Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with hepatitis C have an increased risk of developing hepatocellular carcinoma (HCC). This is related to the stage of chronic liver disease, as characterized histologically by hepatic fibrosis and architectural distortion, but it is unclear whether histological markers can define the risk of developing HCC. We conducted a case-control immunohistochemical study of Ki-67, a marker for hepatocellular proliferation, in livers of 18 patients who had developed HCC more than 2 years after the biopsy specimen had been taken. Using conditional logistic regression analysis, the results were compared with 18 selected controls, who were age-matched patients with hepatitis C of similar histological stage who had not developed HCC. We also examined livers for cellular dysplasia, p53 mutations, and bcl-2 overexpression, and assessed whether the results could be correlated with demographic and disease-related variables, such as gender, region of birth, alcohol consumption, severity of liver disease, HCV genotype, and markers of hepatitis B virus (HBV) infection. Livers from patients who developed HCC were more often positive for Ki-67 (13 of 18 [72%] v 9 of 18 [50%]; P = .06) and tended to have higher mean Ki-67 scores (6 +/- 7.5 v 3 +/- 4.4; P = .10) compared with control cases. In the HCC-predisposed group, three livers showed large cell dysplasia, two were positive for p53 mutations, and two for bcl-2 overexpression. In contrast, in the non-HCC group, only one case had dysplasia, and none were positive for immunostaining for p53 or bcl-2 mutations. With the exception of one case, all livers with large cell dysplasia or p53 mutations and bcl-2 overexpression were also positive for Ki-67. Twelve (55%) of the 22 Ki-67-positive cases were anti-HBc-positive in the serum, in contrast to 2 of 14 (14%) patients in the Ki-67-negative group (P = .01). Patients with evidence of past infection with HBV were more often Ki-67 positive than those who had no evidence of past infection (85% [11 of 13] v 45% [10 of 22]; P = .02). There were no other associations between demographic or disease-related variables and Ki-67 expression. Increased hepatocellular proliferative activity, as assessed by Ki-67 expression, may be one factor indicative of an increased risk of developing HCC among patients with chronic hepatitis C. Furthermore, past infection with HBV appears to be an important correlate of increased hepatocellular proliferation in hepatitis C.
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PMID:Hepatocellular proliferation and development of hepatocellular carcinoma: a case-control study in chronic hepatitis C. 982 7

Sodium butyrate (NaBu) can enhance the expression of genes from some of the mammalian promoters including cytomegalovirus (CMV) and simian virus 40 (SV40), but it can also inhibit cell growth and induce cellular apoptosis. Thus, the beneficial effect of using a higher concentration of NaBu on a foreign protein expression is compromised by its cytotoxic effect on cell growth. To overcome this cytotoxic effect of NaBu, a survival protein, human Bcl-2, was overexpressed in recombinant Chinese hamster ovary (CHO) cells (SH2-0.32), producing a humanized antibody directed against the S surface antigen of hepatitis B virus. When batch cultures of both control cells transfected with bcl-2-deficient plasmid (SH2-0.32-Deltabcl-2) and cells transfected with bcl-2 expression plasmid (14C6-bcl-2) were performed in the absence of NaBu, both cells showed similar profiles of cell viability and antibody production. Compared with the SH2-0.32-Deltabcl-2 culture, under the condition of NaBu addition at the exponential growth phase, overexpression of the bcl-2 gene considerably suppressed the NaBu-induced apoptosis of 14C6-bcl-2 by inhibiting caspase 3 activity and extending culture longevity by >2 days. As a result, the final antibody concentration of 14C6-bcl-2 culture was twofold higher than that of SH2-0.32-Deltabcl-2 culture in the presence of NaBu and threefold higher than that of SH2-0.32-Deltabcl-2 and 14C6-bcl-2 cultures in the absence of NaBu.
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PMID:Overexpression of bcl-2 inhibits sodium butyrate-induced apoptosis in Chinese hamster ovary cells resulting in enhanced humanized antibody production. 1129 Oct 28

