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)

Expression of the ras oncogene p21 product by hepatocytes of cirrhotic liver with hepatocellular carcinoma (HCC) was examined immunohistochemically using mouse monoclonal antibody RAP-5. At the concentration of antibody used, histologically normal liver tissues were negative for p21 antigen, whereas hepatocytes of cirrhotic nodules from 80 of 92 HCC patients (87.4%), and 10 of 32 patients without HCC (59.4%) were positive. This difference was statistically significant (p less than 0.05). The incidence of p21 expression by hepatocytes was significantly higher in macronodular cirrhotic patients than in those with micronodular cirrhosis (p less than 0.05) and tended to be higher in those positive for hepatic hepatitis B virus markers than in those that were negative (p less than 0.1). All 16 patients with liver cell dysplasia, and 17 of 18 with adenomatous hyperplasias showed increased expression of p21 antigen. In HCC it was detected on tumor cells of 63 of 101 patients (62.4%). Characteristically, its expression in well-differentiated HCC was mild and uniformly diffuse, and in moderately differentiated tumors was markedly heterogeneous in both intensity and distribution, whereas no expression was observed in cells of poorly differentiated HCC. These observations suggest that elevated ras p21 antigen expression is important in the development of both cirrhotic nodules and HCC, but that after tumor development, its sustained elevation is no longer necessary for cell proliferation and progression through the grades of anaplasia.
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PMID:Immunohistochemical detection of ras oncogene p21 product in liver cirrhosis and hepatocellular carcinoma. 303 55

In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States.
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PMID:Evidence for hepatitis C viral infection in patients with primary hepatocellular carcinoma. 751 78

The recombinant protein C11 derived from the C region of HCV genome and C7 derived from the nonstructural region NS3 of the HCV genome were used in ELISA to study 442 cases of liver diseases, including chronic hepatitis, cirrhosis and hepatocellular carcinoma in Beijing District. It was found that HBV infection was more prevalent than HCV infection in this district. Both liver cirrhosis and hepatocellular carcinoma were more related to the superinfection of HBV and HCV rather than HBV infection alone or HCV infection alone. It is suggested that there may be some interaction between the HBV and HCV to worsen the prognosis of these patients.
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PMID:[An analysis of HCV infection by using recombinant HCV antigen C11 and C7]. 751 37

Hepatocellular carcinoma is one of the most common cancers worldwide. Epidemiologic studies shows a striking correlation between areas where this tumor is prevalent and where hepatitis virus B and C are endemic, contaminations of food with mycotoxin aflatoxin B1, excessive alcohol intake, prolonged cigarette smoking, sexual hormones. Combination of chemical, physical, and genetic insults to individual hepatocytes involve changes in the genome transformed or neoplastic cell, depending to both the activation of oncogenes (e.g., ras) and the inactivation of tumor supressor genes (e.g., p53). Advances in radiologic techniques such as ultrasonography, computed tomography, angiography and dosages of tumor markers like alpha-fetoprotein offers still the best for diagnosis and screening for hepatocellular carcinoma. Then the diagnosis has become possible during the early stages, characterized to be a very well-differentiated tumour that has returned its preexisting liver structure, with a certain proportion have a multicentric origin. Hepatocellular carcinoma carries an extremely poor prognosis, with a median survival between 2-4 weeks, for those without treatment. Surgical resection are the only curative modality for this disease. In these patients two main patterns of intrahepatic recurrence after hepatectomy are defined, and depends on the growth of residual satellite tumours or synchronous and metachronous multicentric carcinogenesis. This evolution is estimated to be nearly 50%, with 5-year survival rate of nearly 30%. The presence of cirrhosis, satellite nodules, venous invasion, the absence of capsule formation and positive surgical margin (< or = 5 mm) were associated with higher intrahepatic recurrence rates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Small hepatocellular carcinoma. New concepts on intrahepatic recurrence after hepatectomy in orthotopic liver transplantation]. 757 79

The authors investigated the epidemiology of hepatitis C virus (HCV) related to liver diseases in Korea. Anti-HCV was studied by EIA in sera from patients with chronic liver diseases (CLD), individuals at high risk, healthy individuals, and family members of patients with CLD. We also evaluated the efficacy of a new anti-HCV assay kit, HCD EIA, consisting of 3 recombinant peptides derived from CORE, NS3 and NS5 regions of the HCV genome, for screening HCV infection. The prevalence of anti-HCV in HCD EIA was 15.4% of 1055 cases studied, while that in the anti-C100-3 EIA was 11.1%. The incidence of anti-HCV in HCD EIA was 5.9% of 17 cases with acute hepatitis, 18.1% of 293 cases with chronic hepatitis, 24.1% of 79 cases with liver cirrhosis, 28.0% of 100 cases with hepatocellular carcinoma, 19.8% of 81 cases maintained with hemodialysis, 31.3% of 16 cases with blood dyscrasias, 4.4% of 114 cases with fatty liver, 1% of 100 healthy persons, 1.3% of 150 blood donors, and 6.2% of 97 family members from 26 patients with type C CLD. Familial HCV clustering was detected in 3 (11.5%) of 26 patients with anti-HCV(+) CLD. The prevalence of anti-HCV in 190 HBsAg positive CLD was 8.4%. The relative proportions of positive anti-HCV, HBsAg, both positive 17.4%, 40.7%, and 3.7%, respectively, while 38.2% of the cases were negative for both anti-HCV and HBsAg. The prevalence of anti-HCV among CLD increased significantly in relation to age (p < 0.05), and it became higher than that of HBsAg after age 60.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of hepatitis C virus related to liver diseases in Korea. 768 3

