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)

An uncontrolled pilot study of adenine arabinoside monophosphate intramuscularly (ARA-AMP) for 5 days at 10 mg/kg/day and 23 days at 5 mg/kg/day in divided doses, was conducted in 15 consecutive patients known to be HBeAg-positive for a minimum of 12 months. Two patients were lost to follow-up (1 having developed an hepatoma). Of the remaining 13, 11 remained HBeAg-positive at 1 year. During treatment, the median serum DNA polymerase (DNAp) activity fell from 592 cpm to 203 cpm/200 microliters. Of 12 patients initially positive for DNA polymerase, complete inhibition during treatment occurred in 6 and was permanent in 2, who developed anti-HBe. In the remaining 4 and in 6 further patients in whom inhibition was substantial but incomplete, DNAp activity rose to pretreatment levels within 1 month of completing treatment. All these patients remained DNAp + HBeAg-positive at one year. Serum HBV-DNA was measured in 7 patients, 6 who were initially DNAp-positive and 4 of whom had complete inhibition of DNAp during treatment. All 7 remained positive for HBV-DNA during treatment. Although side-effects were common there were no significant changes in biochemical or haematological parameters during or subsequent to therapy. Over the subsequent 48 months 2 more patients have developed an hepatoma and a further 5 have lost HBeAg; the 4 patients who remain alive and HBeAg-positive all had chronic persistent hepatitis initially.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effect of ARA-AMP on serum DNA polymerase activity and serum HBV-DNA in chronic hepatitis B virus infection. A possible reason for lack of efficacy. 243 80

Recent studies suggest that hepatitis B virus (HBV), despite being a DNA virus, replicates via an RNA intermediate (R. H. Miller, P. L. Marion, and S. W. Robinson, Virology 139:64-72, 1984; J. Summers and W. S. Mason, Cell 29:403-415, 1982). The HBV life cycle is therefore a permuted version of the RNA retroviral life cycle. Sequence homology between retroviral reverse transcriptase and the putative HBV polymerase gene product suggests the presence of an HBV reverse transcriptase (H. Toh, H. Hajashida, and T. Miyata, Nature (London) 305:827-829, 1983). As yet, there has been no direct evidence that reverse transcriptase activity is present in the viral particle. We used activity gel analysis to detect the in situ catalytic activities of DNA polymerases after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Our studies demonstrated that HBV-like particles secreted by a differentiated human hepatoma cell line transfected with genomic HBV DNA contain two major polymerase activities which migrate as approximately 90- and approximately 70-kilodalton (kDa) proteins. This demonstrated, for the first time, that HBV-like particles contain a novel DNA polymerase-reverse transcriptase activity. Furthermore, we propose that the 70-kDa reverse transcriptase may be produced by proteolytic self-cleavage of the 90-kDa precursor protein.
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PMID:Two proteins with reverse transcriptase activities associated with hepatitis B virus-like particles. 244 93

Luzopeptin analogues, A, B and C (in decreasing degree of acetylation) were active, less active and inactive, respectively, against several animal tumour models. All bound to isolated DNA avidly. The present studies with cultured Novikoff hepatoma cells showed that luzopeptins A, B and C were inhibitory, less inhibitory and ineffective, respectively, on cell colony formation ability and whole-cell DNA and RNA synthesis. RNA synthesis was more sensitive than DNA synthesis to luzopeptins A and B. All had no direct effect on protein synthesis. All inhibited the DNA and RNA syntheses of isolated nuclei and luzopeptins B and C were slightly more active than luzopeptin A inhibition of RNA synthesis in isolated nuclei. All similarly inhibited DNA polymerase activity in vitro, but luzopeptin C was more active against RNA polymerase activity in vitro. It is concluded that luzopeptin cytotoxicity probably resulted from inhibition of DNA and RNA biosynthesis. Because all analogues bound avidly to isolated DNA and inhibited its functions, the differential anti-tumour activity may be attributed to the differential ability of these luzopeptins to traverse the cell membrane and, to some extent, other intracellular barriers. This probably is a result of difference in acetylation, resulting in differences in hydrophobicity.
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PMID:Effects of structural modifications of anti-tumour antibiotics luzopeptins on cell growth and macromolecule biosynthesis. 245 97

