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)

Soluble serum beta 2-microglobulin has been thought to result from membrane shedding by activated T-lymphocytes. This hypothesis could explain the increase of beta 2-microglobulin serum levels during virally induced mononucleosis, but not elevated levels as observed in other virally induced and in malignant diseases. In this paper we demonstrate that beta 2-microglobulin is a true secretory protein, and that its synthesis in hepatocytes is modulated by IFNs but not by IL-1. While the 45,000 MW HLA antigen can be found only in cell lysates, beta 2-microglobulin is shown to be secreted also into the culture medium like other secretory proteins (e.g. albumin-factor B-complement C3). Furthermore, interferon alpha (IFN alpha) as well as interferon gamma (IFN gamma) directly stimulate, in a dose- and time-dependent manner, beta 2-microglobulin synthesis by human hepatoma cells (Mz-Hep-1 and PLC/PRF5) and murine hepatocyte primary cultures. The increase of beta 2-microglobulin production induced by interferons is demonstrated at both the protein and the RNA level, indicating that interferon acts at a pretranslational level. The interferon effect on beta 2-microglobulin synthesis is specific since synthesis of secretory proteins like complement C3 or albumin, and of a structural protein like actin, remains unchanged. In contrast to IFN, IL-1, the main mediator of acute phase response, does not change beta 2-M biosynthesis rate. These data indicate that (i) beta 2-microglobulin is a secretory protein, (ii) IFNs but not IL-1 can mediate increased beta 2-M serum levels, and (iii) the liver may be its primary source.
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PMID:Alpha- and gamma-interferon (IFN alpha, IFN gamma) but not interleukin-1 (IL-1) modulate synthesis and secretion of beta 2-microglobulin by hepatocytes. 245 38

A panel of six murine monoclonal antibodies against hepatocellular carcinoma-associated antigens, reactive with PLC/PRF/5 human hepatoma cells, was conjugated to Adriamycin (doxorubicin) via a dextran bridge. This library of antibodies includes three monoclonal antibodies against hepatitis B virus surface antigen, one anti-alpha-fetoprotein, and two other IgG2a antibodies against PLC/PRF/5 hepatoma-associated antigens. The use of dextran for conjugation of Adriamycin to antibodies enabled a 5- to 10-fold amplification of the number of drug molecules linked to antibody. Conjugation of Adriamycin to dextran caused an occasional reduction in the pharmacologic activity of dextran-Adriamycin in [3H]thymidine incorporation assays in hepatoma cells as compared to nonconjugated Adriamycin. This loss of anticellular activity was partially compensated for by conjugation of specific antibodies to the dextran-Adriamycin conjugate. Conjugated compounds completely retained their binding activity to purified hepatitis B virus surface antigen and alpha-fetoprotein fixed to a solid matrix as compared to binding of homologous nonconjugated antibodies. However, some reduction of the binding activity to intact hepatoma cells was observed in three of six conjugates. Binding activity to hepatoma cells and, as a consequence, suppression of tumor cell DNA synthesis by the various conjugates was enhanced as compared to the same effect in treated colorectal carcinoma cells that do not express the relevant hepatoma-associated proteins. Furthermore, two conjugates containing nonspecific antibodies did not bind to hepatoma cells and caused minimal suppression of DNA synthesis. These results suggest that this panel of monoclonal antibody-dextran-Adriamycin conjugates was effective in suppression of PLC/PRF/5 cell growth in vitro.
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PMID:Doxorubicin conjugates of monoclonal antibodies to hepatoma-associated antigens. 246 Aug 65

