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)

A complementary DNA (cDNA) for rat hepatic aryl sulfotransferase IV (AST IV) was isolated, characterized, and used as a hybridization probe to evaluate the molecular basis for the differential expression of AST IV during 2-acetylaminofluorine (2AAF)-induced hepatocarcinogensis. The AST IV cDNA clone was obtained by immunochemical screening of a male Sprague-Dawley rat liver cDNA library. The AST IV cDNA was found to be 1.3 kilobases long and to encode a fusion protein which was reactive with an antibody to AST IV and enzymatically able to generate the sulfuric acid ester of N-hydroxy-2AAF. Sequence analysis of the AST IV cDNA showed it to be 1127 residues in length and to have essentially complete homology with PST-I cDNA, a previously reported (S. Ozawa, et al., Nucleic Acids Res., 18: 4001, 1990), 1028-base cDNA for an uncharacterized rat liver aryl sulfotransferase. Comparison of the PST-I/AST IV cDNA-deduced amino acid sequence with data from a partial (51%) amino acid sequence analysis of purified AST IV showed complete amino acid homology, confirming the identity of the cDNA and establishing that AST IV was an N-blocked, 291-amino acid protein with a molecular mass of 33,909 daltons. The AST IV cDNA sequence differed from the PST-I cDNA in two principal ways: the 5' end lacked 18 coding bases, and the 3' end contained a 190-base extention in the untranslated region, including a consensus sequence for signalling polyadenylation. Studies of AST IV gene transcript levels showed that the livers of rats fed 2AAF for 3 wk (early stage hepatocarcinogenesis) and hyperplastic nodules from the livers of rats fed 2AAF for 19 wk (intermediate stage hepatocarcinogenesis) displayed transcript levels similar to those of livers from normal rats. This contrasted with the 60 to 70% lower than normal capacity of the mRNA fractions to express AST IV observed during in vitro translation. These results indicated that modulation of AST IV expression at early and intermediate stages of hepatocarcinogenesis involved regulatory mechanisms at the translational level. In contrast, mRNA fractions isolated from some 2AAF-induced liver tumors or from known chemical carcinogen-derived rat hepatoma cell lines showed losses of both AST IV transcript level and in vitro translation capacity, suggesting that regulation at the transcriptional level may become important at late stages of 2AAF-induced hepatocarcinogenesis. These results indicated that the molecular mechanisms for the 2AAF-mediated down regulation of AST IV expression during 2AAF-induced hepatocarcinogenesis involved alterations in regulation at both translational and transcriptional levels.
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PMID:Characterization of a complementary DNA for rat liver aryl sulfotransferase IV and use in evaluating the hepatic gene transcript levels of rats at various stages of 2-acetylaminofluorene-induced hepatocarcinogenesis. 151 41

We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.
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PMID:[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. 151 41

We produced monoclonal antibodies (mABs) against human integrins. Competitive enzyme-linked immunosorbent assay (ELISA) revealed that each mAB bound to different antigenic determinants. We then developed sandwich-type enzyme immunoassays (EIAs) to measure the concentration of fibronectin receptor (FNR) and vitronectin receptor (VNR). Serum immunoreactive integrin levels were measured using these EIAs in various liver and malignant diseases. In almost all cases of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), serum integrin levels were significantly elevated, but were in the normal range in gastric, colon, lung cancer, and acute hepatitis (AH). The correlation between serum FNR and VNR levels was statistically significant in all cases of liver disease, and no correlation was observed between these integrin levels and conventional biochemical markers such as AST, ALT, and GGT. The serum integrin levels were demonstrated to be a potential diagnostic marker for hepatic fibrogenesis and carcinogenesis, and these sandwich EIAs could be useful for determination of these integrins in clinical laboratory tests.
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PMID:Sandwich enzyme immunoassay for serum integrins using monoclonal antibodies. 172 78

The hepatoma-specific band of serum gamma-glutamyl transferase II (GGT II) and other three markers were evaluated in 77 patients with primary hepatocellular carcinoma (PHC). The positive rate of GGT II (87%) was much higher than that of the increased alpha-fetoprotein (AFP greater than or equal to 400 ng/ml, 54.5%), the increased alpha-1-antitrypsin (AAT greater than or equal to 400 mg/dl, 64.9%) and alkaline phosphatase isoenzyme I (ALP I, 13.0%). In patients with AFP less than 400 ng/ml, the positive rate of GGT II was 95.2%, higher than that of ALP I (22.8%) and AAT (60.0%). The positive rate of GGT II was positively correlated to the volume of PHC (r = 0.324, P less than 0.05), but even in patients with small PHC (less than or equal to 65 cm3), the positive rate of GGT II (78.6%) was higher than that of AFP (50.0%) and AAT (28.6%). The ALP I positivity was only seen in patients with larger PHC. Follow-up study showed that GGT II, like AFP, might occur before liver tumor could be detected by B-mode ultrasonography and computerized tomography. Therefore, GGT II is a valuable marker of PHC, especially in patients whose AFP was negative or slightly increased; GGT II may be useful for relatively early diagnosis of PHC.
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PMID:Reappraisal of diagnostic significance of a hepatoma-specific band of serum gamma-glutamyl transferase. 197 81

