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)

Congenital and neonatal viral infections usually display their acute manifestations in highly recognisable ways, for example, congenital rubella, cytomegalovirus (CMV), varicella, human immunodeficiency (HIV) and herpes simplex virus (HSV) infection. By contrast, congenital hepatitis B virus (HBV) infection may go undetected for years. Some of these are preventable, but what is not immediately apparent is that the long-term consequences are being prevented as well. The long-term consequences of congenital and neonatal infections include endocrine, immunological and cardiovascular disease, deafness, visual problems, intellectual handicap and cerebral palsy. With the survival of HIV-infected infants into adulthood the long-term consequences will soon be described. Maternally and neonatally transmitted HBV infection predisposes to carriage, liver cirrhosis and hepatocellular carcinoma in young adults. Neonatal HBV vaccination prevents adult cancer. Acquired viral infections may predispose to subsequent lung disease, malabsorption, fertility problems or neurological disability. In the prevention of acquired rubella, varicella, HBV, influenza, poliovirus, measles and hepatitis A, one should mention the added bonus of preventing secondary cases by preventing transmission from infants and children to other children and adults. Preventing paediatric HSV, HBV and HIV infection in females may even be preventing subsequent transmission to future generations. Turning to paediatric bacterial infections, vaccinating infants and young children against pertussis could not only prevent transmission to older children and adults but also break the cycle, which then transmits from adults back to infants and young children. There is evidence that disease in older age groups, including adults, has been prevented by virtue of herd immunity from paediatric vaccination, e.g. Neisseria meningitidis Group C and Streptococcus pneumoniae. The add-on benefits for other generations, including for adults, arising from the prevention of paediatric infections are considerable.
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PMID:Paediatric infections: prevention of transmission and disease--implications for adults. 1575 76

The Hepatitis C virus (HCV), a member of the family Flaviviridae, is a major cause of chronic liver disease. Patients are currently treated with alpha interferon (IFN-alpha) that is given alone or in combination with ribavirin. Unfortunately, this treatment is ineffective in eliminating the virus in a large proportion of individuals. IFN-induced antiviral activities have been intensively studied in the HCV replicon system. It was found that both IFN-alpha and IFN-gamma inhibit HCV replicons, but the underlying mechanisms have not yet been identified. Of note is that nearly all of these studies were performed with the human hepatoma cell line Huh-7. Here, we report that genotypes 1b and 2a replicons also replicate in the human hepatoblastoma cell line HuH6. Similar to what has been described for Huh-7 cells, we observed that efficient HCV replication in HuH6 cells depends on the presence of cell culture-adaptive mutations and the permissiveness of the host cell. However, three major differences exist: in HuH6 cells, viral replication is (i) independent from ongoing cell proliferation, (ii) less sensitive to certain antiviral compounds, and (iii) highly resistant to IFN-gamma. The latter is not due to a general defect in IFN signaling, as IFN-gamma induces the nuclear translocation of signal transducer and activator of transcription 1 (STAT1), the enhanced transcription of several IFN-regulated genes, and the inhibition of unrelated viruses such as influenza A virus and Semliki Forest virus. Taken together, the results establish HuH6 replicon cells as a valuable tool for IFN studies and for the evaluation of antiviral compounds.
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PMID:Dissecting the interferon-induced inhibition of hepatitis C virus replication by using a novel host cell line. 1622 97

TGFbeta is a major regulator of extracellular matrix deposition and a potent inducer of type-1 plasminogen activator inhibitor (PAI-1) gene expression. We have reported that liganded glucocorticoid receptor (GR) represses TGFbeta transactivation of PAI-1 in Hep3B human hepatoma cells and that it interacts functionally and physically with the C-terminal activation domain of Smad3, a mediator of TGFbeta signaling. The ligand binding domain of GR is required for GR-mediated transrepression, but the GR DNA binding domain and activation function 1 domains are not. We report here that overexpression of steroid receptor coactivator-1 (SRC-1) and GR-interacting protein-1 (GRIP-1) enhanced repression by liganded GR, and by a GR mutant defective in repression. Surprisingly, SRC-1 and GRIP-1 also enhanced TGFbeta-induced activation from the TGFbeta-responsive sequence of the PAI-1 gene by a GR-independent mechanism. Coimmunoprecipitation and mammalian one-hybrid experiments demonstrated that SRC-1 and GRIP-1 interact physically with endogenous Smad3 and functionally with the C-terminal domain of Smad3 to directly enhance transcription. Thus, the GR coactivators, SRC-1 and GRIP-1, act as both corepressors of the glucocorticoid repression of PAI-1 gene transcription, and coactivators of TGFbeta-induced activation of the PAI-1 promoter.
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PMID:Role of steroid receptor coactivators in glucocorticoid and transforming growth factor beta regulation of plasminogen activator inhibitor gene expression. 1642 81

