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)

It is understood that neuroblastoma (NB) in the liver of patients with clinical stage IV-S disease may disappear, but the mechanism of such regression is unclear. A genetic hypothesis has previously been suggested, although heretofore an immunologic explanation had not been reported. Using C1300 NB in AJ mice, we developed a model of liver metastatic disease by directly injecting tumor cells into a subcutaneously translocated spleen. Intrasplenic inoculation of 2 x 10(6) C1300 NB cells produced liver subcapsular foci of NB in 100% of animals, whose mean survival period was 18 days. Three days after tumor inoculation, interleukin-2 (IL-2) (2,400 U/d) was continuously infused for 14 days via a miniosmotic pump, and daily survival was followed. Animals were sampled serially by histological and immunohistochemical staining. Animal survival was significantly prolonged (P < .05) in the IL-2 group when compared with that of saline controls, but importantly, 50% of the mice were cured. Histological examination showed early infiltration of mononuclear cells, predominantly lymphocytes, around liver metastatic foci; and phenotypic analysis of these cells showed them to be Thy-1.2-positive and asialo GM1-positive, suggesting they are of natural killer (NK) and lymphokine-activated killer (LAK) origin. Most importantly, in cured animals the histological analysis of the liver demonstrated reversion to a scar-free anatomy, akin to that seen in stage IV-S NB survival. These data suggest that immune-mediated regression of NB in the liver is possible; whether the result of therapy or spontaneous, the liver histology reverts to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immune-mediated regression of 'metastatic' neuroblastoma in the liver. 817 85

A serum containing a monoclonal IgM lambda with anti-GM1 and anti-GD1b activity was obtained from a patient with upper motor neuron syndrome. By indirect immunocytochemical techniques with double staining, the patient's IgM strongly stained membranes of neurons in primary cultures of fetal central and peripheral nervous system. It was cytotoxic for neurons in two human neuroblastoma established cell lines in a complement-dependent chromium release assay. These results are in keeping with the hypothesis of a direct pathogenetic role of such monoclonal anti-GM1 and GD1b IgM antibodies.
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PMID:Reactivity of a human monoclonal anti-GM1 and anti-GD1b IgM antibody with human neurons in cultures. 822 8

Cell surface gangliosides are potent modulators of cellular proliferation. We hypothesize that gangliosides shed by tumor cells modulate hematopoiesis and contribute to human tumor-associated suppression of hematopoiesis. To test this hypothesis, we determined the effects on myeloid colony formation by human bone marrow mononuclear cells of total gangliosides isolated from human brain and of seven highly purified individual ganglioside species (GM1, GM2, GD1a, GD1b, GD2, GD3, and GT1b). Total human brain gangliosides and certain individual species, GD1a, GD1b, and GT1b, significantly inhibited myeloid colony formation (number as well as size). The most complex molecules, GD1a, GD1b, and GT1b, were the most inhibitory, suggesting that the degree of inhibition is related to ganglioside structural complexity. To extend these findings, we also investigated certain tumor-derived (neuroblastoma) gangliosides, which we found inhibited both myeloid colony formation and 3H-thymidine incorporation by human bone marrow mononuclear cells. These data suggest a role for gangliosides, which are shed by proliferating cells, in the regulation of human hematopoiesis and may explain the bone marrow hypoplasia observed in association with many human malignancies.
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PMID:Modulation of human myelopoiesis by human gangliosides. 828 59

In a previous study, we showed that microM concentrations of mu or delta opioid agonists increase voltage-dependent outward K+ currents in neuroblastoma x DRG neuron hybrid F11 cells via pertussis toxin-sensitive receptors. The present study demonstrates that much lower concentrations (fM to nM) of these opioids (DAGO and DPDPE) decreased voltage-dependent outward K+ currents during step depolarization. The opioid antagonist, naloxone (3 nM) prevented these decreases in K+ current as did the cholera toxin subunits A or B (ca. 1 nM). Furthermore, the specific mu opioid receptor antagonist, beta-funaltrexamine (5 nM) blocked the decrease by DAGO and the specific delta antagonist, naltrindole (1 nM) blocked that by DPDPE. Acute GM1 ganglioside (1 microM) treatment markedly enhanced the efficacy of opioid-induced decrease in K+ current. After treating the cells with pertussis toxin (1 microgram/ml) for 2 days or more, these opioids decreased the K+ current even when tested at concentrations as high as 1 microM. These results indicate that the decrease in K+ current elicited in F11 cells by low concentrations of mu and delta opioid agonists resembles the opioid-induced prolongation of the action potential duration and decrease in voltage-dependent K+ conductance that occur in DRG neurons in primary cultures. The F11 cell line provides therefore a valuable model system for correlative pharmacologic, electrophysiologic and biochemical analyses of Gs-coupled, GM1 ganglioside-regulated excitatory opioid receptor functions, in addition to G(i)/G(o)-coupled inhibitory receptor functions, in sensory neurons.
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PMID:mu and delta opioid agonists at low concentrations decrease voltage-dependent K+ currents in F11 neuroblastoma x DRG neuron hybrid cells via cholera toxin-sensitive receptors. 838 68

