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 growth characteristics of a newly established cell line, Hep40, derived from a human hepatoma are described. An absolute requirement was found for serum to mediate cell growth. Neither EGF, TGF-alpha, nor HGF altered cell growth in the presence or absence of serum. A partial suppression of cell growth was achieved by several TGF-beta family proteins. Affinity crosslinking gels using 125I-labeled TGF-beta showed a significant decrease in the TGF-beta cell-surface type II receptor in Hep40 cells, compared to the TGF-beta-sensitive Hep3B cell line. However, growth could be completely suppressed by addition of vitamins K to the culture medium in both Hep40 and several other hepatoma cell lines. Growth suppression by vitamins K was accompanied by an increased level of transcripts for c-myc, c-jun, and prothrombin genes, in contrast to the actions of TGF-beta 1 protein, which caused a decrease in the level of c-myc transcripts. These data show that this new human hepatoma cell line has partial resistance to growth inhibition by TGF-beta with a unique TGF-beta receptor defect. However, growth was completely suppressed by vitamins K. The differing gene expression patterns in response to TGF-beta as compared to vitamin K suggest that these two growth inhibitors act through differing pathways.
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PMID:Growth control and gene expression in a new hepatocellular carcinoma cell line, Hep40: inhibitory actions of vitamin K. 759 24

To clarify the mechanism of production of des-gamma-carboxy (abnormal) prothrombin (DCP) by hepatocellular carcinoma (HCC), we measured the levels of vitamin K, DCP, immunoreactive prothrombin and the activity of gamma-glutamyl carboxylase in liver tissues from HCC patients and in the medium of cultured human hepatoma cells. There was no significant difference in vitamin K (K1, MK-4) contents between HCC and non-HCC cirrhotic liver tissues. The activity of gamma-glutamyl carboxylase per unit amount of endogenous microsomal prothrombin precursor was decreased in HCC tissue compared with non-HCC liver tissue (positive plasma DCP: 335 +/- 72 vs 372 +/- 67, negative plasma DCP: 370 +/- 84 vs 393 +/- 56 nmol/min per mg prothrombin precursor, P > 0.05), although the total incorporation of 14COOH into microsomal precursor protein was higher in the former. By contrast, levels of DCP and immunoreactive prothrombin in HCC tissue were greater (P < 0.05) than those in non-HCC cirrhotic liver tissue. Furthermore, production of large amounts of immunoreactive prothrombin was observed in human hepatoma cells huH-1 and huH-2, which produced large amounts of DCP. These results suggest that there was excessive synthesis of prothrombin precursors by human HCC tissue and hepatoma cell lines huH-1 and huH-2. Thus, excessive synthesis of prothrombin precursors seems to be the main mechanism of DCP production by HCC.
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PMID:Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue. 762 Jan 13

A characteristic defect occurs in rat and human hepatocellular carcinoma (HCC) resulting in a loss of function of the vitamin K-dependent enzyme gamma-glutamyl-carboxylase in the tumor but not in the underlying liver. This causes the secretion of elevated levels of the immature or des-gamma-carboxylated form of prothrombin, which is used as a marker of HCC. We investigated whether, using the defined conditions of growing HCC cell lines in tissue culture, addition of the naturally occurring vitamins K1 or K2 or the synthetic vitamin K3 could influence the secretion of immature prothrombin. We found that vitamins K1, K2 and K3 all suppressed the secretion of immature prothrombin into the tissue culture medium. Vitamins K2 and K3 were also found to inhibit growth of the HCC cell line, in an apparently nontoxic and reversible manner. The influence of the vitamins K on the expression of some genes related to vitamin K action was examined and compared with that of another growth inhibitor, TGF beta 1 protein. The vitamins K were found to increase the expression of prothrombin and carboxylase messenger RNA and c-myc messenger RNA, but had no effects on the expression of TGF beta 1 messenger RNA. By contrast, TGF beta 1 increased TGF beta 1 messenger RNA levels, but had no effects on the other genes, suggesting a different pathway. The previously studied vitamin K3-mediated inhibition of growth was antagonized by the addition of catalase to the culture medium, but the inhibitory effects of vitamin K2 were not antagonized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The growth inhibitory effects of vitamins K and their actions on gene expression. 765 95

