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)

Crude tumor cell extract from rat ascites hepatoma AH130 revealed a high thromboplastic activity. Intravenous injection of the extract caused widespread thrombus formation in the capillaries, arterioles, and arteries of the lung. Intravenous inoculation of AH130 after an injection of the tumor cell extract produced metastatic foci in the larger arteries, compared with the case injected with only AH130 which developed metastatic foci mainly in and around the alveolar septa. These results suggest the role of tumor thromboplastin material in the mode of distribution of metastatic foci in the lung.
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PMID:Role of tumor thromboplastin in the mode of distribution of metastatic foci in the lung. 52 Jul 53

Soon after i.v. injection of ascites hepatoma cells of rat, 3 types of tumour-cell emboli were found in arterioles and capillaries of the lung. The first type had marked aggregation of platelets and deposition of fibrin. Many were seen when tumour cells with high thromboplastic activity (AH 130) were injected, and were often followed by detachment and fragmentation of endothelial cells. The second type had loosely aggregated platelets and the third type had no aggregation of platelets or deposition of fibrin. The latter 2 types were mainly seen when the tumour cells with low thromboplastic activity [AH 130 F(N)] were injected, and they did not accompany severe structural changes of the endothelial cells. Tumour cell-platelet complexes appeared to be induced by tissue thromboplastin released from tumour cells rather than from the endothelial cells. One to 6 h after injection of AH 130, tumour cells were found beneath the endothelial cells detached from the basement membrane in areas with microthrombi. Breaching of the endothelial cells with the processes of tumour cells was also seen then. Intrusion of the processes of tumour cells into the endothelial cells was noted in groups injected with either AH 130 or AH 130 F(N), but not in the junctions of the endothelial cells. Metastatic foci 3 days after the injection of AH 130 were more frequent than in the rats injected with AH 130 F(N). These results indicate that thromboplastic activity of tumour cells might be important in forming microthrombi in the lodgement phase and might be one of the factors facilitating blood-borne metastasis.
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PMID:Lodgement and extravasation of tumour cells in blood-borne metastasis: an electron microscope study. 69 45

Recombinant tissue factor pathway inhibitor (rTFPI) has been expressed in four mammalian expression systems using human SK hepatoma, mouse C127, baby hamster kidney (BHK), and Chinese hamster ovary (CHO) cells as hosts. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the immunoaffinity purified rTFPIs all show broad bands and the mean molecular weight of SK hepatoma and C127 rTFPIs (M(r) approximately 38,000) appear larger than those of BHK and CHO rTFPIs (M(r) approximately 35,000). All these proteins inhibit factor Xa and appear to bind factor Xa with 1:1 stoichiometry. The ability of these proteins to inhibit tissue factor-induced coagulation in plasma was examined using a prothrombin time assay. The relative activities of SK rTFPI:C127 rTFPI:BHK rTFPI:CHO rTFPI were found to be 28:15:2.1:1. By Western blot using specific antisera against the amino- and carboxy-termini of TFPI as probes, it is found that all the immunoaffinity purified rTFPIs possess approximately equal amounts of the amino terminus, but the C127 and BHK rTFPIs are deficient in carboxy terminus and the CHO rTFPI is essentially devoid of this region of the protein. Mono S chromatography allowed separation of the full-length and the truncated molecules with high and low anticoagulant activities, respectively. The above results suggest that proteolysis of the carboxy terminus of TFPI occurs to different extent when TFPI is expressed in different cells and that the carboxy terminal region of the TFPI molecule is important for the inhibition of tissue factor-induced coagulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of recombinant tissue factor pathway inhibitors expressed in human SK hepatoma, mouse C127, baby hamster kidney, and Chinese hamster ovary cells. 132 78

Forty-eight patients with hepatic malignancy (47 with hepatocellular carcinoma, one with metastatic colon carcinoma), who underwent transcatheter arterial embolization (TAE) for treatment of hepatic neoplasms, were investigated to determine the effects of TAE on coagulation and fibrinolysis. TAE was followed by a significant decrease in the platelet count (P less than .001); a prolongation of prothrombin time (P less than .001); an early increase in levels of fibrinopeptide A (P less than .01), fibrinopeptide B beta-15-42 (P less than .001), and fibrin(ogen) degradation products (P less than .001); and a delayed increase in the fibrinogen level (P less than .001), without a significant prolongation of the activated partial thromboplastin time. In the three patients who developed disseminated intravascular coagulation (DIC) after TAE, a reduction of both the platelet count and fibrinogen level occurred significantly earlier and in a more severe form than in the other patients without DIC; this reduction preceded the onset of the characteristic symptoms of DIC. Data suggested that close monitoring of platelet count and fibrinogen level is important for early detection of DIC following TAE.
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PMID:Hepatic neoplasms: effects of transcatheter arterial embolization on coagulation and fibrinolysis. 215 36

