Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic infection by hepatitis B and C viruses is frequently associated to the development of primary liver cancer. Liver cirrhosis, induced by these viral infection, plays an important role in the liver carcinogenesis. In addition, HBV has a direct role in liver cell transformation by a transactivating effect of some viral proteins as well as insertional mutagenesis. The role of hepatitis C virus is not known. The strong association, even in France, of primary liver cancer to these viral infections underline the importance of their prevention by vaccination.
 ...
PMID:[Liver cancer and hepatitis B and C virus]. 133 32

Two major aetiological factors have been definitively incriminated in the pathogenesis of HCC: these are chronic hepatitis and hepatic cirrhosis. Chronic infection with hepatotropic viruses may account for the majority of cases of hepatocellular carcinoma in high incidence areas, and a varying prevalence of human hepatitis B and hepatitis C virus infection appears to determine the differing geographical prevalence of hepatocellular carcinoma in high and low incidence areas of the world. Patients with advanced hepatocellular carcinoma have a grave prognosis. However, at-risk groups have been characterized, and recent advances in hepatic imaging and tumour marker testing have made screening for asymptomatic primary liver cancer feasible. It it not clear, however, whether screening for small hepatocellular carcinoma improves the prognosis. Lipiodol has been shown to serve as a useful vehicle for diagnosis of small, centimetre sized nodules of tumour, and for delivery of cancer chemotherapeutic or radioactive agents to HCC. The combination of early diagnosis, and coupled medical and surgical treatments including targeted lipiodol or monoclonal antibody conjugates and hepatic resection or transplantation may lead to an improved outlook for viral-associated hepatocellular carcinoma.
 ...
PMID:Hepatocellular carcinoma associated with chronic viral hepatitis. Aetiology, diagnosis and treatment. 216 44

Data are presented on the frequency of malignant tumours registered at the population-based cancer registry in the southern prefecture of Butare, Rwanda, from May 1991 until 2 months before the outbreak of civil war in April 1994. Beginning in 1992, subjects were also interviewed about socio-demographic and life-style factors that have been associated with cancer risk in the West. The distribution of cancer in Rwanda is similar to that in other countries in sub-Saharan Africa. The most frequent cancers are those with possible infectious aetiologies: liver cancer (12%), cervical cancer (12%) and stomach cancer (9%). In addition, cancers known to be associated with HIV infection are relatively frequent (Kaposi's sarcoma [6%] and non-Hodgkin's lymphoma [3%]). Chronic infection, including infection with HIV, high parity and multiple sexual partners are important determinants of cancer incidence in this population. Tobacco consumption is low in Rwanda and there are few tobacco-related tumours, such as lung and laryngeal cancer. Other tumours believed to be associated with aspects of Western life-style, such as colorectal and breast cancer, are also relatively infrequent.
 ...
PMID:Cancer in Rwanda. 860 71

Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription-polymerase chain reaction (RT-PCR) with a median level of 1003 x 10(3) genomic equivalents ml-1 according to the branched-DNA assay (b-DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype 1a + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non-progressive liver disease groups. Serum HCV-RNA levels were similar in the liver diseased groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlying liver damage.
 ...
PMID:Lack of association between type of hepatitis C virus, serum load and severity of liver disease. 887 79

Chronic infection with hepatitis B virus (HBV) can cause liver cancer in humans. Transgenic mice expressing the major envelope protein of HBV, HBV surface antigen (HBsAg), represent an experimental model for some of the histopathological effects of infection in humans, including prolonged hepatocellular injury, necrosis, hyperplasia, and an elevated incidence of liver tumors. The regenerative hyperplastic response to the chronic liver damage is thought to be a critical factor in the increased risk of cancer. However, little is known about the cellular factors that mediate regenerative proliferation. One candidate is the hepatocyte mitogen transforming growth factor alpha (TGF-alpha); in HBV-infected patients with liver cancer, TGF-alpha and HBsAg accumulate in the same hepatocytes. Transgenic mice overexpressing TGF-alpha demonstrate enhanced hepatocyte proliferation rates and develop hepatocellular carcinomas. In this study, we have analyzed the effect of TGF-alpha and HBsAg coexpression in the liver using a bitransgenic mouse model. We show that hepatocytes harboring both the TGF-alpha and HBsAg transgenes exhibited an increase in growth relative to hepatocytes with either transgene alone. Furthermore, bitransgenic males but not females had a dramatically accelerated appearance of hepatocellular carcinomas, compared to single transgenic TGF-alpha or HBsAg littermates. These results demonstrate synergistic activity between HBsAg and TGF-alpha in the liver, probably by first stimulating quiescent hepatocytes to enter G1 and by subsequently promoting their transit through the cell cycle, respectively. Moreover, our data support the contention that TGF-alpha participates in HBV-induced hepatocarcinogenesis in infected patients.
 ...
PMID:Synergy between transforming growth factor alpha and hepatitis B virus surface antigen in hepatocellular proliferation and carcinogenesis. 927 35

Interpretation of descriptive statistics on liver cancer is affected by misclassification problems, evolving diagnostic procedures and changes in international classifications. Chronic infection with virus B and aflatoxin are major determinants for liver cancer in high-risk areas. In low and intermediate risk areas, including Italy, alcohol and cirrhosis are the most important risk factors. Preventive measures are neonatal vaccination against hepatitis B, reduction in aflatoxin contamination of foods, alcohol and tobacco consumption. Screening programs cannot be recommended as a measure of public health, particularly in western countries.
 ...
PMID:[Epidemiology of malignant liver tumors]. 938 28

