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

Review of the relationship between the degree of immunosuppression and malignancy in patients on immunosuppressive drugs or immunosuppressed by HIV infection, postoperative blood transfusion or pregnancy provides the most convincing evidence of the importance of intact T cell immunity in resistance to cancer. Defective HLA class I and II antigen expression on tumours arising in non-immunosuppressed individuals and correlation of these changes with increased malignancy and diminished TIL provide the most convincing evidence that one factor necessary to ensure survival of most spontaneous tumours is mutation that enables tumour cells to escape rejection by cytotoxic T cells. These changes are less frequent in tumours in immunosuppressed patients, and preliminary data suggest that use of cytokine therapy is more successful in these tumours and the one in five spontaneous tumours demonstrating normal expression of HLA antigens and high levels of T cell infiltration. These observations suggest that future use of this therapy should be focused on these cases. All modalities of cancer therapy except hormone therapy (ie surgery, radiotherapy and chemotherapy) suppress immune responses. Defects of HLA antigen expression are less marked in early cancer. Combinations of immunotherapy with conventional treatment at presentation, including hormone therapy in view of data demonstrating regeneration of the thymus after castration, needs further investigation. Preliminary results from randomized trials involving nearly 300 individuals accidentally exposed to carcinogens demonstrated nearly 60% reduction of incidence of malignancy at 5 years in the arm receiving non-specific immunotherapy. If confirmed, such an approach might be more cost-effective as an approach for cancer prevention than organ specific cancer screening or vaccination against cancer associated viruses such as hepatitis B or papillomaviruses.
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PMID:T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy. 142 23

Based on the know epidemiology of the viruses that account for the bulk of the need for chimpanzees in biomedical research--hepatitis B virus (HBV), non-A, non-B (NANB) hepatitis virus, and human immunodeficiency virus (HIV)--as well as the psychosocial needs of this species, requirements for appropriate isolation conditions for these animals have been reviewed. We believe that animals should generally be housed in groups of at least two in the same cage, and that cages encased in solid-walled isolator boxes for housing of single chimpanzees are unnecessary for virologically adequate isolation for studies of HBV, NANB and HIV, and cause sensory and psychosocial deprivation, which contravenes their psychological well-being.
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PMID:Appropriate conditions for maintenance of chimpanzees in studies with blood-borne viruses: an epidemiologic and psychosocial perspective. 249 32

Proteins of either HIV-1, hepatitis B, or rabies virus were incorporated with the adjuvant substance Quil A and cholesterol into the immunostimulating complex: iscom. Formation and symmetry of this regular complex were analyzed by electron microscopy. Micellar structures with a diameter of about 12 nm, occasionally with a 7-nm stain-filled center, were formed in a 0.03% water suspension of Quil A. Cavities or holes appeared in the smooth structures of cholesterol upon the addition of Quil A, and after mixing Quil A and cholesterol 1:1 fragile and flattened structures of matrix were produced with a diameter of about 40 nm. By freeze-drying the matrix was preserved as a cage-like, isometric particle. Stable iscom particles composed of Quil A, cholesterol, and selected viral proteins had an approximate diameter of 32 nm. The particles had an uniform, cage-like structure, exhibiting icosahedral symmetry, irrespective of the viral proteins incorporated. Tilting experiments and rotational image analysis indicated that the iscoms were composed of 20 morphological subunits assembled in a pentagonal dodecahedron with a hole on each of the 12 pentagonal faces. The symmetrical shape of the iscom might explain both its remarkable stability and its capacity to efficiently present antigens to the immune system.
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PMID:Quaternary structure of the immunostimulating complex (iscom). 263 9

The CAGE/GEM(TM) software toolkit for genetic engineering is briefly described. The system functionally uses color graphics and is menu driven. It integrates genetics and features information ("Overlays") with information based on sequence analysis ("Representations"). The system is structured around CAD (Computer Aided Design) principles. The CAGE (Computer Aided Genetic Engineering) aspects of the software are emphasized and illustrated by a simulated cloning of the hepatitis B core antigen gene into the BAMHI site of plasmid pBR322.
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PMID:Cloning simulation in the cage environment. 300 74

(2'R,5'S-)-cis-5-Fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine (524W91) is a nucleoside analog with potent anti-human immunodeficiency virus and anti-human hepatitis B virus activities in vitro. The pharmacokinetics and bioavailability of 524W91 after oral dosing were studied in mice dosed with 10, 100, and 600 mg of 524W91 per kg of body weight by the oral and intravenous routes. Cynomolgus monkeys were dosed with 10 and 80 mg of 524W91 per kg. In both species, the clearance of 524W91 was rapid, via the kidney, and was independent of dose. In monkeys, the total body clearance of 10 mg of 524W91 per kg was 0.7 +/- 0.1 liter/h/kg, and the volume of distribution at steady state was 0.8 +/- 0.02 liter/kg. The terminal elimination half-life was 1.0 +/- 0.2 h. The absolute bioavailability after oral dosing was 63% +/- 4% at 10 mg/kg. Concentrations of 524W91 in the cerebrospinal fluid were 4% +/- 0.7% of the corresponding levels in plasma. In mice, the total clearance of 10 mg of 524W91 per kg was 2.3 liters/kg/h, and the volume of distribution at steady state was 0.9 liter/kg. Absolute bioavailability in mice after oral dosing was 96% at a dose of 10 mg/kg. The metabolism of orally administered [6-3H]524W91 was studied in cynomolgus monkeys at a dose of 80 mg/kg and in mice at a dose of 120 mg/kg. Monkeys excreted 41% +/- 6% of the radioactive dose in the 0- to 72-h urine, 33% +/- 10% in the feces, and 10% +/- 7% in the cage wash. Unchanged 524W91 was 64% of the total radiolabeled drug recovered in the urine. The glucuronide was a minor urinary metabolite. 5-Fluorouracil was not detected (less than 0.02% of the dose). Mice dosed orally with 120 mg of [6-3H]524W91 per kg excreted 67% +/- 7% of the radiolable in the )- to 48-h urine. Small amounts of the 3' -sulfoxide and glucuronide metabolites were observed in the urine, but 5-fluorouracil was not detected. Good bioavailability after oral dosing and resistance to metabolism recommend 524W91 for further preclinical evaluation.
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PMID:Pharmacokinetics, oral bioavailability, and metabolism in mice and cynomolgus monkeys of (2'R,5'S-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine, an agent active against human immunodeficiency virus and human hepatitis B virus. 769 53