Previous studies demonstrated that several cultured human tumor cell lines potentiate the conversion of prothrombin to thrombin by factor Xa and calcium in the absence of exogenous factor Va. In the present study, the specific binding of radioiodinated preparations of human factor X and factor Xa to a human hepatocellular carcinoma cell line (HepG2) that constitutively synthesizes a factor V/Va molecule, and a human bladder carcinoma cell line (J82) that does not synthesize factor V/Va, was examined. Radioiodinated factor Xa bound specifically to J82 and HepG2 cells, whereas no significant specific binding of 125I-factor X to either cell was observed. The binding isotherm of 125I-factor Xa to each tumor cell line exhibited a hyperbolic profile, and Scatchard analysis demonstrated a single class of binding site for factor Xa on each cell surface with Kd values of 1.66 +/- 0.39 and 1.64 +/- 0.52 nM and 566,000 +/- 71,000 and 28,000 +/- 6,000 binding sites/cell for HepG2 and J82 cells, respectively. Thrombin formation by cell-bound factor Xa was hyperbolic and saturable at 5 nM factor Xa on each cell line. Hanes-Woolf plots of the prothrombin activation data indicated that half-maximal rates of thrombin formation occurred at factor Xa concentrations of 1.50 +/- 0.43 nM and 1.42 +/- 0.48 nM on HepG2 and J82 cells, respectively. Pretreatment of J82 cells with polyclonal anti-human factor V IgG had no measurable effect on either the binding of 125I-factor Xa or prothrombin activation. However, pretreatment of HepG2 cells with anti-human factor V IgG inhibited prothrombin activation in a dose-dependent manner, but did not inhibit the binding of factor Xa to this cell. When both cell lines were preincubated with exogenous human factor Va, the binding of factor Xa to either HepG2 or J82 cells was marginally affected. These data indicate that HepG2 and J82 cells have cell surface factor Xa binding sites proximal to, but independent of, cell surface factor Va of either exogenous or endogenous origin.
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PMID:Binding of human factors X and Xa to HepG2 and J82 human tumor cell lines. Evidence that factor Xa binds to tumor cells independent of factor Va. 216 Sep 56

A polyclonal antibody against a synthetic peptide corresponding to amino acids 3-25 of mature lipoprotein-associated coagulation inhibitor (LACI) was raised in rabbits. The antibody was used to study the production of LACI by Hep G2 hepatoma, Chang liver, and SK hepatoma cells, and to purify LACI from the culture media. By using an amidolytic assay for factor Xa, it was found that the culture media from these liver-derived cell lines contain inhibitors of factor Xa. In Hep G2 hepatoma culture medium, approximately 50% of Xa inhibitory activity was due to LACI. In the Chang liver and SK hepatoma culture media over 95% of the Xa inhibitory activity was due to LACI. The LACIs were purified from these media by immunoaffinity chromatography on an anti-LACI-lg-Sepharose 4B column and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified LA-CIs varied in molecular weight depending on whether the media were concentrated before chromatography. An Mr approximately 38,000 LACI was obtained by chromatography of unconcentrated media. Chromatography of concentrated media yielded a LACI of Mr approximately 35,000 with the same amino-terminal sequence, suggesting partial proteolysis in the carboxyl-terminal region. In addition, an Mr approximately 25,000 form of LACI was also present. The purified Mr approximately 38,000 and approximately 35,000 LACI species from the above cells possess similar specific activities when measured by an anti-Xa/amidolysis assay. To study the role of LACI in the control of coagulation, pooled human plasma was depleted of LACI antigen by immunoaffinity absorption and reconstituted with varying amounts of purified LACI to examine the effect on tissue factor (TF)-induced coagulation. LACI depletion shortens the time of TF-induced clotting of plasma and the clotting time is linearly related to the LACI concentration after reconstitution. These results suggest that LACI plays an important role in limiting TF-induced coagulation in human plasma. Comparison of the potencies of various purified LACIs in the prolongation of TF-induced coagulation revealed that LA-CIs from different sources are not equivalent. The plasma LACI, SK hepatoma LACI, and Chang liver LACI are approximately 7-, 6-7, and 1.3-fold higher in specific activity than Hep G2 hepatoma LACI in the TF-induced clotting assay when compared on an anti-Xa/amidolysis unit basis, suggesting possible differences in post-translational modification of these LA-CIs.
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PMID:Immunoaffinity purification and characterization of lipoprotein-associated coagulation inhibitors from Hep G2 hepatoma, Chang liver, and SK hepatoma cells. A comparative study. 216 80

