Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extracellular matrix (ECM) located in and around tumors is different from normal organ stroma, and there is evidence that it is critically involved in carcinogenesis and malignant growth. Whereas an abnormal composition of ECM in hepatocellular carcinomas (HCC's) has previously been demonstrated, not much is known so far with respect to putative HCC precursor lesions. We have, therefore, systematically analyzed the immunohistochemical reactivity for two major ECM components, tenascin and type IV collagen, in three types of liver cell dysplasia (LCD), and compared the findings with patterns observed in HCC's of different types and grades. Tenascin reactivity was generally stronger in HCC's than in cirrhosis. In cirrhotic nodules harboring areas of LCD, tenascin expression was significantly lower in small cell LCD than in large cell LCD. Type IV collagen reactivity in and around HCC's decreased as a function of a lower differentiation grade. In both groups of cirrhosis, i.e. with or without HCC, cirrhotic nodules occupied by the small cell variant of LCD exhibited a significantly lower type IV collagen reactivity than those with large cell LCD or simple regenerative cells. Taken together these findings suggest that, similar to adenomatous hyperplasia, small cell LCD is characterized by an abnormal tenascin and type IV collagen expression, thus reflecting the defective ECM pattern observed in HCC's.
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PMID:Tenascin and type IV collagen expression in liver cell dysplasia and in hepatocellular carcinoma. 886 54

Cathepsin D serum mass concentrations were determined by enzyme immunoassay in patients with hepatocellular carcinoma (n = 51) and/or liver cirrhosis (n = 92) or benign steatosis (n = 16) and correlated with some biochemical and clinical properties of these diseases. Increased cathepsin D serum mass concentrations (P < 0.001) were observed in all these groups of patients as compared to normal subjects (n = 98). However, patients with steatosis had serum mass concentrations of this enzyme significantly lower (mean 2-3 fold) than those measured in cancer patients (P < 0.05) or cirrhotic patients (P < 0.001). Interestingly, significantly higher cathepsin D serum mass concentrations (mean + 62%) (P < 0.006) were determined in the cirrhosis group as compared to cancer patients. No correlation between cathepsin D and a number of clinical and biochemical properties examined, namely, alpha-foetoprotein, number of neoplastic lesions and tumour size in cancer patients or, Child-Pugh grade of severity of cirrhosis and other enzymes of liver function tests in the cirrhotic group was found. The present data and those from other studies which indicate that cathepsin D may be involved in carcinogenesis suggest that this enzyme may be potentially useful as an additional biochemical marker to identify cirrhotic patients who may develop precancerous hepatic nodules.
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PMID:Cathepsin D serum mass concentrations in patients with hepatocellular carcinoma and/or liver cirrhosis. 886 4

Hepatitis B virus (HBV) plays a major role in liver carcinogenesis. HBV-DNA integration into cellular DNA provides some molecular basis for understanding the mechanisms of neoplastic transformation of the liver cell. Persistence of HBV-DNA episomic forms, necro-inflammation in the liver, and cirrhosis appear to be additional promoting factors. We studied the possible association between hepatocellular carcinoma (HCC) and the defective hepatitis D virus (HDV), a virus that requires the helper function of HBV. Patients infected with HDV and HBV develop HCC about 10 years earlier than those infected with HBV alone. Persistence of active HDV disease and low levels of "wild-type" HBV (i.e., secreting the hepatitis B surface antigen [HBsAg]) are associated with progressive liver disease and HCC. Therefore, HBV replication, in spite of being inhibited by HDV, appears to play a major role sustaining HDV pathogenicity. Detection of antibody to the hepatitis C virus (HCV) in many HCC patients raises the important question whether HCV has oncogenic potential. Clinico-epidemiological data show that the most severe forms of liver disease in patients with multifactorial liver damage occur in those infected with HCV. The prevalence of HBV markers in patients with cirrhosis, HCC, and HCV infection is higher than in individuals with comparable age and other diseases. HBV-DNA integration occurring early during HBV infection can persist in those with and without detectable HBsAg in their serum. Therefore, one can speculate that in patients with integrated HBV-DNA and concurrent HCV infection, cirrhosis and HCC may develop more easily than in patients without HBV-DNA integration. HCV hampering the immune system also might play a role in the genesis of HCC. The evidence that multiple hepatitis viruses are more frequently associated with HCC than infections of one virus alone has important practical consequences. It warrants the identification of high risk patients so that they can be monitored frequently for early diagnosis and treatment.
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PMID:Hepatocellular carcinoma and infections with multiple hepatitis viruses. 887 10