Viruses can contribute to the development of human tumors by different mechanisms: directly by altering host cellular gene expression by viral products or by viral DNA integration; indirectly by modifying the host cell genome co-operated with other factors. Human cancer associated with hepatitis B virus (HBV), hepatitis C virus (HCV), human T cell leukemia virus (HTLV-I), papillomavirus (HPV) and Epstein-Barr virus (EBV) infections are responsible for liver cancer (HBV and HCV), adult T cell leukemia (HTLV-I), cervical cancer (HPV) and malignant lymphoma (EBV) respectively. Based on the clinical and experimental knowledge, viral tumor markers are thought of not as diagnostic markers, but as most important risk factors for various tumorigenesis.
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PMID:[Viral tumor markers]. 869 5

The prevalence of adult cirrhosis in Western countries is estimated to be about 3-5 per cent. Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, is associated with cirrhosis in a majority of cases. The estimated annual incidence of cancer associated with cirrhosis is 1-11 per cent. All cirrhosis may be complicated by cancer, but the cancer risk is reported to be highest in cases of hepatitis B (HBV) or C (HCV) infection, or haemochromatosis. In two Swedish studies, comprising a total of 605 patients with HCC, cirrhosis was present in about 70 per cent. The most common causes of cirrhosis were alcohol abuse and chronic HCV infection, and there was not a single case of chronic HBV infection. Most patients presented with cancer but no history of cirrhosis. In HCC, prognosis is usually very poor, and the results of screening for HCC in cirrhosis patients have been disappointing. Thus, prevention of cirrhosis (e.g., by reducing alcohol consumption), treatment of chronic HCV infection and, in certain cases, vaccination against HBV, is an approach likely to have the greatest impact on the incidence of HCC.
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PMID:[Prevention of cirrhosis is the best measure against hepatocellular cancer]. 1002 24

Clinical and epidemiological data on 93 patients with liver cirrhosis, treated in the Gastroenterological Department of the Republican Clinical Hospital of the of the Republic of Tatarstan MoH in 1998-2000 were analyzed. The retrospective analysis of 856 cases of the liver cancer, diagnosed in the Republic of Tatarstan in 1996-2000, was made. In 20.4% of patients with liver cirrhosis and 16.2% of patients with liver cancer, registered in the Republic of Tatarstan, the serological markers of hepatitis B (HB) and hepatitis C (HC) were detected. The domination of HC markers was observed in the liver cirrhosis and that of HB markers in the cancer of the liver. The liver cirrhosis with HC markers was more often registered in the age group of 45-60 years and with HB markers at the age over 60 years, while the cancer of the liver was more often registered in persons aged 75 years and older. The necessity of introducing the official registration of the liver cirrhosis and cancer associated with chronic infection caused by hepatoviruses B and C is confirmed.
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PMID:[Liver cirrhosis and liver cancer associated with viral hepatitis B and C in republic of Tatarstan]. 1263 Mar 49

Malignant transformation from mortal, normal cells to immortal, cancer cells is generally associated with activation of telomerase and subsequent telomere maintenance. A major mechanism to regulate telomerase activity in human cells is transcriptional control of the telomerase catalytic subunit gene, human telomerase reverse transcriptase (hTERT). Several transcription factors, including oncogene products (e.g. c-Myc) and tumor suppressor gene products (e.g. WT1 and p53), are able to control hTERT transcription when over-expressed, although it remains to be determined whether a cancer-associated alteration of these factors is primarily responsible for the hTERT activation during carcinogenic processes. Microcell-mediated chromosome transfer experiments have provided evidence for endogenous factors that function to repress the telomerase activity in normal cells and are inactivated in cancer cells. At least one of those endogenous telomerase repressors, which is encoded by a putative tumor suppressor gene on chromosome 3p, acts through transcriptional repression of the hTERT gene. The hTERT gene is also a target site for viruses frequently associated with human cancers, such as human papillomavirus (HPV) and hepatitis B virus (HBV). HPV E6 protein contributes to keratinocyte immortalization and carcinogenesis through trans-activation of the hTERT gene transcription. In at least some hepatocellular carcinomas, the hTERT gene is a non-random integration site of HBV genome, which activates in cis the hTERT transcription. Thus, a variety of cellular and viral oncogenic mechanisms converge on transcriptional control of the hTERT gene. Regulation of chromatin structure through the modification of nucleosomal histones may mediate the action of these cellular and viral mechanisms. Further elucidation of the hTERT transcriptional regulation, including identification and characterization of the endogenous repressor proteins, should lead to better understanding of the complex regulation of human telomerase in normal and cancer cells and may open up new strategies for anticancer therapy.
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PMID:Transcriptional regulation of the telomerase hTERT gene as a target for cellular and viral oncogenic mechanisms. 1280 29

Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P <.001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P <.001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
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PMID:Cancer-associated molecular signature in the tissue samples of patients with cirrhosis. 1476 6


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