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)

Apoptosis is a type of cell death which is clearly distinguishable from necrosis in its morphological and biochemical features. To clarify the role of apoptosis in alcoholic liver injury, we investigated the expression of apoptosis-related Lewis(Le)(y) antigen by immunohistochemistry in liver samples from patients suffering from alcoholic liver disease. Liver biopsy samples were taken from 20 patients who drank more than 80 g of ethanol per day on average. Indirect immunohistochemical staining was carried out using anti-cytokeratin and anti-Le(y) antibodies. To examine the relationship between Mallory bodies and apoptosis, double staining was performed using both antibodies. In alcoholic hepatitis, many Mallory bodies were stained with anti-cytokeratin antibody in hepatocytes of the centrilobular area. Le(y) antigen was also detected in hepatocytes in the same area. Immunohistochemical double staining showed that some of the hepatocytes containing Mallory bodies were stained with anti-Le(y) antibody. Few hepatocytes expressing Le(y) antigens, however, were observed in other types of alcoholic liver disease, including steatosis, fibrosis and cirrhosis. From these results, it is suggested that apoptosis may also be involved in alcoholic hepatitis and that hepatocytes containing Mallory bodies can be eliminated by apoptosis.
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PMID:Is apoptosis involved in alcoholic hepatitis? 906 9

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic factor in women with ovarian cancer. To determine the specificity of the M3/M21 test, we investigated M3/M21 serum levels in several benign conditions. This retrospective study comprises 37 patients with ovarian cancer FIGO stages Ia to III. Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases, respectively. With a sensitivity of 57% and a specificity of 95%, M3/M21 is not suitable as a screening marker for ovarian cancer. Although M3/M21 is able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 does not provide information additional to CA 125. M3/M21 serum levels are elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients, elevated M3/M21 serum levels prior to therapy were associated with poor overall and disease-free survival (log-rank test, p = 0.03; log-rank test, p = 0.01, respectively). M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.
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PMID:M3/M21 serum levels in women with adnexal masses and inflammatory diseases. 969 39

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) invariably leads, within 2-4 years, to the appearance of hepatocellular carcinoma (HCC). HCC is preceded by an extended period of chronic liver damage, probably resulting from the immune response to viral antigens. It may be that infection itself also induces changes in the hepatocyte population. To begin to identify some of the changes in the liver prior to the appearance of HCC, monoclonal antibodies (MAbs) were generated from mice immunized with hepatocytes from a woodchuck chronically infected with WHV or with a tumor lysate. Immunofluorescence microscopy was used to select MAbs that reacted with host markers whose patterns of expression would distinguish chronically infected from uninfected liver or from liver tumors. One of these MAbs (2F2) reacted strongly with a subset of hepatocytes in chronically infected liver; a similar staining pattern was not detected in uninfected or transiently infected liver. Evidence is presented that this strong staining reaction reflects the overexpression or accumulation of the hepatocyte-specific intermediate filament protein, cytokeratin K18, a protein previously implicated in cryptogenic cirrhosis of the liver in humans (Ku, N. O. , Wright, T. L., Terrault, N. A., Gish, R., and Omary, M. B. J. Clin. Invest. 99: 19-23, 1997). Double immunofluorescent staining with antibodies to K18 and M-envelope protein of WHV suggested that strong reactivity to K18 was limited to cells expressing high levels of one or both of the large viral-envelope proteins, M and L; however, high expression of these viral proteins was not always associated with a strong K18 staining reaction.
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PMID:Aberrant expression of a cytokeratin in a subset of hepatocytes during chronic WHV infection. 974 Jul 78

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin marker CYFRA 21-1 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic marker in women suffering from ovarian cancer. In order to determine the specificity of the CYFRA 21-1 test, we have investigated CYFRA 21-1 serum levels in several benign conditions. This retrospective study comprises 37 patients suffering from ovarian cancer FIGO stages Ia-III. Sera from patients with benign ovarian cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases respectively. With a sensitivity of 41% and a specificity of 95%, CYFRA 21-1 was not suitable as a screening marker for ovarian cancer. Although CYFRA 21-1 was able to discriminate between ovarian cancer and benign adnexal tumours (univariate regression model, P = 0.0001), CYFRA 21-1 did not reveal additional information to CA 125 in a multivariate regression analysis (P = 0.06). CYFRA 21-1 serum levels were elevated in benign conditions such as liver cirrhosis, but not in endometriosis and inflammatory diseases. In ovarian cancer patients, elevated CYFRA 21-1 serum levels before therapy were associated with a poor overall and disease-free survival (log-rank test, P = 0.02 and log-rank test, P = 0.005 respectively). CYFRA 21-1, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.
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PMID:CYFRA 21-1 serum levels in women with adnexal masses and inflammatory diseases. 979 59

