Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta-All-trans retinoic acid (RA) treatment of murine S91-C2 melanoma cells decreases in vitro growth and modulates the glycosylation of specific cellular and cell-surface glycoproteins. The effect of RA treatment on [3H]fucose, [3H]galactose, and [3H]glucosamine incorporation was investigated by metabolic labeling followed by analysis of labeled cellular glycoproteins using polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS-PAGE) and fluorography. RA treatment dramatically increased the incorporation of the labeled monosaccharides into one glycoprotein of Mr 160,000 (gp160), which has been previously implicated in the growth-inhibitory effect of RA on these cells. Following RA treatment, cell-surface sialic acid residues on gp160 were also more intensely labeled by NaIO4 oxidation and subsequent NaB[3H]4 reduction than were those on gp160 of untreated cells. The activities of fucosyl- and galactosyltransferase increased about 1.5 to 1.9 times after RA treatment. These results suggest that the increased activities of the two glycosyltransferases is responsible for the increased incorporation of fucose and galactose into gp160.
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PMID:Modulation by all-trans retinoic acid of glycoprotein glycosylation in murine melanoma cells: enhancement of fucosyl- and galactosyltransferase activities. 211 Aug 61

Condensation of 3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonyl chloride (4) with ethyl 2-amino-2-cyanoacetate (5) provided 2-[(3',4',6'-tri-O-benzoyl-2',5'-anhydroallonyl)amino]-2-cyanoa cetate (6). Compound 6 was treated with hydrogen chloride gas to give ethyl 5-amino-2-(2',3',5'-tri-O-benzoyl-beta-D- ribofuranosyl)oxazole-4-carboxylate (8). Reductive dediazotization of blocked nucleoside 8 provided ethyl 2-(2',3',5'-tri-O- benzoyl-beta-D-ribofuranosyl)oxazole-4-carboxylate (10), which after deblocking with sodium methoxide and ammonolysis was converted to 2-beta-D-ribofuranosyl-oxazole-4-carboxamide (oxazofurin, 3), an analogue of the antitumor and antiviral C-nucleoside tiazofurin (1). Oxazofurin (3) was found to be cytotoxic toward B16 murine melanoma cells in culture but inactive against murine leukemia P388 and L1210.
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PMID:Synthesis and antitumor activity of 2-beta-D-ribofuranosyloxazole-4-carboxamide (oxazofurin). 212 Apr 42

We have previously shown that blockade of the Na+,K(+)-pump by the cardiac glycoside ouabain produces doxorubicin resistance and decreases topoisomerase II-mediated DNA strand breakage in hamster cells. To determine if this were a general phenomenon, the effect of pump blockade on doxorubicin resistance was assessed in three human tumor cell lines: A549 lung and HT29 colon adenocarcinomas and U1 melanoma. When cells were exposed to 1 microM ouabain prior to and during incubation with doxorubicin, cytotoxicity was markedly reduced. Ouabain had no effect on either the influx or the efflux of doxorubicin. However, all cell lines showed a ouabain-induced decrease in doxorubicin-induced topoisomerase-mediated DNA strand breakage (SSB). These data suggest that blockade of the Na+,K+ pump decreases doxorubicin cytotoxicity in human tumor cells by inhibiting topoisomerase-mediated SSB. Furthermore, they indicate that altered ionic gradients are a potential cause of resistance to drugs that use topoisomerase II as a target.
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PMID:The influence of Na+,K(+)-pump blockade on doxorubicin-mediated cytotoxicity and DNA strand breakage in human tumor cells. 216 43

Currents through ion channels were measured from cells of a human melanin-producing melanoma cell line (IRG 1) with the patch clamp technique. In these cells the most frequently observed channel is a potassium channel. The channel activates slowly at depolarizing voltage steps but does not inactivate. Single channel potassium currents can be measured in cell-attached patches at the resting potential of melanoma cells. The channel has a conductance of approximately 10 pS. As measured from the reversal potentials of single channel currents, the permeability ratio for sodium and potassium, PNa/PK, is between 0.03 and 0.04. Open probability is increased at positive potentials. Mean open times are prolonged at voltage steps to more positive potentials. Closed time histograms are fitted by two exponentials. The slow shut time is decreased at positive potentials. In whole cell measurements, cell conductance measured between -20 and + 70 mV was reduced by 10 mM tetraethylammonium chloride from 6.4 +/- 1.2 nS (n = 4) to 0.8 +/- 0.3 nS (n = 3). Application of isoproterenol decreases the probability of the channel being open without any change in the single channel conductance. A possible role of the 10 pS potassium channel in the growth of melanoma cells is discussed.
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PMID:Properties of a potassium-selective ion channel in human melanoma cells. 217 83