Murine Neuro-2A neuroblastoma cells were exposed to ethanol in culture under two experimental paradigms: (1) short-term (24 hr or less) and low concentrations (0.05 to 0.5%; 8.5 to 86 mM) and (2) long-term (48 hr at 0.5%; 86 mM). Long-term ethanol exposure did not affect Neuro-2A viability, determined by DNA synthesis or the ability to exclude Trypan Blue. Similarly, long-term ethanol treatment did not inhibit differentiation, exhibited by the extension of neurites, promoted by either dibutyryl-cyclic-AMP or by incubation with exogenous ganglioside GM1. The incorporation of exogenous ganglioside GM1 into plasma membranes was not influenced by varying concentrations of ethanol (up to 1.2%; 204 mM). In contrast, ethanol did influence Neuro-2A cell attachment to collagen in a dualistic manner. During short-term ethanol exposure, cell attachment was enhanced. However, when cells were initially exposed to ethanol for 48 hr a marked inhibition of subsequent attachment was observed. Long-term ethanol exposure also inhibited attachment to other substrata, including laminin, fibronectin and vitronectin. Incubation of Neuro-2A cells with either exogenous ganglioside GM1 or a mixture of brain gangliosides partially reversed the inhibition of attachment to collagen. This reversal did not appear to be due to any one particular ganglioside structure, however. Mixed brain gangliosides were fractionated into three fractions, according to the number of sialic acid residues. Each of the three fractions were equally effective in partially restoring Neuro-2A cell attachment to collagen after long-term ethanol treatment. The results suggest that the mechanism by which these effects occur is at the level of plasma membrane fluidity, because both ethanol and glycosphingolipid content are known to influence membrane lateral mobility, although other mechanisms, such as changes in headgroup hydration, are possible.
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PMID:Effects of ethanol on neuroblastoma cells in culture: role of gangliosides in neuritogenesis and substrate adhesion. 858 6

The axonal outgrowth of cells of Neuro2a, a mouse neuroblastoma cell line, was suppressed on expression of the beta-galactoside alpha 1,2-fucosyltransferase (alpha 1,2-FT) gene. We recently cloned two types of rabbit alpha 1,2-FT, RFT-I and RFT-II. RFT-I exhibits comparable kinetic properties and structural homology with human H gene alpha 1,2-FT, and RFT-II shows comparable kinetic parameters with human Se gene alpha 1,2-FT. Neuro2a cells expressing RFT-I (N2A-RFT-I) contained a large amount of fucosyl GM1 instead of GM1 and GD1a, major gangliosides in the parent Neuro2a cells, whereas Neuro2a cells expressing RFT-II (N2A-RFT-II) showed a subtle change in the ganglioside pattern. N2A-RFT-II and parent Neuro2a cells showed axonal outgrowth in serum-free medium on the exogenous addition of GM1, whereas N2A-RFT-I cells exhibited multiple neurite sprouts but not axonal outgrowth. This phenotype was fully recovered by N2A-RFT-I cells on the addition of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and alpha-L-fucosidase to the culture medium, which resulted in pronounced reduction of fucosyl GM1 expression. These results suggested that expression of H-type alpha1,2-FT, and subsequent incorporation of fucose into glycolipids and glycoproteins, especially the formation of fucosyl GM1, modifies the response of neuronal cells to stimuli that induce axonal extension.
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PMID:Expression of the beta-galactoside alpha 1,2-fucosyltransferase gene suppresses axonal outgrowth of neuro2a neuroblastoma cells. 862 20

The effect of ganglioside GM1 on components of the neuronal cytoskeleton was studied in Neuro-2a neuroblastoma cells using immunofluorescent, immunogold-labeled, and Western-blot analysis. Exposure of cells to GM1 for 24 h resulted in an increased microtubular network and level of tubulin, a redistribution of MAP2 immunoreactivity from perikarya to distal neuritic processes, and an increased MAP2 gold label in the subplasmalemmal cytoplasm, neuritic spines, and growth cones. A similar change in the distribution of actin-positive fluorescent immunoreactivity was observed. In contrast to the redistribution of MAP2, immunolocalization of MAP5 and tau did not change following 24 h GM1 exposure. Our results suggest that gangliosides enhance neuritogenesis by selectively altering the distribution of MAP2 from perikaryon to neuritic spines. Furthermore, the enhanced presence of MAP2 in regions known to be rich in microfilaments following GM1 treatment suggests that an interaction of MAP2 with microfilaments may be necessary for early neurite formation.
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PMID:The ganglioside GM1 enhances microtubule networks and changes the morphology of Neuro-2a cells in vitro by altering the distribution of MAP2. 863 55

