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)

The ability of retinoic acid (RA) to modulate acetylcholinesterase (AChE) activity in a human neuroblastoma cell line (LN-N-5) was examined. The specific activity of AChE was significantly increased 3 days after exposure of LA-N-5 to RA and reached its maximum values after 9 or more days of culturing. Dose-response experiments demonstrated that large increases of AChE occurred at RA concentrations between 10(-7) and 10(-6) M with maximum AChE values detected at 10(-6)-10(-5) M. Increased AChE activity paralleled neurite outgrowth in LA-N-5 cultures. These findings demonstrate that RA can regulate specific AChE activity in human neuroblastoma cells in a manner consistent with neuronal maturation.
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PMID:Regulation of acetylcholinesterase activity by retinoic acid in a human neuroblastoma cell line. 638 96

Mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, stimulated outgrowth of neurites and increased acetylcholinesterase activity in C1300-N2A murine neuroblastoma cells cultured in medium containing 10% fetal calf serum. Changes in cell morphology and enzyme activity were concentration-dependent in the range of 0.25-25 microM mevinolin, and were accompanied by decreased incorporation of [3H]thymidine into DNA. The expression of differentiated characteristics induced by 25 microM mevinolin was blocked by simultaneous addition of 100 microM mevalonate to the culture medium. The data suggest that changes in intracellular levels of mevalonate or one of its isoprenoid derivatives may play a role in the regulation of cell differentiation.
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PMID:Induction of differentiation in murine neuroblastoma cells by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. 656 16

The presence of acetylcholinesterase in the tumour cells of neuroblastoma has been shown by enzyme histochemistry. For comparison, some other tumours likely to be found in children and commonly presenting histologically as small cell tumours have also been studied. Acetylcholinesterase activity was seen in rhabdomyosarcoma, but, compared with neuroblastoma, the activity was focal and sparse. One Ewing's tumour and a lymphoblastic lymphoma were negative for the enzyme reaction. Some of the ultrastructural features of neuroblastoma are correlated with the presence of this enzyme. Acetylcholinesterase enzyme histochemistry may provide a useful adjunct in the distinction of neuroblastoma from other small cell tumours.
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PMID:Histochemical demonstration of acetylcholinesterase in neuroblastoma. 669 92

We have used the method of heavy isotope labeling to study the metabolic turnover of acetylcholinesterase forms in the neuroblastoma-derived T 28 hybrid cells in their differentiated state. These cells contain mostly G1 and G4 forms, together with a small proportion of G2, and secrete all these forms into the culture medium. The cells maintained constant and equal levels of acetylcholinesterase, with the same proportions of molecular forms, in a medium containing heavy isotope-labeled amino acids and in a control light medium of similar composition. In addition, they secreted acetylcholinesterase at the same rate in both media. After transfer of the cells into the heavy medium, heavy isotope-labeled acetylcholinesterase molecules progressively replace preexisting light molecules. We analyzed heavy and light components of acetylcholinesterase for each of the two major G1 and G4 forms, by reconstructing the pattern obtained in sucrose gradient differential sedimentation, using combinations of weighted elementary distributions. Heavy molecules were detected in cellular extracts after about 30 min for G1 and 3 h for G4. Both heavy forms also appeared in the medium after a lag of about 3 h. The cellular complement of G1 was renewed much faster than that of G4, the levels of the light forms being reduced to 50% of the original level after 3.5 and 40 h, respectively. Each of these forms appeared to consist of several metabolic pools, and we present simplified models which describe their possible relationships.
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PMID:Heavy isotope-labeling study of the metabolism of monomeric and tetrameric acetylcholinesterase forms in the murine neuronal-like T 28 hybrid cell line. 670 75

The history of a 6-year-old girl with a tumor originating from thoracic spine and finally becoming resistant to surgery, radio-, and chemotherapy is reported. Tumor-biopsy material was studied by light and electron microscopy, in cell culture, by acetylcholinesterase ultracytochemistry, and by quantitative catecholamine analysis and this led to the rejection of the initial diagnosis of a neuroblastoma. Light microscopy revealed a uniform population of undifferentiated cells incompletely lobulated by broad fibrovascular septa. Using the electron microscope, cells were characterized by large intracellular pools of glycogen, little cytoplasm with an abundance of free ribosomes and a paucity of organelles. A few cells displayed desmosome-like attachment sites. Staining for specific and unspecific acetylcholinesterase was negative with light and electron microscopy, as were the results of catecholamine histofluorescence using the glyoxylic acid method. The latter result was confirmed by the negative outcome of quantitative analyses of dopamine, noradrenaline, and adrenaline with high pressure liquid chromatography nd electrochemical detection in tissue samples. Tumor cells could easily be maintained in culture for up to 4 weeks. None of a variety of treatments that are known to favor expression of neuronal characteristics in neuroblastoma cells (serum withdrawal, nerve growth factor, dbcAMP, dexamethasone) induced morphological differentiation in cultured tumor cells. On the basis of the clinical history, morphology, and of our experiments with tumor cells, the diagnosis of a so-called extraskeletal Ewing's sarcoma is most likely. Our results strengthen the view that a cell biology approach may be valuable in neuroblastoma differential diagnosis.
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PMID:Ultrastructural, biochemical, and cell-culture studies of a presumed extraskeletal Ewing's sarcoma with special reference to differential diagnosis from neuroblastoma. 711 92

