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)

Esthesioneuroblastoma (ESTH) is a neuroepithelial-cell-derived neoplasm of the olfactory mucosa composed of homogeneous small round cells which contain neurosecretory granules. Melanin has been detected in such tumours only occasionally. Here we describe a new case of ESTH with divergent differentiation. The primary neoplasm was found in a 67 year-old female, involving the left nasal and maxillary sinus; she died of cerebral metastasis ten months after diagnosis. Histologically only small round cells were seen, with S-100 and NSE positivity. Electron microscopy revealed neurosecretory granules and filaments, as well as the occasional presence of melanosomes. A nude mice xenograft line has been established, and is presently in its ninth transfer. Two cell types are present: small round-to-spindle shaped cells with neural features, and large epithelial-like ones. Both immunohistochemistry and electron microscopy confirm this dual differentiation, with the presence of membrane-bound dense-core neural secretion, as well as melanosomes of neuroectodermal origin. Additionally, an in vitro cell line has been established. Cytogenetic analysis confirmed the presence of both malignant human melanoma patterns; non-random abnormalities in chromosomes 1 and 6, extra copies of chromosome 7. Duplication of the long arm of chromosome 14, as seen in olfactory neuroblastoma, is also seen.
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PMID:Pigmented esthesioneuroblastoma showing dual differentiation following transplantation in nude mice. An immunohistochemical, electron microscopical, and cytogenetic analysis. 249

Nonchromaffin paraganglioma (NCP), also called glomus body tumor or chemodectoma, is rarely found in the orbit. The behavior of orbital nonchromaffin paraganglioma may potentially be more aggressive than in other head and neck locations. Diagnosis depends on electron microscopic demonstration of membrane-bound neurosecretory granules. Results of histopathologic study show a well-circumscribed lesion without a true capsule with alveolar or organoid arrangements of epithelioid cells within a reticulin framework with thin-walled blood vessels. Cells are polygonal with round or oval nuclei containing rare mitotic figures and pale-staining cytoplasm. Differential diagnosis includes alveolar soft-part sarcoma, alveolar rhabdomyosarcoma, neuroblastoma, carcinoid, and granular cell tumor. Of 29 previously reported cases of orbital NCP, 16 have been reclassified as alveolar soft-part sarcoma. The authors report a patient with an electron microscopically established orbital NCP, with the history of a contralateral glomus jugulare tumor irradiated 14 years previously.
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PMID:Orbital nonchromaffin paraganglioma. A case report and review of the literature. 255 86

The aim of this work was to determine if the total (Na+ + K+)-ATPase of the plasma membrane of a cell population could be assayed without cell homogenization and partial purification of the enzyme. Several types of intact cells that were placed in an assay medium containing MgATP, Na+, and K+ hydrolyzed little or none of the added ATP. When the cells were pretreated with the ionophore alamethicin and then placed in the assay medium, they exhibited an ouabain-sensitive (Na+ + K+)-ATPase activity that increased and reached a limiting value with increasing alamethicin concentration. Since alamethicin did not increase the activity of the purified membrane-bound (Na+ + K+)-ATPase, its effects on the intact cells are probably due to the formation of large channels within the plasma membrane that allow the free access of the components of the assay medium to the intracellular domains of (Na+ + K+)-ATPase. Utilizing whole cells treated with alamethicin, total (Na+ + K+)-ATPase activity was determined in clonal pheochromocytoma cells (PC12), neuroblastoma x glioma hybrid cells (NG108-15), and myocytes isolated from adult and neonatal rat hearts. With the use of this whole-cell assay, the ouabain sensitivities of the enzymes in adult and neonatal rat heart myocytes were determined and found to be the same as those that have been determined with the use of partially purified enzymes.
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PMID:Determination of total (Na+ + K+)-ATPase activity of isolated or cultured cells. 256 Mar 48

Recent studies, including ours, on bioactive gangliosides revealed that certain gangliosides have an interesting ability to modulate a variety of cell functions. For instance, we demonstrated that a tetrasialoganglioside, GQ1b, promotes neurite outgrowth when added in nanomolar concentrations to cells from two human neuroblastoma cell lines. Also, phosphorylation of several cell surface proteins was observed on addition of ATP. Several lines of evidence indicated that this phosphorylation is probably catalysed by a novel cell surface membrane-bound protein kinase which is specifically activated by a particular ganglioside (Gg). Because of its location on the cell surface we proposed calling this type of kinase(s) ecto-Gg kinase. A procedure to inhibit the phosphorylation of the cell surface protein resulted in suppression of the GQ1b-dependent promotion of neuritogenesis, strongly suggesting that these two cellular events are intricately coupled. Other evidence also indicated that the GQ1b-dependent neuritogenesis is mediated through a receptor-coupled process of the cell surface membrane. Thus, it is likely that this represents a new type of biosignal transduction that is mediated through cell surface carbohydrate recognition (ecto biosignal transduction system).
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PMID:Bioactive ganglioside-mediated carbohydrate recognition in coupling with ecto-protein phosphorylation. 279 50