Ascitic fluid alpha 1-antitrypsin (AF-AAT) was compared with ascitic fluid total protein (AF-TP) and the serum-ascites albumin gradient (SAAG) in the differential diagnosis of ascites. The study included 82 consecutive patients of which 42 had cirrhosis, 8 hepatoma (with cirrhosis), and 27 malignant ascites (peritoneal 18, liver 9). The concentration of AF-AAT (milligrams per deciliter) was significantly elevated (P less than 0.001) in hepatoma (174 +/- 123), malignant liver disease (232 +/- 119) and peritoneal neoplasms (376 +/- 106) in comparison with cirrhotics (66 +/- 33). In separating ascites caused by cirrhosis or malignancy, AF-AAT (discriminating limit of 120 mg/dl) had a 96% sensitivity, 95% specificity, and 96% diagnostic efficacy, which was superior to the 87% observed for AF-TP and 86% for the SAAG. Similar results were obtained for the A/S AAT ratio but this test was not available in all patients. AF-AAT was particularly useful in patients with malignancy causing portal hypertension as assessed by SAAG (hepatoma, malignant liver disease). We conclude that AF-AAT may be a valuable parameter in the differential diagnosis of ascites.
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PMID:Ascitic fluid alpha 1-antitrypsin. 216 27

The activities of serum malate dehydrogenase (MDH) and its mitochondrial isoenzyme (MDHm) were studied in sera of patients with liver disease. They proved to be more useful than those of aspartate aminotransferase (AST) and its mitochondrial isoenzyme for detection of hepatocellular carcinoma and acute circulatory failure, and for estimation of the severity of acute hepatitis. The N/T value measuring system, which is adaptable for autoanalysis and allows simultaneous determination of activities depending on NAD and thionicotinamide adenine dinucleotide (thio-NAD), yields both the total activity of MDH and the N/T value which was correlated significantly with MDHm/MDH (r = 0.748). Assay of MDH and its mitochondrial isoenzyme in association with the N/T value measuring system seems to be more useful and less time consuming for estimation of the severity of liver diseases than that of AST and its mitochondrial isoenzyme.
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PMID:Clinical usefulness of malate dehydrogenase and its mitochondrial isoenzyme in comparison with aspartate aminotransferase and its mitochondrial isoenzyme in sera of patients with liver disease. 217 15

The aim of our work was to assess the performance of tissue polypeptide antigen in detecting hepatocellular carcinoma in cirrhotic patients, while also checking for any influence of liver dysfunction on the serum level of the marker. One hundred and twenty-five consecutive cirrhotic patients, 35 with and 90 without, hepatocellular carcinoma were studied. Tissue polypeptide antigen had a different distribution in the two groups and the best diagnostic accuracy with 48.6% sensitivity and 85.6% specificity was found at the cut-off value of 240 UL-1. In cirrhotic patients significant linear correlations were found between tissue polypeptide antigen and alanine-transaminase, aspartate-transaminase, G-glutamyl-transpeptidase and alkaline phosphatase; there was no correlation with bilirubin or pseudo-cholinesterase. In patients with hepatocellular carcinoma a significant linear correlation was found only with alanine and aspartate transaminase and G-glutamyl-transpeptidase. The analysis of covariance still showed a significant difference between mean tissue polypeptide antigen levels in the two groups also accounting for covariates. These results suggest that: a) the liver dysfunction may be involved in increasing tissue polypeptide antigen values; b) tissue polypeptide antigen has a different distribution in cirrhotic patients with and without hepatocellular carcinoma also accounting for covariates; these findings further support the specificity of tissue polypeptide antigen.
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PMID:The serum tissue polypeptide antigen in the detection of hepatocellular carcinoma in cirrhotic patients. 217 22