Three human hepatoma cell lines, PLC/PRF/5, Mahlavu and Sk-Hep 1, two of which contain integrated HBV DNA, were grown in culture and treated with human alpha-IFN for up to 14 days. IFN treatment caused a varying suppression of cell growth of the three hepatoma cell lines. While doubling time and cloning efficiency were significantly reduced for all three hepatoma cell lines tested, 3[H]thymidine incorporation was markedly suppressed, in a dose-dependent fashion, only in treated PLC/PRF/5 cells but not in Sk-Hep 1 and Mahlavu cells. The inhibiting effect of interferon treatment on growth of PLC/PRF/5 cells in vitro was neutralized by antibodies to human IFN. IFN treatment caused a significant suppression of HBsAg and alpha FP secretion by PLC/PRF/5 hepatoma cells. This effect, while constant throughout the observation period for HBsAg, was cumulative for alpha FP secretion. Following discontinuation of treatment, suppression of PLC/PRF/5 hepatoma cell growth was rapidly reversed, and HBsAg and alpha FP secretion returned to their pretreatment levels. These experiments suggest that human alpha-IFN suppresses the growth of some human hepatoma cells in culture but that this effect is dependent on the continuous presence of IFN in the growth medium. Finally, the inhibitory effects of IFN on cell growth differed for the various hepatoma cell lines tested.
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PMID:Variable efficacy of interferon-alpha treatment on growth of human hepatoma cell lines in vitro. 246 50

Monoclonal antibodies against human alpha-fetoprotein (AFP) were obtained by the hybridoma technique and studied with regard to their reactivities with the human hepatoma cell lines PLC/PRF/5 and KN, and a spontaneously immortalized cell line derived from fetal liver, NuE, all of which synthesize AFP. One of the monoclonal antibodies, 19F12 (IgG2b) became bound to free AFP which was used as the immunogen with an affinity constant of 3.4 X 10(8) M-1. This value was not much higher than those of two other antibodies, 19B1 (IgG1) and 9D12 (IgG2b). However, only antibody 19F12 showed definite reactivity with AFP-producing cells in analysis using flow cytometry. Immunofluorescence microscopy showed that antibody 19F12 detected AFP over the surface of NuE and PLC/PRF/5 cells with a uniform distribution, whereas definite reactivities of antibodies 19B1 and 9D12 to these cells were not detected. These antibodies did not show the specific binding to a non-AFP-producing human lung cancer cell line, PC-9, or to human peripheral blood lymphocytes. The binding ability of 19F12 to hepatoma cells was shown in both viable and fixed cells. Addition of free AFP inhibited the binding of antibody 19F12 to PLC/PRF/5 cells in a concentration-dependent manner. The specific reactivity of 19F12 to human AFP was also confirmed by immunostaining of a tissue section of human cancer proved to be AFP positive with AFP-specific antisera. In two-dimensional polyacrylamide gel electrophoresis of the antigen (from membrane fraction of PLC/PRF/5 cells)-antibody (19F12) complex, spots derived from the antibody and a spot (pI 4.7, Mr 65,000) corresponding in pI and molecular weight to AFP were detected. Western blot analysis showed that material in the membrane fraction of PLC/PRF/5 cells recognized by antibody 19F12 has the same molecular weight as human AFP derived from placenta. In a study of reactivities to PLC/PRF/5 cells treated with various enzymes, the reactivity of this antibody decreased when cells were treated with protease and trypsin and increased when lipase was used. The binding of 19F12 to AFP was not inhibited by concanavalin A. The antibody 19F12 appeared to recognize an epitope that is considered to be part of the peptide area of AFP. These results indicate that the reactivity, the amount of bound antibodies, and the distribution of monoclonal antibodies on antigen-producing cells vary, respectively, even though these antibodies were produced using the same antigen as an immunogen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Detection of membrane-bound alpha-fetoprotein in human hepatoma cell lines by monoclonal antibody 19F12. 246 75

Recombinant human interferon alpha 2a as well as natural human interferons alpha and beta significantly suppressed the production of hepatitis B surface antigen by PLC/PRF/5 cells (which have been established from a human primary hepatocellular carcinoma and proven to carry the hepatitis B virus DNA) and inhibited proliferation of these cells in vitro. However, the production of alpha-fetoprotein by PLC/PRF/5 cells was less significantly affected by any of the interferons. These results suggest that these interferons not only suppress cellular proliferation but also selectively inhibit the action of the HBV gene which is persistently present in these cells.
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PMID:Suppression of HBsAg production in PLC/PRF/5 human hepatoma cell line by interferons. 246 37

