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)

In the serum of hepatitis B virus (HBV)-infected patients, two different types of particles, a 42 nm virion and a 22 nm subviral particle, were identified. The envelope of both particles is composed of three proteins, the large (L), middle (M), and major/small (S) surface proteins but the ratio between these components varies in each. The M protein appears in a lesser amount than the S protein in both virion and subviral particles, although it is translated from the same subgenomic RNA, and this is due to its poor initiation context of translation. In addition, only the glycosylated form of M protein is secreted in contrast to both glycosylated and unglycosylated forms of L and S proteins that are secreted. To investigate the biogenesis of M protein, human hepatoma cells transfected with plasmids containing a mutated HBV DNA were used to produce a high amount of M protein. Electron microscopic observation revealed that despite a higher proportion of the M protein being found in the transfected cells, the secreted surface antigen particles possess similar size and density to 22 nm subviral particles. Detailed biochemical analyses showed the following. (1) The unglycosylated M protein was predominantly present in the microsomal fraction but not present in any other subcellular fractions. (2) The M protein formed 22-nm-like particles in the endoplasmic reticulum (ER) and was retained in the post-ER or pre-Golgi regions. (3) In addition to the complex glycosylated form of M protein, a high-mannose form of M protein could be secreted. (4) Normally, no unglycosylated M protein was secreted. However, glycosylation was not essential for M protein secretion since M protein deprived of glycosylation by tunicamycin treatment was detected in the medium. These findings suggest that (i) the M protein was probably translated and co-translocated into the ER and at least one site was glycosylated before leaving the ER resulting in no secretion of unglycosylated M protein, and (ii) the M protein had two secretion pathways, one through the conventional pathway and the other probably directly through the ER.
J Gen Virol 1994 Nov
PMID:Biogenesis of the hepatitis B viral middle (M) surface protein in a human hepatoma cell line: demonstration of an alternative secretion pathway. 796 12

The association of hepatitis B virus (HBV) infection with hepatocellular carcinoma (HCC) is well established. Insertional mutagenesis, trans-activation by truncated X or preS2/S regions and activation of growth regulatory genes or oncogenes have all been suggested as possible mechanisms for this carcinogenesis. However, no consensus regarding the mechanism or region of the HBV genome involved has been established. Of the 36 HCC tissues analysed for the presence and extent of the HBV genome, using multiple overlapping PCR, 22 (61%) were found to be positive. Twenty of these showed the presence of a fragment (nucleotides 636 to 746) that covered part of the surface antigen gene. The recognized trans-activators, X and preS2/S, were present in only seven (31.8%) and 12 (54.5%) cases, respectively. In two cases the entire viral genome was detected. The trans-activation potential of the cloned S fragment (nucleotides 426 to 851) covering the frequently detected fragment (nucleotides 636 to 746) was investigated in cotransfection experiments. This fragment was able to trans-activate the HBV enhancer-X promoter target. To define the specificity of the trans-activation and the sequences involved, frameshift and deletion mutants of this fragment were constructed and analysed. The trans-activation activity was lost in the frameshift mutants. The deletion mutants that retained nucleotide sequences 436 to 679 showed trans-activation activity whereas the other ones (nucleotide sequences 436 to 611) did not show any activity. It is suggested that the frequently detected HBV genome fragment belonging to the S gene frame has a trans-activation potential. This may explain the mechanism for pathogenicity of HBV-associated HCC.
J Gen Virol 1994 Feb
PMID:Mapping of the hepatitis B virus genome in hepatocellular carcinoma using PCR and demonstration of a potential trans-activator encoded by the frequently detected fragment. 811 54

