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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gangliosides of 11 different neuroblastoma cell lines, grown to confluence, were extracted and quantified with respect to: (a) total lipid-bound sialic acid, (b) total gangliotetraose family, and (c) GM1 content. The cultured cells were induced to grow neurites in 3 ways: (a) serum reduction, (b) exogenous ganglioside, and (c) retinoic acid. Neurite outgrowth was quantified in terms of % of cells bearing neurites and average number of neurites per cell. No correlation was observed between neurite outgrowth and total ganglioside concentration, but a reasonably good correlation was observed with respect to neuritogenesis and gangliotetraose content. When exogenous ganglioside was the stimulant the best correlation was with GM1, whereas retinoic acid-stimulated outgrowth was approximately proportional to GD1a content. The 'neurite minus' N1A-103 line, which had the lowest level of GM1, GD1a, and total gangliotetraose gangliosides, showed little if any response to any of the stimuli.
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PMID:Correlation of gangliotetraose gangliosides with neurite forming potential of neuroblastoma cells. 172 62

Gangliosides shed by tumors enhance tumor formation, possibly by suppressing host antitumor immune function, and gangliosides purified from animal tissues and cultured cells inhibit human cellular immune function in vitro. Determination of immunosuppressive activity of highly purified gangliosides, to uncover structure-activity relationships, is therefore important. Here we have studied a series of gangliosides obtained from human tissue and determined their effects on human natural killer (NK) activity. Total gangliosides from human brain tissue were moderately inhibitory; 100 nmol/ml reduced NK activity of human nonadherent PBMC by 43%. The influence of carbohydrate structure upon inhibitory activity was determined by study of eight highly (HPLC) purified individual gangliosides. Of these, we unexpectedly found that the two minor brain gangliosides with the simplest carbohydrate structures, GM2 and GM3, were very active inhibitors (75 and 47%, respectively, at 50 nmol/ml). In contrast, the structurally more complex major species, GM1, GD1a, GD1b, GT1b, and two other minor gangliosides, GD2 and GD3, were inactive. Reduced effector-target binding in a single-cell binding assay by GM2 but not GM3 suggests different mechanisms of inhibition by these two active gangliosides. Since GM2 and GM3 are present in high concentrations in, and are shed by, several common human tumors (e.g., neuroblastoma, melanoma, and glioma), their ability to inhibit NK cytotoxicity supports the hypothesis of a role of shed tumor gangliosides in the enhancement of tumor formation.
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PMID:Immunosuppression by human gangliosides. II. Carbohydrate structure and inhibition of human NK activity. 172 65

Murine monoclonal antibody (MAb) 3F8 was previously shown to react with disialoganglioside GD2, but not with GD3, GT1b, GD1b, GD1a, GM1, GM3 and GM4. However, when the base-treatment step was ommitted from the standard neuroblastoma ganglioside extraction procedure, immuno-thin-layer-chromatography (ITLC) using 3F8 and other anti-GD2 MAbs revealed a new ganglioside band, abbreviated as NG (Rf 0.342) besides GD2 (R 0.183). It migrated below GD3 (Rf 0.358) on high-performance (HP) TLC plate and its binding to 3F8 on ITLC could be inhibited by rat anti-3F8 idiotypic antibody Idio-2, while the binding of GD2 to MAb 3F8 was not affected. Immunochemical analysis showed that this new neuroblastoma ganglioside contained alkali-sensitive O-acetylated sialic-acid residues recognized by MAb DI.I. After base treatment, its subsequent identity on ITLC was confirmed to be GD2. Lactonization of GD2 yielded 2 major bands, with Rf values (0.401, 0.583) distinct from that of the new ganglioside band. In addition, MAb DI.I did not bind to any of these GD2 lactones. Of 15 anti-GD2 MAbs studied, 13 reacted strongly with the novel ganglioside NG. By ITLC, this NG was found in ganglioside extracts of fresh surgical tumor specimens (4/4 neuroblastomas, I/I schwannoma and I/I anaplastic astrocytoma), and nude mice/rat xenografts (2/2 neuroblastomas, 2/2 osteogenic sarcomas). These data provided the first evidence that O-acetylated GD2 is a naturally occurring ganglioside derivative in human tumors and that it could cross-react with most anti-GD2 antibodies.
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PMID:A novel O-acetylated ganglioside detected by anti-GD2 monoclonal antibodies. 173 May 13

