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 is a disease with varying rates of progression. The role of hepatitis B virus (HBV) as a cofactor in the development of hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC) has been suggested and the use of HBV vaccine in all HCV-infected patients has been advocated. This review presents the implications of HBV and HCV coinfection and addresses the issues of HBV vaccine immunogenicity and safety in patients with chronic HCV infection.
Infection
PMID:Hepatitis B virus vaccine for patients with hepatitis C virus infection. 1113 51

Hepatitis B virus (HBV), the causative agent of B-type hepatitis in humans, is a hepatotropic DNA-containing virus that replicates via reverse transcription. Because of its narrow host range, there is as yet no practical small-animal system for HBV infection. The hosts of the few related animal viruses, including woodchuck hepatitis B virus and duck hepatitis B virus, are either difficult to keep or only distantly related to humans. Some evidence suggests that tree shrews (tupaias) may be susceptible to infection with human HBV, albeit with low efficiency. Infection efficiency depends on interactions of the virus with factors on the surface and inside the host cell. To bypass restrictions during the initial entry phase, we used recombinant replication-defective adenovirus vectors, either with or without a green fluorescent protein marker gene, to deliver complete HBV genomes into primary tupaia hepatocytes. Here we show that these cells, like the human hepatoma cell lines HepG2 and Huh7, are efficiently transduced by the vectors and produce all HBV gene products required to generate the secretory antigens HBsAg and HBeAg, replication-competent nucleocapsids, and enveloped virions. We further demonstrate that covalently closed circular HBV DNA is formed. Therefore, primary tupaia hepatocytes support all steps of HBV replication following deposition of the genome in the nucleus, including the intracellular amplification cycle. These data provide a rational basis for in vivo experiments aimed at developing tupaias into a useful experimental animal system for HBV infection.
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PMID:Hepatitis B virus (HBV) virion and covalently closed circular DNA formation in primary tupaia hepatocytes and human hepatoma cell lines upon HBV genome transduction with replication-defective adenovirus vectors. 1115 83

Hepatitis B, one of the most common infectious diseases in the world, is closely associated with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Many clinical investigations have revealed that hepatic fibrosis is an important component of these liver diseases caused by chronic hepatitis B. TGF-beta signaling plays an important role in the pathogenesis of fibrosis in chronic hepatitis and cirrhosis. As these diseases are associated with hepatitis B virus (HBV) infection, we examined the possibility that the HBV-encoded pX oncoprotein regulates TGF-beta signaling. We show that pX enhances transcriptional activity in response to TGF-beta, BMP-2, and activin by stabilizing the complex of Smad4 with components of the basic transcriptional machinery. Additionally, confocal microscopic studies suggest that pX facilitates and potentiates the nuclear translocation of Smads, further enhancing TGF-beta signaling. Our studies suggest a new paradigm for amplification of Smad-mediated signaling by an oncoprotein and suggest that enhanced Smad-mediated signaling may contribute to HBV-associated liver fibrosis.
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PMID:The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family signaling through direct interaction with Smad4: potential mechanism of hepatitis B virus-induced liver fibrosis. 1123 Jan 53

Infectious diseases, as tuberculosis, and metastatic cancers are the main causes of multiple pulmonary micronodules on chest radiographs. Many cancers can produce this anomaly, but the most common are thyroid, melanoma and gastrointestinal (colon and pancreas). Hepatocellular carcinoma can produce lung metastasis, but seldom makes bilateral pulmonary micronodules. Here we present the case of a woman with a hepatocarcinoma that appeared as a bilateral micronodular disease on the chest radiograph.
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PMID:[Micronodular pulmonary infiltration as first manifestation of metastatic hepatocellular carcinoma]. 1132 34

Autonomous parvoviruses preferentially replicate in and kill in vitro-transformed cells and reduce the incidence of spontaneous and implanted tumors in animals. Because of these natural oncotropic and oncolytic properties, parvoviruses deserve to be considered as potential antitumor vectors. Here, we assessed whether parvovirus H1 is able to kill human hepatoma cells by induction of apoptosis but spares primary human liver cells, and whether the former cells can efficiently be transduced by H1 virus-based vectors. Cell death, infectivity, and transgene transduction were investigated in Hep3B, HepG2, and Huh7 cells and in primary human hepatocytes with natural and recombinant H1 virus. All hepatoma cells were susceptible to H1 virus-induced cytolyis. Cell death correlated with H1 virus DNA replication, nonstructural protein expression, and with morphological features of apoptosis. H1 virus-induced apoptosis was more pronounced in p53-deleted Hep3B and p53-mutated Huh7 cells than in HepG2 cells which express wild-type p53. In Hep3B cells, apoptosis was partially inhibited by DEVD-CHO, a caspase-3 inhibitor. In contrast, H1 virus-infected primary hepatocytes were neither positive for nonstructural protein expression nor susceptible to H1 virus-induced killing. Infection with a recombinant parvovirus vector carrying the luciferase gene under control of parvovirus promoter P38 led to higher transgene activities in hepatoma cells than in the hepatocytes. Taken together, H1 virus kills human hepatoma cells at low virus multiplicity but not primary hepatocytes. Thus, recombinant H1 viruses carrying antitumor transgenes may be considered as potential therapeutic options for the treatment of hepatocellular carcinomas.
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PMID:Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors. 1133 86

