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)

Seraclear-HE, containing seven enzyme analytes from human sources, was evaluated as an intermethod calibrator for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) to transfer Reference Method values to seven routine methods, including one based on hydrogen peroxide detection for possible unification of values (interlaboratory comparability of data). The commutabilities of AST from erythrocytes and ALT from a hepatoma cell line were studied between the consensus methods of Japan Society of Clinical Chemistry (chosen as the Reference Methods) and each of the automated routine methods at reaction temperatures of 30 degrees C and 37 degrees C. For AST, calibration of patients' sera with Seraclear-HE decreased average intermethod variation (CV) from 12% to 2%; for ALT, the decrease was from 20% to 3%. For both enzymes, Seraclear-HE was judged to be commutable between the Reference Methods and each of the methods investigated. The limitations for such use are discussed.
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PMID:Multienzyme control serum (Seraclear-HE) containing human enzymes from established cell lines and other sources. 2: Evaluation as candidate working enzyme Reference Material for alanine and aspartate aminotransferases. 776 7

We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for serum ornithine carbamoyltransferase (OCT) protein, and examined serum OCT concentrations in patients with various liver diseases. OCT concentrations were markedly elevated in cases of hepatic encephalopathy, 'acute on chronic', and those with the acute phase of acute hepatitis, moderately in chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis, and slightly in those with a fatty liver. High percentages (92-98%) of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma had higher than normal concentrations of serum OCT protein. There was a close correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and moderate correlations with those of mitochondrial AST, glutamate dehydrogenase and gamma-glutamyltranspeptidase. The OCT/ALT ratio was higher in patients with liver cirrhosis than in those with chronic hepatitis (p < 0.001), and was still higher in cases of hepatocellular carcinoma (p < 0.05). In 2 patients with 'acute on chronic' disease, OCT concentrations decreased similarly with or more rapidly than AST or ALT activities after admission. In 2 patients with hepatic encephalopathy, the OCT concentrations changed similarly with AST and ALT activities. This OCT ELISA system will aid in diagnosing various liver diseases and in the follow-up of the patients, and the OCT/ALT ratio may serve for a differential diagnosis of liver diseases.
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PMID:Clinical evaluation of serum ornithine carbamoyltransferase by enzyme-linked immunosorbent assay in patients with liver diseases. 778 67

Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are the accepted sequelae of chronic hepatitis C virus (HCV) infection. However, the real natural history of HCV infection is not still well understood. To approach this problem, we investigated 91 individuals positive for antibodies against HCV (anti-HCV), who have received annual liver function examination in a local town known to have had high carrier rates of hepatitis B virus (HBV) and HCV. Among the 91 anti-HCV-positive individuals, 63 had undertaken the annual examination more than five times in the past 14 years. We analyzed retrospectively the past liver function test results of these 63 subjects and evaluated their present virological status by determining HCV genotypes and estimating quantity of HCV RNA in the sera. Among the 63 subjects, 50 (79.4%) had HCV RNA in the serum and 40 (80%) of the 50 subjects with HCV RNA had abnormal alanine aminotransferase or aspartate aminotransferase level more than once in their records. However, the other 10 (20%) had no abnormal levels during the period examined. Six of 50 (12%) had ultrasonographic findings suggestive of cirrhosis. Thus, HCV-infected individuals in this area did not seem to have progressive liver diseases. Considering the advanced ages of the individuals examined (mean 64 years old), we may have observed a stage in the natural history of HCV infection in which viremia persists in most individuals and the tendency to progress to serious chronic liver disease is mild.
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PMID:A retrospective study of hepatitis C virus carriers in a local endemic town in Japan. A possible presence of asymptomatic carrier. 785 Dec 13

Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer.
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PMID:Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice. 786 54

Rat hepatic aryl sulfotransferase IV (AST IV), which catalyses sulfuric acid esterification of N-hydroxy-2-acetylaminofluorene to its ultimate carcinogenic form, is differentially expressed during multistep 2-acetylaminofluorene (AAF) hepatocarcinogenesis. Two molecular mechanisms associated with this effect involve modulation of mRNA translational capacity at the early stages, and gene transcription at the late stages of the carcinogenic process. To characterize further the molecular mechanisms that may be involved in the transient regulation of the enzyme expression, an AST IV cDNA was used to assess the change in methylation profile and restriction fragment length polymorphism (RFLP) in the gene domain of genomic DNA derived from rats at different stages of carcinogenesis. The onset of hypomethylation of the AST IV gene domain and amplification of a 5.3-kb DNA sequence was found to correlate with the stage in AAF hepatocarcinogenesis, where rats begin to exhibit irreversible loss in hepatic enzyme expression and the liver becomes committed to hepatoma formation. This represents the first observation of both altered methylation status of AST IV gene domain and amplification of a DNA sequence whose expression may play a role in the genesis and/or progression of neoplastic transformation of initiated cells during AAF hepatocarcinogenesis.
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PMID:Hypomethylation of the rat aryl sulfotransferase IV gene and amplification of a DNA sequence during multistage 2-acetylaminofluorene hepatocarcinogenesis. 791 17