The inner mitochondrial membranes from bovine heart, rat liver, and Morris hepatoma 7777 all bound the mitochondrial isozymes of aspartate aminotransferase and malate dehydrogenase with comparable affinities and binding ratios (mg of enzyme bound per mg of membrane protein). A low molecular weight fraction separated from a detergent extract of the heart membrane by chromatography on Sephacryl S-300 contained most of the binding activity of the extract for the aminotransferase and had a dissociation constant for the aminotransferase of 0.2 microM. The protein component of the membrane binding sites for the aminotransferase was apparently present in this fraction because binding activity was largely eliminated by proteolysis with trypsin. When this fraction was chromatographed on an aminotransferase affinity column, only the portion that was bound and eluted by 0.25 M KCl associated with added aminotransferase. Unlike the membrane, which was markedly inhibited by the non-ionic detergent Genapol but was inhibited only 20% by trypsin, the binding activity of this subfraction was completely inhibited by trypsin but not by Genapol. This suggests, on the membrane, that the aminotransferase binds to the binding protein and is then transferred to lipids specifically associated with the binding protein. These putative lipids are presumably removed on the affinity column. Although the yield of the binding protein was low, there is probably ample binding protein in mitochondria to accommodate the aminotransferase. In every case, binding of the aminotransferase to the membrane inactivated the malate dehydrogenase binding site whereas malate dehydrogenase had little effect on the binding of the aminotransferase and only associated with the higher molecular weight fractions from the Sephacryl column that contained Complex I activity. Inactivation of the malate dehydrogenase site by the aminotransferase, but not vice versa, could result from aminotransferase associating with the binding protein and malate dehydrogenase with Complex I followed by association of the enzymes with lipids located in the same region of the membrane. However, since aminotransferase is more cationic, it is not displaced readily from the lipids by malate dehydrogenase. The relevance of these interactions to the organization of the enzymes is discussed.
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PMID:Interactions among mitochondrial aspartate aminotransferase, malate dehydrogenase, and the inner mitochondrial membrane from heart, hepatoma, and liver. 224 39

Rat liver cytosolic sulfotransferase activity forms the highly reactive sulfuric acid ester of N-hydroxy-2-acetylaminofluorene (N-OH-2AAF), an ultimate carcinogen in 2-acetylaminofluorene (2AAF) hepatocarcinogenesis. A previous report demonstrated that 2AAF-induced liver hyperplastic nodules displayed a persistent loss of cytosolic N-OH-2AAF sulfotransferase activity following a hepatocarcinogenesis-producing regimen of 2AAF administration. As an initial step in examining the mechanism responsible for lowering N-OH-2AAF sulfotransferase activity, a monospecific polyclonal antibody to aryl sulfotransferase IV (AST IV) was produced and used in the assessment of AST IV as a candidate enzyme for liver cytosolic N-OH-2AAF sulfotransferase activity. Studies comparing the levels of N-OH-2AAF sulfotransferase activity of highly purified AST IV and rat liver cytosols with corresponding immunochemical analysis of AST IV contents demonstrated that there was sufficient AST IV activity in liver cytosols to indicate that it was the primary enzyme catalyzing cytosolic N-OH-2AAF sulfation. A subsequent immunochemical survey of nine extrahepatic tissues showed no detectable AST IV content and indicated that AST IV expression may be tissue specific. An immunochemical comparison of AST IV levels in control liver cytosols (high in sulfotransferase activity) with cytosols from 2AAF-derived hyperplastic nodules (low in sulfotransferase activity) or liver tumors (no sulfotransferase activity) showed low or no detectable levels, respectively, of AST IV. In addition, an immunochemical analysis of four rat hepatoma cell lines showed they contained no detectable levels of AST IV. These results suggested a strong correlation existed between a decrease in AST IV expression and tumor development. When the liver cytosols of rats taken from early, intermediate, and late stages of 2AAF carcinogenesis were analyzed for the development of a persistent loss of N-OH-2AAF sulfotransferase activity, a parallel loss of cytosolic N-OH-2AAF sulfotransferase activity and AST IV content was observed in rats which had proceeded from a stage of low risk to high risk for liver cancer. These findings indicated that (a) AST IV, a liver-specific enzyme, was the principle enzyme comprising cytosolic N-OH-2AAF sulfotransferase activity and (b) the decrease in sulfotransferase activity in nodules and tumors resulted from a decrease in the level of AST IV expression. Furthermore, it is suggested that a persistent decrease in AST IV expression may reflect a role for AST IV as part of a resistance phenotype in which transforming liver cells are able to escape the cytotoxic effects of highly reactive 2AAF metabolites and progress to cancer.
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PMID:2-Acetylaminofluorene-mediated alteration in the level of liver arylsulfotransferase IV during rat hepatocarcinogenesis. 238 38

The presence and distribution of AFP, AAT and HBsAg in peritumoral non-neoplastic hepatocytes (NNH) of 27 cases and, at the same time, in the neoplastic tissue of 37 liver cell carcinoma (HCC) were studied; AFP and HBsAg were more frequently found in NNH than in HCC cells; no differences were found for AAT. The presence of HBsAg also in normal liver without cirrhosis is probably best explained by its possible role in neoplastic transformation and by the inhibition of replication of the viruses AFP, considered to be expression of dedifferentiated cells, may possible be taken up by NNH for catabolic purposes.
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PMID:Immunohistochemical study of the appearance of some markers in liver adjoining hepatocellular carcinoma. 242 60


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