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)

The effect of zinc on the growth of a transplantable DAB hepatoma in young male Wistar rats was determined. Both a zinc deficiency (less than 0.5 microgram/g feed) as well as high levels of dietary zinc (500 micrograms/g feed) significantly reduced tumor growth. Both high- and low-zinc diets resulted in reduced activity of the salvage pathway of thymidine synthesis as well as reduced 32PO4 incorporation into DNA and diminished DNA polymerase activity. Blockage of the de novo pathway of DNA synthesis by the folate antagonist methotrexate (MTX) resulted in greatly increased flux through the thymidine salvage pathway and increased DNA polymerase activity but decreased 32PO4 incorporation in the transplantable hepatomas in Wistar rats fed normal zinc diets (50 micrograms/g feed). MTX had the effect of reducing all these activities in the groups fed low- and high-zinc diets. These data suggested a site of action of zinc associated with the salvage pathway of thymidine synthesis.
 ...
PMID:Possible site of zinc control of hepatoma cell division in Wistar rats. 657 40

In continuation of efforts to correlate the antitemplate activities of chemically modified polynucleotides with their base composition and structure, four synthetic copolymers, poly(A,C), poly(C,U), poly(A,C,U), and poly(A,C,G) were modified by thiolation of 2.6-4.8% of their pyrimidine bases. The resulting 5-mercaptoheteropolynucleotides and the previously described 5-mercapto-polycytidylate (MPC) and -polyuridylate (MPU) were tested in a comparative manner as inhibitors of the DNA polymerase-alpha from rat hepatoma. A wide scale of inhibitory potencies was obtained in the following (decreasing) order: MPU greater than M-poly(A,C,U) greater than M-poly(C,U) greater than MPC greater than M-poly(A,C) greater than or equal to M-poly(A,C,G). The sensitivity of the hepatoma DNA polymerase toward these antitemplates increased upon further purification of the enzyme through the DNA-agarose step. Partially thiolated DNA-isolates from rat hepatoma and calf thymus, respectively, showed significant inhibition of the hepatoma DNA polymerase, the thiolated hepatoma DNA being the more active inhibitor.
 ...
PMID:Inhibition of DNA polymerase-alpha from rat hepatoma with a series of new synthetic polynucleotides. 661 28

A DNA polymerase activity has been identified in the plasma membranes isolated from a rat hepatoma (the Zajdela Ascitic Hepatoma). The enzyme activity was found specifically associated with the detergent insoluble skeleton of the plasma membranes from which it cannot be dissociated by conventional methods. The properties of the enzyme are indistinguishable from those of DNA polymerase-alpha.
 ...
PMID:A DNA polymerase activity associated with the skeletal framework of the plasma membranes of a rat hepatoma. 688 43

Hepatitis B virus (HBV) of man has several characteristics that distinguish it from viruses of other groups. These include its ultrastructure, viral DNA size and structure, a virion DNA polymerase which repairs a single-stranded region in the viral DNA, liver tropism, character of persistent infection, and association with hepatitis and hepatocellular carcinoma. Recently three other viruses have been found in other animal species that appear to share these characteristics although the viruses are not identical. HBV, Woodchuck hepatitis virus (WHV), ground squirrel hepatitis virus (GSHV), and duck hepatitis virus (DHV) appear to be members of a new virus group that might be designated the Hepadna virus group. Genetic variation among hepatitis B viruses includes the antigenic variation in the surface antigen (HBsAg) which constitutes the known HBsAg subtypes. There is also frequent variation in DNA base sequence among HBVs isolated from different patients.
 ...
PMID:Genetic variation among hepatitis B and related viruses. 701 20

