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)

Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer, being a common cancer type worldwide. Many aetiological factors have been related with HCC development, such as cirrhosis, hepatitis viruses and alcohol. Chronic infection with hepatitis B (HBV) and C viruses (HCV) often results in cirrhosis and enhances the probability of developing HCC. The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. HBV is a DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. Besides, the virus encodes a 17 kDa protein, HBx, which is known to be a causative agent in the formation of HCC. On the contrary, HCV is a RNA virus that does not integrate into the host genome but likely induces HCC through host protein interactions or via the inflammatory response to the virus. Products encoded in the HCV genome interfere with and disturb intracellular signal transduction. Some HCV proteins, such as the core protein, NS3 and NS5A, have seen to have a regulatory effect on cellular promoters, to interact with a number of cellular proteins, and to be involved in programmed-cell death modulation under certain conditions. The identification of these proteins functions in HCC development and the subsequent development of strategies to inhibit protein-protein interactions may be the first step towards reducing the chronicity and/or of the carcinogenicity of these two viruses.
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PMID:Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis. 1535 43

Chronic infection with the hepatitis B virus (HBV) is a major risk factor for development of hepatocellular carcinoma (HCC). The pathogenesis of cancer in HBV infection has been extensively analyzed, and multiple factors appear to play a role. A major factor is chronic inflammation and the effects of cytokines in the development of fibrosis and liver cell proliferation. Also important is the role of integration of HBV DNA into host cellular DNA, which, in some situations, acts to disrupt or promote expression of cellular genes that are important in cell growth and differentiation. In addition, expression of HBV proteins may have a direct effect on cellular functions, and some of these gene products can favor malignant transformation. Several HBV genes have been found in infected tissues more frequently than others, including truncated pre-S2/S, hepatitis B X gene, and a novel spliced transcript of HBV, referred to as the hepatitis B spliced protein. The proteins expressed from these integrated genes have been shown to have intracellular activities that may account for their association with HCC, including effects on cellular growth and apoptosis. Finally, some patients with HCC have no detectable hepatitis B surface antigen in serum but do have low levels of HBV DNA in serum and integrated molecules of HBV DNA in tissue. Occult HBV infection may account for a proportion of cases of HCC that occur in patients without serologic markers for hepatitis B and C and may be a cofactor in HCC in patients with chronic hepatitis C who have coexistent occult HBV infection.
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PMID:Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. 1550 4

Chronic infection with hepatitis B virus (HBV) is associated with the majority of hepatocellular carcinoma (HCC). The diagnosis of HCC is usually made in the late stages of the disease, when treatment options are limited and prognosis is poor. We therefore have developed a method of glycoproteomic analysis in an attempt to discover serum markers that can assist in the early detection of HBV-induced liver cancer. Briefly, a comparative method for analysis of oligosaccharides released from serum glycoproteins and for recovery and identification of proteins with aberrant glycosylation, as a function of cancer diagnosis, is described. The model we have used is the woodchuck (Marmota monax), which shares similarities in the glycosylation pattern associated with liver proteins in human HCC. In this report, we show that woodchucks diagnosed with HCC have dramatically higher levels of serum-associated core alpha-1,6-linked fucose, as compared with woodchucks without a diagnosis of HCC. The coupling of this methodology with 2D gel proteomics has permitted the identification of several glycoproteins with altered glycosylation as a function of cancer. One such glycoprotein, Golgi Protein 73 (GP73), was found to be elevated and hyperfucosylated in animals with HCC. Further, the study showed GP73 to be elevated in the serum of people with a diagnosis of HCC, providing a validation of our approach. The potential of this technology for biomarker discovery and the implications of increased levels of GP73 in liver cancer are discussed.
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PMID:Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. 1564 45