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening, prognostic, and monitoring marker for ovarian cancer and as a predictive marker in patients with adnexal masses. In order to determine the specificity of the M3/M21 test we investigated M3/M21 serum levels in several benign conditions. The cytokeratin tumor markers M3/M21 and Tissue Polypeptide Specific Antigen (TPS) were also investigated in the follow-up of ovarian cancer patients. We evaluated M3/M21 serum levels in 75 patients suffering from ovarian cancer FIGO stages Ia to III, using a prototype immunoradiometric assay (IRMA). Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10, and 20 cases, respectively. Furthermore, we analyzed TPS serum levels by means of IRMA during the follow-up of 40 patients suffering from ovarian cancer. With a sensitivity of 57% and a specificity of 95% M3/M21 was not suitable as a screening marker for ovarian cancer. Although M3/M21 was able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 did not provide additional information (in addition to CA 125) (multivariate logistic regression, p = 0.2). M3/M21 serum levels were elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients elevated M3/M21 serum levels prior to therapy were associated with a poor overall and disease-free survival (log-rank test, p = 0.03, and log-rank test, p = 0.01, respectively). In patients with recurrent ovarian cancer M3/M21 and TPS showed median lead-time effects of 3.2 and 3.9 months, respectively. M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor. M3/M21 and TPS are valuable tumor markers in the follow-up of ovarian cancer patients.
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PMID:[Cytokeratin tumor markers in ovarian carcinoma: tissue polypeptide specific antigen (TPS) and M3/M21]. 981 36

Primary hepatic carcinoid and neuroendocrine carcinoma (NEC) are rare tumors. We experienced three carcinoids and two NEC originating in the liver during the past 25 years and attempted to elucidate the clinicopathological and immunohistochemical features of these tumors. The patients had no endocrine symptoms despite two of them having elevated plasma serotonin. Three of the five patients died of the tumor after operation with an average survival time of 20.6 months. All tumors were large (up to 26 cm in diameter), four of them solitary and one multinodular, and were not associated with liver cirrhosis. The carcinoid tumors showed insular, trabecular or glandular arrangement of argyrophilic cells, whereas in the NEC this histological pattern was distorted. Immunohistochemically the tumors showed expression of chromogranin A (all cases), chromogranin B (three cases), pancreastatin and chromostatin (four cases, respectively), prohormone convertase PC3 (three cases), carcinoembryonic antigen (CEA) and CA19-9 (two cases), cytokeratin 56 kDa (three cases), 160 kDa neurofilament (two cases) and neuron-specific enolase (two cases). Serotonin and glucagon were sporadically detected in two tumors. The most useful marker to confirm the diagnosis was chromogranin A, which was cleaved to pancreastatin and chromostatin in the tumor tissue, and was more reliable than other markers of neuroendocrine differentiation.
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PMID:Primary hepatic carcinoid and neuroendocrine carcinoma: clinicopathological and immunohistochemical study of five cases. 1036 51

We report the case of a 19-year-old woman who presented with a hepatic mass without cirrhosis. Light microscopy revealed a cholangiocarcinoma having both well-differentiated adenocarcinoma and lymphoepithelioma-like undifferentiated carcinoma components. By immunohistochemistry, the tumor showed strong and diffuse expression for cytokeratin AE1, 5D3, and CK22. The tumor cells were positive for p53 protein (more than 75% of the cells) but negative for bcl-2 and LMP1. Abundant Epstein-Barr virus EBER (1/2) oligonucleotides were detected in both tumor components, but not in the lymphoid stroma or the nontumor liver. To the best of our knowledge, this is the third report of an Epstein-Barr virus-associated primary hepatobiliary adenocarcinoma with lymphoepithelioma-like component. Int J Surg Pathol 8(4):347-351, 2000
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PMID:Epstein-Barr Virus-Associated Cholangiocarcinoma with Lymphoepithelioma-Like Component. 1149 16

