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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibodies that bound to 3 human hepatocellular carcinoma cell lines (PLC/PRF/5, SK-SF and Mahlavu) and snap-frozen sections of a patient's tumour were raised by immunising mice with PLC/PRF/5 membrane preparations. The monoclonals designated RF-HCC 1 and RF-HCC 2 were of IgG1 and IgM subclasses respectively. Binding of the antibodies to surface epitopes present on Mahlavu cells in vitro took place in a biphasic fashion, with initial rapid binding of each antibody during the first 15 minutes of incubation followed by a plateau after this period. It was found that the commercially available MOPC 21 myeloma IgG1 (Sigma) monoclonal antibody used a control also bound to a surface antigenic determinant expressed on Mahlavu cells.
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PMID:Production of monoclonal antibodies against human hepatocellular carcinoma by immunisation with a cell membrane preparation. 169 62

The establishment of a new, differentiated, hepatitis B virus DNA-negative, human hepatoma cell line (named PLC/AN/2) is described. Neoplastic liver tissue was obtained during hepatectomy in an HBsAg-negative man. The established cell line is negative for alpha-fetoprotein and carcinoembryonic antigen; it has retained in vitro some of the differentiated functions of normal hepatocytes. Additionally, it presents a distinctive rearrangement (translocation) at the long arm of chromosome 4. The high degree of independence from serum growth factor requirements appears to be a major in vitro characteristic of PLC/AN/2 cells, making them a suitable model system for the more precise definition of the human hepatocellular carcinoma phenotype, including mechanisms of growth control.
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PMID:Growth-factor independence of a new differentiated hepatitis B virus DNA-negative human hepatoma cell line. 169 12

The potential effects of free circulating antigen on the ability of monoclonal antibodies to target tumors in vivo were investigated. Tumor models consisted of HCC, NuE and PLC cell lines producing AFP xenografted in nude mice, and the NuE-treated mouse designated as the NuE-bearing mouse injected with AFP prior to the administration of antibody. Immunoscintigraphy and biodistribution were evaluated by using 125I-labeled monoclonal antibody 19F12 raised against AFP. Gel chromatography analysis of plasma from the PLC-bearing mouse which excreted 400 ng AFP/ml in blood injected with 125I-19F12 indicated that all injected antibody 19F12 formed an immune complex in plasma. No immune complex was present in plasma from the NuE-bearing mice, where blood AFP levels were 7 ng/ml, while the intact antibody was found to remain partly in plasma from the NuE-treated mouse. Radioactivities in the whole body of NuE-bearing and NuE-treated mice eventually cleared at the same rate. Our experimental results indicated that the endogeneous circulating antigen retained the antibody in the whole body for a longer period. The ability of monoclonal antibodies to target tumors was influenced not only by how much antigen was present but also by how rapid the antigen was cleared in the blood.
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PMID:Effects of circulating antigen on monoclonal antibody localization. 169 8

Acyclic retinoid (polyprenoic acid) has a slightly different structure from retinoic acid. However, acyclic retinoid acts similarly to retinoic acid, because both bind to cellular retinoic acid-binding protein and cellular retinoid-binding protein. F-type, with the same strong binding affinity. We studied the effects of acyclic retinoid, the 7-hydroxy derivative of acyclic retinoid (7OH-acyclic retinoid) and retinoic acid on a human hepatoma-derived cell line PLC/PRF/5 (Alexander cells). Acyclic retinoid inhibited cell growth with an ID50 value of 14 microM, and reduced cell viability with an LD50 value of 86 microM. The ratios of LD50 value to ID50 value were 6.1 for acyclic retinoid, 2.4 for 7OH-acyclic retinoid and 1.4 for all-trans-retinoic acid. Taking this ratio as a parameter of relative cytotoxicity, we concluded that acyclic retinoid is the least toxic compound. Growth inhibition of cells by acyclic retinoid was associated with the incorporation of 3H-thymidine in the logarithmic phase. Acyclic retinoid reduced secretion of alpha-fetoprotein (AFP) and reciprocally increased secretion of albumin in the culture media, suggesting that acyclic retinoid influences gene expression of these proteins. Thus, acyclic retinoid, one of the less toxic retinoids, inhibits cell growth of human cancer cell line PLC/PRF/5 and appears to alter gene expression of AFP and albumin toward a "normal" direction.
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PMID:Inhibitory effects of acyclic retinoid (polyprenoic acid) and its hydroxy derivative on cell growth and on secretion of alpha-fetoprotein in human hepatoma-derived cell line (PLC/PRF/5). 170 22

A highly specific monoclonal antibody (anti-AFP) against alpha-fetoprotein (AFP) was linked to N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) to form conjugates which were purified with a protein A-sepharose CL-4B affinity column. The conjugate, PDP-Anti-AFP was then covalently coupled to the toxic abrin-A chain to synthesize immunotoxins. The immunotoxin, anti-AFP-abrin-A conjugate, which was also purified with a protein A-sepharose CL-4B affinity column, had a molecular weight of 180,000 and had 80% antigen-binding activity that of anti-AFP activity and 92% toxicity of abrin-A chain. The immunotoxin showed selective cytotoxicities toward the AFP secreting human hepatoma cell lines, such HepG2 and Hep3B, but not toward AFP non-secreting human hepatoma cell line, PLC/PRF/5.
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PMID:Selective cytotoxic effects of immunotoxin--monoclonal anti-AFP-abrin-A chain conjugate on several human hepatoma cell lines. 170 34

