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

Chronic infection with the hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. The pathogenesis of HCC in HCV infection has extensively been analysed. Hepatitis C virus-induced chronic inflammation and the effects of cytokines in the development of fibrosis and liver cell proliferation are considered as one of the major pathogenic mechanisms. Increasing experimental evidence suggests that HCV contributes to HCC by directly modulating pathways that promote the malignant transformation of hepatocytes. Hepatitis C virus is an RNA virus that does not integrate into the host genome but HCV proteins interact with many host-cell factors well beyond their roles in the viral life cycle and are involved in a wide range of activities, including cell signaling, transcription, cell proliferation, apoptosis, membrane rearrangements, vesicular trafficking and translational regulation. At least four of the HCV gene products, namely HCV core, NS3, NS4B and NS5A, have been shown to exhibit transformation potential in tissue culture and several potentially oncogenic pathways have been shown to be altered by the expression of HCV proteins. Both HCV core and NS5A induce the accumulation of wild-type beta-catenin and the Wnt-beta-catenin pathway emerges as a common target for HCV (and HBV) in human HCCs, also independently from axin/beta-catenin gene mutations. Induction of both endoplasmic reticulum stress and oxidative stress by HCV proteins might also contribute to HCV transformation. Most of the putative transforming functions of the HCV proteins have been defined in artificial cellular systems, which may not be applicable to HCV infection in vivo, and still need to be established in relevant infection and disease models.
 ...
PMID:Viral hepatitis and liver cancer: the case of hepatitis C. 1679 25

The incidence of hepatocellular carcinoma has been rising in the USA in the past two decades. Hepatocellular carcinoma primarily affects older people and reaches its highest prevalence among those aged between 50 and 70 years. Chronic infection by the hepatitis B virus is the most common cause of this disease. Since hepatocellular carcinoma is an indolent tumor, it has a low life expectancy. In patients with suspected hepatocellular carcinoma, CT, MRI, and ultrasound techniques are useful for formulating the diagnosis based on vascularity and specific enhancement features. In this paper we will discuss the multimodal approach for diagnosis and surveillance of hepatocellular carcinoma. We will also furnish the latest staging and treatment, epidemiology, clinical presentation, pathology and laboratory findings in hepatocellular carcinoma.
 ...
PMID:Current staging of hepatocellular carcinoma: imaging implications. 1682 69

Chronic infection of hepatitis C (HCV) and B virus (HBV) frequently causes viral hepatitis. Patients with chronic viral hepatitis are at risk for liver cirrhosis and even hepatocellular carcinoma. In patients with chronic hepatitis C, the most effective therapy is elimination of HCV with interferon (IFN). The most effective initial IFN therapy is the combination of pegylated IFN alpha-2b plus ribavirin. Forty-eight weeks of this combination therapy produces sustained viral response rates of approximately 50%. Moreover, several reports showed that long-term IFN therapy also reduced the risk of liver carcinogenesis. In patients with chronic hepatitis B, seroconversion from HBeAg to anti-HBe antibodies suppresses viral replication and attenuates the hepatitis. Twenty-four weeks of IFN therapy produces HBeAg seroconversion rates approximately 30%.
 ...
PMID:[HCV-HBV infection]. 1683 49

Chronic infection with hepatitis C virus (HCV) is a growing problem worldwide, with up to 300 million individuals infected, and those with chronic infection are at risk for cirrhosis and hepatocellular carcinoma. HCV infection is the most common indication for liver transplantation in the United States and Europe. Unfortunately, although transplantation is effective for treating decompensated cirrhosis and limited hepatocellular carcinoma associated with hepatitis C, HCV reinfection is virtually the rule among transplant recipients. Reinfection of the graft is associated with more rapidly progressive disease, with a median time to cirrhosis of 8 to 10 yr. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments begun for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially from cytopenias, and drug discontinuations in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virological response rates. Future therapies may include ribavirin alternatives with lower rates of anemia, alternative interferons with lower rates of cytopenias, and new antiviral drugs that can be used alone or in combination with either interferon or ribavirin to enhance sustained virological response rates and improve tolerability. Liver Transpl 12:1192-1204, 2006. (c) 2006 AASLD.
 ...
PMID:Treating hepatitis C infection in liver transplant recipients. 1686 44

Chronic infection of hepatitis B virus (HBV) is one of the major causes of hepatocellular carcinoma (HCC) in the world. Hepatitis B virus X protein (HBx) has been long suspected to be involved in hepatocarcinogenesis, although its oncogenic role remains controversial. HBx is a multifunctional regulator that modulates transcription, signal transduction, cell cycle progress, protein degradation pathways, apoptosis, and genetic stability by directly or indirectly interacting with host factors. This review focuses on the biological roles of HBx in HBV replication and cellular transformation in terms of the molecular functions of HBx. Using the transient HBV replication assay, ectopically expressed HBx could stimulate HBV transcription and replication with the X-defective replicon to the level of those with the wild one. The transcription coactivation is mainly contributing to the stimulatory role of HBx on HBV replication although the other functions may affect HBV replication. Effect of HBx on cellular transformation remains controversial and was never addressed with human primary or immortal cells. Using the human immortalized primary cells, HBx was found to retain the ability to overcome active oncogene RAS-induced senescence that requires full-length HBx. At least two functions of HBx, the coactivation function and the ability to overcome oncogene-induced senescence, may be cooperatively involved in HBV-related hepatocarcinogenesis.
 ...
PMID:Molecular functions and biological roles of hepatitis B virus x protein. 1698 72