Solid-phase radioimmunoassays for woodchuck hepatitis virus (WHV) surface antigen (WHsAg) and antibody to it (anti-WHs) were developed. The test for WHsAg could detect as little as 10 ng/ml. In both tests it was necessary to employ radiolabeled WHsAg instead of anti-WHs as the probe because the latter appeared to be labile to the conditions of labeling. The tests were used to characterize naturally acquired and experimental WHV infections of woodchucks. Forty-three of 72 wild-caught woodchucks had serological evidence of WHV infections; 16 of these resulted in chronic infection, and the remainder were self-limiting. All chronically infected animals were positive for WHsAg and DNA polymerase activity. During 3 years of observation, 11 of the 16 WHsAg-positive animals and 3 of the 27 anti-WHs-positive animals, but none of the 21 uninfected animals developed hepatocellular carcinoma. Seroconversion, possibly resulting from infection with WHV, was documented in a chimpanzee inoculated with WHV. An immune adherence hemagglutination test for WHsAg was also developed by using anti-WHs of chimpanzee origin as a reagent, but the test was not useful for detecting anti-WHs of woodchuck origin because of the lability of the latter.
 ...
PMID:Natural and experimental infection of woodchucks with woodchuck hepatitis virus, as measured by new, specific assays for woodchuck surface antigen and antibody. 707 21

The activity of DNA polymerases and thymidine kinase was compared in the MC-29 leukosis virus-induced transplantable hepatoma and in the livers of rats treated with cyclophosphamide (CP), cytosine-arabinoside (ara-C) and 5-fluoro-uracil (5-FU). The specific activity of DNA polymerase was twenty times greater in the MC-29 leukosis virus-induced hepatoma, while thymidine kinase was only 3-5 times greater than in liver. All three enzymes showed Michaelis-Menten kinetics in their substrate and template saturation curves. The template utilization of DNA polymerases from hepatoma and from liver was compared. Both had higher activities on a poly(dA) . poly(dT) template at pH 8.0, than on DNA at pH 7.5. After chromatography on a phosphocellulose column two polymerases were separated. The first peak eluted by 0.15 m KCl preferred DNA as template (polymerase alpha). The second eluted by 0.5 M KCl worked better on poly(dA) . poly(dT) (polymerase beta). Thymidine kinase was eluted by 0.25 m KCl. Inhibition by N-ethylmaleimide (NEM) showed the polymerase alpha to be sensitive and the polymerase beta to be resistant to the sulfhydryl blocking agent; similar to the respective enzymes of other eukaryotic cells. The specific activity of DNA polymerase decreased after CP treatment at 6 h and 72 h and after ara-C treatment at 72 h. The specific activities of thymidine kinase were not changed significantly in response to the drug administrations.
 ...
PMID:DNA polymerase and thymidine kinase activities in MC-29 virus-induced transplantable hepatoma and the effect of cytostatic treatment of these activities. 710 49

DNA polymerase (EC 2.7.7.7) beta was purified to near homogeneity from chick embryos. The final preparation has a specific enzyme activity of 1,100,000 units (nanomoles of dTMP incorporation/h) per mg of protein with (rA)n X (dT)12-18 as a template-primer. The molecular weight of DNA polymerase beta is about 40,000 as judged by gel filtration on Sephadex G-150 column. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the polypeptide of Mr = 40,000 accounted for 95% of total protein in the final preparation. The fingerprint analysis of tryptic peptides of polypeptide shows that 14 out of 24 125I-peptides from the Mr = 40,000 polypeptide are the same as those of the Mr = 40,000 polypeptide of DNA polymerase beta purified from rat ascites hepatoma cells. A Mr = 27,000 polypeptide, which was present in the less pure preparation, did not show any structure similar to Mr = 40,000 polypeptides from rat and chick cells. Thus, it is concluded that chick embryo DNA polymerase beta consists of a single polypeptide of Mr = 40,000. The minimal number of DNA polymerase beta molecules per chick embryo cell was estimated as about 5,000.
 ...
PMID:Chick embryo DNA polymerase beta. Purified enzyme consists of a single Mr = 40,000 polypeptide. 743 Jan 8