A rat hepatoma cell line (Q7) of Morris hepatoma origin was transfected with a construct containing the tandem dimer genome of human hepatitis B virus (HBV) and the neomycin-resistant selection marker. The culture medium of several neomycin-resistant single-cell clones was found to accumulate high levels of secreted HBV surface antigen and core-related e antigen. HBV-specific replication intermediates, including relaxed circular and single-stranded DNA with a minus-strand polarity, could be found in both the intracellular fraction and the extracellular culture medium by the Southern blot procedure. One of these clones, designated Q7 HBV-21, was characterized in further detail. DNA polymerase activity was present in the virus particles produced by Q7 HBV-21 cells. Characteristic transcripts of HBV, including the 3.5-, 2.5-, and 2.1-kilobase mRNA as well as a core-gene-related transcript of 2.2 kilobases could be detected. Electron microscopic examination of the conditioned medium from Q7 HBV-21 cells identified 42-nm Dane-like particles as well as 22-nm subviral particles with a spherical or filamentous shape. This Q7 HBV-21 cell line has been maintained in the absence of neomycin for 1 year without losing the properties of HBV DNA replication and Dane-like particle production. Our results strongly suggest that the species barrier of HBV infection is at an early step of viral absorption onto or penetration into the target hepatocytes. This nonhuman system for HBV production in culture could be used to complement the human HepG2 system.
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PMID:In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. 276 28

The differentiated human hepatoma cell line Hep-G2 was transfected with cloned duck hepatitis B virus (DHBV) DNA. Introduction of closed circular DNA into the human liver cells resulted in the production of viral proteins: core antigen was detected in the cytoplasm, and e antigen, a related product, was secreted into the medium. Moreover, viral particles were released into the tissue culture medium which were indistinguishable from authentic DHBV by density, antigenicity, DNA polymerase activity, and morphology. Intravenous injection of tissue culture-derived DHBV particles into Pekin ducks established DHBV infection. In conclusion, transfection of human hepatoma cells with cloned DHBV DNA results in the production of infectious virus, as occurs with cloned human hepatitis B virus DNA. Human liver cells are therefore competent to support production of the avian and mammalian hepadnaviruses, indicating that liver-specific viral gene expression is controlled by evolutionarily conserved mechanisms. This new DHBV transfection system offers the opportunity to rapidly produce mutated DHBV which then can be further investigated in Pekin ducks.
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PMID:Production of infectious duck hepatitis B virus in a human hepatoma cell line. 283 23

DNA-dependent ATPase IV has been purified to near homogeneity from the Novikoff rat hepatoma. The enzyme is devoid of DNA polymerase, RNA polymerase, exonuclease, endonuclease, phosphomonoesterase, 3'- or 5'-phosphodiesterase, polynucleotide kinase, protein kinase, topoisomerase, helicase or DNA reannealing activities at a detection level of 10(-5) to 10(-7) relative to the ATPase activity. The enzyme is a monomer of Mr 110,000, has a sedimentation coefficient of 5.9 S, a Stokes radius of 40 A and a frictional coefficient of 1.32. In the presence of Mg2+ ion and a polynucleotide effector, ATPase IV hydrolyzes either ATP or dATP to the nucleoside diphosphate plus Pi. Other ribo- or deoxyribonucleoside triphosphates are not substrates. ATPase IV utilizes double-stranded DNA and single-stranded DNA as effector; however, it does not utilize poly(dT). The Km for dsDNA or ssDNA is 2.2 microM (nucleotide). A variety of ATP analogues were found to be competitive inhibitors of ATPase IV.
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PMID:Purification and enzymological characterization of DNA-dependent ATPase IV from the Novikoff hepatoma. 296 5

