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)

The viral infections with greatest impact on the renal transplant recipient are those due to cytomegalovirus, Epstein-Barr virus, and the two hepatitis viruses, hepatitis B and C. All of these are modulated by the administered immunosuppressive therapy, and all have both direct and indirect effects on the transplant patient. The direct effects are the infectious disease clinical syndromes that are produced (fever and malaise, pneumonia, hepatitis, and so forth). The indirect effects are several--all of these viruses contribute to the patient's net state of immunosuppression, predisposing him or her to the development of opportunistic superinfection with a variety of pathogens. In addition, both Epstein-Barr virus and hepatitis B virus have been clearly linked to the development of certain malignancies (lymphoproliferative disease and hepatocellular carcinoma, respectively). Finally, cytomegalovirus has been linked to allograft injury. Although antiviral strategies effective for cytomegalovirus and Epstein-Barr virus infection are being developed, similar programs are not yet available for the hepatitis viruses.
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PMID:Viral infection in the renal transplant recipient. 134 23

In this paper, we emphasize the uses of serum banks in cancer research. These include not only case/control studies but also prospective seroepidemiological studies in which the development of a serological marker, such as a viral antibody or viral antigen, can be correlated with the subsequent development of cancer in either an active surveillance program or the use of cancer registries or hospital records. Several different methods of application of the cohort technique are illustrated by studies of hepatitis B antigen and hepatocellular carcinoma and of Epstein-Barr virus in relation to African Burkitt's lymphoma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Collections of sera done for one purpose can often be utilized for another purpose, if properly stored and documented. Two examples are tests for human T-cell leukemia virus, type 1, antibody from sera done for a health survey in Barbados approximately 8 years earlier and the use of data determined for a prospective study of the incidence of Epstein-Barr virus infection and infectious mononucleosis in West Point Cadets for psychological factors affecting the development of clinical illness among those infected. Archival materials, such as frozen tissues and paraffin sections, may also now be utilized for identifying genomes of potential oncogenic viruses by the polymerase chain reaction.
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PMID:The past is prologue: use of serum banks in cancer research. 139 73

Based on our recent observation that Epstein-Barr virus (EBV) is detected in 37% of the tissues of hepatocellular carcinoma, and especially frequently in cases with hepatitis C virus (HCV), the effect of EBV infection on the replication of HCV was investigated. EBV-infected cell clones and their EBV-uninfected counterparts in cell lines MT-2 (a human T-lymphotropic virus type I-infected T-cell line), HepG2 (a hepatoblastoma cell line) and Akata (a Burkitt's lymphoma cell line) were compared in terms of their permissiveness for HCV replication following inoculation of HCV derived from patients who were HCV carriers. The results indicated that EBV-infected cell clones, but not their EBV-uninfected counterparts, promoted HCV replication. EBV-encoded nuclear antigen 1 (EBNA1), which is invariably expressed in EBV-infected cells, supported HCV replication. Deletion analysis of the EBNA1 gene showed good correlation between transactivation activity and the activity supporting HCV replication. The present findings suggest that EBV acts as a helper virus for HCV replication.
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PMID:Enhancement of hepatitis C virus replication by Epstein-Barr virus-encoded nuclear antigen 1. 1052 18

Several types of virus were found to have a strong association with different types of cancers. Thus, a selective antiviral compound without toxicity upon long-term usage will be useful not only for the treatment of viral diseases but also for the prevention or the delayed onset of those cancers, which have a strong association with viruses. L(-)Nucleoside analogs were discovered recently in my laboratory as an important class of antiviral and anticancer chemical entities. L(-)SddC (3TC, Lamivudine), FTC, Fd4C, and L(-)FMAU are potent anti-HBV compounds with different pharmacological profiles. These compounds may be useful in the prevention or delayed onset of hepatocellular carcinoma associated with HBV. L(-)I-OddU is the most potent anti-Epstein-Barr Virus (EBV) compound without cytotoxicity and animal toxicity upon long-term dosing which gives the pharmacological levels of the drug in plasma. This compound may have the potential to prevent B-cell lymphoma associated with patients undergoing organ transplants in addition to its potential use for the treatment of EBV infection.
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PMID:Potential use of antiviral L(-)nucleoside analogues for the prevention or treatment of viral associated cancers. 1116 88