Cultured hepatoma cells (HepG2) were cotransfected with two different plasmids carrying a head-to-tail dimer of recombinant hepatitis B virus (HBV) DNA cloned from deletion mutants isolated from the circulation of persistently infected hosts. They were tested for the secretion of viral particles with mutant genome encapsidation. A recombinant plasmid defective in the S gene and one defective in both the C and P genes complemented in trans for the production of viral particles. Mutant genomes from either of the recombinants were encapsidated. Similarly, a recombinant defective in the C gene and another defective in the P gene trans-complemented for the production of viral particles containing mutant genomes. A hepatoma cell line with integrated HBV DNA sequences defective in the C and P genes (PLC/PRF/5) when transfected with a recombinant defective in the S gene produced viral particles with the HBV genome from the transfecting recombinants. These results confirm the expected trans-complementation among the S, C and P genes of HBV, when either episomal or integrated into chromosomes, for the maintenance of defective HBV mutants in persistently infected hosts.
J Gen Virol 1993 Mar
PMID:Trans-complementation among naturally occurring deletion mutants of hepatitis B virus and integrated viral DNA for the production of viral particles with mutant genomes in hepatoma cell lines. 838 76

The DNA methylating system of cellular nuclei from intact or virus transformed chicken liver was studied. The presence of multiple forms of methylases different in hydrophobic properties and isoelectric focusing points has been proved. The isoelectrofocusing made it possible to differentiate between the enzymes methylating preferably nonmethylated in vitro or methylated in vivo DNA. The DNA-methylases pool contains both types of methylases (de novo and supporting ones) in intact cells and at neoplastic transformation, however, the specificity of methylation and level of several enzymes in transformed cells is changed in the direction of broad specificity and lower activity. The general level of methylase activity at viral transformation is by 18-20% lower, while the content of 5-methylcytosine in hepatoma cells DNA is twofold lower as compared with the content in the DNA of intact cells.
Mol Gen Mikrobiol Virusol
PMID:[DNA-methylating system of chicken liver nuclei under normal conditions and in viral transformation]. 851 Jun 77

The c-met proto-oncogene product is the tyrosine kinase receptor for hepatocyte growth factor. To gain insights into its functions in the liver, we carried out a study of the expression and tyrosine phosphorylation status of the Met protein during hepatic regeneration and in human hepatocellular carcinomas. Following partial hepatectomy of rats, decreased expression of the proreceptor p170MET and reduced levels of tyrosine phosphorylation were seen within 12 h. These changes were still evident 7 days later. By contrast, there was no significant alteration of the Met beta subunit. The analysis of samples from 18 patients with hepatocellular carcinoma revealed that the expression of p160MET proreceptor was increased in non-cancerous areas, while that of the p145 beta MET proreceptor was significantly greater in the tumor tissue than in the non-tumor areas (p < 0.05). These findings suggest that processing of the Met proreceptor is closely associated with regeneration and carcinogenesis of the liver.
Gen Diagn Pathol 1996 Mar
PMID:Analysis of the hepatocyte growth factor receptor in regeneration and oncogenesis of the liver. 870 80

Metastases to the tonsils are extremely infrequent. Less than 70 cases have been reported in literature since 1858. The commonest sources of tonsillar metastases are malignant melanomas and carcinomas of the breast and the lungs. We report about two new cases of tonsillar metastases, one of which developed from a malignant melanoma, the other one from a hepatocellular carcinoma. We have not found any reports on tonsillar metastases stemming from hepatocellular carcinomas in literature and, moreover, in our case, this was the clinical presentation of the primary tumor.
Gen Diagn Pathol 1996 Mar
PMID:Tonsillar metastases: report on two cases and review of literature. 870 93