Hepatitis B virus (HBV) has been recognized for a long time as a major etiological factor in hepatocellular carcinoma (HCC) in endemic regions. HCCs occurring in Europe, an area with a low prevalence of HBV infections, are in fact also linked to chronic HBV infection, as revealed by the detection of the viral genome and HBV X gene transcripts in the tumor. There is also a significant association with hepatitis C virus (HCV) infection and a complex interplay may occur between HBV, HCV, and other environmental factors such as alcohol, as well as genetic factors. Preliminary evidence exists for a role of HCV in liver carcinogenesis even without the pre-existing cirrhosis.
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PMID:Hepatitis B and C viruses in hepatitis B surface antigen negative hepatocellular carcinoma patients. 887 25

O6-methylguanine DNA methyltransferase (MGMT) is a repair protein that transfers methyl groups from O6-methylguanine to a cysteine acceptor in its own molecule, and restores DNA to its undamaged state. If left unrepaired, O6-methylguanine can pair with either a thymine or a cytosine, causing a C-G to T-A transition, which is considered to be one of the molecular mechanisms of both mutagenesis and carcinogenesis. The expression of MGMT mRNA in liver tissue was quantitatively assessed by the competitive reverse transcription-polymerase chain reaction method in patients with chronic liver diseases with or without alcohol drinking. MGMT mRNA expression was 1.4 +/- 0.9 pg/micrograms RNA in control livers. Its expression in chronic hepatitis was 3.8 +/- 0.7 in alcoholics and 2.7 +/- 0.8 in nonalcoholics, which were not statistically different. MGMT mRNA expression in liver cirrhosis was significantly low, compared with that in chronic hepatitis, and 0.8 +/- 0.3 in alcoholics and 0.5 +/- 0.1 in nonalcoholics, which also were not significantly different. The present study shows that MGMT mRNA was not decreased in patients with chronic liver diseases with alcohol drinking, compared with those without alcohol drinking.
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PMID:Effect of alcohol drinking on gene expression of hepatic O6-methylguanine DNA methyltransferase in chronic liver diseases. 898 26

The pathogenetic mechanisms of hepatitis C virus (HCV) infection are poorly known. An understanding of HCV biology and the potential clinical impact of HCV genetic variability is essential to managing, treating, and preventing HCV infections. HCV is a member of the Flaviviridae viral family. Its genome is a positive, single-strand RNA molecule. The structure of the HCV particles is poorly known due to the lack of an efficient cell culture system as well as a striking heterogeneity in density. The core protein may have a regulatory role on both viral and cellular gene expression. The mechanisms of HCV-RNA replication may include synthesis of negative strand intermediates, which drive synthesis of new positive RNA genomes. New procedures have been developed to better identify and characterize the HCV-RNA genome. The mechanisms of HCV persistence are currently unknown, although it is known that HCV chronicity develops despite humoral and cellular responses to HCV proteins. HCV-RNA shows significant genetic variability with an estimated rate of nucleotide change of approximately 10(-3) substitutions/site/year. Currently, three major HCV genotypes and three to seven minor subtypes can be distinguished. The geographical distribution of these genotypes and subtypes varies significantly. It appears that poor clinical response to interferon (IFN) is more common with HCV genotype 1. In addition, some studies have shown an association between chronic infection, severe chronic hepatitis, and cirrhosis with subtype 1b. Further, there is evidence for a potential direct effect of HCV in liver carcinogenesis, with subtype 1b possibly being an independent risk factor for hepatic carcinoma development. HCV-RNA circulates as a population of RNA molecules, which creates a heterogeneity referred to as "quasispecies." It is possible that some HCV strains might have direct clinical implications. It may be that highly heterogeneous populations observed prior to treatment might correlate with a lower rate of response to IFN therapy.
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PMID:Hepatitis C virus: molecular biology and genetic variability. 901 78

