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)

In the present study we investigated the expression of transforming growth factor alpha and insulin-like growth factor II to explain the role of these growth factors in the development of hepatocellular carcinoma from chronic active hepatitis B and cirrhosis. The expression of transforming growth factor alpha and insulin-like growth factor II was tested in 38 tissue samples from patients with chronic active hepatitis B, 32 cirrhosis and 31 hepatocellular carcinoma, by immunohistochemical staining using monoclonal anti-transforming growth factor alpha and anti-insulin-like growth factor II. All patients were seropositive for HBsAg. Transforming growth factor alpha was expressed in 26 (68.4%) of 38 chronic active hepatitis B, 18 (56.3%) of 32 cirrhosis and 16 (51.6%) of 31 hepatocellular carcinoma tissue samples. Transforming growth factor alpha was found in the periportal hepatocytes of chronic active hepatitis B and in regenerating hepatocytes of cirrhotic nodules. In hepatocellular carcinoma tissues, transforming growth factor alpha-containing tumor cells were evenly distributed within the tumor tissues but focal distribution limited to a part of tumor tissues was also observed. The expression of insulin-like growth factor II was observed in 30 (93.8%) of 32 cirrhosis and all the 31 hepatocellular carcinoma tissue samples tested, but not in chronic active hepatitis B samples. Insulin-like growth factor II was expressed in most hepatocytes of regenerating nodules and in tumorous as well as non-tumorous hepatocytes of hepatocellular carcinoma tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential expression of transforming growth factor alpha and insulin-like growth factor II in chronic active hepatitis B, cirrhosis and hepatocellular carcinoma. 760 79

The study of 226 cases of hepatocellular carcinoma (HCC) in a homogenous rural Southern African population is based on the assessment of histology, HBV infection, p53 oncoprotein and transforming growth factor alpha (TGFa) expression. Epidemiological and morphological observations were compared to HCC observed in 89 cases from pathological files in Poland and published information from Japan and Italy. Comparatively high number of young patients with HCC in Africa presented high rates of HBV infection, p53 oncoprotein overexpression and high HBsAg/p53 correlation rates. In all patients histological grading of HCC was inversely related to p53 and TGFa expression. No significant differences in histological grading of HCC and patients' mean age were noted between various population groups. The association of hepatic cirrhosis was at least twice as common in non-African patients, whereas iron overload was noted almost exclusively in African patients livers. Signs of HBV infection were lowest in Japanese female patients. The mechanism by which early HBV infection contributes to hepatocarcinogenesis at an early stage of life is confirmed by epidemiological observations in Poland and by the clear association of p53 gene with HBsAg and the age of patients.
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PMID:Hepatocellular carcinoma in young patients: histology, cellular differentiation, HBV infection and oncoprotein p53. 866 53

Fumonisin B1 (FB1) is a carcinogenic mycotoxin produced by the fungus Fusarium moniliforme in corn. Feeding of FB1 to rats causes acute liver injury, chronic liver injury progressing to cirrhosis, and sometimes terminates in hepatocellular carcinoma or cholangiocarcinoma. This study describes the histolopathology and changes in gene expression in the rat liver during short-term feeding of FB1. Male Fischer rats were fed either FB1 250 mg/kg or control diet, and were killed weekly for 5 weeks. FB1 caused a predominantly zone 3 'toxic' liver injury, with hepatocyte death due to necrosis and apoptosis. Hepatocyte injury and death were mirrored by hepatic stellate cell proliferation and marked fibrosis, with progressive disturbance of architecture and formation of regenerative nodules. Despite ongoing hepatocyte mitotic activity, oval cell proliferation was noted from week 2, glutathione S-transferase pi-positive hepatic foci and nodules developed and, at later time points, oval cells were noted inside some of the 'atypical' nodules. Northern blot (mRNA) analysis of liver specimens from weeks 3 to 5 showed a progressive increase in gene expression for alpha-fetoprotein, hepatocyte growth factor, transforming growth factor alpha (TGF-alpha) and especially TGF-beta1 and c-myc. Immunostaining with LC(1-30) antibody demonstrated a progressive increase in expression of mature TGF-beta1 protein by hepatocytes over the 5 week feeding period. The overexpression of TGF-beta1 may be causally related to the prominent apoptosis and fibrosis seen with FB1-induced liver injury. Increased expression of c-myc may be involved in the cancer promoting effects of FB1.
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PMID:Histopathology and gene expression changes in rat liver during feeding of fumonisin B1, a carcinogenic mycotoxin produced by Fusarium moniliforme. 1033 99

