UMLS:C0027819 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

In order to elucidate some of the factors that determine the characteristic expression of gangliosides in malignant melanoma and neuroblastoma the levels of ganglioside synthases (glycosyltransferases) were determined in a panel of cell lines from those tumors that exhibited a wide range of ganglioside composition. Sialyltransferases (GM3, GD3, GD1a, and GT1b synthases), N-acetylgalactosaminyltransferases (GM2 and GD2 synthases), and galactosyltransferase (GM1 and GD1b synthases) were analyzed in crude membrane preparations from these cells. The results confirmed the importance of GM3 and GD3 synthases in determining the prominence of the a (GM3 to GT1a) or b (GD3 to GQ1b) biosynthetic pathways. The overall ganglioside composition in cells was found to be dependent on the relative levels of specific enzymes acting sequentially or in competing pathways. In general, the pattern and levels of transferases correlated with the actual ganglioside content of the cell line, although several important discrepancies were noted. For example, in cell lines containing high amounts of GD2 ganglioside, the level of the preceding enzyme in the pathway (GD3 synthase) was unexpectedly low. Thus, the high GD2:GD3 ratios characteristic of most neuroblastomas result from low levels of GD3 synthase as well as high levels of GD2 synthase. In other cell lines, GD3 synthase was completely absent, resulting in the synthesis of GM2, but not GD2, by N-acetylgalactosaminyltransferase I, as would be expected. It was concluded that different glycosyltransferases play key roles in determining glycolipid expression in different cell types.
...
PMID:Glycosylation pathways in the biosynthesis of gangliosides in melanoma and neuroblastoma cells: relative glycosyltransferase levels determine ganglioside patterns. 139 96

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.
...
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.
...
PMID:A novel O-acetylated ganglioside detected by anti-GD2 monoclonal antibodies. 173 May 13

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.
...
PMID:Changes in the ganglioside composition of human neuroblastoma cells under different growth conditions. 190 Aug 12

We previously reported the binding specificities of two anti-ganglioside GD2 murine monoclonal antibodies (MAbs), A1-425 and A1-267, both of which are of IgG3 isotype. A1-425 reacts specifically with ganglioside GD2, whereas A1-267 binds preferentially to GD2 but also reacts with GD3 [Tai, T., Kawashima, I., Tada, N., & Dairiki, K. (1988) J. Biochem. 103, 682-687]. In this paper, they were used for comparative analyses of antibody-mediated cytotoxicity, i.e., antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human melanoma and neuroblastoma cell lines. Melanoma cells were found to contain GD2 and/or GD3, whereas neuroblastoma cells expressed only GD2. Both antibodies induced high levels of ADCC and CDC to GD2/GD3-positive cells with human peripheral large granular lymphocytes (LGL) as effector cells and in the presence of human serum, respectively. A good correlation was obtained between the contents of disialogangliosides and the binding level of the antibodies; both melanoma and neuroblastoma cells with larger amounts of GD2/GD3 showed a higher level of antibody binding than did the cells with a smaller amount of GD2/GD3. Surprisingly, ADCC did not correlate well with the binding level of the antibodies. Thus, A1-425 showed stronger lytic activity than A1-267 in spite of the binding level of A1-425 being similar to or lower than that of A1-267 on the cell surfaces. Antigen-antibody complexes composed of GD2 and A1-425 showed higher binding levels to LGL than complexes of GD2 and A1-267. In contrast, free MAb molecules gave minimum binding to LGL.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Monoclonal antibodies to disialogangliosides: characterization of antibody-mediated cytotoxicity against human melanoma and neuroblastoma cells in vitro. 212 21

Seven monoclonal antibodies (MAbs) directed to tetrasialoganglioside (GQ1b) were established, purified GQ1b being used for immunization and hybridoma screening. All of the MAbs reacted strongly with GQ1b, although they also reacted with other gangliosides, with different specificities and reactivities. Some MAbs (1H10, 2C7, and 3F4) reacted with GD3, GT1a, GQ1b, and GP1c. MAb 1H4 showed broad specificity. It reacted with GD3, GD1b, GD2, GT1a, GT1b, GO1b, GQ1c, and GP1c. MAbs 7F5, 4E7, and 4F10 recognized GT1a, GQ1b, and GP1c. MAb 4F10 was more specific for GQ1b than the other MAbs. Using MAb 4F10, we determined, by means of an immunoassay, the quantities of endogenous GQ1b in some neuronal and adrenal cell lines, GOTO (human neuroblastoma), Neuro2a (mouse neuroblastoma), and PC12 (rat pheochromocytoma). PC12 and Neuro2a cells contained at least 5.1 X 10(6) and 3.9 X 10(5) molecules/cell of GQ1b, respectively. In contrast, no GQ1b was detected in GOTO cells, which are known for their specific neuritogenic response to this particular ganglioside when exogenously added.
...
PMID:Tetrasialoganglioside GO1b reactive monoclonal antibodies: their characterization and application for quantification of GQ1b in some cell lines of neuronal and adrenal origin(s). 229 50

Three monoclonal antibodies (IgG2) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gamma-interferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectoderm-derived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 125I-labelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.
...
PMID:New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells. 246 85