Treatment of B-16 melanoma cells in culture with d-alpha-tocopheryl succinate (vitamin E succinate) at concentrations of 11.3 and 15.1 microM inhibited growth and induced cell differentiation in culture. Vitamin E succinate treatment decreased the levels of c-myc and H-ras specific mRNAs in melanoma cells. Similar results were obtained by the vitamin retinoic acid and the nonvitamin agents R020-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone), an inhibitor of cyclic nucleotide phosphodiesterase (0.72 mM), and sodium butyrate (1 mM), which induced differentiation and (or) inhibited growth of melanoma cells in culture. The extent of inhibition of c-myc mRNA was greater than that of H-ras mRNA. These results indicate that vitamin E succinate induced reduction of the levels of c-myc and H-ras mRNAs is related to growth inhibition of melanoma cells in culture.
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PMID:Decreased expressions of c-myc and H-ras oncogenes in vitamin E succinate induced morphologically differentiated murine B-16 melanoma cells in culture. 217 40

Histamine receptors are present on the surface of various normal and tumor-derived cell types, where their biological function is incompletely understood. Here we report that histamine not only stimulates cell proliferation under serum-free conditions, but also is chemotactic for human carcinoma (Hela and A431) and melanoma (A875) cells expressing H1 type receptors. Histamine was found to be a potent activator of phospholipase C, leading to polyphosphoinositide hydrolysis and subsequent intracellular Ca2+ mobilization. In addition, histamine also causes the protein kinase C-mediated activation of Na+/H+ exchange, as evidenced by an amiloride-sensitive rise in cytoplasmic pH. All histamine-induced responses, including chemotaxis and DNA synthesis, are completely inhibited by the H1 receptor antagonist pyrilamine, but not by cimetidine, an inhibitor of histamine H2 type receptors. Our results suggest that histamine may have a previously unrecognized role in the migration and proliferation of cells expressing H1 receptors.
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PMID:Histamine as a growth factor and chemoattractant for human carcinoma and melanoma cells: action through Ca2(+)-mobilizing H1 receptors. 218 46

Spleen cells from inbred Biozzi mice, immunized against the human breast cancer cell line T47D, were fused with murine myeloma SP2O cells to generate monoclonal antibodies. One of these, 1BE12, of IgM isotype, reacted with five of six human breast tumor cell lines, while no binding was detectable with normal lymphocytes, RBC, or fibroblasts. The antigen recognized by monoclonal antibody 1BE12 was localized on the surface of T47D and MCF7 cells and was detected in cell-free supernatants of cultures. The antigen was found also on the surface of milk secretory cells. Immunohistochemical staining of frozen and paraffin-embedded sections of human tissues showed apical polarized reactivity in normal breast glands, while in all breast cancers staining was either cytoplasmic or membranous and heterogeneously distributed. Immunostaining was also observed in some other normal epithelia, including salivary gland, gastroduodenal mucosa, exocrine pancreas, and cervix. The antigen was not detectable in secretory endometrium, whereas proliferative endometrium was strongly stained. Colon carcinoma, and cancers of the bladder and endometrium were strongly reactive. No staining was detected in melanoma, lymphoma, mesothelioma, non-small cell lung carcinoma, and thyroid, renal, and ovarian carcinomas. Lectin absorption of MCF7 membrane extracts reduced 1BE12 binding. A large reduction in 1BE12 reactivity was observed after digestion of T47D and MCF7 membrane extracts with proteases. Treatment with sodium periodate resulted in complete loss of antigenicity, while neuraminidase treatment did not affect 1BE12 binding. These findings suggest that the 1BE12 epitope is expressed on the carbohydrate moiety of a glycoprotein and does not contain sialic acid. Immunoblotting of the perchloric acid-soluble fraction of MCF7 membrane extracts after electrophoresis in 1% agarose detected the antigen as a high molecular weight species (Mr greater than 900,000). The antigen was purified by perchloric acid extraction of MCF7 membrane preparations followed by affinity chromatography on 1BE12 antibody coupled to Sepharose-4B and gel exclusion fast protein liquid chromatography. No reactivity of the purified material was found with monoclonal antibodies directed against human milk fat globule membrane-associated mucins HMFG1 and DF3.
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PMID:Characterization and distribution in human tissues of a glycoproteic antigen defined by monoclonal antibody 1BE12 raised against the human breast cancer cell line T47D. 222 61

