Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) is the cause of the majority of transfusion-associated hepatitis and a significant proportion of community-acquired hepatitis worldwide. Infection by HCV frequently leads to persistent infections that result in a range of clinical conditions including an asymptomatic carrier state, severe chronic active hepatitis, cirrhosis and, in some cases, hepatocellular carcinoma. The HCV genome consists of a single-stranded, positive sense RNA containing an open reading frame of approximately 9060 nucleotides. This is translated into a single polyprotein of approximately 3020 amino acids (C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B), which in turn is processed by a series of host and viral proteinases into at least 10 cleavage products. The N-terminal portion of the NS3 protein encodes a serine proteinase that is responsible for the cleavage at the NS3-4A, NS4A-4B, NS4B-5A and NS5A-5B junctions. The 54 amino acid NS4A protein is a cofactor that binds to the NS3 protein and enhances its proteolytic activity. This report describes the expression of a recombinant NS3-4A proteinase fusion protein in Escherichia coli and the in vitro characterization of the enzyme activity using synthetic peptide substrates. It then demonstrates how these results were employed to guide the design of potent inhibitors of this enzyme.
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PMID:The design and synthesis of potent inhibitors of hepatitis C virus NS3-4A proteinase. 1057 81

Hepatitis-B viral (HBV) infection and schistosomiasis are among the most common causes of liver cancer (hepatocellular carcinoma; HCC) in Egypt. The present study investigates the effects of both infectious diseases and other demographical and environmental factors on the risk of HCC among a representative group of Egyptian patients with HCC (n = 102) and controls with no signs of hepatopathology (n = 96). Factors associated with an increased risk of HCC in Egypt were age over 60 yrs-old, farming, cigarette smoking and occupational exposure to chemicals such as pesticides. However, schistosomiasis (relative risk, RR: 5.22; 95% confidence intervals, C.I.: 2.93-9.31) and HBV infection (RR: 12.51; 95% C.I.: 6.11-25.59) were the major risk factors in the development of HCC. Schistosomiasis increased the severity of HBV infection and elevated the risk of HCC over that associated with the HBV infection alone. Understanding these relationships may enable us to determine the susceptibility to HCC among high risk groups and to provide these individuals with effective measures for early prevention or intervention.
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PMID:Risk factors for hepatocellular carcinoma in Egypt: the role of hepatitis-B viral infection and schistosomiasis. 1065 Aug 11

Transcription of the p53 gene can regulate progression of apoptosis in a wide variety of tissues. Three categories of human hepatocyte culture have been used to show the initiation of apoptosis after treatment with p53-bearing adenovirus. Chang liver cells are derived from normal liver tissue and express native p53, whereas hepatocellular carcinoma (HCC)-derived cell lines were Hep3B (p53-deleted) and PLC/PRF/5 (p53-mutant). Cultures were infected with Ad-p53 (15 particles per cell; 36 hours), and after treatment, morphological changes in all cell categories were observed by electron microscopy. Infection was evident in the cytoplasm of all treated cell types: after entry across the plasma membrane viruses translocated and came to rest surrounding and adjacent to nuclei, cytoplasm proximal to nuclear membranes became dense with virus- and membrane-derived debris, but intact viruses did not enter nuclei. Apoptosis, recognized morphologically by characteristic chromatin and cytoplasmic condensation, occurred more frequently in HCC-derived cells, and the ultimate fate of apoptotic bodies was phagocytosis and degradation by neighboring cells.
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PMID:Detection of adenovirus and initiation of apoptosis in hepatocellular carcinoma cells after Ad-p53 treatment. 1073 44

It has been estimated that presently hepatitis B kills more people every day than AIDS kills in a year world-wide. Infection with hepatitis B produces a wide range of manifestations ranging from asymptomatic carriers to persistent infections leading to chronic liver diseases and hepatocellular carcinoma. Availability of effective and safe vaccine has made all this preventable. To formulate on appropriate vaccination strategy for India the epidemiology of hepatitis B needs to be defined. This report critically reviews the available data. The burden of long term sequelae of HBV infection is probably under-diagnosed and under-reported in India. Prevalence studies of HBV markers indicate that India falls under the area of intermediate endemicity. Limited data on age-specific prevalence of HBV markers suggests that the majority of the infection seems to take place below 15 years of age, and most of it under one year. Perinatal transmission appears to contribute significantly to the carrier pool. Childhood vaccination for HB among the general population is the obvious strategy of choice. But more information is required to decide on the timing of the first dose.
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PMID:Epidemiology of childhood hepatitis B in India: vaccination related issues. 1082 39

Infection with hepatitis B virus can lead to serious long-term complications including chronic hepatitis B virus infection leading to hepatocellular carcinoma, liver failure, and death. We report a case of prolonged hepatitis B antigenemia after routine vaccination with Engerix B. A positive hepatitis B surface antigen was found when the individual donated blood 18 days after vaccination. This resulted in rejection of the donated blood and permanent deferral from further donation. It also led to referral to a physician, creating anxiety in the individual and additional unnecessary testing. Additional studies are needed to identify the length to time of hepatitis B surface antigenemia after hepatitis B vaccination, and blood collection centers should be aware of the potential for donors to have a prolonged false-positive hepatitis B surface antigen after vaccination against hepatitis B. hepatitis B, hepatitis B vaccine, hepatitis B surface antigen, vaccine-induced positive hepatitis B surface antigen, Engerix B.
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PMID:Prolonged hepatitis B surface antigenemia after vaccination. 1083 94