Human plasma contains a lipoprotein-associated coagulation inhibitor (LACI) which inactivates factor Xa directly, and in a Xa-dependent fashion also inhibits the VIIa-tissue factor complex of the extrinsic coagulation pathway. Rabbit polyclonal anti-LACI antiserum was used to screen human placental and fetal liver lambda gt11 cDNA libraries for the expression of LACI antigens. Immunologically positive clones were further tested for their ability to bind 125I-factor Xa. Seven clones were obtained which are immunologically and functionally active. The longest cDNA insert (lambda P9) of these isolates is 1.4 kilobases (kb) while other clones are 1.0 kb in length. Nucleotide sequence analysis shows that lambda P9 consists of 1431 bases that include a 5'-noncoding sequence of 132 nucleotides, an open reading frame of 912 nucleotides, and a 3'-noncoding region of 387 nucleotides. The open reading frame encodes a signal peptide of 28 residues followed by a 32-kilodalton protein of 276 residues. The predicted sequence of mature LACI contains 18 cysteines and three potential N-linked glycosylation sites. The amino acid sequence analysis of purified LACI's NH2 terminus and two of its proteolytic fragments match exactly those deduced from the cDNA sequence, indicating that the cDNA codes for LACI. The translated amino acid sequence of LACI shows several discernible domains, including a highly negatively charged NH2 terminus, three tandem Kunitz-type inhibitory domains, and a highly positively charged carboxyl terminus. Northern blot analysis shows that the following liver-derived cell lines, Chang liver, HepG2 hepatoma, and SK hepatoma all, contain two major species of mRNA (1.4 and 4.4 kb) which hybridize with LACI cDNA.
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PMID:Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. 245 57

Incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone rapidly inhibits plasminogen activator (PA) activity secondary to the induction of a specific acid-stable inhibitor of plasminogen activation (Cwikel, B. J., Barouski-Miller, P.A., Coleman, P.L., and Gelehrter, T.D. (1984) J. Biol. Chem. 259, 6847-6851). We have further characterized this inhibitor with respect to its interaction with both urokinase and tissue plasminogen activator, and its protease specificity. The HTC PA inhibitor rapidly inhibits urokinase and tissue plasminogen activator with an apparent second-order rate constant of 3-5 x 10(7) M-1 X s-1. The inhibitor forms stable covalent complexes with both urokinase and tissue plasminogen activator, with which plasmin, trypsin, and factor Xa apparently do not compete. Complex formation is saturable and requires the active site of the PA. The mass of the inhibitor-PA complex is 50,000 daltons greater than that of PA alone, consistent with an Mr for the PA inhibitor of 50,000 as demonstrated directly by reverse fibrin autography. The HTC PA inhibitor does not inhibit thrombin and differs in its kinetic and biochemical properties from protease nexin.
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PMID:Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells. 293 42

Tissue factor (TF) is a lipoprotein cofactor that markedly enhances the proteolytic activation of factors IX and X by factor VIIa. The functional activity of TF is inhibited by serum in a time- and temperature-dependent fashion. The inhibitory effect is also dependent on the presence of calcium ions and can be reversed by calcium chelation (EDTA) and dilution, thus excluding direct proteolytic destruction of TF as the mechanism for inhibition. Using crude TF, serum immunodepleted of factor VII, and serum depleted of the vitamin K-dependent coagulation factors by BaSO4 absorption, it is shown that TF factor inhibition requires the presence of VII(a), X(a), and an additional moiety contained in barium-absorbed serum. When each of the other required components were at saturating concentrations, half-maximal inhibition of TF occurred in reaction mixtures containing 2% (vol/vol) of TF at a factor VII(a) concentration of 4 ng/mL (80 pmol/L), a factor X concentration of 50 ng/mL (850 pmol/L), and a concentration of barium-absorbed serum of 2.5% (vol/vol). Catalytically active factor Xa appeared to be required for the generation of optimal TF inhibition. The results are consistent with the conclusions of Hjort that barium-absorbed serum contains a moiety that inhibits the VIIa-Ca2+-TF complex. The role of factor X(a) in the generation of the inhibitory phenomenon remains to be elucidated. The inhibitor present in serum (plasma) may in part be produced by the liver in vivo since cultured human hepatoma cells (HepG2) secrete this inhibitory activity in vitro.
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PMID:Characterization of the inhibition of tissue factor in serum. 302 56

Progressive inhibition of tissue factor activity occurs upon its addition to human plasma (serum). This process requires the presence of factor VII(a), facto-X(a), Ca2+, and another component in plasma that we have called the tissue factor inhibitor (TFI). A TFI secreted by HepG2 cells (human hepatoma cell line) was isolated from serum-free conditioned medium in a four-step procedure including CdCl2 precipitation, diisopropylphosphoryl-factor Xa affinity chromatography, Sephadex G-75 superfine gel filtration, and Mono Q ion-exchange chromatography. The purified TFI contained a predominant band at Mr 38,000 on NaDodSO4/polyacrylamide gel electrophoresis that comigrates with inhibitory activity. Like the activity present in plasma, this TFI requires the presence of factor VII(a), factor X(a), and Ca2+ to express inhibitory activity. Its specific activity (assuming an extinction coefficient of 10 at 280 nM, for a 1-cm path length through a 1% solution) was 9800 units/mg of protein, where 1 unit of TFI activity was defined as that present in 1 ml of normal pooled serum.
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PMID:Isolation of the tissue factor inhibitor produced by HepG2 hepatoma cells. 303 57


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