In recent years, the pathology and pathogenesis of bile duct loss have been extensively studied, and a number of hepatobiliary diseases have been added to the list of ductopenic diseases. In addition, the biology of biliary epithelial cells is now being studied with respect to bile duct loss, as well as biliary epithelial neoplasia. In this review, recent advances in pathogenetic and pathological studies of intrahepatic bile duct loss are described, with an emphasis on immune-mediated cholangiopathies. The bile duct loss, an acquired and pathologic process that occurs in the biliary tree, is recognizable as an absence of bile duct in an individual portad tract, and also as such absence in the vicinity of parallel running hepatic arterial branches that constitute the portal triad. Immunostaining with biliary cytokeratin and other carbohydrate materials is useful for the identification of biliary elements in the inflamed portal tracts or fibrous septa. The underlying processes responsible for bile duct loss include immunological, ischemic, infectious, metabolic, and toxic processes. Bile duct loss in primary biliary cirrhosis and primary sclerosing cholangitis is immune-mediated, that in interventional radiology using hepatic arterial branches is related to biliary ischemia, while that in hepatic allograft rejection is related to both immunological and ischemic insults. Bacterial and viral cholangitis with bile duct loss is an example of infectious cholangitis. The biliary tree maintains its homeostasis by renewal and dropout, and bile duct loss occurs mainly via biliary apoptosis. In some patients with bile duct loss, such as occurs in drug-induced injuries, the bile ducts regenerate and finally redistribute in the liver, while in other types of bile duct loss, the loss is progressive and is followed by vanishing bile duct syndrome, leading to biliary cirrhosis or liver transplantation. More analysis of the biology of biliary epithelial cells is mandatory for the evaluation of the pathobiology of bile duct loss, as well as for the effective restoration of biliary epithelial cells, in ductopenic liver diseases.
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PMID:Pathology and pathogenesis of intrahepatic bile duct loss. 1152 Nov 75

Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and alpha1 -antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal-infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of H BV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically-induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy.
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PMID:Hepatocellular carcinoma: an update. 1178 14

Combined hepatocellular-cholangiocarcinoma (CHC) forms a small but significant proportion of primary liver carcinomas. However, its diagnostic features are not well established, and this has possibly contributed to the variability in its reported clinical outcome in the literature. Many such tumors with features intermediate between hepatocellular carcinoma and cholangiocarcinoma (CC) may have been considered CC in the past based on positivity for "biliary differentiation" cytokeratins and the lack of availability of highly sensitive and specific hepatocellular markers. The utility of in situ hybridization for albumin mRNA, a recently available sensitive and specific hepatocellular marker, has not been reported in CHC. We investigated 27 CHCs with regard to their histomorphologic spectrum and association of these morphologies with immunohistochemical staining for different cytokeratins (CK7, CK19, and CK20; AE1; Cam 5.2), epithelial membrane antigen, polyclonal carcinoembryonic antigen and alpha-fetoprotein, and in situ hybridization for albumin mRNA. All 27 tumors contained areas morphologically intermediate between hepatocellular carcinoma and CC (transitional-type tumors), and in each case such areas formed at least 25% of the tumor. Nine (33%) tumors showed areas with "antler-like" morphology, a feature not previously described in CHC. Twenty-two of 23 tumors (96%) showed positive signals on in situ hybridization for albumin mRNA. Positivity for both hepatocellular (albumin mRNA) and biliary (keratin immunohistochemical profile) markers confirmed the light microscopic impression of biphenotypic differentiation in these tumors. Immunohistochemical positivity for all cytokeratins (except CK7) and epithelial membrane antigen, as well as the expression of albumin mRNA by in situ hybridization, did not show significant differences between hepatocellular carcinoma and CC-like areas. Based on the cytokeratin profile and results on polyclonal carcinoembryonic antigen/alpha-fetoprotein alone, many such tumors would be classified as CC. However, the positivity for albumin mRNA by in situ hybridization proves that such an interpretation would not have been accurate. Clinically, CHCs showed many differences from pure hepatocellular carcinoma, including the absence of cirrhosis (0 of 27), rarity of serum hepatitis B or C marker positivity (4 of 27), and normal to only mildly elevated serum alpha-fetoprotein levels (median 187 ng/mL). The tumor followed an aggressive clinical course, with overall 3-and 5-year survival rates of 30% and 18%, and in the resected cases of 38% and 24%, respectively.
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PMID:Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study. 1217 85


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