Infection with hepadnaviruses and exposure to aflatoxin B1 (AFB1) are considered to be major risk factors in the development of hepatocellular carcinoma (HCC) in humans. A high rate of p53 mutations at codon 249 has been reported in these tumors. The tree shrew (Tupaia belangeri chinensis) is a useful animal model for the development of HCC after human hepatitis B virus (HBV) infection or AFB1 treatment. Therefore, it was of particular interest to determine whether the p53 gene in tree shrew HCCs associated with HBV infection and/or with exposure to AFB1 is affected in the same manner as in human HCCs. We determined the tree shrew p53 wild-type nucleotide sequences by RT-PCR and automatic DNA-sequencing. Tree shrew wild-type p53 sequence showed 91.7 and 93.4% homologies with human p53 nucleotide and amino acids sequences, respectively, while it showed 77.2 and 73.7% homologies in mice. One HCC and normal liver tissue from AFB1 treated and one HCC from AFB1- and HBV-treated tree shrew showed no change in p53 sequences, while three HCCs from AFB1- and HBV-treated tree shrews showed point mutations in p53 sequences. One HCC showed point mutations at codon 275, which is on the DNA-binding domain of p53 gene, which might be a cause of gain-of-function during the development of HCC. As a result, our finding indicates that tree shrews exposed to AFB1 and/or HBV had neither codon 249 mutations nor significant levels of other mutations in the p53 gene, as is the case with humans.
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PMID:Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin B1. 1086 98

Infection by hepatitis B virus remains a major health problem in the world despite the availability of effective vaccines. Although vaccination programs targeting high risk groups have been pushed to their limits, high prevalence rates persist especially in endemic zones. More recently mass vaccination programs conducted on Taiwan have demonstrated the efficacy of this approach with a decrease in the number of chronic hepatitis B virus carriers in the general population in association with a decrease in the incidence of hepatocellular carcinoma, one of the most serious complications of chronic hepatitis B virus infection. Side effects have been reported including the risk of central nervous system demyelination. However studies have shown no evidence of a significant correlation between vaccination and this type of disease. Occurrence of hepatitis B in properly vaccinated subjects could result from selection of mutant viral strains able to escape detection by the immune system. The recently revised benefit-to-risk ratio remains highly favorable for vaccination. Current data indicates that the policy of mass vaccination of the population should be pursued.
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PMID:[Vaccination against hepatitis B virus: current data]. 1090 55

This report summarizes a state-of-the-art workshop held in September 1998 on the "Natural History and Outcome of Hepatitis C Infection". Sixteen Canadian and two internationally renowned hepatologists were invited. A practical classification of HCV infection served as a framework for the meeting. The concepts of modelling of chronic disease, the epidemiology of HCV infection before the introduction of anti-HCV testing, and the outcome of various forms of chronic hepatitis C in adults and children were presented. Lectures on the outcome of HCV cirrhosis, hepatocellular carcinoma, the role of liver transplantation, the influence of host factors on outcome, iron overload in chronic hepatitis C and possible modification of the natural history by antiviral therapy were followed by discussion and consensus statements pertaining to each presentation. "The European Experience in Assessing Chronic Hepatitis C" was presented by Prof G Dusheiko from the United Kingdom, and Prof Leonard Seeff from the National Institutes of Health (United States) presented "The Epidemiology and Outcome of Hepatitis C Infection in the United States and the World".
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PMID:Hepatitis C infection: its sequelae and outcomes--State-of-the-Art Workshop, September 24 to 25, 1998. Canadian Association for the Study of the Liver. 1093 6

It is estimated that over 350 million people live with a chronic hepatitis B virus (HBV) infection, claiming over one million deaths per year due to progress of the chronic disease to cirrhosis and/or hepatocellular carcinoma (HCC). An extended program of immunization including hepatitis B vaccine for children under one year of age has been launched in more than 110 countries. Recent studies conclude that mass hepatitis B immunization is effective in preventing HBV infection and has resulted in a decrease in the occurrence of HCC in children living in countries where hepatitis B is endemic. However, the vast majority of infected children live in the poorest developing countries in Africa and Asia that currently cannot afford the vaccine or lack the basic infrastructure necessary to deliver a national immunization service. The Global Alliance for Vaccines and Immunization (GAVI) was established in 1999 as an alliance of WHO, UNICEF, the World Bank, industry, foundations, and other partners to reinvent immunization for the 21st century, by forging a common vision and new ways of working together at global, regional and national levels. WHO recommends global elimination of hepatitis B by universal infant and/or adolescent immunization, but health planners in Sweden and the other Scandinavian countries, the Netherlands and UK have not yet been convinced of the cost-effectiveness of HB-prevention through routine childhood immunization with HB-vaccine. The inclusion of hepatitis B vaccine in already available multivalent vaccines may alter this situation in the future, but until then an intensified vaccination strategy aimed at those groups of individuals that are particularly at risk for hepatitis B should be adopted in accordance with the recommendations of The Swedish National Board of Health (SOSFS 1991:2) and local instructions from the County Medical Officer for Communicable Disease Control.
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PMID:[WHO spearheads global initiative to eradicate hepatitis B]. 1101 26

Many heat shock proteins, e.g. gp96, HSP90, HSP70, etc have elicited rejection and immunotherapy immunogenicity of tumor and infectious diseases. Further study indicated that hsps can chaperone the endogenous repertoire of peptides, and the antigenicity of hsp-peptide complexes lies in the peptides, not HSPs. HSPs present peptides associated with them to MHC class I molecules for recognition by CTL and memory T cells, and elicit cellular immune responses. The latest finding shows that gp96 may present antigenic peptides directly to T lymphocytes functionally as MHC. In recent years the mechanism of immunogenicity and advantages as vaccine therapy of gp96 and HSP70, the two main hsps in mammals have been studied in detail, which offers a new opportunity for immunotherapy of hepatitis B and hepatocellular carcinoma.
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PMID:[Role of heat shock protein-peptide complexes on tumor and infectious diseases immunity]. 1105 11


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