Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A spontaneous neuroblastoma (NB-85, H-2a/a) was tested for hybrid resistance (HyR) after subcutaneous (s.c.) inoculation into syngeneic and semisyngeneic mice. The hybrids (F1) (H-2a/b) between A/Sn and Leaden mice and the F1 between A/Sn X C57BL/6 mice were more resistant to the s.c. inocula of 10(6) to 5 X 10(5) cells than syngeneic recipients. Thymectomy, followed by irradiation and fetal liver reconstitution, abrogated the HyR against NB-85, whereas intravenous (i.v.) administration of anti-asialo-GM1 antibodies had no influence on the resistance. Surface phenotypic analysis revealed that NB-85 expressed H-2 Kk (-), Dd (+) and beta 2-microglobulin (-), showing a dissociation of the cell surface. Anti-H-2a-specific cytotoxic T lymphocytes exhibited a significant lytic activity against NB-85, while NB-85 was highly refractory to natural killer cell (NK)-mediated lysis. In vivo NK-mediated rejection assays showed that 125I-iododeoxyuridine (IUdR) labeled NB-85 cells were not eliminated more efficiently from the highly resistant F1 hybrids than from the parental strain. Furthermore, genotypic study with segregating (A/Sn X Leaden) F1 X A/Sn backcross mice showed that the HyR was attributable primarily to heterozygosity within the H-2 complex. Taken together, it was suggested that the HyR to an NK-resistant mouse NB-85 neuroblastoma might involve a T cell-dependent immunosurveillance with H-2 genetic control.
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PMID:[Experimental analysis of anti-tumor cytotoxic mechanism for hybrid resistance to mouse neuroblastoma]. 224 94

Taurine-induced differentiation was examined in the murine neuroblastoma Neuro-2a cell line in the presence or absence of the monosialoganglioside GM1 and under conditions in which Ca2+ levels were manipulated. Taurine (4 mM), GM1 (200 micrograms/ml), or taurine with GM1 were applied to culture media that contained either various concentrations of Ca2+ or the Ca2+ ionophore A23187. Taurine or GM1 and taurine with GM1 increased the number of cells emitting neurites above that found for controls. A significant interaction was found between treatment (taurine, GM1 or taurine + GM1) and the manipulations of Ca2+ levels, affecting the number of neurites and producing changes on the neuritic and perikaryal surfaces. Treatment with both taurine and taurine + GM1 and the various concentrations of Ca2+ resulted in a significant increase in neurite elongation. The Ca2+ ionophore A23187 in the presence of taurine or taurine + GM1 caused neurites to grow longer than observed in media containing Ca2+, either in a low concentration (about 125 microM) or at 1-2 mM. Taurine-treated cultures in the presence of extracellular Ca2+ or A23187 were characterized by surfaces with numerous microvillar, spine-like projections. This effect was enhanced with GM1 and was less pronounced in the medium containing low levels of Ca2+. Transmission electron microscopy of the taurine-stimulated neurons revealed an excessive number of clear-core vesicles (40-200 nm in diameter) in perikarya, neurites and neuritic varicosities and growth cones. In addition, numerous aggregates of intermediate filaments were seen. They were most abundant in the taurine + GM1 treated cultures. The taurine + A23187 cultures also exhibited numerous microtubules within the elongated processes. The different neuritic patterns induced by taurine under conditions in which Ca2+ levels were manipulated and/or when cells were exposed to exogenous GM1 suggest that taurine's actions depend in part on Ca2+ flux.
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PMID:Taurine-induced neuronal differentiation: the influence of calcium and the ganglioside GM1. 225 36

The ability of S20Y cholinergic, and N115 adrenergic, murine neuroblastoma cells to adhere to immobilized gangliosides was studied. Viable S20Y cells adhered more strongly to GM1-coated plastic wells than to those coated with GM2, GD1a, or GT1b. The oligosaccharide portion of GM1 inhibited adherence of S20Y cells to GM1-coated wells, indicating that the carbohydrate moiety of GM1 bore the recognition site. Analysis of S20Y cell adherence to wells coated with derivatives of GM1 indicated that the cells did not adhere to asialo-GM1 and adherence to the methyl ester or de-N-acetyl derivatives was significantly reduced. Expression of the GM1 binding sites by S20Y cells appears to be density dependent; cells harvested at the confluent stage of growth were more adherent than those harvested at the preconfluent stage. Trypsin treatment of the S20Y and N115 cells resulted in a loss of binding to GM1-coated wells, suggesting that the cell surface GM1 binding site is a protein. In contrast, N115 cells showed no significant difference in their adherence to wells coated with GM1, GD1a, GT1b, Gal-Cer, asialo-GM1, or the methyl ester of GM1 when assayed under the same conditions as those imposed on the S20Y cells. The N115 cells did show a reduction in adherence to GM2-coated wells, suggesting that they recognized the terminal galactosyl moiety.
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PMID:Murine neuroblastoma cells express ganglioside binding sites on their cell surface. 232 49

