepatocytes on a collagen-coated substratum. The population of cells selected and defined as differentiated hepatocytes had a proliferative potential of about 4 cumulative population doublings. EGF and insulin synergistically stimulated DNA synthesis in the absence of other hormones and growth factors. Although neural extracts enhanced hepatocyte number, no effect on DNA synthesis of neural extracts or purified heparin-binding growth factors from neural extracts could be demonstrated in the absence or presence of defined hormones, hepatoma-conditioned medium or serum. Hepatoma cell-conditioned medium had the largest impact on both hepatocyte cell number and DNA synthesis under all conditions. Dialyzed serum protein (1 mg/ml) at 10 times higher protein concentration had a similar effect to hepatoma cell-conditioned medium (100 micrograms/ml). The results suggest that hepatoma cell conditioned medium may be a concentrated and less complicated source than serum for purification and characterization of additional normal hepatocyte growth factors.
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PMID:Direct analysis of growth factor requirements for isolated human fetal hepatocytes. 244 74

Forskolin synergistically potentiated adenosine 3',5'-cyclic monophosphate formation by prostaglandin E1 (PGE1) in rat normal hepatocytes freshly prepared by collagenase digestion and rat ascites hepatoma AH66 cells, but dose-dependently inhibited the accumulation by PGE1 in AH66F cells. Forskolin activated adenylate cyclase in a dose-dependent manner in homogenates of all cell lines. In normal hepatocytes and AH66 cells, simultaneous addition of forskolin and other adenylate cyclase activators [isoproterenol (IPN), PGE1, guanosine 5'-triphosphate sodium salt (GTP), 5'-guanylylimidodiphosphate sodium salt (Gpp (NH)p), NaF, cholera toxin, islet activating protein and MnCl2] gave greater than additive responses. On the other hand, in AH66F cells, the effect of forskolin on adenylate cyclase was hardly influenced by GTP, but forskolin diminished the activities induced by high concentrations of GTP to that by the diterpene alone. Forskolin also significantly inhibited the PGE1-stimulated and the guanine nucleotide binding regulatory protein-stimulated activities. Because AH66F cells were insensitive to IPN, the combination with forskolin and IPN gave similar activity to that obtained with the diterpene alone. The effect of forskolin on the activation by manganese ion was neither synergistic nor inhibitory but was additive in AH66F cells. These results suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide binding regulatory protein and the catalytic unit in normal hepatocytes and AH66 cells, but in AH66F cells forskolin interferes with the coupling of the two components of adenylate cyclase.
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PMID:Stimulatory and inhibitory effects of forskolin on adenylate cyclase in rat normal hepatocytes and hepatoma cells. 254 54

The pharmacological properties of beta-adrenoceptors in rat ascites hepatoma cells were compared with those in normal rat liver cells which were cultured for 24 hr after collagenase digestion. Adenylate cyclases in the homogenates of cultured normal rat liver cells and rat ascites hepatoma cells, AH44, AH66, AH109A, AH130 and AH7974, were all activated by isoproterenol or NaF to different degrees. The enzyme in rat liver cells was activated by several beta 2-agonists but those in all hepatoma cells hardly responded. Furthermore, salbutamol, a beta 2-partial agonist, antagonized the cyclase activation by isoproterenol in AH130 cells. The Kact value of isoproterenol for the activation of adenylate cyclase in AH130 cells was smaller than that in rat liver cells. A comparison of the Ki values of beta-antagonists for the inhibition of isoproterenol-stimulated cyclase activity shows that while the Ki values of propranolol and butoxamine in AH130 cells were similar to those in rat liver cells, a significant difference was observed in the values for beta 1-selective antagonists between AH130 cells and rat liver cells. The Ki values of metoprolol and atenolol for AH130 cells were 137- and 90-fold lower, respectively, than for normal rat liver cells. From these findings, it is strongly suggested that beta-adrenoceptors in rat ascites hepatoma cells including AH130 cells have similar properties to the mammalian beta 1-receptor.
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PMID:Studies on responsiveness of hepatoma cells to catecholamines. II. Comparison of beta-adrenergic responsiveness of rat ascites hepatoma cells with cultured normal rat liver cells. 286 1

