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 surgical specimen of solitary, encapsulated tumor tissue obtained from a 52-year-old male, diagnosed histologically as well-differentiated hepatocellular carcinoma (Grade II, Edmondson and Steiner) with liver cirrhosis, Type A' (and B is some parts), was found to have a supernormal level of pyruvate kinase Type L and subnormal level of Type M2; the activities (units/mg protein) being 1.21 and 0.12 respectively. The resulting isozyme pattern was apparently "superdifferentiated" as compared with those of not only the tumor-bearing, cirrhotic liver (Type L, 0.19; Type M2, 0.67) but also the normal liver (Type L, 0.47+/-0.05; Type M2, 0.18+/-0.02). The electrophoretic and kinetic properties of the type L isozyme were identical with those of the cirrhotic host liver and a non-cirrhotic control liver. Other enzyme levels in the hepatoma tissue were as follows: Glucose-6-phosphatase, norma; fructose-1,6-bisphosphatase, reduced; glucokinase, absent; and hexokinase Types I and III, and glucose-6-phosphate dehydrogenase, slightly increased. The serum alpha-fetoprotein level was 95 ng/ml. The whole enzyme profile is consistent with the minimal deviation hepatomas in rats. The results were compared with those of other human hepatomas, and the mechanisms of disordered regulation in hepatoma gene expression were discussed.
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PMID:A case of minimal deviation hepatoma in man with elevated liver-type pyruvate kinase isozyme. 19 53

Two series of interspecific hybrids have been generated between liver cells (which actively secrete several serum proteins) and fibroblasts (which do not). In each series, one of the parental cells was a normal diploid cell: mouse hepatoma cells were fused with normal diploid rat fibroblasts, and normal rat liver cells were fused with mouse fibroblasts of the permanent line A9. The production of albumin, alpha-fetoprotein (AFP) transferrin and the third component of complement (C3) was analysed in these hybrids. Most hepatoma cell hybrids exhibit extinction of albumin, AFP and (to a lesser extent) transferrin; they retain the capacity to secrete C3. Normal liver cell hybrids are also characterized by the absence of albumin and transferrin production and by retention of C3 secretion. These results, when compared to previous results obtained with hybrids derived exclusively from different differentiated cells of permanent and transformed lines show that the phenotype of such hybrids is not determined by the abnormal character per se of the aneuploid parental cells. Amongst the rat fibroblast-mouse hepatoma cell hybrids, a few clones retain the capacity to actively secrete mouse albumin, AFP and transferrin, without the concomitant production of the rat serum proteins. These hybrids have lost more rat (fibroblast) chromosomes than the other clones and also have an increased number of mouse (hepatoma) chromosomes. Thus, their phenotype must result from either the complete loss of 'extinguisher' chromosomes, or gene dosage effects. The significance of the lack of rat serum protein production is also discussed, and it is suggested that retention, without concomitant activation, could be explained in terms of diffusible regulators and heritable differences in chromatin conformation.
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PMID:Production of serum proteins in normal diploid fibroblast-hepatoma cell hybrids and in A9-normal liver cell hybrids. 21 85

A significant aspect of primary hepatic carcinoma in man is the high positive correlation of hepatocellular carcinoma with infection with hepatitis B virus (HBV)1. Analysis of the relationship between HBV infection and oncogenesis is difficult because natural infection with HBV is limited to man and experimental infection has been achieved only in chimpanzees and gibbons. Furthermore, because HBV has not been successfully propagated in cell culture, basic study of virus-cell interaction of the aetiological agent of one of the most widespread infections of man has been impossible. Recently, however, a cell line (PLC/PRF/5) derived from a human hepatoma biopsy was described which produces the HRV surface antigen (HBsAg) and so provides a tool for the experimental investigation of HBV in viro. We now report the derivation and characterisation of two additional cell lines primary liver carcinomas. In contrast to the PLC/PRF/5 cell line, these cell lines retain the capacity to synthesise many human plasma proteins, including both albumin and alpha-fetoprotein (AFP). One of these lines also produces BHsAg. We also present evidence that HBsAg synthesis and secretion in this cell line are correlated with the growth state of the culture. This finding is in contrast to the continuous HBsAg production found in the PLC/PRF/5 cell line.
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PMID:Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. 23 37

A quantitative immunoenzymatic assay has been developed for alpha-fetoprotein which is sensitive and specific. Seventy-eight percent of United States hepatoma patients have detectable serum alpha-fetoprotein elevations over 50 ng/ml, whereas only 2 of 93 other gastrointestinal tumors were positive. Thirteen percent of patients with acute viral hepatitis, 44% of patients with massive hepatic necrosis, and 23% of patients with chronic active hepatitis had measurable serum alpha-fetoprotein concentrations. However, patients with non-viral acute or chronic liver disease were largely alpha-fetoprotein negative and alpha-fetoprotein was undetectable on multiple postoperative samples from 6 patients after hepatic lobectomy in the rapidly regenerating phase. Therefore, alpha-fetoprotein elevations in nonmalignant liver diseases are not due solely to hepatic regeneration but appear to be related to viral injury. The immunoenzymatic assay does not require purified antigen or radioisotope equipment and can detect and quantitate clinically significant alpha-fetoprotein levels greater than 50 ng/ml.
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PMID:Serum alpha-fetoprotein (AFP) in benign and malignant gastrointestinal diseases: evaluation of an immunoenzymatic assay. 112 34

