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)

Upregulated gene 19 (U19)/ELL-associated factor 2 (Eaf2) is a potential human tumor suppressor that exhibits frequent allelic loss and downregulation in high-grade prostate cancer. U19/Eaf2, along with its homolog Eaf1, has been reported to regulate transcriptional elongation via interaction with the eleven-nineteen lysine-rich leukemia (ELL) family of proteins. To further explore the tumor-suppressive effects of U19/Eaf2, we constructed and characterized a murine U19/Eaf2-knockout model. Homozygous or heterozygous deletion of U19/Eaf2 resulted in high rates of lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostate intraepithelial neoplasia. Within the mouse prostate, U19/Eaf2 deficiency enhanced cell proliferation and increased epithelial cell size. The knockout mice also exhibited cardiac cell hypertrophy. These data indicate a role for U19/Eaf2 in growth suppression and cell size control as well as argue for U19/Eaf2 as a novel tumor suppressor in multiple mouse tissues. The U19/Eaf2 knockout mouse also provides a unique animal model for three important cancers: lung adenocarcinoma, B-cell lymphoma and hepatocellular carcinoma.
 ...
PMID:U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia. 1787 10

Hepatitis C virus (HCV) is well known for its aetiological role in chronic non-A, non-B viral hepatitis, liver cirrhosis and hepatocellular carcinoma; in addition, the virus has also been implicated in a number of extra-hepatic "autoimmune" disease manifestations. A causative association between HCV and non-Hodgkin lymphoma (NHL) was postulated relatively recently and has been the subject of intense investigation, as well as some debate. On the strength of epidemiological data, emerging biological investigations and clinical observations, HCV appears to be involved in the pathogenesis of at least a proportion of patients with NHL. Morphologically, HCV-associated lymphomas represent a variety of histological subtypes including marginal zone lymphoma (splenic, nodal and extranodal), small lymphocytic lymphoma/chronic lymphocytic leukaemia, lymphoplasmacytic lymphoma and diffuse large B-cell lymphoma. Remarkably, some HCV-associated NHL appears to be highly responsive to antiviral therapy, providing some clinical evidence for this relationship, as well as the prospect for novel therapeutic intervention.
 ...
PMID:Hepatitis C virus and lymphoma. 1804 94

A primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) is very rare. We found a solitary mass 27 mm in size in the left lobe of the liver of a 58-year-old Japanese man with a history of hepatitis-C infection. Based on the results of imaging studies, the tumor was diagnosed as a hepatocellular carcinoma (HCC). The left lobe of the liver was lobectomized and microscopic findings showed that the tumor was a hepatic MALT lymphoma, while immunohistochemistry showed it to be positive for CD20 and CD79a. In a fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning (FDG-PET CT) before surgery, the tumor was revealed to have a high standardized uptake value (SUV) for FDG. The patient received chemotherapy after surgery. To the best of our knowledge, 45 cases had been reported with a mean age for all patients of 61.4 years. The pathogenesis remains unclear, although half of the patients had a past history of chronic inflammatory liver disease. Surgical resection was performed in most cases and some patients received postoperative chemotherapy or radiotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.
 ...
PMID:Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type: case report and review of the literature. 1880 27

Telomeres are nucleoprotein structures located at the termini of chromosomes that protect the chromosomes from fusion and degradation. Hepatocyte cell-cycle turnover may be a primary mechanism of telomere shortening in hepatitis C virus (HCV) infection, inducing fibrosis and cellular senescence. HCV infection has been recognized as potential cause of B-cell lymphoma and hepatocellular carcinoma. The present study sought to assess relative telomere length in leukocytes from patients with chronic HCV infection, patients after eradication of HCV infection (in remission), and healthy controls. A novel method of manual evaluation was applied. Leukocytes derived from 22 patients with chronic HCV infection and age- and sex-matched patients in remission and healthy control subjects were subjected to a fluorescence-in-situ protocol (DAKO) to determine telomere fluorescence intensity and number. The relative, manual, analysis of telomere length was validated against findings on applied spectral imaging (ASI) in a random sample of study and control subjects. Leukocytes from patients with chronic HCV infection had shorter telomeres than leukocytes from patients in remission and healthy controls. On statistical analysis, more cells with low signal intensity on telomere FISH had shorter telomeres whereas more cells with high signal intensity had longer telomeres. The findings were corroborated by the ASI telomere software. Telomere shortening in leukocytes from patients with active HCV infection is probably due to the lower overall telomere level rather than higher cell cycle turnover. Manual evaluation is an accurate and valid method of assessing relative telomere length between patients with chronic HCV infection and healthy subjects.
 ...
PMID:Telomere length in Hepatitis C. 1899 39