Epstein-Barr virus (EBV) was recently linked to hepatocellular carcinogenesis in Japanese patients. It is not clear whether EBV infection is also associated with hepatocellular carcinoma (HCC) occurring in American patients. We studied 41 cases of HCC from the Los Angeles area for evidence of EBV infection by in situ hybridization, immunohistochemistry, and polymerase chain reaction methods. Of 41 cases, 16 were seropositive for hepatitis B virus surface antigen (39%), 9 of 29 tested were seropositive for hepatitis C virus antibody (31%); in total, 22 cases were seropositive for hepatitis B virus and/or hepatitis C virus (53%). Of 41 cases, 1 was positive for EBV-encoded small nonpolyadenylated RNA (EBER)-1 (2%) by in situ hybridization. By immunohistochemistry, two cases were positive for EBV nuclear antigen (EBNA)-1 (5%), one was positive for the transactivating immediate early BZLF1 (ZEBRA) (2%), and none was positive for latent membrane protein-1. None of the 41 cases was positive for latent membrane protein-1 and EBV nuclear antigen (EBNA)-4 DNAs by polymerase chain reaction assay. All four positive cases showed rare EBER-1-, ZEBRA-, or EBNA-1- positive cells (<0.1%); in none of these cases was there expression of any other EBV viral genes. In the one case each that was positive for EBER-1 and ZEBRA, both of which occurred in patients of non-Asian ethnicity, the staining was limited to infiltrating small lymphocytes, and tumor cells were negative. In the two cases that were positive for EBNA-1, both of which occurred in patients of Asian ethnicity, the staining was limited to tumor cells, and infiltrating small lymphocytes were negative. Our study indicates that rare cases of American HCC may contain EBV-infected cells, but it is unlikely that EBV plays a major role in the carcinogenesis of HCC.
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PMID:No direct role for Epstein-Barr virus in American hepatocellular carcinoma. 1158 56

It has been established that several types of cancers have a strong association with viruses. Thus, a potent antiviral compound without toxicity upon long-term usage will be useful not only for the treatment of viral diseases but also for the prevention or the delayed onset of those cancers that have a strong association with viruses. These compounds, depending upon their mechanism of action, could also potentially be useful for the treatment of those viral-associated cancers. L(-)Deoxynucleoside analogues were discovered in my laboratory and by others as an important class of antiviral and anti-cancer chemical entities. L(-)SddC (3TC, lamivudine), L(-)FTC, L(-)Fd4C, and L(-)FMAU are compounds with potent activity against hepatitis B virus (HBV), but with different biological and pharmacological profiles. These compounds may be useful in the prevention or delayed onset of hepatocellular carcinoma associated with HBV. L(-)I-OddU is a potent anti-Epstein-Barr virus (EBV) compound without cytotoxicity and animal toxicity upon long-term dosing, which allows drug concentration in plasma that are much higher than those that are antivirally active. This compound may have the potential to prevent B-cell lymphoma associated with patients undergoing organ transplants in addition to its potential use for the treatment of EBV infection. Furthermore, it may also be useful for the treatment of EBV-associated cancers. In this manuscript, the metabolism, mechanism of action and the resistance, as well as the potential use of this class of compounds targetted against HBV, will be discussed.
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PMID:L-Nucleoside analogues against cancer-causing viruses have potential in the prevention, delayed onset and treatment of viral associated cancers. 1159 88

The Epstein-Barr virus (EBV) is associated with several human tumours including lymphoid and epithelial malignancies. Most EBV-associated tumours are rare or occur at higher incidence only in certain geographical regions. The recently reported detection of EBV in gastric, breast, and hepatocellular carcinomas raises the possibility of involvement of the virus in the pathogenesis of common cancers. This article reviews the evidence linking EBV infection to epithelial tumours. It is concluded that at present, there is no convincing evidence to suggest that breast carcinoma and hepatocellular carcinoma are EBV-associated tumours.
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PMID:Epstein-Barr virus-associated carcinomas: facts and fiction. 1253 25