Clinical evidence suggests that hepatitis C virus (HCV) is etiologically involved in hepatic cancer and liver cirrhosis. To investigate whether the HCV nonstructural protein NS3 has oncogenic activity, NIH 3T3 cells were transfected with an expression vector containing cDNA for the 5'- or 3'-half sequence of the HCV genome segment encoding NS3. Only cells transfected with the 5'-half cDNA rapidly proliferated, lost contact inhibition, grew anchorage independently in soft agar, and formed tumors in nude mice. PCR analysis confirmed the presence of the 5'-half DNA in the transfectants. These results suggest that the 5' region of the HCV genome segment encoding NS3 is involved in cell transformation.
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PMID:Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. 774 41

Expression of oncogene mRNA was investigated in 37 cases of hepatocellular carcinoma (HCC) surgically resected using in situ hybridization (ISH) technique. C-myc, c-Ha-ras and N-ras DNA probes labeled with biotin were used. The hybrids were detected by streptavidin-biotin alkaline phosphatase staining. Thirteen cases of liver cirrhosis and 16 cases of non-cirrhotic liver were also examined as controls. In HCC cases, c-myc mRNA was expressed in 15 of 37 cases. The c-myc positive cells were found unevenly both in cancerous regions and in non-cancerous regions, being mainly distributed near the cancer capsule. The hybrids were detected mostly in cytoplasm of cancer cells. In some cases, they were seen not only in the parenchymal cells but also in the non-parenchymal cells, such as histiocytes, Kupffer cells and fibroblastic cells. In control cases, c-myc mRNA was expressed in five of 13 cases of liver cirrhosis and in three of 16 cases of non-cirrhotic liver. The expression of c-Ha-ras mRNA could be detected in only three of 37 cases of HCC. These three cases were early staged HCC. The expression of N-ras mRNA was detected in five of 32 cases examined of HCC. These five cases were differentiated type HCC. These results suggest that c-myc gene might play an important role in evolution and progression of HCC, and that ras genes might play a role in hepatocarcinogenesis at early stage.
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PMID:[Study on the expression of oncogene mRNA in hepatocellular carcinoma using in situ hybridization technique]. 783 Jul 8

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.
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PMID:Immunohistochemical localization of lysyl oxidase in normal human skin. 791 5

Two major hepatitis C virus genotypes, F1 and F2, corresponding to hepatitis C virus type I and type II respectively, were found in France. To investigate the correlation between infection with these genotypes (F1 and F2) and clinical features of patients, serum samples proven to be hepatitis C virus positive by polymerase chain reaction amplification on 5' non-coding region were further amplified in the NS3 region with nested polymerase chain reaction. The NS3-polymerase chain reaction products were Southern blotted and hybridized with specific probes to identify the genotype of hepatitis C virus. Of 70 samples 64 were NS3-polymerase chain reaction positive. Twenty-eight (40%) samples were hepatitis C virus type I (F1) and 34 (49%) were hepatitis C virus type II (F2), while one sample (HB) hybridized with both probes and another (HN) hybridized with neither. Some samples were sequenced, with results consistent with those of hybridization. The HB sample was related more to hepatitis C virus type II than to type I and the HN sample was divergent from both type I and type II genotypes. Clinical profiles of patients infected with hepatitis C virus type I and type II were compared. Type I infected patients were younger (p < 0.01) and more often male (p < 0.05) than those of the type II group. Nine of 28 patients in the type I infected group had a history of drug abuse, whereas none did in the type II group. Five of 22 (23%) type I infected patients and 19 of 32 (59%) type II infected patients had cirrhosis (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatitis C virus genotypes in France: comparison of clinical features of patients infected with HCV type I and type II. 796 24

Fifty-five cases representing a spectrum of disease states of the human liver and 10 normal liver controls were examined for the presence of the ras oncogene product p21. Conventional formalin-fixed, paraffin-embedded sections were immunostained by the avidin-biotin complex method with the broadly reactive ras p21 monoclonal antibody (Mab) RAP-5. The specificity of the reactions was confirmed by immunostaining selected samples with Mab Y13-259. In the normal liver, virtually no hepatocytic immunostaining was noted. Variable, often extensive, and convincing immunoreactions were noted in diverse forms of hepatitis, cirrhosis, and allograft rejection; the strongest immunostaining was found in samples of focal nodular hyperplasia. Hepatic adenomas and hepatocellular carcinomas showed unevenly distributed, moderate to weak reactions or no reaction at all; cholangiocarcinomas did not immunostain. In reactive but non-transformed liver cell populations, enhanced p21 ras reactions seemed to correlate with the severity of the injury and the intensity of the proliferative response. The uneven and comparatively weak ras p21 reactions noted in adenomas and carcinomas suggest that this oncogene product may be involved only transitorily in their transformation processes and possibly may not be involved in certain variants thereof.
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PMID:Immunolocalization of ras oncogene p21 in human liver diseases. 838 Dec 45


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