Clones of F11 hybrid (neuroblastoma X dorsal root neuron) cells have been tested for adherence and neurite outgrowth on three different substrata on which the parental cells display some competence--plasma fibronectin (pFN) with its multiple receptors, cholera toxin subunit B(CTB) as a model ganglioside GM1-binding substratum, and platelet factor-4 (PF4) as a model proteoglycan-binding substratum. This paradigm tests for independently segregating and overlapping mechanisms of neuritogenesis via transmembrane processes in pluripotent hybrid cells based on random loss of chromosomes contributed by the parent neural cells. For the nine clones tested, attachment was significantly lower on CTB but much higher on PF4 for all clones when compared to their attachment on pFN. Supplementation of cells with GM1 stimulated attachment of only two clones (on all three substrata). Neurite outgrowth was observed in a substratum-specific pattern and varied from 0 to greater than 60% on pFN; on CTB and PF4 substrata, the patterns were similar to each other but differed markedly from the pattern on pFN. In contrast, PF4- and CTB-directed neurites differed morphologically from each other while sharing some characteristics with neurites on pFN. Supplementation with GM1 or GT1b, but not GD1a, was inhibitory for neurite outgrowth in certain clones. Cycloheximide pretreatment distinguished several classes of clones based on inhibition of neuritogenesis. While most clones on pFN were unaffected, all clones on CTB and PF4 displayed significant and comparable degrees of inhibition, suggesting the sharing of some protein intermediate(s) on these substrata. Exposure to cycloheximide only during the active period of neuritogenesis generated higher percentages and longer neurites for all clones, indicating a widely-used negative regulation mechanism. Based on substratum type and cycloheximide protocols, these data have resolved six or more different transmembrane signalling processes for generating different classes of neurites. Some mechanisms have been segregated into individual clones while others overlap in other clones, providing cell systems for biochemical and molecular biological dissection of these processes.
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PMID:Clonal segregation of multiple and overlapping matrix adhesive responses in dorsal root neuronal derivative cells. 233 51

Ganglioside profile was evaluated in 19 samples of tumor tissue obtained from 13 surgical patients with various morphological patterns of neuroblastoma. In six of those cases, two samples from each proving most different in terms of cell maturity were selected for examination. The relative content of GD2 gangliosides was 27.0-37.6% in sympathoblastoma and as low as 5.1-14.8% in ganglioneuroblastoma. Ganglioneuroblastomas showed fairly high levels of GM1 and GD1a gangliosides which were almost completely absent in sympathoblastomas. Ganglioside profile variations seen within each tumor type were incomparable with differences in profile established between morphological patterns of neuroblastoma studied.
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PMID:[The immunological cellular phenotype and the prognosis in neuroblastoma in children]. 237 89

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.
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PMID:Five new epitope-defined monoclonal antibodies reactive with GM2 and human glioma and medulloblastoma cell lines. 247 68

To investigate the effect of interferon-gamma (IFN-gamma) on the immunotherapy, we used the autocrinically stimulated system in which a mouse IFN-gamma cDNA was transferred by infection with a chimeric retrovirus containing the IFN-gamma gene. First, we established a tumor specific CTL clone (E-4) against 203-glioma cells (a 20-methylcholanthrene induced mouse ependymoblastoma line of C57BL/6 mouse origin), and then transferred murine IFN-gamma cDNA into E-4 by using retroviral vector (pSVX(Mu gamma delta A]. Out of five gene-transferred subclones, E gamma-4, E gamma-5, E gamma-6, E gamma-7 and E gamma-9, two subclones (E gamma-6 and E gamma-9) constitutively produced 8- to 10-fold amounts of IFN-gamma as compared with the parental E-4. Moreover, these two subclones exhibited two to three times higher killing activity against 203-glioma than the parental cells. The enhancement of the killing activities was abrogated by an adequate addition of anti-IFN-gamma antibody. No alteration was seen after the gene transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+3+ and asialo-GM1-. Fluorescence-activated cell sorter (FACS) analysis showed that the surface expression of major histocompatibility complex (MHC) Class I antigen, H-2Kb, of parental E-4 was augmented remarkably, and it was not altered by the IFN-gamma gene transfer, but the Class II antigen, I-Ab, was slightly enhanced on the two IFN-gamma-producing sublines. Since it is considered that in the vicinity of the constitutively IFN-gamma-producing CTL cells, tumor cells are exposed to a high concentration of IFN-gamma and may be stimulated to induce or enhance the expression of surface antigens including MHC antigens as well as tumor associated antigens in relation to immune recognition. The 203-glioma cells pretreated with IFN-gamma were more efficiently killed by both the parental E-4 and the gene-transferred sublines. It was thus suggested that the specific tumor killing activity of the gene-transferred CTLs was augmented by the constitutive production of IFN-gamma derived from the exogenous gene. As the next step, a mouse IFN-gamma cDNA was transferred into a neuroblastoma line C1300 of A/JAx mouse origin. Two infected subclones C gamma 3 and C gamma 22, were obtained as a low and a high producers, respectively. Both IFN-gamma gene transferred cells remained unchanged as regards in vitro cell growth, morphological appearance and differentiation antigen expression such as neurofilaments after the IFN-gamma gene transfer. On the other hand, expression of MHC Class I antigens of both subcloned lines was extremely augmented at the surface expression level as well as at the transcription level, re
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PMID:[A novel experimental approach to immunotherapy against malignant brain tumor with the mouse IFN-gamma gene transfer]. 250 89