Chronic infection with HCV represents second most common cause of end-stage liver diseases and hepatocellular carcinoma in Korea. The introduction of new agents and regimens for the treatment of chronic hepatitis C, such as pegylated forms of interferon-alpha (Peg-IFN) and combination with oral ribavirin has resulted in substantial improvement in sustained virologic response (SVR) rates. SVR rate of Peg-IFN and ribavirin combination therapy can be 40-46% of individuals infected with genotype 1 and approximately 75-85% with genotype 2 and 3. Peg-IFN/ribavirin combination therapy represents current standard therapy of chronic hepatitis C. This article reviews the treatment objectives, outcomes, optimal regimens, efficacy and predictors of response, monitoring during treatment, adverse events, retreatment of persons who failed to respond to previous treatments, and treatment of special patient groups in chronic hepatitis C.
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PMID:[Treatment of chronic hepatitis C]. 1566 73

Chronic infection with hepatitis B virus (HBV) is endemic to sub-Saharan Africa and parts of Asia where persistence of the virus is commonly associated with complicating cirrhosis and hepatocellular carcinoma (HCC). Licensed therapies for HBV are partially effective in selected patients and development of novel treatments remains an important global medical objective. HBV has an unusually compact genome that restricts the ability of the virus to evade potentially therapeutic nucleic acid hybridization. Thus, exploiting the RNA interference (RNAi) pathway, which enables sequence-specific target RNA degradation using small interfering RNA (siRNA), is well suited to developing novel treatment for HBV infection. Several studies, both in vitro and in vivo, have demonstrated that HBV replication can be inhibited in transfected cells by synthetic siRNA duplexes and also Pol III-derived short hairpin RNA (shRNA) sequences. The effectiveness of anti-HBV sequences varies considerably, and is likely to result from differences in activation of the RNAi pathway by individual siRNA species. Exclusion of potentially toxic off-target effects and also development of efficient methods of hepatotropic nucleic acid delivery are important prerequisites before RNAi can be used successfully for anti-HBV treatment.
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PMID:Exploiting the RNA interference pathway to counter hepatitis B virus replication. 1569 93

Chronic infection of the hepatitis B virus (HBV) is one of the causes leading to liver cancer. The 3.2kb genome of HBV encodes four proteins: core antigen, surface antigen, a DNA polymerase and the X protein (HBx). The biological functions of HBx are not fully understood. It has been shown that HBx is a potent trans-activator, which activates transcription of many cellular and viral promoters indirectly via protein-protein interactions. These transactivating activities of HBx may contribute to the development of hepatocellular carcinoma. In this paper a truncated mini-HBx(-Cys) (18-142) protein, where the cysteines had been either deleted or substituted by serines, was constructed by site-directed mutagenesis and overexpressed as a 6xHis fusion protein in Escherichia coli. The 6xHis-mini-HBx(-Cys) protein was isolated from inclusion bodies, purified by Ni-affinity chromatography under denaturing conditions and refolded by sequential dialysis. The structure of the 6xHis-mini-HBx(-Cys) protein was analyzed by circular dichroism, fluorescence and one-dimensional NMR spectroscopic assays. The data presented here suggest that HBx is unstructured but has a propensity to gain secondary structure under specific experimental conditions. Its conformational flexibility might partially explain its functional complexity, namely its capacity to interact with a wide array of signaling proteins, transcriptional regulators and nucleic acids.
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PMID:Expression and spectroscopic analysis of a mutant hepatitis B virus onco-protein HBx without cysteine residues. 1584 20

Chronic infection with hepatitis B virus (HBV) is one of the most common causes of cirrhosis of the liver and hepatocellular carcinoma worldwide, frequently requiring liver transplantation. Other nonliver organ transplants get infected de novo or through reactivation from previous active or inactive infections. With significant improvements in the surgical techniques and immunosuppressive regimens over the last 20 years, organ transplantation has become the most effective and lifesaving therapy for patients with chronic renal failure, cirrhosis, hepatocarcinoma, and heart failure. Until recently chronic HBV infection was considered a formal contraindication for liver transplantation, since recurrence of infection without prophylaxis occurs in 75% to 90% of the patients, with significant morbidity and mortality and few therapeutic alternatives. However, the introduction of hepatitis B immunoglobulin (HBIG) a decade ago to reduce the risk of reinfection of liver grafts, and more recently the availability of nucleoside analogues with few side effects and easy administration, have led to a dramatic improvement in patient outcomes with a risk of long-term HBV reinfection of less than 10% with combined HBIG and lamivudine prophylaxis. Chronic HBV infection in kidney, heart, and other organs has become a serious long-term problem and one of the most frequent and important comorbidities affecting graft and patient survival. Fortunately the introduction of nucleoside analogues allows significant control of viral replication and prevents progression of liver disease and other organ damage. In the present article we discuss the current indications for HBV prophylaxis and treatment prior to and after organ transplantation, as well as the most cost-effective way to apply different regimens to reduce side effects and improve survival and quality of life after transplantation.
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PMID:Is hepatitis B immunoglobulin prophylaxis needed for liver transplantation in the era of new antivirals? 1596 78