We have found that neuroendocrine tumors (including neuroblastoma, ganglioneuroma, gut carcinoid, pheochromocytoma, medullary thyroid carcinoma, insulinoma, glucagonoma, prolactinoma, carotid body tumor, and small cell lung carcinoma) produce considerable amounts (about 1000-80,000 ng/g tissue) of the alpha subunit of guanine nucleotide-binding protein, GO (GO alpha), whereas nonneuroendocrine tumors contain less than 300 ng of GO alpha/g tissue. GO alpha in the neuroendocrine tumors was present both in the soluble fraction, and cholate-extractable membrane-bound fraction of tissues. Immunoblots of membrane fractions of neuroblastoma and carcinoid tissues confirmed that the immunoreactive substance in the tumor tissues was GO alpha. Immunohistochemically, GO alpha was localized consistently in the cell membrane and occasionally in the cytoplasm of neuroendocrine tumors. GO alpha was also detected in sera of 73% patients with neuroblastoma at diagnosis, whereas serum GO alpha concentrations in control children, or patients with nonneuroendocrine tumors were lower than the detection limit of the immunoassay method employed. Serum GO alpha concentrations in patients with neuroblastoma changed with the clinical course; they fell in patients responding to treatment and increased in patients who relapsed. Since GO alpha, a specific protein in the neural and neuroendocrine cells, was found to be produced in considerable amounts by all types of neuroendocrine tumors but not in nonneuroendocrine tumors, GO alpha might be a useful biomarker for neuroendocrine tumors.
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PMID:Production of the alpha subunit of guanine nucleotide-binding protein GO by neuroendocrine tumors. 282 34

A potential mechanism for valproate (VPA)-induced increases in glial cell-substratum adhesivity has been demonstrated. Metabolically labelled glioma (C6) and primary astrocytes showed a statistically significant accumulation of protein when cultured in the presence of therapeutic concentrations of VPA (1 mM). This was mainly accounted for by a 10-fold increase in the production of a single polypeptide of 43 kDa molecular weight. Fractionation studies and metabolic labelling with N-acetyl-D-mannosamine showed this to be a sialoglycoprotein which was plasma membrane-bound. VPA-induction of the polypeptide was apparently specific to glioma and primary astrocytes and was not observed in neuroblastoma (neuro-2a), fibroblasts (3T3), pituicytes (GH3) and epithelial cells (NCTC). The 43 kDa component of glia was demonstrated to be the receptor for type IV collagen by binding metabolically labelled and solubilised cells to Sepharose beads which had been individually coated with laminin, fibronectin and type IV collagen. The protein has also been shown to be a heat shock product as metabolically labelled glioma showed a 10-fold increase in its expression when cultured at 42 degrees C. This heat shock induced expression was transient and was in marked contrast to that seen with VPA where it increased with time and was sustained. The expression of 43 kDa is suggested to arise by VPA and heat shock induced delays in cell cycle progression and this is discussed in relation to teratogenic action.
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PMID:The anticonvulsant sodium valproate specifically induces the expression of a rat glial heat shock protein which is identified as the collagen type IV receptor. 284 60

The cellular mechanism of action of the cannabimimetic drugs is examined using cultured cells. In membranes from N18TG2 neuroblastoma cells and the neuroblastoma X glioma hybrid cells, NG108-15, the psychoactive cannabinoid drugs and their nantradol analogs could inhibit adenylate cyclase activity. This response was not observed in either the soluble adenylate cyclase from rat sperm or membrane-bound adenylate cyclases from C6 glioma or S49 lymphoma cells. This cellular selectivity provides further evidence for the existence of specific receptors for the cannabimimetic compounds. Receptor-mediated inhibition of adenylate cyclase requires the presence of a guanine nucleotide-binding protein complex, Gi. Gi can be functionally inactivated as a result of an ADP-ribosylation modification catalyzed by pertussis toxin. The present study demonstrates that pertussis toxin treatment of cells abolished the cannabimimetic response in intact cells and in membranes derived therefrom. The action of pertussis toxin required NAD+ as substrate for in vitro modification of neuroblastoma membranes. Furthermore, pertussis toxin was able to catalyze the labeling of a neuroblastoma membrane protein in vitro using [32P] NAD+ under conditions similar to those by which attenuation of the cannabimimetic inhibition of adenylate cyclase could be demonstrated. This evidence demonstrates the requirement for a functional Gi in the action of cannabimimetic drugs.
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PMID:Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. 286 5