Basic fibroblast growth factor (FGF) is thought to be involved in carcinogenesis and, to clarify its clinical significance, the study of its blood level in cancer patients is important. Plasma levels of basic FGF are reported to be elevated in some cancers. However, little is known of basic FGF levels in plasma in hepatocellular carcinoma (HCC). In this study, we measured basic FGF plasma levels in patients with chronic liver disease and compared the levels in chronic hepatitis (CH), liver cirrhosis (LC), and HCC. We also examined whether these levels were related to serum levels of asparate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, total bilirubin, total protein, and albumin, and to the indocyanine green test (i.e., liver function tests) and to type III procollagen. 7S domain of IV type collagen, and hyaluronic acid (i.e., markers of liver fibrosis). Levels of basic FGF, determined by a quantitative "sandwich" enzyme immunoassay, were significantly elevated with the progression of liver disease; being 3.67 +/- 2.37 (mean +/- SD). 7.78 +/- 6.61, and 12.37 +/- 7.67 pg/ml in the CH, LC, and HCC groups, respectively. FGF levels were elevated to a greater extent in the HCC patients than in the CH (P < 0.0001) and LC patients (P = 0.0117). Levels were higher in LC than in CH (P = 0.0204). None of the liver function test findings or levels of markers of liver fibrosis were correlated with levels of basic FGF. These results suggest that circulating basic FGF could serve as a new indicator of the progression of chronic liver disease. The extremely elevated plasma of level basic FGF in the HCC group suggests that basic FGF may be related to the development of HCC.
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PMID:Plasma level of basic fibroblast growth factor increases with progression of chronic liver disease. 905 7

Telomeres shorten progressively with age in normal somatic cells in culture and in vivo. The maintenance of telomere length is assumed to be an obligatory step in the progression and immortalization of most human tumor cells. To understand the role of telomere dynamics in the development of hepatocellular carcinoma (HCC), we examined the length of terminal restriction fragment (TRF), as an indicator for telomere length, in HCC and surrounding tissues with chronic active hepatitis (CAH) or liver cirrhosis (LC). The study was performed in 12 hepatitis C virus (HCV) antibody-positive, 12 hepatitis B virus (HBV) antigen-positive tissues, and 4 tissue samples from virus-negative patients with HCC. The peak TRFs in all 3 types of HCC were significantly shorter than those of the surrounding tissues (i.e., LC or CAH). TRFs examined in one patient with atypical adenomatous hyperplasia (AAH) also was shortened. Thus, progressive TRF shortening occurs from normal to CAH to LC to HCC(AAH). Telomerase, an enzyme that adds repeated telomere sequences onto the chromosome ends and stabilizes telomere length in immortal cells, also was examined in tissues and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AAH case was similar to that of HCC. In addition, the telomerase activity of biopsy samples with a fine 21-gauge needle also was examined in 10 HCCs, 2 adenomatous hyperplasias (AHs), 2 LCs, and 2 CAHs. We found strong telomerase activity in all the HCCs and surprisingly in the 2 cases that were pathologically diagnosed as AH. Thus, the findings strongly suggest that persistent cell proliferation or rapid cell turnover through damage of hepatic cells result in a process of multistep hepatocellular carcinogenesis. Thus, progressive shortening of telomeres and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease.
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PMID:Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis. 906 81

Various criteria have been proposed for the identification of early neoplastic changes in the setting of both small hepatocellular carcinomas and macroregenerative nodules. In this study we have applied those criteria to cases of liver cirrhosis without tumour (group I) and hepatocellular-carcinoma-associated cirrhosis (group II) to assess their discriminatory value in these two situations. Group I included 50 liver biopsies with uncomplicated cirrhosis while group II encompassed 48 liver biopsies of cirrhotic nodules adjacent to hepatocellular carcinomas. The histological changes sought were large cell dysplasia, small cell dysplasia, cytoplasmic basophilia, small microacinar structures, peripheral distribution of nuclei, nuclear irregularities and thickened liver cell plates. These changes were also assessed in macroregenerative nodules (nine in group I and seven in group II). None of these changes was useful to discriminate between group I and group II cirrhotic nodules when assessed separately. On the other hand, cirrhotic nodules showing three or fewer changes were never associated with malignancy, whereas those exhibiting four or more alterations were often located in the vicinity of a tumour. Acinar structures, thickened cell trabeculae, peripheral distribution of nuclei and nuclear irregularities seem to be the most specific indicators of proximity to a hepatocellular carcinoma. Similar results were obtained for macroregenerative nodules. These results may be helpful as guidelines to the probability of having a hepatocellular carcinoma elsewhere in livers containing atypical cirrhotic nodules, and may also prove valuable in the selection of appropriate material for investigating early molecular events in hepatic carcinogenesis.
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PMID:Liver cell atypias: a comparative study in cirrhosis with and without hepatocellular carcinoma. 906 32

We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.
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PMID:Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues. 909 64


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