Pheonix is developing ADI-PEG-20, a PEGylated arginine deiminase for the potential treatment of hepatocellular carcinoma, for which the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products have granted the drug Orphan Drug status, and melanoma, for which the FDA has also awarded ADI-PEG-20 Orphan Drug status. ADI-PEG-20 is also being investigated for the potential treatment of influenza virus infection and hepatitis C virus infection.
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PMID:Drug evaluation: ADI-PEG-20--a PEGylated arginine deiminase for arginine-auxotrophic cancers. 1677 44

Arbidol (ARB) is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV) infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 microM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.
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PMID:Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection. 1685 26

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs.
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PMID:Antiviral effects of Glycyrrhiza species. 1788 24

Chronic hepatitis B in children is mainly asymptomatic, but they are at life long risk for severe complications. Treatment is considered to suppress the virus and to prolong the survival by preventing the progression to cirrhosis and HCC. Therapeutic options for children are interferon-alpha (IFN-alpha) with antiviral, antiproliferative and immuno-modulatory effects and lamivudine (LAM) which inhibits HBV replication and increases cellular immune response. IFN-alpha, 5 MU/m(2), thrice weekly for 6 months is used in patients with high ALT levels which is associated with virologic response rate of 30-40%. Predictors of response are high ALT levels, low HBVDNA levels and high histological activity index. The response is sustained in 85%-90% of responders. Adverse events include flu-like syndrome, bone marrow suppression, hair loss, and psychiatric side effects, induction of autoimmunity and temporarily suppression of weight gain and growth velocity. LAM, a nucleoside anolog, leads to a virologic response rate of 20-30% when used for 12 months. High ALT levels, low HBVDNA levels and high histological activity index predict better response. Maintenance of HBeAg seroconversion is 56-80%. Longer courses of treatment with LAM increases the seroconversion rate but with high mutation rate and viral resistance. Except for causing mutations, LAM doesn't have serious adverse events. Different timing and durations of combination treatment with IFN and LAM were also evaluated without any significant superiority over monotherapy. In conclusion, the best approach for treatment of chronic HBV infection in children haven't been determined yet. Future developments concerning new drugs and different treatment strategies are needed.
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PMID:Treatment of chronic hepatitis B in children. 1822 Nov 87

In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.
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PMID:Vaccination greatly reduces disease, disability, death and inequity worldwide. 1829 69

Chronic hepatitis C is associated with substantial morbidity and mortality and poses a considerable socioeconomic burden. Improved treatment regimens, including the standard of care pegylated interferon alfa and ribavirin, have increased sustained virologic response rates; however, treatment has a long duration and is often associated with adverse events that may affect adherence. The goal of therapy is viral eradication and reduced disease-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. The clinical outcome of hepatitis C virus infection is altered with antiviral treatment, which can be influenced by host (e.g., weight, ethnicity, health) and viral (e.g., genotype, baseline viremia) factors. Overall, sustained virologic response was attained by 54-63% of patients in clinical trials treated with pegylated interferon alfa-2a or -2b and ribavirin. However, this benefit is not without risk. Interferon-induced adverse events include flu-like symptoms, bone marrow suppression, and emotional or cognitive effects, whereas hemolytic anemia accounts for most ribavirin dosage reductions. These adverse events may be ameliorated with dosage adjustments, symptom therapy, and judicious use of preventive strategies (e.g., antidepressants, hematopoietic growth factors). Appropriate management of adverse events can increase treatment adherence, thereby enhancing outcomes and improving quality of life. Pharmacists are in an ideal position to improve the treatment of patients with chronic hepatitis C by providing education about the disease and its treatments and associated adverse events and by emphasizing the importance of treatment adherence for successful outcomes.
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PMID:Treatment options for patients with hepatitis C: role of pharmacists in optimizing treatment response and managing adverse events. 1875 86

Many factors play into the complexity of viral pathogenesis. Understanding viral pathogenesis is key to developing vaccines and treatments for viral diseases. One emerging area of research is proteomics, which is the study of the protein complement and functions of the genome. Many different proteomic approaches have been utilized by researchers worldwide to further elucidate viral pathogenesis. For example, a high throughput MALDI-MS approach was recently employed to study the antigenicity of the influenza virus. Another study utilized MALDI-TOF MS and liquid chromatography MS/MS of proteins present in lipid droplets of hepatoma cell lines to identify proteins involved in the pathogenesis of hepatitis C virus that contribute to its carcinogenic properties. In conjugation with MS, yeast two-hybrid systems have also been shown to be useful in identifying potential host receptors of various viruses as well as revealing the interaction of viral proteins with other host proteins and viral proteins. In this review, the focus is on various proteomic approaches to dissecting the mechanisms of viral pathogenesis.
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PMID:Proteomic dissection of viral pathogenesis. 1881 85


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