We describe in this paper a method for studying transient gene expression in a primary culture of adult rat hepatocytes. After isolation by collagenase perfusion, hepatocytes in a monolayer were transfected with foreign DNA by the calcium phosphate precipitation technique during the first 24 hours after plating. When they were transfected with a plasmid containing the gene for chloramphenicol acetyltransferase driven by the early promoter of simian virus 40, hepatocytes reproducibly expressed high levels of chloramphenicol acetyltransferase (CAT); this transient expression was much higher than that obtained with the rat hepatoma cell line H4II. Different medium conditions have been tested; an optimal level of CAT activity can be obtained using a serum-free, hormonally defined medium. Using these techniques, we have investigated the expression of liver-specific genes transferred into hepatocytes. We show that the L-pyruvate kinase promoter is active in these hepatocytes while it is silent in fibroblasts. Moreover, the use of serum-free medium may allow investigation of the role of hormones and nutrients in cells which respond normally to these effectors.
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PMID:Transfection of hepatic genes into adult rat hepatocytes in primary culture and their tissue-specific expression. 292 66

Three preparations known to be angiogenic in vivo and which stimulate production of latent collagenase by cultured bovine capillary endothelial (BCE) cells were tested for their ability to stimulate production of latent collagenase by cultured human umbilical vein endothelial (HUVE) cells. Bovine retinal extract and murine adipocyte-conditioned medium had no effect on production of latent collagenase by HUVE cells at concentrations that were effective in stimulating production of latent collagenase by BCE cells. However, with higher concentrations of bovine retinal extract, production of latent collagenase by HUVE cells was stimulated. Human hepatoma cell sonicate stimulated production of latent collagenase by HUVE cells in a dose-dependent manner. The concentration of human hepatoma cell sonicate which stimulated production of latent collagenase by HUVE cells was lower than the concentration that was effective for the stimulation of production of latent collagenase by BCE cells. Plasminogen activator production by HUVE cells was unaffected by human hepatoma cell sonicate. Varying the concentration of serum in HUVE cultures did not affect the stimulation of latent collagenase production by human hepatoma cell sonicate, suggesting that serum components neither block nor stimulate the action of the collagenase-inducing factor. Although human hepatoma cell sonicate is reported to stimulate endothelial cell multiplication, purified and partially purified endothelial cell mitogens had no effect on production of latent collagenase. Thus, at least two preparations which contain angiogenic activity will stimulate production of latent collagenase by HUVE cells.
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PMID:Production of latent collagenase by human umbilical vein endothelial cells in response to angiogenic preparations. 298 92

Zajdela ascitic hepatoma cells exist as small islands of two or more cells in addition to single cells. It is now shown that the number of cells per island is directly proportional to the age of the tumor. The number of single cells is maximal 24 h after transplantation of the tumor. Various types of inter-cellular connections are seen between adjacent cells in the island. These junctions are predominant in the apical regions of the cells. The electron-dense material present at junctional sites disappears from several sites after treatment of the islands with chelating agents such as EDTA, EGTA and citrate; the latter being most effective. No appreciable effect on the removal of electron-dense material from the junctional sites is observed when the islands are treated with either collagenase or trypsin.
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PMID:Cell to cell association in Zajdela ascitic hepatoma. An ultrastructural study. 299 47

A 17,500-dalton protein which stimulates plasminogen activator production in cultured bovine capillary endothelial cells has been purified from a SK-Hep-1 human hepatoma cell lysate by using heparin affinity chromatography and fast protein-liquid ion exchange chromatography. The purified molecule stimulated plasminogen activator production in a dose-dependent manner between 0.01 and 1 ng/ml. It also stimulated collagenase synthesis, DNA synthesis, and motility in capillary endothelial cells in the same concentration range. This molecule was identified as a basic fibroblast growth factor-like molecule on the basis of its biological activity, its affinity for heparin-Sepharose, and its cross-reactivity with a polyclonal antibody raised against the human placental basic fibroblast growth factor.
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PMID:Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration. 302 28