Cytokines are synthetized and secreted in the liver mostly by Kupffer cells and play a key role in inflammatory processes and immunological response related to liver diseases, which are initiated by hepatocytes damage. This type of signalling between different types of liver cells, can produce contrary reactions. For instance transforming growth factors beta as well as inetrleukins 1 beta, 4 and 6 induce fibrosis. In contrast, transforming growth factor alpha, tumor necrosis factor alpha, interleukins 1 alpha and interferons are inhibitory to fibrosis. Lost of the balance between these stimuli seems to be responsible for activation of nonparenchymal cells, that result in accumulation of extracellular matrix proteins (including collagens) with liver cirrhosis as a clinical effect. Connections between cytokines, cells located in the liver and diseases with hepatic fibrosis are reviewed in this article.
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PMID:[Cytokines in the pathogenesis of liver fibrosis]. 1069 68

A change in the balance between proliferation and apoptosis in the course of hepatocellular carcinoma (HCC) development and progression has been suspected. We wanted to identify related genes whose mRNA levels could provide markers of severity and prognosis after resection. The extent of cell apoptosis, proliferation, and differentiation was measured with a terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick-end labeling assay, and the Ki-67 index was determined in paired tumor and cirrhotic tissue samples from patients who had undergone HCC resection after diagnosis of hepatitis C-related or alcoholism-related cirrhosis. These patients included two groups with highly versus poorly differentiated tumor cells, and the latter was split into two subgroups of those with versus without early recurrence. The mRNA levels for various apoptosis-related or proliferation-related genes and those for the growth factor/receptor systems were measured by quantitative reverse transcriptase-polymerase chain reaction in paired tumor and cirrhotic liver samples from every patient, and some of the corresponding proteins were detected by immunohistochemistry. In all instances, protein expression was highly heterogeneous within groups and similar between groups. In contrast, some differences in mRNA level between tumor and cirrhotic tissues were quite informative. Low levels of hepatocyte growth factor and transforming growth factor alpha mRNAs were found concomitantly in highly differentiated tumors, whereas overexpression of mRNAs for the cognate receptors c-met and epidermal growth factor receptor were found in poorly differentiated tumors and primarily in patients with early tumor recurrence. These results argue for growth factor-dependent HCC development and provide novel and combined prognosis markers after HCC surgery.
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PMID:Hepatocyte growth factor, transforming growth factor alpha, and their receptors as combined markers of prognosis in hepatocellular carcinoma. 1261 35

Epidermal growth factor receptor (EGFR) binds transforming growth factor alpha (TGF-alpha) which is mitogenic for hepatocytes. Diverse lines of evidence suggest that activation of the TGF-alpha /EGFR pathway contributes to hepatocellular carcinoma (HCC) formation. Herein, we developed an experimental model of cirrhosis giving rise to HCC and tested the antitumoral effect of gefitinib, a selective EGFR tyrosine kinase inhibitor, in this model. Rats received weekly intraperitoneal injections of diethylnitrosamine (DEN) followed by a 2-week wash-out period that caused cirrhosis in 14 weeks and multifocal HCC in 18 weeks. Hepatocyte proliferation was increased in diseased tissue at 14 weeks compared with control liver and at even higher levels in HCC nodules compared with surrounding diseased tissues at 18 weeks. Increased proliferation was paralleled by upregulation of TGF-alpha messenger RNA expression. A group of DEN-treated rats received daily intraperitoneal injections of gefitinib between weeks 12 and 18. In rats treated with gefitinib, the number of HCC nodules was significantly lower than in untreated rats (18.1 +/- 2.4 vs. 3.7 +/- 0.45; P < .05), while EGFR was activated to a lesser extent in the diseased and tumoral tissues of these animals compared with untreated rats. HCC nodules from both untreated and gefitinib-treated animals displayed insulin-like growth factor 2 overexpression that contributed to tumor formation in treated animals. In conclusion, the blockade of EGFR activity by gefitinib has an antitumoral effect on the development of HCC in DEN-exposed rats, suggesting that it may provide benefit for the chemoprevention of HCC.
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PMID:Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis. 1566 Mar 82