Chronic infection with hepatitis C virus (HCV) is causally associated with the development of hepatocellular carcinoma (HCC). HCV is not cytolytic and replicates entirely in the cytoplasm. Viral interaction with the host leads to subversion of immune response and other defense mechanisms. The recent development of robust cell culture systems for HCV infection provides new opportunities for the study of virus-cell interaction and viral pathogenesis. HCV infection causes active inflammation and fibrosis, which ultimately progresses to cirrhosis. The onset of cirrhosis usually precedes the multistage process of tumor development, in which common themes of viral carcinogenesis can be identified. While chronic inflammation and cirrhosis are thought to play an important role in tumor initiation, the underlying mechanisms are incompletely understood. Recent studies have revealed that infection with HCV induces genome instability, leading to further genetic and epigenetic alterations which contribute to the full development of HCC tumor. The expression of viral oncoproteins such as C and NS5A is critically involved both in the induction of genome instability and in dysregulating cellular control of growth and signal transduction. A better understanding of the molecular pathogenesis of HCV will reveal novel strategies for the prevention and treatment of related diseases including HCC.
 ...
PMID:Molecular pathogenesis of hepatitis C virus-associated hepatocellular carcinoma. 1712 95

Hepatocellular carcinoma (HCC) is one of the world's leading fatal malignancies. Chronic infection with the hepatitis B virus (HBV) has been implicated with the development of HCC. For the past three decades, intensive research has focused on the role of HBV in hepatocarcinogenesis. Various HBV-associated models have emerged, but increasing evidence points to two major HBV-specific mechanisms that contribute to the development of HCC. The first is the integration of the viral genome into the host chromosome causing cis-effects, resulting in loss of tumor suppressor gene functions, and/or activation of tumor-promoting genes. The second mechanism involves the expression of trans-activating factors derived from the HBV genome, which have the potential to influence intracellular signal transduction pathways and alter host gene expression. A major player involved in this form of viral transactivation is the X protein (HBx). The HBx protein was found to display pleiotropic functions and has been implicated in the malignant transformation of chronically-infected liver cells. By disrupting cellular gene expression, viral products such as HBx may modulate cellular growth, repair and death, consequently resulting in the transformation of hepatocytes to an oncogenic state.
 ...
PMID:Oncogenesis and transforming viruses: the hepatitis B virus and hepatocellularcarcinoma--the etiopathogenic link. 1712 96

Despite effective prophylactic vaccines against hepatitis B virus existing for over 20 years, more than 2.5 billion people worldwide have been exposed to the disease and approximately 370 million people are chronically infected with it. Chronic infection in more than two thirds of infected patients results in chronic liver disease, which may lead to cirrhosis, exposure to noncarcinomatous complications and hepatocellular carcinoma. Currently available therapies fail to allow complete control of viral replication in most patients. Viral persistence has been associated with a defect in the development of hepatitis B virus-specific cellular immunity. Immunomodulatory strategies to boost or to broaden the weak virus-specific T-cell response have been proposed to bypass the chronic hepatitis B infection, including hepatitis B virus envelope- and nucleocapsid-based vaccines, and new formulations for recombinant and DNA-based vaccines, which are currently being evaluated in clinical trials.
 ...
PMID:Therapeutic vaccination in chronic hepatitis B virus carriers. 1718 43

Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway.
 ...
PMID:Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways. 1739 59

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the major risk factors include chronic infections with the hepatitis B (HBV) or C (HCV) virus, and exposure to dietary aflatoxin B(1) (AFB(1)) or alcohol consumption. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC, for example, somatic mutations in the p53 tumor suppressor gene (TP53) and the activation of the WNT signal transduction pathway. AFB(1) frequently induces G:C to T:A transversions at the third base in codon 249 of TP53 and cooperates with HBV in causing p53 mutations in HCC. The detection of TP53 mutant DNA in plasma is a biomarker of both AFB(1) exposure and HCC risk. Chronic infection with HBV and HCV viruses, and oxyradical disorders including hemochromatosis, also generate reactive oxygen/nitrogen species that can both damage DNA and mutate cancer-related genes such as TP53. Certain mutant p53 proteins may exhibit a 'gain of oncogenic function'. The p53 biological network is a key responder to this oxidative and nitrosative stress. Depending on the extent of the DNA damage, p53 regulates the transcription of protective antioxidant genes and with extensive DNA damage, transactivates pro-oxidant genes that contribute to apoptosis. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC and the integrated HBx is frequently mutated. Mutant HBx proteins still retain their ability to bind to p53, and attenuate DNA repair and p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology of TP53 mutations during the molecular pathogenesis of HCC.
 ...
PMID:TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. 1740 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>