Based on studies in intact animals, the presence of humoral factors, "coagulopoietins", which regulate the synthesis of vitamin K-dependent plasma proteins has been proposed. These proposed factors are produced in response to vitamin K deficiency, coumarin treatment, or specific antibody depletion of vitamin K-dependent clotting factors. The production of prothrombin by rat hepatoma H4IIEC3 cells has now been shown to be dependent on the source of bovine serum in the media. Cells grown in serum from cows treated with dicoumarol produce about 20% more prothrombin in 24 h than those cells grown in control serum. The humoral factor causing this response is present early in the course of dicoumarol treatment, and the increase in prothrombin production is dependent on the amount of serum from a dicoumarol-treated cow in the media. Based on membrane filtration studies, the factor appears to be associated with the protein fraction of serum.
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PMID:Prothrombin synthesis in rat hepatoma H4IIEC3 cells: response to the proposed "coagulopoietin factor". 768 32

In this study, the diagnostic significance of PIVKA-II concentrations in various liver diseases was evaluated, and the use of PIVKA-II as a tumour marker for hepatocellular carcinoma (HCC) was discussed. Also, the location of abnormal prothrombin (PIVKA-II) production in HCC by indirect immunoperoxidase staining was examined. There was a good correlation between plasma and serum PIVKA-II concentrations, indicating that serum samples are adequate for PIVKA-II measurements. Fifty-four of 97 (55.7%) patients with HCC, one of 10 (10%) patients with metastatic liver cancer and two of 47 (4.3%) patients with liver cirrhosis had positive serum PIVKA-II concentrations. Positive serum PIVKA-II concentrations were found more frequently in patients with HCC than in any other liver disease (P < 0.01). Of the 97 patients with HCC, 54 (55.7%) were PIVKA-II positive, 76.3% had serum concentrations of either PIVKA-II or alpha-fetoprotein, indicating the usefulness of both tumour markers in the diagnosis of HCC. Using frozen sections of tissue specimens obtained at autopsy or during surgery, the localization of PIVKA-II was examined by indirect immunoperoxidase staining with specific anti-PIVKA-II antibodies. Tissues from 12 of 22 patients with HCC had positive PIVKA-II indirect immunoperoxidase staining only in the cancer cells. Cells with greater atypia tended to have stronger cytoplasmic staining. No specific staining was observed in non-cancerous cells. These findings suggest that PIVKA-II is synthesized specifically in hepatic cancer cells.
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PMID:Abnormal prothrombin: evaluation as a tumour marker and localization in tissues of patients with hepatocellular carcinoma. 768 54

A fraction of serum alpha-fetoprotein (AFP) reactive with lens culinaris agglutinin (LCA) was measured by affinity chromatography in serum samples from 102 patients with hepatocellular carcinoma (HCC) and 48 patients with chronic liver diseases without HCC. Its usefulness as a marker of HCC was evaluated. The mean +/- SD percentage of this fraction in total AFP was 3.10 +/- 3.17% in 48 patients with chronic liver diseases without HCC. When the cut-off level was set at 12.6% (mean + 3 SD), the sensitivity was 36.3%, the specificity was 100%, and the accuracy was 56.7% in the 102 patients with HCC. This lentil lectin-reactive AFP was positive in 7 of 25 patients (28%) who had single small liver cancer (phi < 20 mm), suggesting its clinical usefulness as a tumor marker. The lentil lectin-reactive AFP showed no correlation with the serum concentration of AFP or des-gamma-carboxy prothrombin (DCP). In patients with HCC showing an AFP level of 20 ng/ml or above, the lentil lectin-reactive fraction is a highly specific tumor marker. We consider it to be useful as an adjunct in the diagnosis of HCC.
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PMID:Serum alpha-fetoprotein and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein in patients with hepatocellular carcinoma. 769 Aug 73

Eleven liver function tests were used for preoperative estimations of the hepatic function reserve in 103 patients with primary hepatocellular carcinoma (HCC) and underlying liver cirrhosis. Postoperatively, the patients' liver function could be classified as good recovering (Grade A, n = 38), functional damage (Grade B, n = 37) and liver failure (Grade C, n = 28). Single factor analyses showed 6 of those tests were significant indicators, including the ratio of blood glucose level at 120 minutes and 60 minutes by oral glucose tolerance test, total bilirubin, the ratio of albumin and globulin, prealbumin, prothrombin time and indocyanine green retention at 15 minutes. The correlations between 11 preoperative parameters (xi) and postoperative course scored (Y) were analysed by Fisher's discriminant test. The multiple regression equation Y1 was obtained by comparing from groups of Grade A with B and formula Y2 from groups of Grade B with C. The predictive accuracy of both equations were 88.0%, 83.1%, respectively. To select adequate surgical procedures with the best therapeutic effect and minimal liver damage for the patients with HCC, we proposed a method of "two-stage predications" combining use of Y1 and Y2 for evaluation of liver function reserve.
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PMID:[Two-stage multivariant analyses for prediction of hepatic function reserve]. 777 27