Chronic infection by hepatitis B virus is a leading cause of human liver cancer and liver disease. The hepatitis B virus HBx protein is a regulatory factor that is essential for virus infection in mammals and is implicated in development of liver cancer and liver disease. Among the reported activities of HBx is the ability to stimulate Src tyrosine kinases, Ras-GTPases and transcriptional activation. We now demonstrate that HBx activation of Src tyrosine kinases, but not Ras, promotes a high level of viral replication in cell culture. HBx is shown to stimulate reverse transcription of the viral pregenomic mRNA into genomic DNA through a Src-mediated pathway in tissue culture cells. Targeted inhibition of Src tyrosine kinase activity, mutational inactivation of the HBx gene or retargeting of HBx to the nucleus to abolish cytoplasmic signal transduction activity, are shown to impair viral reverse transcription strongly. These studies implicate HBx stimulation of the Src family of tyrosine kinases in stimulation of viral polymerase activity.
 ...
PMID:Src kinases involved in hepatitis B virus replication. 1048 54

Chronic infection by HBV is the leading cause of hepatocellular carcinoma in man. Several lines of evidence suggest that the viral transactivator HBx plays a critical role in the molecular pathogenesis of HBV-related HCC. To study the actual impact of HBx and the mechanism of its action, we have recently cloned and characterized a set of X-sequences from HCC in patients with chronic infection by HBV. In the present study, we have compared the effects of HBx and its naturally arising mutants on cell growth and viability. We report that HBx inhibits clonal outgrowth of cells and induces apoptosis by a p53-independent pathway. Furthermore, HBx expression induced a late G1 cell cycle block prior to their counterselection by apoptosis. Importantly, mutations in the HBx-gene evolving in hepatocellular carcinoma abolished both HBx-induced growth arrest and apoptosis. Using a panel of engineered mutants we have mapped the growth suppressive effect of HBx to domains shown to be required for its transactivating function. Based on these results, we propose that abrogation of the anti-proliferative and apoptotic effects of HBx by naturally occurring mutations might render the hepatocytes susceptible to uncontrolled growth and contribute to multistep hepatocarcinogenesis associated with HBV-infection.
 ...
PMID:Hepatitis B virus X mutants, present in hepatocellular carcinoma tissue abrogate both the antiproliferative and transactivation effects of HBx. 1049 Aug 18

Liver cancer (LC) ranks fifth in frequency in the world, with an estimated 437,000 new cases in 1990. The estimates are different when LC frequency is analyzed by sex and geographical areas. In developed areas, the estimates are 53,879 among men and 26,939 among women. In developing areas, the estimates are 262,043 in men and 93, 961 in women. Areas of highest rates include Eastern and South Eastern Asia, Japan, Africa and the Pacific Islands (LC age-adjusted incidence rates [AAIRs] ranging from 17.6 to 34.8). Intermediate rates (LC AAIRs from 4.7 to 8.9 among men) are found in Southern, Eastern and Western Europe, Central America, Western Asia and Northern Africa. Low rates are found among men in Northern Europe, America, Canada, South Central Asia, Australia and New Zealand (LC AAIRs range from 2.7 to 3.2). In Europe, an excess of LC incidence among men compared with women is observed, and the age peak of the male excess is around 60 to 70 years of age. Significant variations in LC incidence among different countries have been described and suggest differences in exposure to risk factors. Chronic infection with the hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of LC is well established. In Europe, 28% of LC cases have been attributed to chronic HBV infection and 21% to HCV infection. Other risk factors such as alcohol consumption, cigarette smoking and oral contraceptives may explain the residual variation within countries. Interactions among these risk factors have been postulated. New laboratory techniques and biological markers such as polymerase chain reaction detection of HBV DNA and HCV RNA, as well as specific mutations related to LC, may help to provide quantitative estimates of the risk related to each these factors.
 ...
PMID:Epidemiology of liver cancer in Europe. 1097 49

Chronic infection by hepatitis B virus results from an inability to clear the virus, which is associated with liver disease and liver cancer. Tumor necrosis factor alpha (TNF-alpha) is associated with noncytopathic clearance of hepatitis B virus in animal models. Here we demonstrate that the nuclear factor kappaB (NF-kappaB) signaling pathway is a central mediator of inhibition of hepatitis B virus by TNF-alpha and we describe the molecular mechanism. TNF-alpha is shown to suppress hepatitis B virus DNA replication without cell killing by disrupting the formation or stability of cytoplasmic viral capsids through a pathway requiring the NF-kappaB-activating inhibitor of kappaB kinase complex IKK-alpha/beta and active transcription factor NF-kappaB. Hepatitis B virus replication could also be inhibited and viral capsid formation could be disrupted in the absence of TNF-alpha solely by overexpression of IKK-alpha/beta or strong activation of NF-kappaB. In contrast, inhibition of NF-kappaB signaling stimulated viral replication, demonstrating that HBV replication is both positively and negatively regulated by the level of activity of the NF-kappaB pathway. Studies are presented that exclude the possibility that HBV inhibition by NF-kappaB is carried out by secondary production of gamma interferon or alpha/beta interferon. These results identify a novel mechanism for noncytopathic suppression of hepatitis B virus replication that is mediated by the NF-kappaB signaling pathway and activated by TNF-alpha.
 ...
PMID:Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid Integrity through activation of NF-kappaB. 1263 63


1 2 3 4 5 Next >>