Hepatitis C virus (HCV) is the aetiological agent responsible for most cases of non-A non-B hepatitis. Hepatitis C is a disease of clinical importance because of its high infection rate in blood donors and its persistence as chronic infections which may lead to cirrhosis and hepatocellular carcinoma in the long term. The variability of the HCV genome has posed difficulties in serological detection and vaccine design. The recent advance in phage technology offers a means of cloning human anti-HCV antibodies of a defined specificity that may have potential therapeutic use. We now report the generation of a phage display library using the V(H) genes of a HCV-infected patient and the V(L) genes of two non-immune individuals. From this library we were able to obtain specific IgG single-chain Fvs (scFvs) that recognize viral core and envelope proteins by selection on synthetic peptides derived from the core sequence PKARRPEGRTWAQPG and the envelope E2 sequence RPIDDFDQGWGPITY. The specificity of the scFvs was demonstrated by their specific reactions with homologous peptides in ELISA and the specific blocking of scFv binding by homologous peptides, in a dose-dependent manner, in inhibition ELISA. The binding of the anticore 4c2 to homologous peptide was blocked by HCV-positive human sera in an antibody-concentration-dependent manner, suggesting that the scFv recognizes a similar if not identical epitope to those of one or more of the polyclonal antibodies present in the sera.
J Gen Virol 1996 Oct
PMID:Human recombinant antibodies specific for hepatitis C virus core and envelope E2 peptides from an immune phage display library. 888 87

We analysed the binding and infectivity of dengue virus serotype 1 (DEN-1) for the human hepatoma cell line HepG2 in comparison with the simian kidney cell line Vero. The higher susceptibility of Vero cells to DEN-1 correlated with greater binding affinity of DEN-1 to these cells. In contrast, the capacity of virus attachment was higher for HepG2 than for Vero cells. Profiles of DEN-1 binding at different pH were markedly different between the two cell types. A type-specific neutralizing monoclonal antibody reduced initial virus binding to both cell types similarly but complex- and group-specific neutralizing antibodies affected virus adhesion differently. Altogether, these results suggest the involvement of different receptors or receptors presented in a different environment on the cell surface in the two cell lines. The sensitivity to proteolytic enzymes and to ionic detergent of the binding sites on the two cell types was tested and results indicated that they may be multimeric proteins or protein complexes.
J Gen Virol 1996 Oct
PMID:Dengue 1 virus binding to human hepatoma HepG2 and simian Vero cell surfaces differs. 888 89

The phenomena of peroxisome proliferation in rodent liver has received considerable attention due to its association with hepatocellular carcinoma. Chemicals that cause peroxisome proliferation include several structurally unrelated hypolipidemic drugs, phthalate esters and halogenated solvents. The mechanism by which peroxisome proliferators exert their beneficial (hypolipidemia) as well as their toxic (cancer) effects is still largely unknown. Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator in rodent liver that resembles other members of this chemical class in many aspects, including its effects on gene expression and fatty acid metabolism. However, there are many dissimilarities between PFDA and hypolipidemic peroxisome proliferators that have not been extensively explored. PFDA is unlike other peroxisome proliferators in parent compound metabolism, hypolipidemia, and tumor promotion. The present review article will discuss what is currently known about PFDA and how it may be utilized to dissect the mechanism of action of an important group of hypolipidemic drug and environmental pollutant, the peroxisome proliferators.
Gen Pharmacol 1996 Oct
PMID:Perfluorodecanoic acid as a useful pharmacologic tool for the study of peroxisome proliferation. 898 Oct 56

Extracellular matrix proteins participate in tumor cell growth and progression. Their role in the extratumoral liver tissue needs to be elucidated. Eight patients with hepatocellular carcinoma on noncirrhotic livers are investigated by means of light microscopical and ultrastructural immunohistochemistry for collagen type III and type IV. In the tumor collagen type III, staining is weaker, and collagen type IV is increased. It is topographically located near perisinusoidal stromal cells. In the extratumoral liver tissue, the immunostaining for the two antibodies is stronger perisinusoidally. The number of Ito cells increases significantly in the extratumoral liver tissue. A lot of transitional cells are found there. Sinusoids in the extratumoral tissue are dilated and filled with lymphoid cells and platelets. The presence of matrix proteins between tumor cells is necessary to regulate their growth and differentiation. The increase in extracellular matrix content perisinusoidally in the extratumoral tissue probably erects a protective barrier against metastasizing tumor cells. There, collagen type III and type IV accumulation is probably initiated by signals coming from tumor cells, or from inflammatory cells and platelets in sinusoids.
Gen Diagn Pathol 1997 Feb
PMID:Collagen type III and type IV detection in and around human hepatocellular carcinoma. 906 79


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