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)

Plasminogen activator activity and plasmin-like amidolytic activity were investigated in two experimental rat tumours, using human plasminogen and chromogenic peptide substrate, S-2251. The invasive hepatocarcinoma and non-invasive nephroma were induced with the same chemical carcinogen, dimethylnitrosamine, in F-344 rats and they were continuously transplanted under the renal capsule. While there was no difference in plasmin-like activities of the tumours, the plasminogen activator activity was very low in the nephroma, but high in the hepatocarcinoma. Since the activator activity was completely inhibited by amiloride, it was considered to be of urokinase-type. These results were in accordance with the assumed role of urokinase in the invasion. However, of the respective control organ, kidney was rich in both activities but rat liver contained only very low activities. Therefore the comparison of the plasminogen activator activity of a tumour to the control organ probably does not provide information concerning the malignant transformation as it is suggested in the literature.
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PMID:Plasminogen activator and plasmin-like activities in experimental rat tumours. 255 73

Ascitic fluid from tumour patients (hepatoma, gastric cancer, gallbladder cancer, colorectal cancer, ovarian cancer) and from non-malignant diseases (liver cirrhosis, congestive heart failure) were compared with respect to their content of determinants of the fibrinolytic system, tissue-type plasminogen activator antigen (t-PAag) and activity (t-PAact), urokinase-type plasminogen activator antigen (u-PA) and plasminogen activator inhibitor activity (PAI). Furthermore, SDS-polyacrylamide slab-gel electrophoresis (SDS-PAGE) was performed to evaluate molecular weight distribution of the detectable fibrinolytic parameters. In malignant ascites, PAI activity was three to four times higher, and increased complex formation of PAI with t-PA could be demonstrated, compared with non-malignant ascitic fluid. Tissue-type plasminogen activator antigen and activity showed a similar concentration in ascites of both study groups. Urokinase-type plasminogen activator antigen was detectable neither in ascites of malignant nor in ascites of non-malignant origin. It is concluded that t-PA is the physiological plasminogen activator in ascites and that increased PAI levels followed by increased complex formation between t-PA and PAI might reflect a reaction of the peritoneum.
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PMID:Plasminogen activators and plasminogen activator inhibitor in malignant and non-malignant ascitic fluid. 285 12

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

Two hundred sixty-six cases of hepatocellular carcinoma (HCC) were treated between June 1980 and October 1985 (4 years and 4 months) at our hospital. Hepatectomy was performed in 118 patients, 82 of which had received transcatheter arterial embolization with iodized oil (Lipiodol) 58 of then with an intraarterial catheter. HCC tumors were often multiple when they were combined with liver cirrhosis and smaller than 3 cm in diameter. For this reason treatment of HCC by surgery alone has limitations for prolongation of life. A multidisciplinary treatment is therefore necessary. We have found hepatectomy and transarterial embolization to be the most effective treatment for HCC. In order to perform repeated embolizations after hepatectomy, we developed a heparinized catheter with notches to permit safe fixation. This is suitable for long-term intraarterial use. While previous arterial catheters only permitted infusion of drugs due to their small diameters, our new catheter can be used for embolizations with Lipiodol and Gelfoam and for angiography. It is inserted through the right gastroepiploic artery into the gastroduodenal artery so that its tip lies at the level of the hepatic artery. It is brought out through the abdominal skin and flushed at two-week intervals with heparin-urokinase. The indications for the use of the catheter have been repeated embolizations 1) for prevention of tumor recurrence (surgical adjuvant therapy), and 2) after absolutely non-curative operations. For the first indication, we have found that multiple tumors and tumors larger than 5 cm frequently recur within 1 year after surgery. We have, since July 1983, used the catheter treatment to prevent recurrence in 30 such cases. Embolization with Lipiodol + Adriamycin followed by Gelfoam cubes is performed at three-month intervals for one year after surgery, starting one month after surgery, as a rule. The preliminary results indicate an improved survival rate after the treatment.
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PMID:[Multidisciplinary therapy of hepatocellular carcinoma--TAI. TAE treatment by intra-arterial catheterization]. 301 35