To determine the mechanisms of the neuritogenesis induced by synthetic sialyl cholesterol (SC) in a mouse neuroblastoma cell line, Neuro2a, the biochemical fate of SC and ganglioside GM1 (IV3NeuAc-GgOse4Cer) was investigated. The kinetics of incorporation of SC and GM1 into cells for the two compounds were similar. SC was not degraded nor modified for at least 24 h after the incorporation, indicating that SC itself and not its metabolites were responsible for the neuritogenic activity. Cell fractionation experiments showed that approximately 40% of the incorporated SC was localized in the nucleus, 25% in the plasma membrane fractions, and 11-14% in the granule fraction. This distribution was different from that of GM1. The nuclear SC was found to affect de novo RNA synthesis, indicating its biological effect may be mediated at the level of transcription. SC also increased the rates of both Ca2+ influx and efflux, although the intracellular level of total Ca2+ remained unchanged. Levels of inositol 1,4,5-triphosphate (IP3) also remained unchanged and the SC dependent neuritogenesis was not inhibited by an excess amount of W-7, an inhibitor of Ca2+/CaM kinases. These results again accord with the suggestion that SC and GM1 do not utilize Ca2+, IP3 or Ca2+/CaM as a second messenger for neuritogenesis. Rather it appears very likely that the nuclear localized SC may play a key role in neuritogenesis.
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PMID:Sialyl cholesterol is translocated into cell nuclei and it promotes neurite outgrowth in a mouse neuroblastoma cell line. 182 58

Several lines of evidence suggest that gangliosides may play a role in the regulation of growth in many cell types. Here we describe the effects on growth of two different cell lines by the addition of two different chemicals which have been reported to elevate the cellular ganglioside content through different mechanisms. Growth of neuroblastoma (Neuro 2a) cells in medium containing fetal bovine serum was inhibited in a dose-dependent fashion by both exogenous GM1 ganglioside and NeuAc2en, an inhibitor of sialidase activity. In contrast, growth of glioma cells (U-1242 MG) was not affected by exogenous GM1 or NeuAc2en in the presence of as little as 1% calf serum. However, NeuAc2en inhibited growth of U-1242 MG cells stimulated by platelet-derived growth factor in serum-free medium. These results demonstrate that the growth inhibitory effects of ganglioside on U-1242 MG but not Neuro 2a cells can be counteracted by serum, suggesting that the mechanisms through which gangliosides affect cell growth may be different for different growth factors and cell types.
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PMID:Effects of GM1 and 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en) on neuroblastoma (Neuro 2a) and human glioma cells (U1242 MG). 182 41

Subclones of F11 neuronal hybrid cells (neuroblastoma x dorsal root ganglion neurons) have segregated differing and/or overlapping neuritogenic mechanisms on three substrata--plasma fibronectin (pFN) with its multiple receptor activities, cholera toxin B subunit (CTB) for binding to ganglioside GM1, and platelet factor-4 (PF4) for binding to heparan sulfate proteoglycans. In this study, specific cell surface receptor activities for the three substrata were tested for their modulation during neuritogenesis by several experimental paradigms, using F11 subclones representative of three differentiation classes (neuritogenic on pFN only, on CTB only, or on all three substrata). When cycloheximide was included in the medium to inhibit protein synthesis during the active period, neurite formation increased significantly for all subclones on all three substrata, virtually eliminating substratum selectivity for differentiation mediated by cell surface integrin, ganglioside GM1, or heparan sulfate proteoglycans. Therefore, one or more labile proteins (referred to as disintegrins) must modulate functions of matrix receptors (e.g., integrins) mediating neurite formation. To verify whether cycloheximide-induced neuritogenesis was also regulated by integrin interaction with cell surface GM1, two approaches were used. When (Arg-Gly-Asp-Ser)-containing peptide A was added to the medium, it completely inhibited cycloheximide-induced neuritogenesis on all three substrata of all subclones, indicating stringent requirement for cell surface integrin function in these mechanisms. In contrast, when CTB or a monoclonal anti-GM1 antibody was also added to the medium, cycloheximide-induced neuritogenesis was amplified further on pFN and sensitivity to peptide A inhibition was abolished. Therefore, in some contexts ganglioside GM1 must complex with integrin receptors at the cell surface to modulate their function. These results also indicate that (a) cycloheximide treatment leads to loss of substratum selectivity in neuritogenesis, (b) this negative regulation of neurite outgrowth is affected by integrin receptor association with labile regulatory proteins (disintegrins) as well as with GM1, and (c) complexing of GM1 by multivalent GM1-binding proteins shifts neuritogenesis from an RGDS-dependent integrin mechanism to an RGDS-independent receptor mechanism.
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PMID:Neurite outgrowth in dorsal root neuronal hybrid clones modulated by ganglioside GM1 and disintegrins. 182 96