Recent studies suggest that Epstein-Barr virus (EBV) may act as a helper virus for the development of hepatocellular carcinoma by promoting replication of the hepatitis C virus (HCV) in the infected liver. Detection of EBV DNA in a high percentage of HCV-positive human hepatocellular carcinomas (HCC) from Japanese patients has supported this concept. In order to determine whether EBV infection is associated with HCC, we examined paraffin-embedded tissues from 31 cases of non-cirrhotic livers with hepatocellular carcinoma for the presence of EBV, HCV and hepatitis B virus (HBV) infection. RNA prepared from tumor samples were used as a template for reverse transcription followed by double-nested PCR with primers for the 5' untranslated region (NT) of HCV. DNA extracts of tumor samples were tested by single polymerase chain reaction for the detection of EBV and HBV (X- and/or S-gene) DNA sequences. To control for nucleic acid integrity, all tumor samples were amplified for human beta-globin DNA by polymerase chain reaction and subjected to Southern blot hybridization. None of the cases was found to be positive for EBV. Ten HCC cases (32%) tested positive for HCV and 12 HCC cases (38%) tested positive for HBV. Six of the surveyed patients had nucleic acids of both HCV and HBV in their tumor tissue. All HCC tumor samples were positive for beta-globin. Our study shows that HCV and HBV infections, but not EBV infection, are associated with hepatocarcinogenesis in non-cirrhotic livers. Other unknown risk factors seem to be in effect in the development of hepatocellular carcinoma in non-cirrhotic livers.
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PMID:Epstein-Barr virus and human hepatocellular carcinoma. 1263 52

Epstein Barr virus (EBV) infection causes asymptomatic liver-associated enzyme abnormalities in 80 to 90% of cases which are often unrecognized. Patients with acute EBV infections may also develop cholestatic hepatitis with associated jaundice and hepatitis with moderate elevations in the transaminase levels. Other gastrointestinal complications associated with EBV may include splenic rupture, liver failure due to acute and/or chronic EBV infection, and perhaps, autoimmune hepatitis and hepatocellular carcinoma. This article presents a case series of EBV infections with clinically significant hepatitis and reviews the literature on the gastrointestinal complications of EBV.
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PMID:Epstein Barr virus hepatitis: case series and review. 1671 24

Orthotopic liver transplantation (OLT) remains a major medical and surgical challenge in small pediatric patients. From April 2003 through October 2005, 17 infants (each of whom weighed less than 10 kg) underwent the procedure. Four were girls and 13 were boys (mean age, 15.7 +/- 9.3 months [range, 2-36 months]; mean weight at the time of transplantation, 7.4 +/- 2.6 kg [range, 6-10 kg]). All transplants were obtained from living-related donors. Sixteen left lateral segments and 1 left lobe were transplanted. The median graft-to-recipient weight ratio was 3.5% +/- 1.2% (range, 1.5%-6.1%). During the early postoperative period, hepatic arterial thrombosis was identified in 2 infants, and a biliary leak in 1. Hepatic arterial thrombosis was treated by reanastomosis with polytetrafluoroethylene grafting in the first patient and by surgical embolectomy in the second. The biliary leak was treated with percutaneous drainage. In 1 infant, portal vein stenosis, which was identified during the late postoperative period, was treated by percutaneous balloon dilatation. At this time, 14 (82.3%) infants were alive, exhibiting good graft function at a median follow-up of 11 months (range, 2-36 months). Three infants died: 1 on postoperative day 47 from adult respiratory distress syndrome, 1 on postoperative day 12 from sepsis, and 1 on postoperative day 65 from sepsis associated with EBV infection. Episodes of acute rejection, which occurred in 5 patients, were treated with pulse steroid therapy. On follow-up, histologic examination revealed hepatocellular carcinoma in 2 infants and Burkitt's lymphoma in 1 infant. Our data confirm that extensive use of living-related donors in liver transplantation can result in an excellent outcome for small pediatric patients.
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PMID:Liver transplantation in children weighing less than 10 kilograms. 1717 38


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