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)

The factors which control the balance between proliferation and cell death in hepatocellular carcinoma (HCC) remain unclear. The kinetic state of the tumor growth was investigated in the present study with references to transforming growth factor (TGF)-alpha and -beta 1 in 50 resected HCCs without preceding therapies. three-micrometer sections were cut from formalin-fixed, paraffin-embedded tumors. Proliferating cell nuclear antigen (PCNA), Lewis Y antigen (LeY). TGF-alpha, and -beta 1 were immunohistochemically stained and quantitatively assessed with an image analyzer. By means of immunohistochemical staining, a reciprocal correlation was observed between PCNA and LeY. A similar pattern was found between TGF-alpha and -beta 1, although not so strikingly as in the case of PCNA and LeY. The expression of LeY and PCNA labeling index (LI) ranged from 0 to 56.1% and from 0 to 52.8%, respectively. A correlation was observed between LeY and tumor size (r = 0.302, p < 0.04), while there was no significant relationship between PCNA LI and tumor size (r = -0.048, p > 0.05). The positive area ranged from 0 to 61.6% for TGF-alpha, and from 0.6 to 71.5% for TGF-beta 1. Analysis of these data showed a significant correlation between TGF-beta 1 and tumor size (r = -0.327, p < 0.03). Among HCCs < 5 cm, PCNA LI positively correlated with tumor size (r = 0.399, p < 0.04), but negatively with TGF-beta 1 (r = -0.431, p < 0.03). In conclusion, the present investigation indicates that the simultaneous analyses of proliferating and apoptotic activities by means of PCNA and LeY could yield more accurate data to determine the kinetic state of the tumor growth compared with either alone. In addition, TGF-beta 1 might act as a suppressive factor in the growth of HCC < 5 cm.
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PMID:Growth kinetic study of human hepatocellular carcinoma using proliferating cell nuclear antigen and Lewis Y antigen: their correlation with transforming growth factor-alpha and beta 1. 914 7

The expression of the gene encoding the rat beta 1-adrenergic receptor is suppressed by glucocorticoids (Kiely et al., 1994). Within the 3.2-kb 5'-flanking region of the promoter, two potential glucocorticoid response elements (GREs) at -950 and -2791 relative to the translational ATG were identified. Characterization of the glucocorticoid-responsive sequences in the 5'-flanking region of the beta 1-adrenergic receptor gene was explored in rat C6 glioma cells and human HepG2 hepatoma cells using transient expression of beta 1-adrenergic receptor-luciferase fusion genes. The ability of glucocorticoids to suppress luciferase expression was not altered when the most 5'-localized GRE was deleted. Deleting the potential GRE at -950, in contrast, abolished glucocorticoid-induced suppression of the beta 1-adrenergic receptor-luciferase gene transcription. A 25-bp element containing the GRE sequence between nucleotides -950 and -926 confers glucocorticoid-dependent inhibition of transcription to a neutral promoter. Gel mobility shift assays with the alpha-subunit of the human glucocorticoid receptor (hGR alpha) expressed in reticulocyte lysates demonstrated specific binding to the 25-bp sequence harboring the putative GRE. We report an inhibitory GRE in the promoter of the rat beta 1-adrenergic receptor gene that is conserved among the rat, human, and mouse genes.
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PMID:Identification of a glucocorticoid repressor domain in the rat beta 1-adrenergic receptor gene. 925 49

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage-derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage-derived cell line was sensitive to the growth inhibitory effects of TGF-beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.
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PMID:Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production. 935 45