A cell surface Mr approximately 90,000 glycoprotein (gp90) was found in higher amounts on brain-colonizing than on lung-colonizing murine B16 melanoma sublines. The possible role of gp90 in determining the brain-associated metastatic properties of B16 cells was examined by purifying the glycoprotein and studying the effects of anti-gp90 on the growth, adhesion, and organ colonization properties of B16 cells. The specificity of the anti-gp90 was demonstrated in immunoprecipitation studies where a cell surface- or metabolically labeled Mr approximately 90,000 glycoprotein of pI approximately 4 was exclusively found upon two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Immunoprecipitation analysis, enzyme-linked immunosorbent assays, and the lectin-binding properties of gp90 on lectin affinity columns indicated that it is a Mr approximately 180,000 disulfide-linked dimer, probably related to the transferrin receptor. B16 sublines selected for various organ colonization properties differentially expressed gp90, bound 125I-labeled transferrin, and responded differently to purified transferrin in proliferation assays in relation to their metastatic properties (B15b greater than O13 greater than F10 greater than F1). Anti-gp90 immunoglobulin G affected the growth of brain-colonizing B16-B15b more than B16-F1 cells, but had no effect on the adhesion of B16-B15b or -F1 cells to microvessel endothelial cells in vitro, and anti-gp90 immunoglobulin G F(ab')2 had little effect on the brain colonization properties of B16-B15b cells in syngeneic mice. In blocking assays, anti-gp90 inhibited the binding of 125I-labeled transferrin to B16-B15b cells in a dose-dependent manner. The results suggest that the differential growth-stimulating effects of transferrin on highly metastatic B16 melanoma cells may be due to their differential expression of a Mr approximately 90,000 glycoprotein that is related to the transferrin receptor. In organ sites, such as the brain, differential expression of a transferrin-like receptor may allow metastatic cells to respond to low concentrations of growth factors known to be present in certain organs.
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PMID:Differential expression of a Mr approximately 90,000 cell surface transferrin receptor-related glycoprotein on murine B16 metastatic melanoma sublines selected for enhanced brain or ovary colonization. 229 94

The synthesis of S100 protein in cultured human melanoma cells was examined using metabolic labeling with [35S]methionine, immunoprecipitation with anti-S100 protein antiserum, and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Six of seven cell lines derived from melanomas synthesized relatively large amounts of S100 protein, whereas three cell lines derived from normal melanocytes synthesized lesser amounts. Synthesis of S100 protein was not detected in 10 human cell lines of nonneuroectodermal origin. Analysis of poly(A+) RNA from one melanoma cell line by Northern blot hybridization with a probe specific for the beta subunit of rat S100 protein revealed a single mRNA species of 1.0 kb coding for the human protein. Flow cytometric analysis of individual cells of two melanoma cell lines and the rat glioma cell line C6 indicated that G0/G1 cells were heterogeneous with respect to S100 protein expression, while almost all the cells in S + G2 + M expressed S100 protein. These results suggest that expression of S100 protein in G0/G1 could be a prerequisite for progression of the cells through the cell cycle.
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PMID:S100 protein expression in human melanoma cells: comparison of levels of expression among different cell lines and individual cells in different phases of the cell cycle. 229 61

Several studies suggest that beta-carotene reduces the risk of some cancers. Except for its function as an antioxidant, the effect of this vitamin on mammalian cells remains poorly defined. This study was performed to show whether beta-carotene treatment of murine B-16 melanoma cells in culture induces differentiation and alters the adenylate cyclase (AC) system. The AC system mediates the action of agents which regulate cell differentiation and transformation. Results showed that beta-carotene treatment for a period of 24 hours or more caused morphological differentiation without changing the level of melanin, and reduced basal and melanocyte-stimulated hormone (MSH)-, sodium fluoride (NaF)-, and forskolin-stimulated AC activity in vitro. Retinol, a metabolite of beta-carotene, inhibited growth without morphological differentiation and reduced basal and MSH- and NaF-stimulated AC activity. However, butylated hydroxyanisole, a lipid-soluble antioxidant, also reduced growth without morphological differentiation, but it failed to alter basal or MSH-stimulated AC activity. The present and previous studies show that the AC system represents a common site where some antitumor-promoting vitamins (beta-carotene, retinol, retinoic acid, and alpha-tocopheryl succinate) act.
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PMID:Beta-carotene induces morphological differentiation and decreases adenylate cyclase activity in melanoma cells in culture. 233 63


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