Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nonhistone chromatin protein, C-14, was extracted from chromatin of Novikoff hepatoma ascites cells and isolated in high purity as shown by its migration as a single dense spot on two-dimensional polyacrylamide gels. Its mobility on sodium dodecyl sulfate gels is consistent with a molecular weight of approximately 70 000. The amino acid composition shows that protein C-14 has an acidic:basic amino acid ratio of 1.8. Its amino terminal amino acid is lysine. Protein C-14 stimulated the incorporation of [3H]UMP into RNA by approximately 30% when added to naked DNA and homologous RNA polymerase I. A 30% stimulation of [3H]UMP incorporation into RNA was also found when protein C-14 was added to an E. coli RNA polymerase system containing either E. coli or Novikoff hepatoma DNA.
 ...
PMID:Isolation and characterization of nonhistone chromosomal protein C-14 which stimulates RNA synthesis. 19 58

The variations of the main plasma inhibitors of coagulation were prospectively studied in 33 cirrhotic patients, of which 9 presented with hepatocellular carcinoma, 5 of those associated with portal vein thrombosis. The mean prothrombin index was 49 +/- 16 percent. All plasma values of inhibitors were diminished, but to varied degrees: the mean values were: protein C (PC): 33 +/- 15 percent, antithrombin III (AT III): 50 +/- 23 percent, total protein S (PST): 67 +/- 20 percent. The more severe the cirrhosis, the more decreased were the values of antithrombin II and protein C. According to Child classes A, B, and C, antithrombin III plasma values were 64 +/- 20, 50 +/- 21 and 26 +/- 11 percent and protein C values were 43 +/- 16, 32 +/- 8 and 19 +/- 9 percent, respectively. We were able to define expected plasma values of the plasma inhibitors as a function of coagulation factors during cirrhosis; AT III (percent) = 1.16 x factor II (percent) - 7.85; PC (percent) = 0.49 x AT III (percent) + 8.96; PC (percent) = 0.55 x factor II (percent) + 5.55; PST (percent) = 0.76 x factor II (percent) + 28.74. However those equations cannot be extrapolated to patients presenting with cirrhosis complicated with portal thrombosis.
 ...
PMID:[Changes in levels of blood coagulation inhibitors in cirrhosis. Prospective study in 33 patients]. 131 44

Multiple elements in the upstream region of the GAPDH gene play a role in mediating the acute and chronic effect of insulin on GAPDH gene expression. The complexity of this regulation provides many layers of control. In differentiated tissues, the transcriptional response to insulin results from the additive effects of g/TRE, IRE-A and IRE-B. The gTRE may interact with newly synthesized c-fos/c-jun heterodimer to activate GAPDH gene transcription. Studies are underway to determine whether protein synthesis inhibitors affect the regulation of GAPDH. Because there are several elements that mediate the effect, it will be difficult to determine the significance of these findings until each cis-acting factor and its binding protein can be studied in isolation. IRE-A and IRE-B act together to promote a 5- to 8-fold insulin effect on HGAPDH-CAT in H35 hepatoma cells and a 3-fold effect in 3T3 adipocytes. We have succeeded in detecting an insulin-sensitive DNA-binding protein referred to as IREA-BP with an element -480 to -435. Insulin treatment of differentiated 3T3 adipocytes for 1 hr results in a 4-fold increase in the amount of this binding protein, as estimated by the amount of 32P-labelled oligonucleotide retarded on non-denaturing PAGE (11). The effect of insulin on IRP-B is comparable. Furthermore, IREA-BP is induced during the process of fasting and refeeding rats, an important in vivo correlate with our tissue culture models (11). These observations imply that the binding proteins IREA-BP and IRP-B are essential components in the signal transduction pathway of insulin action on GAPDH gene expression in metabolically active tissues such as fat and liver. Differentiation-dependence and tissue-specificity are achieved through multiple regulatory elements and involve pre- and post-translational regulation of multiple transcription factors. IREA-BP is present in preadipocytes but activity in highly induced upon differentiation of preadipocytes to adipocytes. The IRE-B (-408 to -269) DNA binding protein is not detected in 3T3 preadipocytes. A gC/EBP like-protein takes part in the formation of this complex which may explain the inductive effect of differentiation on binding. Finally, footprint and cotransfection studies indicate that the differentiation-dependent protein C/EBP also regulates GAPDH gene transcription through a motif located within one hundred nucleotides of the promoter. We have begun to clone the IRE-A and IRE-B DNA binding proteins. An IRE-A binding protein that footprints the 3' domain of the IRE-A has been cloned.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Multiple insulin-responsive elements regulate transcription of the GAPDH gene. 138 8