The gene expression of integrin a5 beta 1 and the ability of cell adhesion of SMMC-7721 hepatocellular carcinoma cell are reported to be altered in the presence of 100nM phorbol 12-myristate-13-acetate (PMA). The ability of cell adhesion to extracellular matrix-fibronectin (Fn) was 18.8%, 38.7% and 56.6% enhancement for 30.60 and 120 mins treatment with 100nM PMA, respectively, as compared with the PMA control. But after 6 and 12 hours, it decreased to 57.4% and 61.1%, whereas the adhesion to polylysine remained the same. Using sufficient amount of anti-a5 and anti-beta 1 mAb to pre-block the adhesion sites we found that cell adhesion to Fn was inhibited by approximately 40%. It seems that other integrins mediate cell adhesion to Fn besides alpha 5 beta 1. The results obtained from the Northern blot with alpha 5 cDNA probe showed that PMA could downregulate the transcription of integrin alpha 5 beta 1 gene from 10 mins to 12 hours. The transcription was lowered to 16.9% of the control after 30 mins. The inhibition rate was still 43.6% after 12-hour treatment. The possible mechanism by which PMA influences the cell adhesion and integrin gene expression is discussed here.
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PMID:Effect of phorbol 12-myristate-13-acetate on cell adhesion in SMMC-7721 human hepatocellular carcinoma cell line and its mechanism. 970 May 75

N-Acetylglucosaminyltransferase III (GnT III) catalyses the addition of N-acetylglucosamine through a beta 1-4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin A (Con A)-reactive glycan into a non-reactive state. In this study, we measured GnT III activity to evaluate its diagnostic efficacy and its therapeutic effect on hepatocellular carcinoma (HCC). Concanavalin A-non-reactive fraction of serum transferrin (Tf) was also determined since the sugar chains of Tf are one of the possible candidates for the product of GnT III. Serum samples (159) were used from patients with HCC (89), liver cirrhosis (30), chronic hepatitis (19), alpha-fetoprotein (AFP) producing gastric carcinoma metastatic to the liver (five) and healthy controls (16). N-Acetylglucosaminyltransferase III activity was determined by high performance liquid chromatography. The reactivity of serum Tf to Con A was also analysed in 21 paired HCC samples before and after treatment by crossed immuno-affinoelectrophoresis. N-Acetylglucosaminyltransferase III activity from the HCC group (153 +/- 72pmol/mL/h) was significantly higher than that from liver cirrhosis (99 +/- 67 pmol/mL per h), chronic hepatitis (84 +/- 39 pmol/mL per h) and the normal controls (62 +/- 16 pmol/mL per h). N-Acetylglucosaminyltransferase III activity of 21 patients with HCC was significantly reduced after treatment such as transcatheter arterial chemoembolization and/or percutaneous ethanol infection therapy, (123 +/- 77 to 100 +/- 60 pmol/mL per h). Commensurate decreases of AFP and des-gamma-carboxy prothrombin with GnT III activity were also observed after treatment. The Con A-non-reactive fraction (n = 21; 6.4 +/- 2.3%) in patients with HCC after treatment was significantly lower than before (8.2 +/- 2.4%). The present study suggests that GnT III activity is a possible aid in the diagnosis and evaluation of HCC, especially when other tumour markers are negative.
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PMID:Serum N-acetylglucosaminyltransferase III activities in hepatocellular carcinoma. 971 5