Two spontaneously arising variant clones were selected from the N18 neuroblastoma cell line solely on the basis of their flattened morphology and tight adherence to the culture flask. Two other clones having the round loosely adherent morphology typical of the parent line were also selected, and flat variants were shown to arise in them upon prolonged cultivation. The flat variant clones have slower growth rates in culture, lower cloning efficiencies in suspension, and reduced acetylcholinesterase inducibility when compared with either the parent N18 line or the round cell clones. Cells of both morphologic types have high levels of plasminogen activator and are tumorigenic, although the variants have a slower growth rate in vivo, consistent with their slower growth rate in culture. SDS-polyacrylamide gel electrophoresis of total protein from the two cell types shows that the flat variants have increased amounts of a 200,000 molecular weight polypeptide that has tentatively been identified as the heavy chain of myosin. Round morphological revertants from one of the flat variant clones exhibited growth characteristics typical of the parent N18 line, but their content of myosin heavy chain, although reduced, was not so low as that in the round cell clones originally isolated. The possibility of a causal relationship between flat morphology, reduced suspension cloning efficiency, and increased content of myosin heavy chain is discussed.
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PMID:Clonal variation in cultured neuroblastoma cells. I. Isolation and characterization of variants. 719 8

The cellular localization of the molecular forms of acetylcholinesterase was explored in chick sympathetic neurons and in mouse T28 cells (neuroblastoma X sympathetic ganglion cell hybrids) using the reversible, poorly lipid-soluble inhibitor of acetylcholinesterase, BW284C51, to protect cell surface activity while inactivating cytoplasmic activity with DFP, an irreversible, lipid-soluble inhibitor. Our results show protection of over 80% of the chick 11 S form and over 90% of the corresponding mouse 10 S form under these conditions, while over 90% of the chick 6.5 S and mouse 4 S forms are inhibited. The results suggest that the avian 11 S and mouse 10 S forms are predominantly or exclusively ectoenzymes while the respective 6.5 S and 4 S forms are confined to the cytoplasm.
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PMID:Cellular localization of the multiple molecular forms of acetylcholinesterase in cultured neuronal cells. 721 57

After exposure to increased oxygen tension for 3 days, cultured mouse neuroblastoma cells were found to undergo morphological differentiation and to significantly increase their ecto-acetylcholinesterase activity. Differentiation could not be blocked by KCN or lipid-soluble antioxidants, indicating that neither an increased respiration, nor an increased oxidation of membrane lipids was responsible for the effect.
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PMID:Differentiation of mouse neuroblastoma cells under increased oxygen tension. 738 75

Studies were carried out on the polymorphism of acetylcholinesterase (AChE, EC 3.1.1.7) in a neuroblastoma x sympathetic ganglion cell hybrid cell line (T28) and its parental clone (N18TG2). These cells contain the tetrameric (G4, 10S), dimeric (G2, 6.5S) and monomeric (G1, 4S) forms of AchE, but not the collagen-tailed A12(16S) form of the sympathetic ganglion. Three variants of these forms could be distinguished on the basis of their solubility properties: (i) secreted forms which do not interact with the detergent Triton X-100; (ii) cellular forms which may be solubilized in detergent-free buffer and which interact reversibly with Triton X-100; (iii) cellular forms which require detergent for solubility, and aggregate in its absence. By using a nonpenetrating inhibitor, we demonstrated that, in T28 stationary cells, the cellular G4 form is associated with the plasma membrane, whereas the G1 form is intracellular. During induction of AChE activity in T28 cells, the relative proportion of the G4 form increases, suggesting, in agreement with previous observations, that G1 is a metabolic precursor of G4. The evolution of AChE molecular forms released into the culture medium closely resembles that of the cellular forms. The preferential accumulation of the G4 molecules does not simply depend on the cellular level of G1. It is favoured by culture conditions which promote morphological differentiation, but does not require the actual extension of neurites. T28 cells as well as other neuroblastoma-derived cells appear to be useful experimental materials to investigate the regulatory mechanisms underlying the maturation of AChE globular forms.
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PMID:Modulation of the distribution of acetylcholinesterase molecular forms in a murine neuroblastoma x sympathetic ganglion cell hybrid cell line. 745 5

The relationship of genes associated with contact inhibition of cell growth and the commitment for differentiation was studied in the human neuroblastoma cell line SH5Y. These cells could be induced to differentiate in vitro into neuronal-like cells upon incubation with retinoic acid, an event that was accompanied by an enhancement in levels of neuron-specific acetylcholinesterase. The kinetics of differentiation, based on morphology and acetylcholinesterase levels, showed that proliferation arrest always preceded differentiation and may be a prerequisite for differentiation. To determine if this growth arrest is mediated by the same pathway underlying contact inhibition of proliferation, the expression of a gene associated with the induction of contact inhibition, protein disulfide isomerase (PDI), was quantified by Northern blot analysis and enzymatic activity after retinoic acid treatment. Retinoic acid caused a significant elevation of PDI-mRNA within 24 hrs. after treatment with a corresponding increase in enzyme activity which immediately preceded proliferation arrest and differentiation. Bacitracin, a specific inhibitor of PDI, abrogated the ability of retinoic acid to induce differentiation. However, treatment with interferon also increased PDI activity and caused proliferation arrest and SH5Y differentiation but into a fibroblastoid cell without neurite outgrowth. These results suggest that the commitment for differentiation of SH5Y cells involves a form of proliferation arrest in which activation of PDI activity is a required and early event but one that does not determine the final differentiation pathway.
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PMID:Induction of protein disulfide isomerase during proliferation arrest and differentiation of SH5Y neuroblastoma cells. 754 84


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