Molecular genetic studies have revealed that the human hepatitis B viral (HBV) Pol protein, a polypeptide of about 94 kDa, contains four domains. These are the 5'-terminal protein, spacer, RNA reverse transcriptase/DNA polymerase, and RNase H, respectively, from the amino (N) to carboxy (C) terminus. No evidence indicates as yet the involvement of a specific protease in cleaving the Pol protein or the presence of protease-cutting sites in the Pol protein. An in vitro-translated Pol protein was shown to be cleaved by purified thrombin but not in the presence of its inhibitor, hirudin. Two thrombin-cutting sites, spanning 194 amino acids, were then deduced by thrombin digestion of Pol protein with various lengths of C-terminal deletion. These two putative cutting sites, one located in the spacer region and the other in the beginning of the polymerase region, were found to be conserved at similar positions in the Pol protein of all hepadnaviruses. By using a novel method called the LacZ localization assay (LLA), it was demonstrated that a tripartite fusion protein containing the nucleus localization sequence (NLS) of SV40 large T Ag, the putative thrombin cutting sequence (Ile-Arg-Ile-Pro-Arg320-Thr) of HBV Pol protein and the full length beta-galactosidase of E. coli, exhibited a lower percentage (approximately 53%) of targeting into the nucleus of transfected hepatoma cells when compared with a similar tripartite protein containing a single mutation (Arg320 residue into Trp320) of HBV Pol protein (approximately 78%) or with a bipartite protein of SV40 NLS-beta-galactosidase (approximately 90%). These results indicate that the putative thrombin-cutting site in the spacer region of HBV Pol protein could be cleaved by a cellular protease resulting in the separation of NLS sequence from the beta-galactosidase and rendering a lower frequency of X-gal staining in the nucleus.
 ...
PMID:Demonstration of the presence of protease-cutting site in the spacer of hepatitis B viral Pol protein. 773 Apr 38

Proliferating cell nuclear antigen (PCNA), also known as cyclin, is an auxiliary protein of DNA polymerase-delta and is found only in the nuclei of proliferating cells in the late G1 and S phases. The proliferation of hepatocellular carcinoma (HCC) by immunohistochemical staining for PCNA using paraffin sections of 20 surgically resected HCC specimens was analysed. The mean percentage of PCNA-positive nuclei in the HCC tissue was 10.3% in grade I of Edmondson and Steiner's classification, 25.5% in grade II, 28.4% in grade III and 41.5% in grade IV. In early HCC, we observed only a few PCNA-positive tumour cells. However, PCNA-positive nuclei were numerous in the tumour thrombi found in portal vein branches, in regions of extracapsular tumour growth, and in the inner nodules of tumours with a nodule-in-nodule formation. Proliferating cell nuclear antigen positivity was correlated with an increase of the nucleocytoplasmic ratio of tumour cells as determined by image analysis. Our findings showed that PCNA positivity was correlated with the histological grade and invasiveness of HCC, suggesting that this antigen may be used as an indicator to predict tumour invasion in patients with HCC.
 ...
PMID:Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma: relationship to histological grade. 810 98

Protein B23 is a major RNA-associated nucleolar protein and putative ribosome assembly factor which exists in at least two isoforms designated B23.1 and B23.2. Recently, it has been reported that B23 is copurified with DNA polymerase alpha-primase complex. To examine its possible role in DNA replication, the effects of B23 on DNA polymerase activities were investigated. B23.1 purified from rat Novikoff hepatoma ascites cell nucleoli stimulated the activity of DNA polymerase alpha by as much as 3-to 4-fold in a dose-dependent manner, while it showed little effect on the activities of DNA polymerase beta, gamma, and primase. Rat recombinant B23.1 showed the same stimulation as that of B23.1 from Novikoff cells. In contrast, isoform B23.2 showed no effect on the activity of DNA polymerase alpha, suggesting that C-terminal region of B23.1 is important in its activity in the stimulation of DNA polymerase alpha.
 ...
PMID:Stimulation of calf thymus DNA polymerase alpha activity by nucleolar protein B23. 812 45


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