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 activity of demeclotetracyclin, and ADH antagonist, is studied in 11 ethylic patients with cirrhosis of the liver, under a large hydric diet (1500 cm3). The prescription of the cyclin (600 mg daily) is always determined by a fall of the urinary osmolarity (-36%) and by a dramatic improvement of the free water clearance (+ 60%); consecutively, we observe an increase of natremia in 8 out of 9 cases. Associated with Spironolactone (200 mg daily) the anti-ADH activity persists (the free water clearance becomes positive in 5 out of 10 patients), in spite of the natriuretic activity of anti-aldosterone ; a minimal fall of the natremia is observed in only 2 cases. The indication of Demeclotetracyclin in the curative or preventive treatment of the hyponatremia of the liver cirrhosis is discussed.
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PMID:[Use of demeclotetracycline in the treatment of hyponatremia in cirrhotic ascitis]. 40 86

The authors studied histochemically the morphologic features of proliferating hepatocytes positive for proliferating cell nuclear antigen (PCNA/cyclin) to analyze the process of liver regeneration in embedded tissues fixed with formaldehyde using an anti-PCNA/cyclin monoclonal antibody. In liver specimens from patients with acute viral hepatitis (AVH) and confluent necrosis, many small basophilic hepatocytes surrounding large clear hepatocytes were positively stained in the areas next to the confluent necrosis. Therefore these small hepatocytes may be daughter cells derived from large clear hepatocytes that probably enter the mitotic cell cycle repeatedly to repair a large necrotic area. In the case of AVH with spotty necrosis, the positively stained hepatocytes were scattered around the necrotic foci. In the liver specimens from patients with chronic active hepatitis, most of the positively stained hepatocytes were located next to the necrotic area. As for cirrhosis of the liver, the number of hepatocytes positive for PCNA/cyclin varied greatly in different pseudolobules, and in the specimens of hepatocellular carcinoma (HCC), the HCC cells positive for PCNA/cyclin were detected throughout the cancer nests.
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PMID:Analysis of proliferating hepatocytes using a monoclonal antibody against proliferating cell nuclear antigen/cyclin in embedded tissues from various liver diseases fixed in formaldehyde. 134 35

The authors investigated whether immunocytochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) could be used to identify proliferative hepatocytes in frozen sections fixed in a mixture of periodate, lysine, and 2% paraformaldehyde. Paraffin sections also were used, which were fixed in 10% formaldehyde. Specimens of liver tissue were obtained from 27 patients with various hepatic diseases. Hepatocytes that were positive for PCNA/cyclin were observed in both types of substrate specimens. In acute hepatitis and chronic active hepatitis, most hepatocytes that were labeled for PCNA/cyclin were located near necrotic foci. However, in cirrhosis, they were detected most often near fibrotic septa; the number of immunoreactive cells varied greatly in different areas of tissue sections in such cases. In hepatocellular carcinoma, many PCNA/cyclin-positive tumor cells were seen throughout the neoplasms. Hepatocytes that were positive for DNA polymerase-alpha showed a similar distribution pattern in serial sections of study cases.
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PMID:Immunocytochemical identification of proliferative hepatocytes using monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin). Comparison with immunocytochemical staining for DNA polymerase-alpha. 137 17

Accumulating evidence has revealed that malignant cell growth is regulated by complex mechanisms involved in genetic and epigenetic factors. Among human cancers, cancer in the liver (hepatocellular carcinoma (HCC)) is characterized by the evidence that it is usually based on chronic liver diseases such as liver cirrhosis or chronic hepatitis, in which the liver is persistently regenerating following hepatic injury. This raises the possibility that repeated hepatocyte proliferation may cause disorder of genes that are regulating the cell cycle in hepatocytes, thus causing HCC. In this article, recent studies focusing on liver regeneration and cancer are reviewed from the viewpoint of the cell cycle that is regulated by cyclin and the associated proteins.
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PMID:Liver regeneration, liver cancers and cyclins. 979 41