Sera from 31 HBsAg-positive Chinese patients with inoperable hepatocellular carcinoma (HCC) were tested for hepatitis B virus DNA (HBV DNA) by means of dot hybridisation and Southern blot technique. HBV DNA probes were prepared from human plasma. Eighteen of the patients were HBeAb-positive, 12 were HBeAg-positive and one case had neither marker. Serial specimens were obtained from 16 cases over 5-42 weeks, while the patients were treated with recombinant leukocyte A interferon (rIFN-A) or adriamycin. Seven patients (2 HBeAg-positive, 5 HBeAb-positive) were positive for HBV DNA. In two patients HBV DNA and HBV DNA polymerase (DNAp) appeared in serum weeks after rIFN-A or adriamycin treatment was started. In two other cases, HBV DNA that was initially present disappeared during rIFN-A treatment. In a fifth patient HBV DNA persisting after adriamycin treatment diminished after change of treatment to rIFN-A. With one possible exception the HBV DNA detectable by Southern blot technique was composed chiefly of sequences 2.2-3.2 kb size indicating the presence of unintegrated DNA forms. DNAp activities were raised in the presence of HBV DNA in 4 patients. These findings show that HBV replication can be activated or suppressed in advanced HCC. Treatment with rIFN-A may have been effective in suppressing HBV DNA synthesis, but the number of cases studied was too small to arrive at a definite conclusion on this point.
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PMID:Serum hepatitis B viral DNA in HBsAg-positive hepatocellular carcinoma treated with interferon or adriamycin. 301 83

Closed-circular HBV DNA was introduced into cells of the established human hepatoma culture HepG2. The culture medium of one of 40 single-cell clones contained HBV surface antigen (HBsAg), core-related antigens (HBc/eAg), and HBV DNA sequences. HBV DNA and DNA polymerase activity were detected in particles resembling both nucleocapsids and complete virions (Dane particles). Intracellular integrated and extrachromosomal HBV DNA sequences were detected. Relaxed-circular and single-stranded forms of viral DNA were identified as likely replicative intermediates of the HBV genome. In conclusion, in vitro production of Dane-like particles by transformed human hepatocytes has been achieved. This model should be valuable as a cell culture system for studying virus replication and virus-host cell interactions.
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PMID:Production of hepatitis B virus by a differentiated human hepatoma cell line after transfection with cloned circular HBV DNA. 301 65

Transfection of human hepatoma cell lines with cloned HBV DNA resulted in the secretion of large amounts of hepatitis B surface antigen (HBsAg) and core-related antigens (HBc/HBeAg) if well-differentiated cell lines were employed. Synthesis of both viral antigens was the highest in cell line HuH-7 and continued for approximately 25 days. Particles resembling hepatitis B virions (Dane particles) by morphology, density and by the presence of the preS1 surface antigen were released from the transfected HuH-7 cells into the culture medium. These particles produced in vitro were also indistinguishable from the naturally occurring hepatitis B virions in containing the virus-associated DNA polymerase and mature HBV genomes. Restriction analysis of these DNA molecules was compatible with the nucleotide sequence of the transfecting HBV DNA sequence. Viral surface antigens and core proteins present in the culture medium were fractionated and characterized by immunoprecipitation and SDS--PAGE after labeling with [35S]methionine. Antisera specific for X-gene products identified in cell extracts two hitherto unknown HBV gene products. This system thus provides a new approach to open questions regarding HBV-related gene function and HBV replication.
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PMID:Production of hepatitis B virus in vitro by transient expression of cloned HBV DNA in a hepatoma cell line. 303 5

We have utilized an electrophoretic assay of misincorporation to investigate the possibility that ionization of 5-bromouracil (BU) may play a role in its mispairing during DNA synthesis in vitro. We examined the effects of increasing pH on the relative rates of formation of BU.G and T.G mispairs during chain elongation catalyzed by various DNA polymerases. For the Klenow fragment of Escherichia coli DNA polymerase I, increasing pH facilitated BU.G mispair formation (relative to T.G mispairing) when BU was present in the template strand. This effect showed a strong dependence on sequence context. Increasing pH had little effect on the relative rate of misincorporation of BrdUMP versus dTMP (at template G) by the Klenow polymerase. Misincorporation opposite template BU residues catalyzed by Maloney murine leukemia virus DNA polymerase and DNA polymerase beta (Novikoff hepatoma) also increased with pH, but for these two enzymes, there was no apparent dependence on sequence context. With T4 DNA polymerase and E. coli DNA polymerase III holoenzyme, a similar occurrence of BU.G and T.G mispairing during polymerization was observed, whether BU was present in the template or in the incoming nucleotide, and there was little effect of pH. The results reported here are consistent with a mispairing mechanism for template BU wherein the anionic form of the base mispairs with G.
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PMID:Effect of pH on the base-mispairing properties of 5-bromouracil during DNA synthesis. 328 89


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