The human hepatoma line Hep G2 produces an acid- and SDS-sensitive plasminogen activator inhibitor (PAI). This protein has been previously purified and used to raise polyclonal antibodies. This antiserum has been used to isolate cDNA clones from a human placental lambda gt11 cDNA library. The immunologically positive clones were screened for expression of recombinant proteins which inhibit urokinase activity and form an inhibitor-enzyme complex with 125I-urokinase. Two positives (lambda PAI 11.1 and lambda PAI 14.1) have been obtained. The cDNA insert of the longer isolate (lambda PAI 14.1) consists of 1962 base pairs encoding the entire mature Hep G2 PAI and a 3'-noncoding region of 801 base pairs. The clone apparently lacks portions of 5'- and 3'-untranslated sequences. The translated amino acid sequence matches the sequence obtained for the mature Hep G2 PAI and consists of 379 amino acids with a molecular mass of 42 770 Da. Interestingly, this PAI clone is quite different from the placental-type PAI-2 sequence as expected, but matches the sequence of the endothelial-type PAI (PAI-1) reported to be acid-insensitive and SDS-enhancible.
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PMID:cDNA cloning and expression in E. coli of a plasminogen activator inhibitor (PAI) related to a PAI produced by Hep G2 hepatoma cell. 302 37

Two nearly full-length cDNAs for placental plasminogen activator inhibitor (PAI) have been isolated from a human placenta lambda gt11 cDNA library. One positive (lambda PAI-75.1) expressed a protein that could adsorb and purify anti-PAI antibodies. The expressed protein inhibited the activity of human urokinase in a fibrin autography assay, and formed a 79-kDa (reduced) covalent complex with 125I-urokinase that could be immunoprecipitated with anti-PAI. The cDNA insert of the longer isolate (lambda PAI-75.15) consisted of 1909 base pairs, including a 5'-noncoding region of 55 base pairs, an open reading frame of 1245 base pairs, a stop codon, a 3'-noncoding region of 581 base pairs, and a poly(A) tail. The size of the mRNA was estimated to be 2.0 kilobases by Northern blot analysis. The translated amino acid sequence consisted of 415 amino acids, corresponding to a 46.6-kDa protein. The sequence was related to members of the serpin gene family, particularly ovalbumin and the chicken gene Y protein. Like these avian proteins, placental PAI appears to lack a cleavable NH2-terminal signal peptide. Residues 347-376 were identical to the partial sequence reported recently for a PAI isolated from the human monocytic U-937 cell line. Placental PAI mRNA was apparently expressed at low levels in human umbilical vein endothelial cells, but was not detectable in HepG2 hepatoma cells. It was present in U-937 cells and was inducible at least 10-fold by phorbol 12-myristate 13-acetate. Thus placental PAI is a unique member of the serpin gene family, distinct from endothelial-type PAI. It is probably identical to monocyte-macrophage PAI.
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PMID:cDNA cloning and expression in Escherichia coli of a plasminogen activator inhibitor from human placenta. 302 22

Incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone rapidly inhibits tissue-type plasminogen activator activity by inducing a specific plasminogen activator-inhibitor (PAI-1). Using immobilized polyclonal antibodies raised against HT-1080 human fibrosarcoma PAI-1, we have purified HTC PAI-1 from serum-free medium conditioned by dexamethasone-treated HTC hepatoma cells and shown it to be antigenically related to human PAI-1. Greater than 100-fold purification with greater than 75% yield was achieved in a single step. The purified PAI-1 migrates on SDS-polyacrylamide gels as a single major band of 49 kDa with a minor band of 46 kDa. Digestion of PAI-1 with endoglycosidase F causes a shift toward faster migrating species which retain inhibitory activity. The purified PAI-1 was stable at pH 2.5, lost 50% of its activity after 15 min at 45 degrees C, and showed marked activation after treatment with SDS or guanidine-HCl. Purified PAI-1 rapidly inhibited and formed complexes with both tissue-type and urokinase-type plasminogen activators. Polyclonal rabbit antirat PAI-1 antibodies were raised which immunoprecipitate both free and complexed PAI-1.
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PMID:Immunoaffinity purification of HTC rat hepatoma cell plasminogen activator-inhibitor-1. 312 13