Mammalian cell cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (CDKs) and CDK inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address the role of these cell cycle proteins in hepatocellular carcinomas, we analyzed the expression of cyclin E and CDK2. A panel of livers with human hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis were used as a human experimental system. The inbred LEC (Long-Evans with a cinnamon-like coat color) rats were used as an animal experimental HCC model. Immunohistochemical staining of serial paraffin sections was performed using antibodies to cyclin E and CDK2. The results showed that cyclin E and CDK2 were concurrently overexpressed in hepatocellular carcinomas both in human and rat livers. Western blot analysis and CDK2 kinase assay demonstrated expression levels of cyclin E and CDK2 and CDK2 kinase activity, respectively, and both were shown to increase along with the development of hepatocellular carcinomas. Analysis of the correlation between expression of cyclin E and CDK2 and clinicopathological parameters revealed a significant correlation between expression of cyclin E and tumor grade (P=0.013), and PCNA index (P=0.006) as well as CDK2 expression (P=0.015). Overexpression of CDK2 tended to be associated with poorly differentiated HCCs. The results suggest that overexpression of cyclin E and CDK2 plays an important role in the development of hepatocellular carcinoma.
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PMID:Overexpression of cyclin E and cyclin-dependent kinase 2 is correlated with development of hepatocellular carcinomas. 1147 Jun 26

Since p21WAF1/CIP1 (p21) is a universal inhibitor of cyclin-dependent kinases and is regulated transcriptionally by p53, which is activated by DNA stress, its expression reflects DNA stress in chronic hepatitis. Recently an association with both hepatitis B and C virus and the expression of p53 or p21 was reported. We analyzed p21 expression in 18 cases of HBV-associated chronic liver diseases and 32 cases of HCV-associated chronic liver diseases by immunohistochemical analysis, and investigated the possible association between hepatocyte p21 expression and hepatic inflammation, fibrosis, and especially hepatitis virus type. The p21-positive hepatocytes were more numerous in areas of intense inflammation and spotty necrosis and areas close to fibrosis, and they increased according to the degrees of grading and staging. The p21 labeling index (LI) in patients with liver cirrhosis was significantly higher than that in patients with chronic hepatitis of both hepatitis viral types (5.84 +/- 0.61 vs 12.0 +/- 0.83, P < 0.0001 in hepatitis B, 10.28 +/- 0.80 vs 15.6 +/- 1.09, P = 0.0004 in hepatitis C), Furthermore, the p21 LI was significantly higher in HCV-associated liver disease than in HBV-associated liver disease in every group (4.02 +/- 0.48 vs 7.74 +/- 0.96, P = 0.021 in low grade group, 7.35 +/- 0.46 vs 12.8 +/- 0.57, P < 0.0001 in high grade, 12.0 +/- 0.83 vs 15.6 +/- 1.09, P = 0.034 in liver cirrhosis). In, conclusion, p21 expression was up-regulated by the stress of inflammation and fibrosis and might be influenced by viral proteins in human chronic liver disease.
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PMID:p21WAF1/CTP1 expression and hepatitis virus type. 1168 May 78

p21(WAF1/CIP1) (p21) protein is a universal inhibitor of cyclin-dependent kinases and is regulated transcriptionally by p53, which is activated by DNA stress. Hepatocytes in chronic hepatitis receive several DNA stresses by lymphocytes and Kupffer cells. Therefore, we analyzed p21 expression of hepatocytes in hepatitis C virus (HCV)-associated chronic liver diseases and investigated the possible involvement of p21 in hepatocarcinogenesis. We examined p21 expression in 35 cases of HCV-associated chronic hepatitis and 25 cases of HCV-associated liver cirrhosis by immunohistochemical analysis. The p21 labeling index (LI) was calculated as the ratio of positive cells to total cells. p21-positive hepatocytes were more numerous in areas of intense inflammation and spotty necrosis and areas close to fibrosis, and were increased according to the degrees of grading and staging. The p21 LI with liver cirrhosis was significantly higher than that with chronic hepatitis (14.4 +/- 5.9 versus 11.1 +/- 4.2, P = 0.014). The cumulative incidence of hepatocellular carcinoma (HCC) was significantly higher in the p21 LI >or=14% group than in the p21 LI <14% group (P = 0.0079). Multivariate analysis demonstrated that p21 expression can be recognized as an independent significant factor for HCC development (relative risk 5.00, P = 0.039). p21 LI decreased significantly after interferon therapy. These results suggested that p21 is up-regulated by the stress of inflammation and fibrosis in HCV-associated chronic liver diseases and that high p21 expression might be related to hepatocarcinogenesis in cirrhotic patients.
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PMID:High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma in patients with hepatitis C virus-associated chronic liver diseases. 1205 78