To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the major histocompatibility complex class I antigens at the cell surface and the transcription levels, irrespective of their IFN-gamma-producing potential. Although in vitro cell growth of these cells was unaffected by the IFN-gamma production, their s.c. tumor growth in syngeneic A/J mice was dependent upon levels of IFN-gamma production; tumors induced by a low-producer line grew well at a rate similar to those induced by the parental one, but tumor growth of a high-producer line was strongly suppressed. This apparent tumor suppression was abolished by simultaneous i.p. injection of anti-Lyt2.2 and/or anti-IFN-gamma monoclonal antibodies, and subsequently large tumors of the high producer were generated. Anti-asialoganglioside GM1 antibodies allowed the high-producer line to induce a substantial but only transient tumor growth, whereas other antibodies, such as anti-Lyt2.1, anti-IFN-beta, and anti-activated macrophage, had no such effect. The mice immunized with the high-producer line were resistant to tumor growth of the parental cells but permitted another kind of A/J tumor line, Sa-1, to induce remarkable tumors. These results indicate that the reduced tumorigenicity of the IFN-gamma high-producer line was due to the augmented specific anti-tumor immunity, in which cytotoxic T lymphocytes seemed to play a decisive role, probably as a result of the immunomodulatory effects of the IFN-gamma derived from the tumor.
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PMID:Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. 251 80

Binding of type C neurotoxin (C1 toxin) from Clostridium botulinum (strain Stockholm) to neuroblastoma cell lines was studied by using biotinylated anti-toxin antibody and avidin-biotinylated peroxidase complex. The neurotoxin bound with high efficiency to mouse neuroblastoma (NS-20Y and NIE-115) cells and to hybridomas of rat glioblastoma and mouse neuroblastoma (NG108-C15) cells. The toxin bound little to human neuroblastoma, rat astrocytoma, and nonneural cell lines. Binding of the neurotoxin to NG108-C15 cells was inhibited by gangliosides (GT1b and GM1) and by monoclonal antibodies (CA-12 and C-9), although inhibition was not complete. Sequential preincubation of C1 toxin with GT1b and CA-12 caused complete inhibition. A Scatchard plot of binding of 125I-labeled C1 toxin to NG108-C15 cells showed a hyperbolic curve. Monoclonal antibody CA-12 but not C-9 neutralized the lethal activity of the toxin toward mice. Only C-9 clearly inhibited toxin binding to GT1b. These results suggest that NG108-C15 cells have at least two kinds of receptors for C1 toxin. From the results of binding tests with neuraminidase-, pronase-, and trypsin-treated NG108-C15 cells, the chemical nature of the high-affinity site was presumed to be a glycoprotein containing sialic acid. GT1b may have an important role in low-affinity sites.
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PMID:Binding of Clostridium botulinum type C neurotoxin to different neuroblastoma cell lines. 253 34

The enzymatic basis for ganglioside regulation during differentiation of NG108-15 mouse neuroblastoma x rat glioma hybrid cells was studied. This cell line contains four gangliosides that lie along the same biosynthetic pathway: GM3, GM2, GM1, and GD1a. Chemically induced neuronal differentiation of NG108-15 cells led to an 80% drop in the steady-state level of their major ganglioside, GM3, a sixfold increase in the level of a minor ganglioside, GM2 (which became the predominant ganglioside of differentiated cells); and relatively little change in the levels of GM1 and GD1a, which lie further along the same biosynthetic pathway. The enzymatic basis for this selective change in ganglioside expression was investigated by measuring the activity of two glycosyltransferases involved in ganglioside biosynthesis. UDP-N-acetylgalactosamine: GM3 N-acetylgalactosaminyltransferase (GM2-synthetase) activity increased fivefold during butyrate-induced differentiation, whereas UDP-galactose: GM2 galactosyltransferase (GM1-synthetase) activity decreased to 10% of its control level. Coordinate regulation of these two glycosyltransferases appears to be primarily responsible for the selective increase of GM2 expression during NG108-15 differentiation.
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PMID:Coordinate regulation of ganglioside glycosyltransferases in differentiating NG108-15 neuroblastoma x glioma cells. 254 Feb 74


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