Hepatoma cell lines can be characterized by their expression of hepatocyte- and biliary-specific genes and by their response to differentiating agents in a lineage-dependent manner. These characteristics can be used to map the maturational lineage position of the cell lines. Tissue-specific gene expression and regulation by heparin, dimethylsulfoxide (DMSO), and sodium butyrate (SB) were examined in three rat hepatoma cell lines and two rat liver epithelial cell lines. Based on antigenic profiles and gene expression in serum-supplemented medium, the hepatoma cell lines could be organized in distinct categories of hepatic differentiation. All three hepatomas expressed the following five genes: gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase pi (Yp), glutamine synthetase, and alpha 5 and beta 1 integrin. Cell line H4AzC2 also expressed alpha-fetoprotein (AFP), albumin. IGF II receptor, and the biliary/oval cell antigens OC.2 and OC.3, a phenotype characteristic of fetal hepatocytes. FTO-2B cells lacked AFP, OC.2, and OC.3 but expressed albumin and IGF II receptor in addition to the five commonly expressed genes, consistent with a more hepatocyte-like phenotype. Cell line H5D-7 expressed neither albumin nor the IGF II receptor, but did express OC.2, OC.3, and alpha 3 integrin in addition to the five commonly expressed genes, characteristic of biliary epithelial cells. Regulation of gene expression by heparin, DMSO, and SB was examined in cells cultured in hormonally defined medium. The patterns of regulation of AFP, albumin, GGT, and Yp were dependent upon the state of differentiation of the cell. FTO-2B cells regulated genes in a manner similar to that of E16 fetal hepatocytes, H4AzC2 regulated genes characteristic of both hepatocytic and biliary lineages, and H5D.7 regulated only biliary genes. Suppression of GGT by DMSO was uniformly observed. The three cell lines expressed equal amounts of HNF-4, but FTO-2B cells expressed more HNF-3 beta and less HNF-3 alpha, while the reverse was true of H4AzC2 and H5D.7 cells.
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PMID:Phenotypic characterization of rat hepatoma cell lines and lineage-specific regulation of gene expression by differentiation agents. 974 12

The level of sulfo-Lea (SO3-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc) epitope recognized by monoclonal antibody (mAb) 91.9H in hepatic metastasis of colon carcinoma is known to be lower than at the primary sites. We examined 19 human colon carcinoma cell lines for their production of this epitope. Sixteen cell lines were found to produce high M(r) components that metabolically incorporated [35S]sulfate and were resistant to heparitinase I and chondroitinase ABC, and 8 of them were reactive with mAb 91.9H as shown by western blotting analysis. These were all of the 4 cell lines derived from well differentiated primary tumors (HCCP-2998, LS174T, GEO, and CBS), 2 of 10 cell lines (DLD-1 and HCT116) from moderately to poorly differentiated primary tumors, and 2 of 5 cell lines (SW480 and HCC-M1544) from metastases. Incubation of LS174T cells with benzyl-N-acetyl-alpha-D-galactosaminide abrogated the incorporation of [35S]sulfate and the reactivity of mAb 91.9H with high M(r) components in the cell lysates. Sodium chlorate, which inhibits the formation of 3'-phosphoadenosine 5'-phosphosulfate, also inhibited the [35S]sulfate incorporation and reactivity with mAb 91.9H. These treatments did not change the incorporation of [14C]threonine into high M(r) components. These results indicated that sulfo-Lea epitopes were expressed on O-linked carbohydrate chains in sulfomucins. Immunohistochemical studies of tumor tissues in nude mice indicated that sulfo-Lea was expressed at the site of orthotopic transplantation in the cecum. The expression appeared to be suppressed in liver metastatic foci in nude mice.
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PMID:Expression of mucin-associated sulfo-Lea carbohydrate epitopes on human colon carcinoma cells. 1008 87

Hepatic expression of CMP-NeuAc:Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase (ST6Gal I) is induced as part of the acute phase response in mammals by mechanisms that remain poorly understood. Previous work suggests that murine liver ST6Gal I mRNA contains an additional and novel region that is not found on ST6Gal I mRNA from human HepG2 hepatoma cells and from rat liver. This novel region, residing 5' of the common Exon I sequence, is encoded by a discrete upstream exon, Exon H. Here we provide evidence that the Exon H-containing transcript is the murine counterpart of the human and rat ST6Gal I mRNAs transcribed from the hepatic-specific promoter, P1. Exon H-containing ST6Gal I mRNA is expressed in all three mice strains examined: balb/c, C57B46, and 129Sv. Furthermore, murine RNA tissue survey indicates that presence of Exon H-containing transcripts is restricted to the liver. When mice are subjected to subcutaneous injection of turpentine to elicit the hepatic acute phase response, greater than 4-fold elevation in liver ST6Gal I mRNA was observed. Consistent with the view that Exon H-containing transcripts is regulated by the murine P1 promoter, 5'-RACE analysis indicates that the majority of these transcripts contains the Exon H sequence. This is consistent with the view that Exon H-containing transcripts are regulated by the murine P1 region. To assess the mechanism of ST6Gal I response in the hepatic acute phase reaction, mice harboring lesions in both alleles of the IL-6 gene were examined. IL-6(-/-) animals expressed normal levels of ST6Gal I mRNA in liver, with Exon H-containing transcripts remaining the predominant mRNA isoform. However, hepatic ST6Gal I is not elevated upon turpentine injection in the IL-6(-/-) animals. These results indicate that ST6Gal I induction in mouse liver during the acute phase reaction is mediated predominantly by the IL-6 pathway, and results in the induction of the Exon H-containing class of ST6Gal I mRNA that is specific to the liver.
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PMID:Hepatic acute phase induction of murine beta-galactoside alpha 2,6 sialyltransferase (ST6Gal I) is IL-6 dependent and mediated by elevation of exon H-containing class of transcripts. 1052 36