Cdc6 play crucial roles in DNA replication and carcinogenesis. The biological significance of the Cdc6 G1321A polymorphism (V441I, rs13706) is still not elucidated. Here we examined the influence of this polymorphism on the function of Cdc6 and the individual's susceptibility to non-Hodgkin lymphoma (NHL) and hepatocellular carcinoma (HCC). Unconditional logistic regression analysis revealed that the risk for NHL was significantly reduced in both AG heterozygotes [odds ratio (OR)=0.67, P=0.019] and AA homozygotes (OR=0.54, P=0.026), compared with GG homozygotes. Further stratification by subtypes of NHL showed that the AG as well as combined AA/AG genotypes were associated with decreased risk for B-cell-NHL (OR=0.62, P=0.011 and OR=0.61, P=0.006, respectively), especially for diffuse large B-cell lymphoma (DLBCL, OR=0.63, P=0.025 and OR=0.62, P=0.012, respectively). In addition, male individuals with the AA genotype displayed borderline significantly reduced risk for HCC (OR=0.48, P=0.054). Interestingly, the G1321A polymorphism did not affect caspase-mediated cleavage of Cdc6 during etoposide-induced apoptosis, but it was predicted to alter the secondary structure of Cdc6 mRNA. Our data provide the first evidence that the Cdc6 G1321A polymorphism is associated with decreased risk of cancer. Further studies are necessary to confirm the general validity of our findings.
 ...
PMID:Association analysis between the Cdc6 G1321A polymorphism and the risk for non-Hodgkin lymphoma and hepatocellular carcinoma. 1910 72

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and probably also non-Hodgkin's B-cell lymphoma. The molecular mechanisms of HCV-associated carcinogenesis are unknown. Here we demonstrated that peripheral blood mononuclear cells obtained from hepatitis C patients and hepatocytes infected with HCV in vitro showed frequent chromosomal polyploidy. HCV infection or the expression of viral core protein alone in hepatocyte culture or transgenic mice inhibited mitotic spindle checkpoint function because of reduced Rb transcription and enhanced E2F-1 and Mad2 expression. The silencing of E2F-1 by RNA interference technology restored the function of mitotic checkpoint in core-expressing cells. Taken together, these data suggest that HCV infection may inhibit the mitotic checkpoint to induce polyploidy, which likely contributes to neoplastic transformation.
 ...
PMID:Hepatitis C virus causes uncoupling of mitotic checkpoint and chromosomal polyploidy through the Rb pathway. 1979 24

Recent advances in cancer therapeutics stress the need for a better understanding of the molecular mechanisms driving tumor formation. This can be accomplished by obtaining a more complete description of the genes that contribute to cancer. We previously described an approach using the Sleeping Beauty (SB) transposon system to model hematopoietic malignancies in mice. Here, we describe modifications of the SB system that provide additional flexibility in generating mouse models of cancer. First, we describe a Cre-inducible SBase allele, RosaSBase(LsL), that allows the restriction of transposon mutagenesis to a specific tissue of interest. This allele was used to generate a model of germinal center B-cell lymphoma by activating SBase expression with an Aid-Cre allele. In a second approach, a novel transposon was generated, T2/Onc3, in which the CMV enhancer/chicken beta-actin promoter drives oncogene expression. When combined with ubiquitous SBase expression, the T2/Onc3 transposon produced nearly 200 independent tumors of more than 20 different types in a cohort of 62 mice. Analysis of transposon insertion sites identified novel candidate genes, including Zmiz1 and Rian, involved in squamous cell carcinoma and hepatocellular carcinoma, respectively. These novel alleles provide additional tools for the SB system and provide some insight into how this mutagenesis system can be manipulated to model cancer in mice.
 ...
PMID:A modified sleeping beauty transposon system that can be used to model a wide variety of human cancers in mice. 1980 65