Insulin produced increases in cell number, DNA synthesis and alpha-fetoprotein secretion of a human hepatoma cell line PLC/PRF/5. The insulin-treated cells showed a decrease in binding of 125I-insulin. The decreased binding was due to the decreased numbers as well as the low affinity constant of insulin receptor. These data suggest that insulin is a growth factor for the human hepatoma cells and that insulin receptor plays a role in the growth-promoting effect of insulin.
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PMID:Effect of insulin on the growth of a human hepatoma cell line PLC/PRF/5: a possible role of insulin receptor. 246 33

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (TNF-alpha), interferons (IFN-alpha, IFN-beta, and IFN-gamma) and heat-stress was demonstrated in vitro. The toxicity of these agents was assessed in the human cervical carcinoma HeLa cell line: the toxic effect was greatly increased when cells pretreated with IFNs or TNF were submitted to a 1-h heat-shock at 45 degrees C. Moreover if the heat-stress followed simultaneous treatment with both cytokines, a synergistic effect between these treatments could be observed. The same observations were made for two other transformed cell lines: the oral epidermoid carcinoma KB cells and the hepatocarcinoma PLC/PRF/5 cells. In contrast, the survival of normal cells (normal foetal lung MRC5 cells and foreskin F 7000 fibroblasts) was only slightly decreased by such treatments. These results suggest that combining a heat-stress with cytokines treatment might be one way of enhancing the sensitivity of cancer cells to the growth inhibitory effects of the individual cytokines.
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PMID:Synergistic cytotoxic effects of recombinant human tumor necrosis factor, interferons, and heat-stress. 247 47

The localization of PIVKA-II in liver tissue was studied by the immuno-staining method using monoclonal antibody. The cell lines derived from hepatoblastoma (huH-6), hepatocellular carcinoma (PLC/PFR/5), and normal liver (Chang) were used as materials for staining. We succeeded to stain PIVKA-II, when the materials were fixed in a formalin solution and frozen. In patients with hepatocellular carcinoma, PIVKA-II was stained in the cytoplasm of both hepatoma and non-hepatoma cells.
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PMID:[A staining method of PIVKA-II by an indirect immunoenzyme technic]. 248 Oct 50

Our study was undertaken to determine whether human recombinant interferon alpha(rIFN alpha), gamma(rIFN gamma), and tumor necrosis factor alpha(rTNF alpha) exert an effect on the HLA-A, B, C expression of human liver cell lines. The HLA-A, B, C expression was assayed by immunoperoxidase staining and enzyme-linked immunosorbent assay. rIFN alpha and gamma enhanced the HLA-A, B, C expression of the three cell lines tested, Chang cells, SK-Hep-1, and PLC/PRF/5. The activity of rIFN gamma proved more than 8000 times more potent than that of rIFN alpha in Chang cells, 30 times in SK-Hep-1, and 20 times in PLC/PRF/5, respectively. rTNF alpha also enhanced the HLA-A, B, C expression of the three cell lines. The enhancement of HLA-A, B, C expression by rIFN alpha and gamma reached a peak on day 3, and that by rTNF alpha on day 5. These findings suggest that IFN alpha, IFN gamma, and TNF alpha may play similar roles in enhancement of HLA-A, B, C expression of hepatocytes in hepatitis and hepatoma cells.
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PMID:Effect of interferon alpha, gamma, and tumor necrosis factor alpha on the HLA-A, B, C expression of cell lines derived from human liver. 249 41

A primary liver cell carcinoma was disclosed in 11 cases out of a total of 61 patients with a focal hepatic lesion. The authors investigate the diagnostic significance of abdominal ultrasonography (US) as a major diagnostic modality in early detection of PLC. It is concluded that abdominal US is an important contribution to diagnosis of hepatic lesions smaller than 1 cm in diameter. The echographic features of PLC are often unspecific thus requiring a complementary targetted cytologic examination. A short comparison of US computed tomography and liver scintigraphy is given.
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PMID:Ultrasonography of primary liver carcinoma (PLC) and targetted cytologic examination. 253 Aug 19


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