To determine alpha-fetoprotein (AFP) in human saliva, a highly sensitive sandwich enzyme immunoassay for saliva AFP was developed. AFP standards and saliva samples were added into the wells of a polystyrene plate coated with goat IgG antibody against human AFP. After incubation, the wells were washed and horseradish peroxidase-labelled antibody was added. The enzyme activity specifically bound to the well was assayed using 3,3',5,5'-tetramethylbenzidine and hydrogen peroxide as substrate. The reaction was stopped by addition of 2 M sulphuric acid and the AFP concentration was determined from the absorbance at 450 nm. The minimum detectable concentration was 8 ng/L. The recovery of AFP mixed with human saliva was 91.1-102.4%. The within-assay and between-assay coefficients of variation were 6.5-8.9% and 7.6-10.8%, respectively. The assay correlated well with a radioimmunoassay for human AFP (r = 0.985, n = 13, P less than 0.001). The mean concentration of AFP in normal human saliva was 14.3 ng/L (SEM = 4.9 ng/L, n = 10) and significantly higher levels of saliva AFP were observed in hepatocellular carcinoma patients with positive serum AFP (mean 1367.8 ng/L, SEM 595.4 ng/L, n = 6; P less than 0.001). Strong correlation was observed between saliva AFP and serum AFP (r = 0.978, P less than 0.01, n = 13).
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PMID:Highly sensitive sandwich enzyme immunoassay for alpha-fetoprotein in human saliva. 128 27

Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma.
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PMID:Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis. 128 Feb 43

We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.
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PMID:Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire. 128 Mar 14

We describe the case of a 56-yr-old man with primary gastric adenocarcinoma, who had an extremely high plasma level of des-gamma-carboxy prothrombin (2.45 AU/ml) and of serum alpha-fetoprotein (2810 ng/ml). Histopathologically, the gastric cancer was a IIc type of early cancer which consisted of a combination of a poorly differentiated adenocarcinoma and a well-differentiated tubular adenocarcinoma. The association of a hepatic tumor including hepatocellular carcinoma or liver metastasis was ruled out by ultrasonography, computed tomography, radiocolloid liver scan, magnetic resonance imaging, and angiography. Foci strongly resembling hepatocellular carcinoma (hepatoid differentiation) were noted in the gastric tumor. Localization of des-gamma-carboxy prothrombin and alpha-fetoprotein within the tumor cells, especially within the hepatoid differentiated foci, was demonstrated by the immunohistochemical staining of tissue obtained at biopsy and the resected specimen. This case seems to be the first case reported in which des-gamma-carboxy prothrombin was produced by the gastric cancer. This finding supports the theory of hepatoid differentiation of a gastric cancer.
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PMID:Des-gamma-carboxy prothrombin (PIVKA-II) and alpha-fetoprotein-producing IIc-type early gastric cancer. 128 Apr 6

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes; however, in certain human hepatoma cell lines, the growth is inhibited by HGF. In the present study, the effect of HGF on the alpha-fetoprotein (AFP) gene expression was analyzed in PLC/PRF/5 human hepatoma cells. HGF did not inhibit cell proliferation, but dose-dependently suppressed AFP secretion at the concentrations of 10 ng/ml or less. By Northern blot analysis, the levels of AFP mRNA were suppressed by HGF, whereas the levels of beta-actin mRNA used as a control did not show any significant changes. In the transient chloramphenicol acetyltransferase plasmid transfection assays, the AFP promoter activity was repressed by HGF, in contrast, the AFP enhancer activity was not affected by HGF. These results suggest that the AFP gene expression is down-regulated by HGF through the suppression of its promoter activity in human hepatoma cells.
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PMID:Hepatocyte growth factor down-regulates the alpha-fetoprotein gene expression in PLC/PRF/5 human hepatoma cells. 128 Apr 22

The effect of transforming growth factor beta (TGF beta) on the expression of a group of liver genes has been investigated in the hepatoma cell line Hep 3B. TGF beta induces a decrease of the basal level of apolipoprotein A-II (ApoA-II), retinol binding protein (RBP) and alpha-fetoprotein (alpha Fp). Furthermore, TGF beta efficiently antagonizes the IL-6-induction of hemopexin (Hpx) and haptoglobin (Hp) and alpha 1-acid glycoprotein (AGP). These effects of TGF beta are apparently mediated by post-transcriptional mechanism(s). These findings, together with previously reported data on the inhibitory effect of TGF beta on acute phase genes (e.g. ApoA-I and albumin), suggest a role for TGF beta in the regulation of expression of liver genes.
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PMID:Effect of TGF beta on liver genes expression. Antagonistic effect of TGF beta on IL-6-stimulated genes in Hep 3B cells. 128 May 99


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