The in vitro effect of sodium butyrate (SB) on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T was investigated. SB was added at the non-toxic but cytostatic concentration of 1 mM. In all these cell lines, SB reduced cell proliferation and changed the morphology of the cells into a fibroblast-like shape. In PLC/PRF/5, alpha-fetoprotein production and c-myc expression were inhibited. In contrast, gene expression of albumin, one of the normal liver-cell products, and that of integrated hepatitis B virus genome, was increased. In HCC-M and HCC-T, c-myc expression, which was enhanced in the naive state, was reduced. In HCC-M, fos expression was inhibited but the expression of N- and K-ras genes did not change. SB seemed to induce normal or mature properties of hepatocytes in human hepatoma cell lines.
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PMID:Differentiating effect of sodium butyrate on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T. 170 67

PLC/PRF/5 human hepatoma cells cultured with teleocidin reduced the rate of cell proliferation and were transformed into large cells with many vacuole-like subcellular structures. In these vacuolated cells, the protein content per cell increased without changing the total cellular protein synthesis. Cytokeratin was one of the proteins which increased quantitatively. This intermediate filament formed fibrous network structures throughout the enlarged cytoplasm. The assembly of other cytoskeletal proteins such as actin, tubulin, and vimentin was not altered remarkably, suggesting that teleocidin morphologically transformed the hepatoma cells by changing the assembly of cytokeratin protein selectively. On the other hand, the alterations of cell proliferation, cell morphology, and cytokeratin assembly induced by teleocidin were not associated with either down-regulation of protein kinase C or reduced number of epidermal growth factor receptors. In addition, these teleocidin effects were not mimicked by the protein kinase C agonist 1-oleoyl-2-acetylglycerol or inhibited by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. From these results it can be speculated that the morphological transformation and reduced cell proliferation induced by teleocidin may be mediated by still unknown mechanisms unrelated to protein kinase C.
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PMID:Vacuole formation and cytokeratin rearrangement of hepatoma cells induced by teleocidin are not associated with down-regulation of protein kinase C. 170 98

Alpha-2-macroglobulin (alpha 2-M), a serum protease inhibitor that also binds cytokines, neutralized the inhibitory effect exerted by transforming growth factor-beta (TGF-beta) on IL-6-induced C-reactive protein (CRP) production by the human hepatoma cell line PLC/PRF/5. alpha 2-M was found to bind noncovalently with TGF-beta to form a complex that, upon acidification, released TGF-beta inhibitory activity as detected by IL-6-induced CRP production. Although alpha 2-M also binds IL-6, it did not alter IL-6-induced CRP production by the hepatoma cells. The interaction between alpha 2-M and TGF-beta may influence the production of acute-phase proteins by liver hepatocytes.
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PMID:Effect of alpha-2-macroglobulin on cytokine-mediated human C-reactive protein production. 171 12

The acute-phase response to tissue injury and inflammation is accompanied by a dramatic increase in the hepatic synthesis of plasma proteins known as acute-phase reactants (APRs). This response is mediated by cytokines produced in part by activated macrophages at the site of inflammation; glucocorticoids have also been implicated as playing a regulatory role. The effects of the cytokines interleukin (IL)-1 beta and -6, alone or in combination, and in the absence or presence of the synthetic glucocorticoid dexamethasone, on the levels of APR mRNAs in the human hepatoma cell line PLC/PRF/5 were analysed. The accumulation of APR mRNAs [the complement components C3, factor B and Cl inhibitor; the major APRs C-reactive protein (CRP) and serum amyloid A protein and the CRP analogue serum amyloid P protein] was determined in dose-response and time-course studies. The APRs differed from each other in their responses to IL-1 beta alone, IL-6 alone, and IL-1 beta plus IL-6. Dexamethasone enhanced the cytokine-driven induction of a subset of APR mRNAs. These studies detail the heterogeneity of the 'in vitro' acute-phase response to defined mediators.
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PMID:Heterogeneous modulation of acute-phase-reactant mRNA levels by interleukin-1 beta and interleukin-6 in the human hepatoma cell line PLC/PRF/5. 171 47

Inhibition of human hepatocellular carcinoma (PLC/PRF/5 and Hep3B) or hepatoblastoma (Hep G2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (DFX) in the culture medium was evaluated. When PLC/PRF/5 cells were maintained for 7 days in 30 or 60 microM DFX, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (AFP) was produced, and supernatant endpoint dilution titers of hepatitis B surface antigen (HBsAg) were reduced 1-2 logs. PLC/PRF/5 cells maintained for 7 days without DFX (simultaneous controls) grew to confluence, produced AFP that reached 10-60 ng/ml in the supernate, and the HBsAg titer remained constant or increased 1 log. Similar effects were observed in Hep3B and Hep G2 cells maintained in DFX (except that Hep G2 cells do not produce HBsAg), compared to simultaneous control cells grown in the absence of DFX. The growth of a human embryonic lung fibroblast cell line (Wl 38) was not significantly inhibited by DFX, although it grew at a slower rate than simultaneous control cells grown without DFX. Subsequent growth in FeSO4 of PLC/PRF/5, Hep3B, and Hep G2 cells that previously had been maintained in DFX did not reverse the effects of DFX. PLC/PRF/5 cells were also inhibited when maintained in medium containing equimolar concentrations of DFX and FeCl3 and in medium containing equimolar concentrations of DFX and FeSO4. PLC/PRF/5 cells were not inhibited by maintenance in up to 60 microM of another chelating agent that has a similar affinity for iron, calcium disodium versenate (EDTA). These studies show that DFX inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines regardless of the presence (PLC/PRF/5, Hep3B) or absence (Hep G2) of integrated hepatitis B virus DNA. The findings also suggest that the inhibition may have been due to mechanisms other than iron chelation.
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PMID:Inhibition of human hepatocellular carcinoma and hepatoblastoma cell lines by deferoxamine. 171 97


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