It has been shown that atypical reactive bile ductules (ARBD) display positive immunoreactivity of neural cell adhesion molecules (NCAM) and bcl-2. We investigated the clinicopathological features of intrahepatic cholangiocarcinoma (CC) arising in cases of viral hepatitis B or C (VHBC) and examined their relation to ARBD by means of immunohistochemical analysis. Sixty-eight surgical cases with CC were included in this study. The cause of the background liver disease was hepatitis B surface antigen (HBsAg)(+) in eight cases, antihepatitis C virus antibody (HCVAb)(+) in 13 cases, both HBsAg(+) and HCVAb(+) in one case, and both HBsAg(-) and HCVAb(-) in 46 cases. The average age of patients with CC arising in the HBsAg(+) group was significantly less than that of patients with CC in the HCVAb(+) group (P = 0.0192). Immunohistochemically, CC arising in the HBsAg(+) and HCVAb(+) groups was correlated with coexpression of NCAM/bcl-2 in the tumor cells (P = 0.0068 and P = 0.0382, respectively). Among the 12 cases of CC coexpressing NCAM/bcl-2, 11 were of mass-forming and peripheral type (P = 0.0437), and lymph node metastasis was a rare finding compared with CC showing negative coexpression of NCAM/bcl-2 (P = 0.0213). The tumor cells of CCs arising in VHBC have some characteristics of ARBD. In such tumors, because lymph node metastases were rarely seen and lymph node dissection did not improve patient's survival, lymph node dissection can be limited.
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PMID:Coexpression of neural cell adhesion molecules and bcl-2 in intrahepatic cholangiocarcinoma originated from viral hepatitis: relationship to atypical reactive bile ductule. 1203 Oct 86

Adoptive therapy with antigen-specific T cells is a potential treatment against cancers and viral diseases. To establish a system to modify the genes of these cells to increase their effectiveness, we examined whether the combined use of retroviral vector, which only infects dividing cells, and in vitro sensitization of T cells with antigen-loaded dendritic cells (DCs) could selectively modify antigen-specific T cells with a bcl-2 gene. Human CD4(+) T cells were used as target cells. Autologous DCs transfected with genes of hepatitis B virus (HBV) stimulated a specific T cell proliferation. Importantly, these proliferating T cells were selectively transduced by a bcl-2-retrovirus, and CD25(+) T cells isolated from them contained higher levels of integrated provirus. To select bcl-2-transduced, activated T cells, cells were subjected to interleukin-2 (IL-2) withdrawal. In contrast to CD25(-) and mock-infected CD25(+) T cells, 70% of CD25(+) T cells transduced with bcl-2-retrovirus survived IL-2 withdrawal. These surviving T cells were demonstrated to contain integrated bcl-2 provirus and exhibited HBV-specific proliferation and interferon-gamma secretion. In addition, bcl-2 overexpression protected HBV-specific T cells from transforming growth factor (TGF)-beta-induced cell death. These results demonstrate the feasibility of our strategy in the generation of genetically modified antigen-specific CD4(+) T cells and show that bcl-2-transduced antigen-specific T cells survive IL-2 withdrawal and TGF-beta-induced apoptosis.
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PMID:Selective modification of antigen-specific CD4(+) T cells by retroviral-mediated gene transfer and in vitro sensitization with dendritic cells. 1213 48

The bcl-2 gene is involved in the regulation of programmed cell death by providing a survival advantage to rapidly proliferating cells. This study investigates bcl-2 protein expression in liver biopsies with acute or chronic viral hepatitis B (HBV) or C(HCV). The study comprised 60 liver biopsies with hepatitis B or C. These included 10 biopsies from cases with acute lobular hepatitis (ALH), and 50 with chronic hepatitis (CH). In addition, 10 liver biopsies were used as controls. In CH cases, HAI grade ranged from 3/18 to 15/18, and stage from 1 to 6 (6HBV/8HCV). Immunohistochemical bcl-2 expression was assessed using the streptavidin-biotin method and the presence of apoptotic cells was evaluated by TUNEL method. Immunohistochemical and in situ hybridization (TUNEL) results were expressed following morphometric analysis. In CH cases, bcl-2 was detected in portal and intralobular lymphocytes, and in cholangiolar epithelial cells of the interface area. In ALH and control cases, bcl-2 was expressed only in lymphocytes. Lymphocytic bcl-2 expression was correlated directly with categories A, C and D of HAI (P < 0.001), whereas the degree of fibrosis was reversibly correlated to bcl-2 expression. In conclusion, in cases of chronic hepatitis, bcl-2 expression in cholangioles of interface area suggests that this oncoprotein may be involved in regulation of growth of these epithelial cells.
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PMID:Expresssion of bcl-2 oncoprotein in cases of acute and chronic viral hepatitis type B and type C: a clinicopathologic study. 1214 25