Barbiturates in pharmacologically relevant concentrations inhibit binding of (R)-N6-phenylisopropyl[3H]adenosine ([3H]PIA) to solubilized A1 adenosine receptors in a concentration-dependent, stereospecific, and competitive manner. Ki values are similar to those obtained for membrane-bound receptors and are 31 microM for (+/-)-5-(1,3-dimethyl)-5-ethylbarbituric acid [(+/-)-DMBB] and 89 microM for (+/-)-pentobarbital. Kinetic experiments demonstrate that barbiturates compete directly for the binding site of the receptor. The inhibition of rat striatal adenylate cyclase by unlabelled (R)-N6-phenylisopropyladenosine [(R)-PIA] is antagonized by barbiturates in the same concentrations that inhibit radioligand binding. The stimulation of adenylate cyclase via A2 adenosine receptors in membranes from N1E 115 neuroblastoma cells is antagonized only by 10-30 times higher concentrations of barbiturates. It is concluded that barbiturates are selective antagonists at the A1 receptor subtype. In analogy to the excitatory effects of methylxanthines it is suggested that A1 adenosine receptor antagonism may convey excitatory properties to barbiturates.
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PMID:Barbiturates are selective antagonists at A1 adenosine receptors. 299 96

A membrane-bound enkephalin (ENK) -hydrolyzing amino-peptidase (AP) was partially purified from neuroblastoma (clone N1E-115) cell membranes; enzyme activity was assayed by determination of the leu-enkephalin (LENK) degradation product, tyrosine (Tyr), with HPLC. The enzyme was extracted with Triton X-100, resolved by anion-exchange chromatography and further purified by gel filtration. The overall purification was about 100-fold with a yield of 43%. The apparent Mr value of the AP by gel filtration in the presence of 0.3% Triton X-100 was approx. 400 kDa. In the absence of detergent the apparent Mr value was about 305 kDa. In the elution buffers, where Triton X-100 was omitted, the peptidase activity was lost. The enzyme had a Km of 0.13 mM and a Vmax of 450 nmoles per mg protein per min at 25 degrees C for LENK and exhibited little sensitivity to bestatin (IC50: 200 microM) and puromycin (IC50: 500 microM), but it was strongly inhibited by amastatin (IC50: 8 microM). The enzyme is an amphiphilic membrane protein; the native primary structure is preserved only in the 'detergent form'. It seems to be AP N (EC 3.4.11.2) with an optimum of pH 7.2 to 7.4. We assume that this AP plays the important role in inactivating ENKs on the neuronal level. The ENK-degrading AP, partially purified from primary rat brain astrocyte cell membranes, exhibited a smaller apparent Mr value (130 kDa) and a higher sensitivity to amastatin (IC50: 0.4 microM), bestatin (IC50: 90 nM) and puromycin (IC50: 5 microM) than did the N1E-115 enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the enkephalin-degrading aminopeptidase of neuroblastoma (N1E-115) cell membranes. 312 43

The anti-benzodiazepine monoclonal antibody 21-7F9 has been used for the identification and study of endogenous benzodiazepine-like molecules in the human, rat and bovine brains. A sandwich radioimmunoassay has been designed for the quantification of the membrane-bound endogenous benzodiazepine-like molecules. The localization of these molecules is not restricted to the brain tissue. They are also present in kidney, liver and spleen as well as in the neuroblastoma X glioma NG108-15 hybrid cell line. Immunoblots show benzodiazepine-like immunoreactivity in the membrane proteins of all of these tissues. The membrane-bound benzodiazepine-like molecules are resistant to limited proteolysis of the membranes. Moreover, this treatment increases the binding of the monoclonal antibody 21-7F9 to the membranes, probably by exposing sites that normally are not accessible to the antibody. Immunocytochemistry experiments show that benzodiazepine-like molecules are also present in samples of human cerebella that have been stored in paraffin since 1940, 15 years before the first chemical synthesis of benzodiazepines. The results indicate that the cerebellar benzodiazepine-like molecules recognized by the antibody are the product of biological (not chemical) synthesis. Benzodiazepine-like immunoreactivity has also been detected in NG108-15 cells that have been cultured for 3 months in serum-free medium. These results suggest that the cells could biosynthesize benzodiazepine-like molecules.
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PMID:Endogenous benzodiazepine-like molecules in the human, rat and bovine brains studied with a monoclonal antibody to benzodiazepines. 330 Aug 53


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