N-linked beta 1-6 branched oligosaccharides may contribute directly to the malignant phenotype including metastatic potential of tumour cells. Increased beta 1-6 branching was associated with an increased level of N-acetylglucosaminyltransferase V (GnT V). In this report, the tissues from two metastatic models of human hepatocellular carcinoma (HCC) in nude mice were obtained. GnT V activity and mRNA level were determined. Results showed that GnT V activity in highly metastatic LCI-D20 models (Liver Cancer Institute, passage time: 20 days) (413.1+/-86.4U) was much higher than that in low metastatic LCI-D35 model (passage time 35 days) (155.3+/-31.9U). Northern blot showed that the mRNA level of GnT V in two models had no change. During the selection of a highly metastatic LCI-D20 model, GnT V activity increased from 301.6+/-57.3U to 413.1+/-86.4U while the highly metastatic LCI-D20 model acquired higher metastatic ability after selection. When highly metastatic LCI-D20 model tissues were implanted subcutaneously (s.c.), the GnT V activity decreased dramatically from 413.1+/-86.4U to 94.9U. This is the first report that GnT V activity increased in HCC during metastasis in vivo.
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PMID:N-acetylglucosaminyltransferase V activity in metastatic models of human hepatocellular carcinoma in nude mice. 1060 78

Integrin alpha 5 beta 1 and alpha 2 beta 1 are the major integrin receptors in human hepatocytes. However, in human hepatocellular carcinoma cells it was found that the expression of integrin alpha 5 beta 1 was decreased and another integrin alpha 6 beta 1 increased. In this study, the SMMC7721 human hepatocellular carcinoma cells cotransfected or singly transfected with integrin alpha 5 and/or beta 1 cDNAs were established, and designated alpha 5 beta 1.6-7721, alpha 5.3-7721, and beta 1.6-7721 cell lines, respectively. Transfection with cDNAs of integrin alpha 5 and beta 1 subunits resulted in the over expression of each integrin and modified biological properties, including a slowed growth rate, changes in the cell cycle from 15.5% of control cells in the G2/M phase to 12.1%, 9.6% and 9.4% in alpha 5.3-7721, beta 1.6-7721, alpha 5 beta 1.6-7721, respectively, and a decrease in the Cell Mitosis Index from 1.6 in controls to 0.96, 0.95, and 0.72, and 34%, 28% and 52% derived from colony forming ability, respectively. Tumorigenicity was also tested in nude mice with inoculation of cells subcutaneously. Tumor masses growing in nude mice following inoculation with beta 1.6-7721, and alpha 5 beta 1.6-7721 cells weighed only 52% or 31% those of control cells. These results indicated that deletion or low expression of integrin alpha 5 beta 1 may play an important role in the development of hepatocellular carcinoma. Therefore, induction of expression of the integrin alpha 5 beta 1 in malignant cells could be a potential means of treating hepatocellular carcinoma.
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PMID:Over expression of integrin alpha 5 beta 1 in human hepatocellular carcinoma cell line suppresses cell proliferation in vitro and tumorigenicity in nude mice. 1088 26


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