Although recent studies have shown that hepatocyte growth factor (HGF) is a potent mitogen in vivo, the significance of serum HGF in liver diseases remains unclear. To clarify clinical significance of serum HGF in liver diseases, serum HGF was measured in 127 patients with liver diseases and in 200 healthy individuals, using a highly sensitive immunoradiometric assay (IRMA). This assay is specific for HGF and is sensitive enough to detect 0.1 ng/mL of HGF. Mean values for serum HGF in acute hepatitis (AH), chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), primary biliary cirrhosis (PBC), fulminant hepatic failure (FHF), and normal controls were 0.45, 0.40, 1.05, 1.06, 0.44, 16.40, and 0.27 ng/mL, respectively. Serum HGF levels in these diseases were significantly increased compared with those in the controls (P < .001), and exhibited a positive correlation with total bilirubin, indocyanine green (ICG) test (R15), asparate aminotransferase (AST), and a negative correlation with albumin and prothrombin time (P < .001). Cirrhotic patients with modified Child class C had higher levels of serum HGF than those graded as modified Child class A or B (P < .001). In CH, serum HGF levels were significantly related to the histological activity index (HAI) score (P < .002). Seven patients with HCC who underwent transcatheter arterial embolization (TAE) exhibited a gradual increase in serum HGF levels up to day 4 after treatment; these higher levels were maintained until day 7, although AST reached a peak on day 2 and then decreased gradually.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum hepatocyte growth factor levels in liver diseases: clinical implications. 780 42

We measured urokinase-type plasminogen activator (u-PA) plasma levels in patients with various chronic liver diseases, including hepatocellular carcinoma (HCC), also measuring these levels in healthy volunteers. Plasma u-PA levels in the group of patients with decompensated liver cirrhosis (mean modified Pugh score of 14 points) were markedly elevated and significantly higher than those in the patients with decompensated liver cirrhosis with HCC (modified Pugh score of 10 points), those with compensated liver cirrhosis with HCC, and those with compensated liver cirrhosis. Patients in all these three latter groups had moderately and significantly elevated u-PA levels compared to levels in the chronic hepatitis group and the healthy volunteers, but the levels were not significantly different from each other. There was no relationship between u-PA plasma level and the type of HCC tumor invasion or number or size of tumors. Significant correlations were found between u-PA plasma levels and the results of seven different liver function tests in three groups without associated HCC; u-PA antigen and prothrombin time (%), hepaplastin test (%), serum cholinesterase, serum albumin, serum total cholesterol, and indocyanine green clearance correlated negatively, while u-PA antigen and serum total bilirubin correlated positively. These results suggest that plasma u-PA is associated with deterioration of liver function but not with HCC invasion.
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PMID:Elevated urokinase-type plasminogen activator plasma levels are associated with deterioration of liver function but not with hepatocellular carcinoma. 787 70

We experienced two patients with a prosthetic heart valve, who underwent hepatic resection for hepatoma while on anticoagulation therapy. Patients with a prosthetic heart valve have the following characteristics; an increased risk of thromboembolism due to diminished anticoagulation in the perioperative period, a greater risk of endocarditis due to the artificial material in the heart, and impaired cardiopulmonary function including possible arrhythmia and heart failure. Furthermore, when such patients also have liver cirrhosis with a hepatoma, there is an increased risk of perioperative bleeding while on anticoagulation due to coagulopathy and also a risk of infection due to decreased cellular immunity. Patients with a prosthetic heart valve therefore require special care and attention whenever they have to undergo hepatic resection. With respect to anticoagulation, a minimal level is required to prevent bleeding and thromboembolism. Warfarin being administered preoperatively may be switched to heparin while closely monitoring the activated clotting time (biomaterial valve: 130-150 sec, non-biomaterial valve: 150-180 sec); the heparin should then be changed back to warfarin immediately after starting oral intake following operation. For the prevention of infection, a broad spectrum antibiotic should be used prophylactically both intra-operatively and postoperatively. The cardiopulmonary function must also be carefully monitored. For the assessment of postoperative liver function, lecithin: cholesterol acyltransferase, serum bilirubin and albumin are useful because there is no relevance of coagulation parameters such as prothrombin time under anticoagulation.
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PMID:Major hepatic resection in patients with a prosthetic heart valve receiving anticoagulation treatment. 795 57


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