The signal transducer and activator of transcription (STAT) family proteins are transcription factors critical in mediating cytokine signaling. Among them, STAT3 is often constitutively phosphorylated and activated in human cancers and in transformed cell lines and is implicated in tumorigenesis. However, cause of the persistent activation of STAT3 in human tumor cells is largely unknown. The hepatitis C virus (HCV) is a major etiological agent of non-A and non-B hepatitis, and chronic infection by HCV is associated with development of liver cirrhosis and hepatocellular carcinoma. HCV core protein is proposed to be responsible for the virus-induced transformation. We now report that HCV core protein directly interacts with and activates STAT3 through phosphorylation of the critical tyrosine residue. Activation of STAT3 by the HCV core in NIH-3T3 cells resulted in rapid proliferation and up-regulation of Bcl-XL and cyclin-D1. Additional expression of STAT3 in HCV core-expressing cells resulted in anchorage-independent growth and tumorigenesis. We propose that the HCV core protein cooperates with STAT3, which leads to cellular transformation.
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PMID:Activation of STAT3 by the hepatitis C virus core protein leads to cellular transformation. 1220 79

To determine the possible role of the epigenetic mechanisms in carcinogenesis of the hepatocellular carcinoma, we methylation-profiled the promoter CpG islands of twenty four genes both in HCC tumors and the neighboring non-cancerous tissues of twenty eight patients using the methylation-specific PCR (MSP) method in conjunction with the DNA sequencing. In comparison with the normal liver tissues from the healthy donors, it was found that while remained unmethylated the ABL, CAV, EPO, GATA3, LKB1, NEP, NFL, NIS and p27KIP1 genes, varying extents of the HCC specific hypermethylation were found associated with the ABO, AR, CSPG2, cyclin a1, DBCCR1, GALR2, IRF7, MGMT, MT1A, MYOD1, OCT6, p57KIP2, p73, WT1 genes, and demethylation with the MAGEA1 gene, respectively. Judged by whether the hypermethylated occurred in HCC more frequently than in their neighboring normal tissues, the hypermethylation status of the AR, DBCCR1, IRF7, OCT6, and p73 genes was considered as the event specific to the late stage, while that the rest that lacked such a distinguished contrast, as the event specific to the early stage of HCC carcinogenesis. Among all the clinical pathological parameters tested for the association with, the hypermethylation of the cyclin a1 gene was more prevalent in the non-cirrhosis group (P=0.021) while the hypermethylated p16INK4a gene was more common in the cirrhosis group (P=0.017). The concordant methylation behaviors of nineteen genes, including the four previously studied and their association with cirrhosis has been evaluated by the best subgroup selection method. The data presented in this report would enable us to shape our understanding of the mechanisms for the HCC specific loss of the epigenetic stability of the genome, as well as the strategy of developing the novel robust methylation based diagnostic and prognostic tools.
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PMID:Methylation profiling of twenty four genes and the concordant methylation behaviours of nineteen genes that may contribute to hepatocellular carcinogenesis. 1467 55

Alpha-lipoic acid (alpha-LA) is an antioxidant used for the treatment of a variety of diseases, including liver cirrhosis, heavy metal poisoining, and diabetic polyneuropathy. In addition to its protective effect against oxidative stress, alpha-LA induces apoptosis in different cancer cells types. However, whether alpha-LA acid induces apoptosis of hepatoma cells is unknown. Herein, we investigated whether alpha-LA induces apoptosis in two different hepatoma cell lines FaO and HepG2. The results showed that alpha-LA inhibits the growth of both cell lines as indicated by the reduction in cell number, the reduced expression of cyclin A and the increased levels of the cyclin/CDKs inhibitors, p27(Kip1) and p21(Cip1). Cell cycle arrest was associated with cell loss, and DNA laddering indicative of apoptosis. Apoptosis was preceded by increased generation of reactive oxygen species, and associated with p53 activation, increased expression of Bax, release of cytochrome c from mitochondria, caspases activation, decreased levels of survivin, induction of pro-apoptotic signaling (i.e JNK) and inhibition of anti-apoptotic signaling (i.e. PKB/Akt) pathways. In conclusion, this study provides evidence that alpha-LA induces apoptosis in hepatoma cells, describes a possible sequence of molecular events underlying its lethal effect, and suggests that it may prove useful in liver cancer therapy.
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PMID:Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells. 1713 95


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