The authors measured immunoenzymatically circulating intercellular adhesion molecule-1 (cICAM-1) concentration in 135 patients with liver disease of either viral or toxic etiology: 13 had acute hepatitis; 58 had mild chronic liver disease; and 64 had cirrhosis (superimposed in 30 by hepatocellular carcinoma). Forty patients with extrahepatic diseases (19 with malignancies) and 28 healthy blood donors were tested as controls. One-way analysis of variance demonstrated a significant variability of cICAM-1 concentration among groups (F = 76.67, P < .0001), the highest value being recorded in acute hepatitis (Bonferroni's test for pairwise comparisons, P < .01). Total bilirubin showed a strong correlation with cICAM-1 (R = 0.766, P < .001). By stepwise multiple regression analysis the independent predictors of cICAM-1 concentration were chosen in the following order: total bilirubin; aspartate aminotransferase; cholinesterase; alpha-1-antitrypsin; and immunoglobulins. Thus, in addition to inflammation, cholestasis and decline of functioning hepatic mass may influence cICAM-1 concentration.
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PMID:Circulating intercellular adhesion molecule-1 (cICAM-1) concentration in liver disease. Relationship with cholestasis and functioning hepatic mass. 794 24

Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, gamma-glutamyltranspeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second-generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. 798 43

The pharmacokinetics and clinical activity of epirubicin were investigated in 16 patients with hepatocellular carcinoma (HCC) who received epirubicin at 75 mg/m2; the drug was given intravenously to 7 patients and via the hepatic artery to 9 patients (7 of whom also underwent embolisation). Lignocaine (1 mg/kg) was also given intravenously to 15 patients, and the metabolite monoethylglycinexylidide (MEGX) was measured as an indicator of liver function. Epirubicin clearance correlated with serum aspartate aminotransferase (AST), albumin and bilirubin values in patients treated intravenously or intraarterially. Although the route of administration did not affect the median total plasma clearance of epirubicin, early- and intermediate-phase clearance was higher following intraarterial administration. MEGX levels correlated with serum bilirubin levels but there was no correlation with albumin or AST values or epirubicin clearance. The rate of response to epirubicin was 3/13 (23%; 95% confidence interval, 8%-50%). Intravenous epirubicin was tolerated well, but intraarterial treatment was associated with significant morbidity. These data confirm that although current recommended dose adjustments are based primarily on serum bilirubin levels, altered epirubicin pharmacokinetics correlate more strongly with AST and albumin values than with serum bilirubin concentrations. However, at this dose and schedule, epirubicin has only modest activity against HCC.
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PMID:Epirubicin in hepatocellular carcinoma: pharmacokinetics and clinical activity. 807 7

To assess the features of multicentric occurrence in hepatocellular carcinoma, we analyzed 10 of 72 patients (14%) who had undergone hepatic resection for hepatocellular carcinoma from May 1989 to October 1992 both clinically and pathologically. The multicentric occurrence of hepatocellular carcinoma was defined among the simultaneously detected small tumors as (a) at least one tumor consisting of extremely well-differentiated (grade I) hepatocellular carcinoma growing in a replacing pattern or (b) one of a group of hepatocellular carcinomas growing in an area of adenomatous hyperplasia. Of the 10 patients, the tumors in 9 were diagnosed as synchronous multicentric hepatocellular carcinomas, whereas the tumor in 1 was considered metachronous. All patients had cirrhosis; one of them had hepatitis B virus infection and nine patients had HCV infection. The inflammatory findings in the parenchyma were determined on the basis of serum enzyme values (AST, 89 +/- 27 IU/L; ALT, 96 +/- 43 IU/L). One or two tumors in 9 of 10 patients had thin trabecular or trabecular patterns showing replacing growth. In addition, one of the two tumors in two of nine patients was observed growing in areas of adenomatous hyperplasia. Recurrences were found in 4 of 10 patients. The 3-yr disease-free survival rate was 23%. Multiple recurrences were recognized in the two patients, and in the patients who underwent repeat surgery, grade I tumors were also found. Even though these tumors were small and well-differentiated, the recurrence rate was high. Therefore to detect the recurrence of metachronous multicentric hepatocellular carcinoma at an earlier stage, careful follow-up after surgery should be carried out.
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PMID:Possible multicentric occurrence of hepatocellular carcinoma: a clinicopathological study. 813 62

Large cell liver cell dysplasia (LCD), a suggested preneoplastic change progressing to hepatocellular carcinoma, has been reported associated with alpha-1-antitrypsin deficiency which in some countries has an increased frequency of hepatocellular carcinoma. We examined the nonneoplastic liver from 13 alpha-1-antitrypsin deficiency patients for LCD and, using a labeled streptavidin-biotin technique, for immunohistochemical markers: AAT (1/200), hepatitis B surface (HBsAg, prediluted) and core (HBcAg, 1/400) antigens, and monoclonal (1/20) and polyclonal (1/40) mutant p53, a tumor suppressor gene. There were eight males and five females ranging from 2 mo to 76 yr (mean 40 yr). Nine livers showed cirrhosis, one chronic persistent hepatitis, one portal fibrosis, and two cholestatic hepatitis (in the two infants). The nine cases with LCD included five males and four females of mean age 46 yr (range, 17-71), eight with cirrhosis and one with portal fibrosis. Only one liver with LCD and cirrhosis had HBcAg in cirrhotic and dysplastic cells. No patient had developed hepatocellular carcinoma. All 13 livers were immunonegative for HBsAg and mutant p53, and immunopositive for AAT present in normal, cirrhotic, and dysplastic liver cells. Thus, LCD was identified in 82% of adult alpha-1-antitrypsin deficiency livers (69% including infantile patients), 89% with cirrhosis, and none with malignancy. HB expression was rarely present; serology for HB and/or hepatitis C was positive in 46% adults. Immunoreactive AAT was present in dysplastic cells. p53 gene mutations do not appear to have a role in the pathogenesis of LCD in alpha-1-antitrypsin deficiency.
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PMID:Liver cell dysplasia in alpha-1-antitrypsin deficiency. 815 50


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