A human hepatoma cell line, Hep G2, which synthesizes and secretes several components of the fibrinolytic system, was examined for the capacity to produce plasminogen activator (PA). PA activity was found to accumulate in medium conditioned by the cells but was not detected in cell extracts. Analysis of Hep G2 conditioned medium by SDS-polyacrylamide gel electrophoresis revealed multiple PAs of Mr 100,000, 60,000, and 52,000 daltons. In addition, a heterogeneous band of activity was present between the 100,000 and 60,000 dalton PAs. All detectable PA activity in conditioned medium fractionated at a single position after isoelectric focusing. The isoelectric point of this material (pI 8.6) was identical to that of purified urokinase. Anti-urokinase IgG, but not anti-tissue activator IgG, neutralized the activity of these PAs. Treatment of conditioned medium with 25 mM diisopropylfluorophosphate for 5 hr at 37 degrees C inactivated the 52,000 and 60,000 dalton PAs but had no effect on the 100,000 dalton PA or the heterogeneous zone of activity. The possibility that the absence of detectable PA activity in the cell extracts resulted from the presence of fibrinolytic inhibitors was considered. Addition of cell extract to purified urokinase resulted in a concentration-dependent reduction of urokinase-mediated fibrinolytic activity, consistent with the presence of such inhibitors. Acidification of the cell extracts to inactivate the inhibitor(s) revealed the presence of a latent, cell-associated PA activity. Thus, in addition to the other major components of the fibrinolytic system, Hep G2 cells produce multiple forms of a urokinase-like PA. Detection of these PAs may be obscured by the presence of cellular inhibitors.
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PMID:Human hepatoma cell line plasminogen activator. 631 24

We have reported previously that derivatives of adenosine cyclic 3':5'-monophosphate dramatically stimulate the activity of plasminogen activator (PA), an arginine-specific serine protease, in HTC rat hepatoma cells. We report here that these derivatives also cause striking alterations in hepatoma tissue culture cell morphology. Because PA has been shown to alter cell morphology in other cell lines, we investigated whether the morphological changes induced by cyclic nucleotides were mediated by the stimulation of PA activity. Alterations in PA activity, measured by the plasminogen-dependent solubilization of 125I-labeled fibrin, and in cell morphology, detected by evaluation of cell flattening and process extension with phase-contrast microscopy, were assessed in the same cultures under various experimental conditions. Several lines of evidence clearly dissociate these two adenosine cyclic 3':5'-monophosphate-mediated phenomena. (a) The morphological changes precede increases in either cell-associated or extracellular PA activity. (b) Upon removal of the effectors, the morphological effects are completely reversed at a time when PA activity is still considerably elevated. (c) when protein synthesis is inhibited by the addition of cycloheximide, the stimulation of PA activity by cyclic nucleotides is blocked completely, whereas the induction of morphological alterations still occurs. (d) An exogenous PA, urokinase, does not elicit the characteristic changes in cell shape. We conclude that the morphological alterations induced by adenosine cyclic 3':5'-monophosphate derivatives in HTC cells are not mediated by the stimulation of PA activity and that these two membrane-associated properties are regulated independently.
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PMID:Role of plasminogen activator in the morphological alterations induced by derivatives of adenosine cyclic 3':5'-monophosphate in hepatoma tissue culture cells. 631 21

Incubation of HTC rat hepatoma cells with dexamethasone causes a rapid decrease in cellular plasminogen activator (PA) activity. Mixing experiments show the presence of an inhibitor of PA in dexamethasone-treated cells. This study investigates whether the decrease in PA activity is secondary to the induction of an inhibitor by glucocorticoids, to a decrease in the amount of PA, or to a combination of both mechanisms. PA and its inhibitor are dissociated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions, and both activities are then recovered and quantitated. HTC cells have two major forms of PA with Mr values of 110,000 and 64,000. Although PA activity in the unfractionated extracts from dexamethasone-treated cells is inhibited by 90% relative to control, there is no decrease in the total activity of sodium dodecyl sulfate-dissociated PA activity, suggesting that dexamethasone causes no decrease in the amount of the enzyme. PA inhibitor activity migrates as a single band of Mr = 50,000. The total activity of inhibitor increases in a time-dependent fashion, reaching a maximum of greater than 10 times control after a 4-6-h incubation with 0.1 microM dexamethasone. The induction of inhibitor requires both RNA and protein synthesis and shows a dependence on dexamethasone concentration identical to that for responses known to be mediated by glucocorticoid receptors. We conclude that dexamethasone inhibits PA activity by inducing the synthesis of an inhibitor rather than by decreasing the amount of PA.
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PMID:Dexamethasone induction of an inhibitor of plasminogen activator in HTC hepatoma cells. 642 25


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