At least five hepatitis viruses are known to date. Infection by enterically transmitted viruses (HAV and HEV) is generally benign compared with the disease caused by parenterally transmitted viruses (HBV, HCV, and HDV). Chronic infection by HBV is common and may evolve to cirrhosis and hepatocellular carcinoma (HCC). Eight HBV genotypes (A-H) have been described, with the South American genotype F being the most divergent. Seven clades of HDV have been described; among them, the South American genotype III is associated to a high frequency of fulminant hepatitis. HCV infection leads to a high rate of chronicity and HCC. From the six HCV genotypes, infection with genotype 1 might have the worst prognostic. Chronic infection by HCV and HBV is the major risk factor for HCC, which occurs, in the majority of the cases, as a consequence of cirrhosis. However, there is growing evidence that some HBV and HCV proteins might contribute to the generation of HCC. Some HBV and HCV variants and specific mutations within the viral genomes might be more frequently associated with the evolution to HCC. Although more studies are needed, emerging evidence indicates that it might be important to address the genetic variability of these viruses and their contribution to the development of HCC.
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PMID:Genotypic variability of hepatitis viruses associated with chronic infection and the development of hepatocellular carcinoma. 1600 Sep 30

Hepatitis C virus is an RNA virus that is associated with chronic infection in the majority of people infected. Chronic infection with hepatitis C virus is the cause of significant morbidity and mortality worldwide and is associated with a large spectrum of liver disease including cirrhosis and hepatocellular carcinoma. End-stage liver disease due to chronic hepatitis C virus infection is currently the leading indication for liver transplantation in the USA. Hepatitis C virus genotyping of viral isolates circulating in the blood during chronic infection has become an important part of hepatitis C virus monitoring in chronically infected patients, and is useful as a prognostic indicator and to direct duration of therapy. This review will summarize information on hepatitis C genotyping, describe the limitations of current commercially available methods, give information on more recently developed methods, and provide a look to the future in terms of where advances in hepatitis C virus genotyping assays need to be made.
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PMID:Molecular methods of hepatitis C genotyping. 1601 69

Chronic infection with hepatitis C virus (HCV) is known to be a risk factor for not only cirrhosis and steatosis but also hepatocellular carcinoma (HCC). A number of diagnostic and prognostic molecular markers are being identified by transcriptomic and proteomic analysis of HCC today. However, the analyses are performed on HCC in general, and the studied tissues are HCV infected, HBV infected, infected with both or neither, or the infection status may be unknown. The authors performed proteomic analysis of cancerous and noncancerous tissues from HCC patients with HCV infection, and determined that, in the cancerous tissues, HSP70 family proteins such as GRP78, HSC70, GRP75 and HSP70.1, glutaine synthetase isoforms, HSP60, alpha-enolase, phosphoglycerate mutase 1, ATP synthetase beta chain and triosephosphate isomerase were increased whereas albumin, ferritin light chain, smoothelin, tropomyosin beta chain, arginase 1, aldolase B and kietohexokinase were decreased. The aim of this study is to understand the pathogenesis of HCV-HCC using proteomic analysis of samples from HCV-HCC patients on which transcriptomics has already been performed.
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PMID:Current progress in proteomic study of hepatitis C virus-related human hepatocellular carcinoma. 1609 91


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