SK hepatoma cells and SK hepatoma conditioned media contain an 18,000-dalton factor which is pyrogenic, stimulates collagenase and prostaglandin production in skin and synovial fibroblasts, induces bone resorption, and stimulates the proliferation of murine thymocytes. These results are consistent with the finding that this tumor cell line produces interleukin 1 [Doyle, M. V., Brindley, L., Kawasaki, E., & Larrick, J. (1985) Biochem. Biophys. Res. Commun. 130, 768-773] since all these activities have been associated with this cytokine. Greater than 80% of the cellular activity has a molecular weight of 30,000, while in contrast, greater than 80% of the activity in the tumor-conditioned media has a molecular weight of 18,000. When active material from the cells is incubated with trypsin, this high molecular weight material is completely converted into an active 18,000 molecular weight species. The isoelectric point of all active material is always between pI 4.0 and 5.1, regardless of molecular weight. All of these results are consistent with the hypothesis that active, high molecular weight interleukin 1 alpha is first synthesized and stored by the tumor cell. This cytokine is then cleaved by a trypsin-like protease to an active, lower molecular weight species which can be secreted into the media.
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PMID:Production of interleukin 1 by SK hepatoma tumor cells. 302 59

The effect of fumaric acid was examined on DNA synthesis in hepatocytes or hepatoma cells from rats treated with toxic agents. Male Donryu rats were injected with mitomycin C or aflatoxin B1, singly or in combination with fumaric acid. After a specified period, hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activities for DNA synthesis were measured. The iv injection of rats with mitomycin C (0.5 mg/kg) reduced the semiconservative DNA synthesis of the hepatocytes, but simultaneous dosing of fumaric acid (40 mg/kg) enhanced the recovery of the DNA synthesis. The DNA synthesis of hepatoma cells, a 3'-methyl-4-(dimethylamino)azobenzene-induced transplantable cell line growing in the abdominal ascites of rats, was also reduced by the iv injection of mitomycin C but, in contrast to that of the hepatocytes, was little influenced by the simultaneous dosing of fumaric acid. The ip injection of fumaric acid also reduced the toxicity of aflatoxin B1 (0.25 mg/kg, ip), preventing the reduction of DNA synthesis as well as the occurrence of nuclear degenerative changes in the aflatoxin B1-exposed hepatocytes.
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PMID:Fumaric acid enhances DNA synthesis of rat hepatocytes by counteracting the toxicities of mitomycin C and aflatoxin B1. 309 24

Although several investigators have attempted to identify the site of synthesis of factor VIII (FVIII), the cellular species responsible for maintenance of plasma FVIII has not been clearly defined. Indications point at hepatocytes and certain endothelial cells. The present study investigated the FVIII coagulant antigen (VIII:Ag) of hepatocytes obtained by two-step collagenase digests of human liver pieces. Following Percoll gradient centrifugation, less than 1% of cells harvested were non-parenchymal. Lysates of freshly isolated and purified hepatocytes contained 165-250 mU of VIII:Ag/10(6) cells as defined by a two-site ELISA employing a haemophilic antibody against human FVIII. This material contained a single peak of VIII:Ag polypeptides as judged from the VIII:Ag ELISA profile of Mono-Q fast protein liquid chromatography fractions. A haemophilic antibody specific for epitopes of the light chain of FVIII, employed in immunoisolation of VIII:Ag in lysate of human hepatocytes, extracted a polypeptide pattern that was studied in a reduced SDS-PAGE electrophoresis gel and compared to that of immunoisolate from normal plasma. After electroblotting onto nitrocellulose and reaction with a monoclonal antibody towards the light chain of FVIII, the appearance of a doublet at 78-79 kDa in both these materials indicated the presence of the light chain of FVIII in human hepatocyte lysate. During culture, human hepatocytes secreted 20-80 mU of VIII:Ag per 1 x 10(6) cells per 24 hours. Further, a significant secretion of VIII:Ag was found in media of cultured human hepatoma cells, Hep-G2, whereas human blood monocytes and human fibroblasts did not secrete detectable VIII:Ag. In all of these cell cultures, vWf:Ag was indetectable or present as trace.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis of factor VIII in human hepatocytes in culture. 314 45


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