Serum level of vitamin K1 (= phylloquinone, hereinafter K1) and K dependent blood coagulation factors were determined by HPLC in normal subject, liver cirrhosis, hepatocellular carcinoma, acute hepatitis, chronic hepatitis, chronic renal failure with hemodialysis and patients under warfarin therapy. Normal range of serum K1 concentration was decided on 0.20-2.30 (0.87 +/- 0.53, n = 96) ng/ml. Serum K1 level showed no significant differences among normal subject, various diseases and warfarin therapy. Correlation between serum K1 level and F-VII (r = 0.879, p less than 0.001) or protein C activity (r = 0.839, p less than 0.01) was found in patients whose thrombotest was 20% and less. However serum K1 level didn't correlate with any K dependent coagulation factors in patients if thrombotest was over 20%.
 ...
PMID:[Study on changes of serum vitamin K1 level and K dependent coagulation factors in patients with coumarin derivatives (warfarin) therapy]. 150 98

The authors conducted an investigation focusing mainly on the activities of the inhibitory factors of the coagulation and fibrinolysis processes in 35 normal adults and 72 liver cirrhosis and/or hepatoma patients. The activities of antithrombin III, protein C, and alpha 2-plasmin inhibitor were reduced to less than 50% in patients with decreased hepatic synthetic function while lupus anticoagulant was detected in more than 50% of patients with decreased hepatic synthetic function. Hemostatic abnormalities in advanced lived diseases may be caused partly by a decrease of coagulation and fibrinolysis inhibitors and the presence of lupus anticoagulant.
 ...
PMID:A study on changes of coagulation inhibitors and fibrinolysis inhibitors in patients with liver cirrhosis and hepatoma. 165 74

Previous studies have demonstrated that plasma tissue plasminogen activator (t-PA) level was elevated in patients with liver disease. In this study, t-PA antigen levels were investigated in patients with acute hepatitis (AH; N = 12), chronic hepatitis (CH; N = 8), compensated liver cirrhosis (CLC; N = 40), decompensated liver cirrhosis (DLC; N = 23) and hepatocellular carcinoma (HCC; N = 35). The increased t-PA levels (higher than 14 ng/ml) were found in 33% (4/12) of AH on the early hospital days, 25% (2/8) of CH, 45% (18/40) of CLC and 91% (21/23) of DLC, and 60% (21/35) of Hcc cases. In patient with LC, the correlations between t-PA levels and serum total bilirubin (T.Bill) and hepatic synthetic functions were investigated. The results were that the t-PA levels correlated positively with T. Bil and negatively with liver synthetic functions such as albumin, protein C and choline-esterase, indicating that t-PA increased almost in proportion to the deterioration of hepatic function. Serial determination of t-PA in patients with HCC treated by transcatheter arterial embolization (TAE) revealed that TAE failed to normalize the t-PA levels. In one case of HCC complicated with disseminated intravascular coagulation (DIC), t-PA showed a marked increase at acute phase of DIC and subsequent decrease after the successful treatment for DIC by gabexate mesilate (FOY) infusion. These results suggest that increased t-PA in liver disease is due mainly to deterioration of hepatic function, and that secondary fibrinolytic state, such as DIC, is also a contributing factor.
 ...
PMID:[Evaluation of plasma tissue plasminogen activator (I-PA) levels in patients with liver diseases]. 210 6

Bleeding complications during liver transplantation have been attributed to accelerated fibrinolysis. In order to determine its cause, 11 adults (mean age: 38.9 +/- 13.2 yr) undergoing liver transplantation were studied. There were three groups of patients: cirrhosis (n = 4), fulminating hepatitis (n = 4) and one group including a primary biliary cirrhosis, a hepatic metastasis and a hepatoma. The following factors were studied in the immediate preoperative period, at different surgical times throughout the procedure and 2-3 h after the end of the abdominal sutures: platelet count, prothrombin concentration, fibrinogen, activated kephalin time, factors II, V, VII + X and VIIIc, antithrombin III, protein C, D-dimers, fibrinogen and fibrin degradation products (PDF), plasma plasminogen, tissue plasminogen activator (tPA) and the fast tPA inhibitor (PAi). Preoperatively, only the two patients with hepatic cancer had a normal haemostatic profile. Throughout the procedure, all patients had only moderate changes in platelets, coagulation factors and their inhibitors, and plasminogen, because platelet concentrates and fresh frozen plasma were transfused. Levels of tPA rose, becoming very high during the anhepatic period and just after graft reperfusion. An abrupt fall occurred at the end of surgery. There were important individual differences in tPA activity. PAi activity was low during the preanhepatic and anhepatic stages, rising rapidly after revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Fibrinolytic activity in patients undergoing hepatic transplantation]. 249 27