1-Phenyl-2-decanolyamino-3-morpholino-1-propanol (PDMP), an effective inhibitor of UDP-glucose:ceramide glucosyltransferase, caused inhibition of cell growth in murine neuroblastoma cell lines. Metabolic labeling of glycosphingolipids with [14C]galactose in NS-20Y, Neuro2a, and N1E-115 cells showed reduced incorporation of radioactivity into gangliosides and neutral glycosphingolipids when threo-PDMP was present in the medium. Treatment of NS-20Y cells with threo-PDMP resulted in a time-dependent decrease in mass levels of gangliosides and neutral glycosphingolipids. After 24 h in the presence of 50 microM threo-PDMP, neutral glycosphingolipid mass was reduced to 32%, where glucosylceramide was the most affected (90% decrease). The ganglioside mass was reduced to 57% of the original content. Neurite outgrowth from neuroblastoma cells in serum-free medium was significantly inhibited by threo-PDMP in a dose-dependent manner. Threo-PDMP also caused retraction of neurites which had been induced to extend in serum-free medium. Pretreatment of cells with GM1 partially restored the ability of NS-20Y cells for neurite outgrowth in the medium containing threo-PDMP. These results suggest a possible role for glycosphingolipids in neurite outgrowth of murine neuroblastoma cells.
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PMID:Effects of an inhibitor of glucosylceramide synthase on glycosphingolipid synthesis and neurite outgrowth in murine neuroblastoma cell lines. 183 39

The ganglioside composition of human neuroblastoma cells (LA-N-1 and LA-N-5) was studied in samples obtained from (1) original cells in tissue cultures, (2) tumors grown in nude mice inoculated with original cells and (3) cells in tissue cultures re-established from the mouse tumors. The amounts of "a" pathway gangliosides (GM2, GM1 and GD1a) and those of the "b" pathway (GD3, GD2, GD1b and GT1b) differed according to the culture conditions. The "b" pathway gangliosides were markedly increased in the tumors grown in nude mice. In contrast, the "a" pathway gangliosides were abundant in cultures of both original and re-established cells. We also measured the enzymatic activities of UDP-N-acetylgalactosamine: GM3, N-acetylgalactosaminyl transferase (EC 2.4.1.92) and of CMP-N-acetylneuraminic acid: GM3 sialyl transferase (EC 2.4.99.8) in neuroblastoma cells cultured under these conditions. These enzymes are thought to be the key enzymes involved in the synthesis of the "a" and "b" pathway gangliosides. Though there was no significant difference in the activity of N-acetylgalactosaminyl transferase between original cells and tumors in nude mice, re-established cells showed a definitely higher activity (3.5 times higher than in the original cells). On the other hand, tumors grown in nude mice had a markedly higher activity of sialyl transferase than that of original cells or re-established cells. These findings suggest that the culture conditions and/or the type of cell growth play some role in the synthesis and expression of gangliosides in neuroblastoma cells.
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PMID:Changes in the ganglioside composition of human neuroblastoma cells under different growth conditions. 190 Aug 12

Treatment of three neuroblastoma cell types in culture with neuraminidase resulted in enhanced neurite outgrowth. These included the mouse Neuro-2A and rat B104 and B50 lines. The morphological changes depended on the presence of exogenous Ca2+ and were accompanied by modest but statistically significant increases in 45Ca2+ influx. Neuraminidase-stimulated neuritogenesis was blocked by the B subunit of cholera toxin (cholera B) and anti-GM1 antibody, a finding suggesting the effect was due to an increased amount of GM1 on the cell surface. Cholera B also blocked the increase in 45Ca2+ influx. The mouse N1A-103 line, previously characterized as "neurite minus," did not respond to neuraminidase with either neurite outgrowth or enhanced Ca2+ influx. These results point to an influence of GM1 on neuritogenesis in cells with differentiation potential and suggest a mechanism involving modulation of Ca2+ flux.
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PMID:Stimulation of neurite outgrowth in neuroblastoma cells by neuraminidase: putative role of GM1 ganglioside in differentiation. 198 26

During the normal course of neuronal differentiation gangliosides undergo marked changes in both quantity and quality. These changes, i.e. several-fold increase in concentration and appearance of the gangliotetraose family, have been observed both in vivo and in neuronal cell cultures. In addition to these naturally occurring (endogenous) manifestations, exogenously administered gangliosides have been observed to exert neuritogenic and/or neuronotrophic effects on a variety of neuroblastoma cell lines and primary neuronal culture systems. Unlike the endogenous effects, which appear to require gangliotetraose structures, the structural specificity of the exogenous effect is quite broad. Thus, all of 11 different gangliosides proved neuritogenic with neuro-2A neuroblastoma cells. Furthermore, synthetic sialoglycolipids possessing a beta-ketosidic sialic acid linkage and/or a glyceride-like moiety in place of ceramide all caused enhanced neurite outgrowth in neuro-2A, PC12, and embryonic chick dorsal root ganglia. A derivative of GM1 lacking the negative charge was also active in the same 3 systems. These results point to general perturbation of the membrane, probably a physical-chemical effect, in a manner which triggers intracellular events leading to differentiation. In contrast to these in vitro results, use of the above GM1 derivative in two in vivo models proved ineffective in maintaining the level of cholinergic markers that were preserved by GM1 in lesioned brains. These results point to fundamentally different mechanism for the trophic effects of administered gangliosides in vivo and in vitro.
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PMID:Gangliosides as neurotrophic agents: studies on the mechanism of action. 213 Jun 60


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