Recent molecular investigation revealed that two closely related structural genes encode distinct GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferases (alpha1,2-fucosyltransferases). Some human cancer cells or tissues may express an aberrant alpha1, 2-fucosyltransferase other than H- and Secretor-type alpha1, 2-fucosyltransferase. However, definite evidence of the existence of a third type of alpha1,2-fucosyltransferase has not been demonstrated. Here we report the molecular cloning of a third type of rabbit alpha1,2-fucosyltransferase (RFT-III) from a rabbit genomic DNA library. The DNA sequence included an open reading frame coding for 347 amino acids, and the deduced amino acid sequence of RFT-III showed 59 and 80% identity with those of the previously reported two types of rabbit alpha1,2-fucosyltransferase, RFT-I and RFT-II, respectively. COS-7 cells transfected with the RFT-III gene exhibited alpha1,2-fucosyltransferase activity toward phenyl-beta-Gal as a substrate. Neuro2a (a murine neuroblastoma cell line) cells transfected with the RFT-III gene expressed fucosyl GM1 (type 3 H) but not Ulex europaeus agglutinin-1 lectin reactive antigens (type 2 H). Kinetic studies revealed that RFT-III exhibits higher affinity to types 1 (Galbeta1, 3GlcNAc) and 3 (Galbeta1, 3GalNAc) than to type 2 (Galbeta1, 4GlcNAc) oligosaccharides, which suggests that RFT-III as well as RFT-II is a Secretor-type alpha1, 2-fucosyltransferase. RFT-III was expressed in the adult gastrointestinal tract. The RFT-I, -II, and -III genes were assigned within 90 kilobases on pulsed field gel electrophoresis analysis. These results constitute direct evidence that, at least in one mammalian species, three active alpha1,2-fucosyltransferases exist.
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PMID:Molecular cloning and expression of a third type of rabbit GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase. 866 68

Gangliosides of the plasma membrane are important modulators of cellular functions. Previous work from our laboratory had suggested that a plasma membrane sialidase was involved in growth control and differentiation in cultured human neuroblastoma cells (SK-N-MC), but its substrates had remained obscure. We now performed sialidase specificity studies in subcellular fractions and found ganglioside GM3 desialylating activity in presence of Triton X-100 to be associated with the plasma membrane, but absent in lysosomes. This Triton-activated plasma membrane enzyme desialylated also gangliosides GD1a, GD1b, and GT1b, thereby forming GM1; cleavage of GM1 and GM2, however, was not observed. Sialidase activity towards the glycoprotein fetuin with modified C-7 sialic acids and towards 4-methylumbelliferyl neuraminate was solely found in lysosomal, but not in plasma membrane fractions. The role of the plasma membrane sialidase in gangliosides desialylation of living cells was examined by following the fate of [3H]galactose-labelled individual gangliosides in pulse-chase experiments in absence and presence of the extracellular sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. When the plasma membrane sialidase was inhibited, radioactivity of all gangliosides chased at the same rate. In the absence of inhibitor, GM3, GD1a, GD1b, GD2, GD3 and GT1b were degraded at a considerably faster rate in confluent cultures, whereas the GM1-pool seemed to be filled by the desialylation of higher gangliosides. The results thus suggest that the plasma membrane sialidase causes selective ganglioside desialylation, and that such surface glycolipid modification triggers growth control and differentiation in human neuroblastoma cells.
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PMID:Selective ganglioside desialylation in the plasma membrane of human neuroblastoma cells. 872 44

This study demonstrates modulation by GM1 ganglioside of prostaglandin E1 (PGE1)-induced cAMP formation in Neuro-2a neuroblastoma cells. Pretreatment of the cells with neuraminidase, an enzyme that increases cell surface GM1, resulted in significant elevation of PGE1-induced cAMP formation, as did preincubation of the cells with nmolar concentrations of GM1. Pretreatment with brain ganglioside mixture lacking GM1 had no effect. Cholera toxin B subunit, a specific GM1-binding ligand, inhibited adenylyl cyclase. When the concentration of exogenous GM1 in which the cells were preincubated was increased from nmolar to mu molar levels there was a dose-responsive fall off in cAMP elevation, attributed to progressive inhibition of adenylyl cyclase by increasing GM1. These results are interpreted as indicating modulation of this PGE1 receptor in Neuro-2a cells by plasma membrane-localized GM1 in a structure-specific manner.
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PMID:GM1 ganglioside modulates prostaglandin E1 stimulated adenylyl cyclase in neuro-2A cells. 873 48


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