A 70-year-old woman diagnosed to have a hepatitis C virus (HCV) infection was referred to our hospital because of a solitary liver tumor. because of a solitary liver tumor. She underwent a partial hepatectomy, and the tumor was histologically diagnosed as a hepatocellular carcinoma (HCC). diagnosed as a hepatocellular carcinoma (HCC). In addition, a focal follicle consisting of atypical lymphoid cells was seen within the HCC. cells was seen within the HCC. Two months later, she was readmitted because of weakness and rapidly developing abdominal fullness. developing abdominal fullness. An abdominal computed tomography scan showed widespread tumors with ascites. with ascites. A cytological examination of the ascites showed large-sized atypical lymphoid cells. showed large-sized atypical lymphoid cells. An immunohistochemical stain confirmed that the atypical lymphoid cells within the HCC were positive for the CD 20 antigen. antigen. Taking these findings into account, the hepatic tumor was determined to be a HCC infiltrated with diffuse large B-cell lymphoma. diffuse large B-cell lymphoma. The coexistence of HCC and non-Hodgkin's lymphoma (NHL) is extremely rare. and non-Hodgkin's lymphoma (NHL) is extremely rare. We herein report a case of HCC infiltrated with NHL. We herein report a case of HCC infiltrated with NHL.
 ...
PMID:Hepatocellular carcinoma infiltrated with non-Hodgkin's lymphoma: report of a case. 1988 28

Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling is one of the major pathways for cytokine signal transduction. However, the role of the JAK/STAT pathway in liver ischemia/reperfusion is not clear. This study focuses on Janus kinase-2 (JAK2), which functions upstream of signal transducer and activator of transcription 1 (STAT1) in JAK/STAT, and its role in the mechanism of liver ischemia/reperfusion injury (IRI). Partial warm ischemia was produced in the hepatic lobes of C57BL/6 mice for 90 minutes, and this was followed by 6 hours of reperfusion. Mice were treated with a JAK2 inhibitor (tyrphostin AG490; 40 mg/kg intraperitoneally) or vehicle 60 minutes prior to ischemic insult. JAK2 blockade resulted in a significant reduction of hepatocyte apoptosis and liver injury. Macrophage and neutrophil infiltration, as assessed by immunohistochemistry, was markedly decreased in AG490-treated livers in comparison with controls. The expression of pro-inflammatory cytokines [tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-1beta] and chemokines [chemokine (C-X-C motif) ligand 10 (CXCL-10) and CXCL-2] was also significantly reduced in the AG490-treated group in comparison with controls. AG490-treated livers showed fewer cells positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and reduced cleaved caspase-3 protein expression in parallel with increased B-cell lymphoma extra large expression. We employed AG490 (75 mM) in primary bone marrow-derived macrophage (BMM) and hepatoma cell (CRL1830) cultures, which were both stimulated with lipopolysaccharide (LPS; 10 ng/mL). In BMM cultures, AG490 depressed otherwise LPS-induced pro-inflammatory gene expression programs (IL-6, IL-12p40, IL-1beta, CXCL-10, and inducible nitric oxide synthase). In hepatoma cells, AG490 reduced cleaved caspase-3 expression. Moreover, JAK2 blockade inhibited STAT1 and STAT3 phosphorylation. This is the first report documenting that JAK2 signaling is essential in the pathophysiology of liver IRI, as its selective blockage ameliorated the disease process and protected livers from inflammation and apoptosis.
 ...
PMID:Blockade of Janus kinase-2 signaling ameliorates mouse liver damage due to ischemia and reperfusion. 2111 57

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and putatively also non-Hodgkin's B cell lymphoma. In this study, we demonstrated that PBMCs obtained from HCV-infected patients showed frequent chromosomal aberrations and that HCV infection of B cells in vitro induced enhanced chromosomal breaks and sister chromatid exchanges. HCV infection hypersensitized cells to ionizing radiation and bleomycin and inhibited nonhomologous end-joining repair. The viral core and nonstructural protein 3 proteins were shown to be responsible for the inhibition of DNA repair, mediated by NO and reactive oxygen species. Stable expression of core protein induced frequent chromosome translocations in cultured cells and in transgenic mice. HCV core protein binds to the NBS1 protein and inhibits the formation of the Mre11/NBS1/Rad50 complex, thereby affecting ATM activation and inhibiting DNA binding of repair enzymes. Taken together, these data indicate that HCV infection inhibits multiple DNA repair processes to potentiate chromosome instability in both monocytes and hepatocytes. These effects may explain the oncogenicity and immunological perturbation of HCV infection.
 ...
PMID:Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes. 2097 81


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