In order to investigate GM2 expression in gliomas, the GM2-positive human glioma cell line (HGL) D-54 MG, which contains 0.6 nmol GM2/mg protein, representing 77% of the total monosialoganglioside fraction, was used as an immunogen for the production of anti-GM2 monoclonal antibodies. For ganglioside designations, see IUPAC-IUB (Eur. J. Biochem., 79: 11-21, 1977) and Svennerholm (J. Neurochem., 10: 613-623, 1963). Five IgM monoclonal antibodies (DMAb-1 through DMAb-5) specifically recognizing the GalNAc beta1-4(NeuAc alpha 2-3)Gal-terminal epitope common to GM2 and GalNAC-GD1a are reported. The antibodies did not react with GM1, GM3, GD2, GD3, GD1a, GD1b, and GQ1b. Purified anti-GM2 MAbs were used to define the expression of the "GM2" terminal epitope by cultured human malignant and normal cells by radioimmunoassay and membrane immunofluorescence. Among neuroectodermal tissue-derived cell lines, DMAb-3, at an optimal concentration of 5 micrograms/ml, showed high reactivity (radioimmunoassay binding ratios greater than 20) with 9 of 19 HGLs, 3 of 5 medulloblastoma, 4 of 5 neuroblastoma, and 1 of 3 melanoma lines. Moderate reactivity (binding ratio, 10-20) was exhibited by 3 HGL, 2 medulloblastoma, and 1 neuroblastoma lines and low reactivity (binding ratio, 3-10) by 5 HGL lines; no reactivity was detected with 2 HGL and 2 melanoma lines. Densitometric evaluation of monosialoganglioside extracts from human glioma and medulloblastoma cell lines in conjunction with immunostaining on thin-layer chromatograms showed that GM2 represents the major monosialoganglioside in 8 of 10 HGL and in 3 of 4 Med lines. In these lines the amount of GM2 ranged from less than 0.1 to 0.6 nmol/mg protein. These results indicate that GM2 represents a proportionally increased ganglioside of most glioma, medulloblastoma, and neuroblastoma cells in vitro.
...
PMID:Five new epitope-defined monoclonal antibodies reactive with GM2 and human glioma and medulloblastoma cell lines. 247 68

Seven monoclonal antibodies (mAbs) reactive with ganglioside II3(NeuAc)2-LacCer (GD3) were generated; four of these mAbs (DMAb-21, DMAb-22, DMAb-23, and DMAb-24) by immunizing mice with GD3 adsorbed to Salmonella minnesota and the remaining three (DMAb-7, DMAb-8, and DMAb-17) with melanoma line SK-MEL 28, which contains 1.4 nmol sialic acid of GD3 per mg protein. The specificities of the mAbs were defined by high-performance thin-layer chromatography (HPTLC) immunostain and solid-phase radioimmunoassay (SP-RIA) with a panel of purified gangliosides. DMAb-7 and DMAb-8 reacted with GD3, IV3(NeuAc)2nLcOse4Cer(3',8'-LD1), and very weakly with IV3(NeuAc)2II3NeuAcGgOse4Cer (GT1a), but not with II3NeuAc-LacCer (GM3), II3NeuAcGgOse3Cer(GM2), II3NeuAcGgOse4Cer (GM1), II3NeuAc, IV3NeuAcGgOse4Cer (GD1a), II3(NeuAc)2GgOse3(GD2), II3(NeuAc)2GgOse4Cer (GD1b), IV3NeuAcII3(NeuAc)2, GgOse4Cer(GT1b), suggesting the binding epitope to be a terminal tetrasaccharide NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4(Glc or GlcNAc). DMAb-7 and DMAb-8 were used to investigate the expression of GD3 on cultured human tumor cells of neuroectodermal origin. Thirteen of 19 gliomas, 3 of 5 medulloblastomas, 5 of 5 neuroblastomas, 2 of 2 melanomas, and 1 of 3 teratomas were shown to react with DMAb-8 and/or DMAb-7 by cell surface-RIA (CS-RIA) and immunofluorescence (IF) assays. HPTLC and densitometric analysis confirmed these results, as positive immunostains in the GD3 region were obtained with oligoganglioside fractions from 9 glioma, 1 medulloblastoma, 2 neuroblastoma, 1 melanoma, and 1 teratoma cell line. Glioma cell line U-105 MG and medulloblastoma cell line Daoy contain GD3 as shown by HPTLC immunostain analysis of extracts, although GD3 was undetectable on the cell surface as determined by CS-RIA and IF.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:GD3 expression by cultured human tumor cells of neuroectodermal origin. 260 39

Human melanoma cells express high levels of GM3 and GD3 gangliosides whereas normal melanocytes have only low levels of GD3 but maintain their expression of GM3. In order to understand the basis for this difference, the levels of the sialyltransferase that converts GM3 to GD3 (CMP-N-acetylneuraminic acid:GM3 sialyltransferase or GD3 synthase, EC 2.4.99.8) were analyzed in melanoma and other cell lines. Enzyme levels were determined in vitro using membrane preparations and measuring the addition of [14C]-N-acetylneuraminic acid from CMP-[14C]-N-acetylneuraminic acid to GM3 in the presence of Triton CF-54. Sialyltransferase levels in 44 human cancer cell lines (including melanoma, neuroblastoma, astrocytoma, various carcinomas, and leukemias) and cultures of normal melanocytes and kidney epithelial cells were compared, and the products were identified by thin layer chromatography and fluorography. Melanoma cell lines exhibited the highest levels of incorporation and GD3 was found to be the major product. GM3 was also formed, apparently from endogenous lactosylceramide. Very low levels of GD3 synthase were found in normal melanocytes. Neuroblastoma and some astrocytoma cell lines also had significant levels of GD3 synthase. Some other cell lines incorporated high levels of radioactivity but the products did not correspond to GD3 and the major product was usually GM3. In general the levels of GD3 synthase correlated with the expression of GD3 in the various cell types. These results point to higher levels of GD3 synthase being directly responsible for the enhanced expression of GD3 in melanoma.
...
PMID:Sialyltransferase levels and ganglioside expression in melanoma and other cultured human cancer cells. 280 71

1 2 3 4 5 6 Next >>