Liver necropsy from patients infected with human immunodeficiency virus was analyzed in 117 cases. Wide ranges of opportunistic infections were recorded in 47%. Cryptococcosis (21.4%) was the most outstanding infection, followed by tuberculosis (16.2%), cytomegalovirus (5.1%) and penicillosis (3.4%). Non-specific alterations of the liver tissues included fatty steatosis (49.6%), fibrosis (55.6%), portal inflammation and reactive hepatitis. Cases of chronic active and chronic passive hepatitis and one case of hepatocellular carcinoma were reported. In the infected liver, predominant pathological changes included granuloma and spotty necrosis, which were attributed to tuberculous hepatitis. Infection with Cryptococcus usually showed no associated pathological change. The sensitivity for the clinical diagnosis of Cryptococcus was 88.8% and specificity was 91.7%. For tuberculosis, sensitivity was 20% and specificity was 67.9%.
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PMID:Opportunistic infections in the liver of HIV-infected patients in Thailand: a necropsy study. 1141 8

Viral hepatitis features with an incidence of 500 Mio infected individuals worldwide. Chronification of the infection as seen in hepatitis C, B, and D may lead to liver cirrhosis and its associated complications in later stages of the disease. Especially the chronification of acute hepatitis C is observed in a majority of cases (50-80%). Chronic Hepatitis C (cHC) should be treated in generally when elevated serum concentrations of liver enzymes are found or symptoms of disease occur. Treatment goals are viral elimination, improve in histology, prevention of HCC, and a better quality of life for the patients. As HCV and HIV share the same transmission routes, a relatively high rate of HCV-HIV co-infection is observed. Co-infection is characterized by a more progressive natural course of HCV-infection, leading to an increased mortality due to liver failure in the afflicted patients. The development of treatment options for anti-HCV-specific therapy in dually infected patients is urgently needed. The European Conference on Infectious Diseases and Tropical Medicine, EuCID 2001, which took place in May 3-6, 2001, in Leipzig covered aspects of viral hepatitis and its treatment in several sessions and gave latest results on treatment with interferon-alfa, lamivudine, and adefovir in hepatitis B as well as interferon-alfa, pegylated interferon-alfa, and ribavirin in hepatitis C and HCV-HIV co-infection respectively.
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PMID:Therapy of chronic hepatitis B and C and treatment options in HCV-HIV co-infection--European Conference on Infectious Diseases and Tropical Medicine, EuCID 2001, 3-6 May 2001, Leipzig. 1143 99

Infection by hepatitis B virus (HBV) is mainly restricted to humans. This species specificity is likely determined at the early phase of the viral life cycle. Since the envelope proteins are the first viral factors to interact with the cell, they represent attractive candidates for controlling the HBV host range. To investigate this assumption, we took advantage of the recent discovery of a second virus belonging to the primate Orthohepadnavirus genus, the woolly monkey HBV (WMHBV). A recombinant plasmid was constructed for the expression of all WMHBV envelope proteins. In additional constructs, N-terminal sequences of the WMHBV large envelope protein were substituted for their homologous HBV counterparts. All wild-type and chimeric WMHBV surface proteins were properly synthesized by transfected human hepatoma cells, and they were competent to replace the original HBV proteins for the production of complete viral particles. The resulting pseudotyped virions were evaluated for their infectious capacity on human hepatocytes in primary culture. Virions pseudotyped with wild-type WMHBV envelope proteins showed a significant loss of infectivity. By contrast, infectivity was completely restored when the first 30 residues of the large protein originated from HBV. Analysis of smaller substitutions within this domain limited the most important region to a stretch of only nine amino acids. Reciprocally, replacement of this motif by WMHBV residues in the context of the HBV L protein significantly reduced infectivity of HBV. Hence this short region of the L protein contributes to the host range of HBV.
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PMID:A short N-proximal region in the large envelope protein harbors a determinant that contributes to the species specificity of human hepatitis B virus. 1168 38

Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin.
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PMID:Chronic Hepatitis C. 1169 76

Hepatitis C virus (HCV) is a widespread infectious disease in humans with the negative implication of becoming chronic in most persons. Patients infected with HCV are at risk of liver cirrhosis or hepatocellular carcinoma at later stages. In contrast to hepatitis A and hepatitis B, there is no immunization yet available, neither prophylactic nor therapeutic. Thus, there is an urgent need to develop a safe, protective vaccine against this fatal disease. Developing countries are even more at risk for HCV. There are currently a number of scientific approaches aimed towards solving this problem. Taking both risks and costs of immunization into consideration, a peptide-based vaccine may be a reasonable prophylactic protection. Also, it might be of therapeutic use in already infected patients by increasing a specific CTL response against HCV. In our lab, we are focusing on immunopotentiating reconstituted influenza virosomes (IRIVs) as carriers for immunogenic HLA-A2-restricted core epitopes to induce peptide-specific cytotoxic T lymphocytes (CTLs). The IRIVs are similar to liposomes, but in addition contain influenza-derived hemagglutinin and neuraminidase on their outer surface which makes them fusogenic, thus, permitting antigen delivery to host cells. So far, virosomes have been successfully used for vaccine development and as a result a virosomal vaccine against both influenza virus (Inflexal) BERNA) and hepatitis A virus (HAV) (Epaxal) BERNA) already exist on the market. This paper focuses on the importance of development of a successful vaccine against HCV and, more specifically, we discuss the use, advantages and disadvantages of a peptide-based vaccine. A brief report of our latest findings will be included.
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PMID:Perspectives: towards a peptide-based vaccine against hepatitis C virus. 1174 97


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