We have isolated three cDNA clones for human alpha 2-plasmin inhibitor (alpha 2-PI). Two clones are from human hepatoma cell line, Hep G2, and cover the entire protein coding region plus the 3'-flanking region up to the poly(A) sequence, and the other clone is from human liver and contains the carboxyl-terminal half. The total length of the cDNAs is 2.29 kb, corresponding to more than 95% of the full-length mRNA. alpha 2-PI seems to consist of 452 amino acid residues plus 39 amino acid residues for the signal peptide. The amino acid sequence shows 23 to 28% homology to those of five other protease inhibitors, plasminogen activator inhibitor (PAI), protein C inhibitor (PCI), alpha 1-antitrypsin (alpha 1-AT), antithrombin III (AT III), and alpha 1-antichymotrypsin (alpha 1-AC). alpha 2-PI seems to be the most distantly related among these inhibitors. Comparison of the phylogenetic trees of proteases and their inhibitors indicates that four proteases, namely elastase (or trypsin), chymotrypsin, plasminogen activator, and thrombin, may have evolved concurrently with the corresponding inhibitors. However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates. The data suggest that alpha 2-PI may originally have inhibited some protease other than plasmin, and protein C may have had an inhibitor different from the present one early in its evolutionary history.
 ...
PMID:Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence. 283 Feb 48

Protein C, one of the vitamin K-dependent plasma proteins synthesized in the liver, was measured immunologically in normal subjects (n = 20), patients with hepatocellular carcinoma (n = 60), liver cirrhosis (n = 60), acute hepatitis (n = 16), chronic hepatitis (n = 19), malignant neoplasms other than hepatocellular carcinoma (n = 35) and patients on warfarin treatment (n = 20). We also assayed gamma-carboxyglutamic acid-complete (carboxylated) protein C in these population by using a monoclonal antibody directed against human protein C, JTC-1, which recognizes the gamma-carboxyglutamic acid domain-related conformational change induced by metal ions. We demonstrated that the plasma of patients with hepatocellular carcinoma contains considerable amounts of gamma-carboxyglutamic acid-incomplete protein C, evidenced by the significantly reduced protein C:gamma-carboxyglutamic acid/protein C:antigen ratios in hepatocellular carcinoma as compared to those seen in normal controls, other liver diseases and other malignant neoplasms (p less than 0.01). In two patients with hepatocellular carcinoma with the reduced protein C:gamma-carboxyglutamic acid/protein C:antigen ratios, successful treatment (transcatheter hepatic arterial embolization or lipiodolization of antitumor agent) led to the very rapid normalization of the ratios. Intravenous administration of vitamin K, however, induced no such effects in three other patients with hepatocellular carcinoma with the abnormality. We conclude that the impaired vitamin K-dependent gamma-carboxylation observed in patients with hepatocellular carcinoma involves not only prothrombin, but also protein C, and that the impairment is not due to vitamin K deficiency.
 ...
PMID:The acquired vitamin K-dependent gamma-carboxylation deficiency in hepatocellular carcinoma involves not only prothrombin, but also protein C. 283 89

The site of synthesis of protein C inhibitor, a recently identified human plasma inhibitor against activated protein C, is not known. We have studied the production and secretion of protein C inhibitor by an established human liver cell line derived from hepatocellular carcinoma (Hep G2). The concentration of protein C inhibitor, as measured by a specific radioimmunoassay, increased in the medium of Hep G2 cells with time. There was no evidence for a significant intracellular pool of this protein. Protein C inhibitor secreted from Hep G2 cells (G2 protein C inhibitor) inhibited the activity of purified activated protein C in a functional assay. De novo synthesis of protein C inhibitor was demonstrated by the presence of specific immunoprecipitable radioactivity in the medium after 5 h of labeling of the cells with [35S]methionine. Analysis of the immunoprecipitates by SDS-polyacrylamide gel electrophoresis showed a peak of radioactivity corresponding to Mr 57 000. These results indicate that the liver is a site of protein C inhibitor production.
 ...
PMID:Synthesis and secretion of protein C inhibitor by the human hepatoma-derived cell line, Hep G2. 298 24


1 2 3 4 5 6 7 8 9 10 Next >>