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 neuronal growth-associated protein GAP-43 is expressed during axonal outgrowth and regeneration (for review, see Benowitz and Routtenberg, 1987). In the present study, we demonstrate that GAP-43 is constitutively expressed by NB2a/d1 neuroblastoma cells. The initial, most rapid outgrowth period of neuritogenesis [0-4 hr after dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) treatment] is accompanied by intense GAP-43 immunoreactivity along the entire length of most neurites. However, this immunoreactivity declined nearly to background levels within hours during continued neurite outgrowth and persisted only at varicosities and growth cones. GAP-43 was detectable by metabolic labeling and immunoblot analysis in undifferentiated cells, and synthetic rates and steady-state levels of GAP-43 underwent only a modest (approximately twofold) increase during dbcAMP-induced differentiation. Unlike levels observed in neurites, perikarya of undifferentiated and differentiated cells contained similar, intense levels of GAP-43 immunoreactivity. Neurite elaboration and GAP-43 immunoreactivity were unaffected by treatment with cycloheximide, suggesting that translocation of perikaryal GAP-43 pools, rather than de novo synthesis, contributes to the transient burst of GAP-43 observed in developing neurites. Phosphatidylcholine-mediated delivery of anti-GAP-43 antibodies (alpha GAP) into cells immediately before dbcAMP treatment arrested neuritogenesis but did not induce the retraction of existing neurites. These results indicate that, while GAP-43 expression is insufficient to induce neuritogenesis in NB2a/d1 cells, GAP-43 is nevertheless essential for the initial, dynamic phase of neurite outgrowth.
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PMID:Phospholipid-mediated delivery of anti-GAP-43 antibodies into neuroblastoma cells prevents neuritogenesis. 164 99

Protein kinase inhibitor H-7 and dibutyryl (dB)-cAMP were found to induce neuritic processes in mouse neuroblastoma N18TG2 cells (36). In the present study, morphological differences between the neurites induced by H-7 and those by dB-cAMP were examined using electron microscopy (TEM and SEM) and tubulin immunohistochemistry. It was observed that: 1) The neurites induced by H-7 were relatively thin and frequently had varicosities. On the other hand, the neurites induced by dB-cAMP were thick but they had few varicosities. 2) Centrioles were frequently observed in the cells treated with dB-cAMP but were not encountered in the H-7-treated cells. 3) TEM and tubulin immunohistochemistry revealed that the main shafts of the neurites induced either by H-7 or dB-cAMP were filled with microtubules, but that the varicosities induced by H-7 contained a smaller amount of microtubules. 4) The stability to colchicine was greater in the neurites induced by H-7 than in those by dB-cAMP. From these features of the neurites, it was inferred that neurite outgrowth induced by dB-cAMP is deeply related to the formation of microtubules and that the neurites induced by H-7 were involved in other processes probably including an adhesive property of cell surfaces.
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PMID:Morphology of neurites from N18TG2 cell induced by protein kinase inhibitor H-7 and by cAMP. 165 Nov 49

Cultures of mouse Neuro-2a neuroblastoma cells treated with 3-6 mM extracellular Ca2+ exhibited enhanced neurite extension characterized by increased neurite numbers and lengths. The ganglioside GM1 potentiated the effect of extracellular Ca2+ by increasing further the number and length of the neurites formed in response to exogenous Ca2+. Maximal neuritic numbers were achieved with 4 mM Ca2+ while the longest neurites were observed in medium containing 4-6 mM Ca2+. Stimulation of the Ca2+ influx with the ionophore A23187 or the amino acid taurine also enhanced neurite formation and GM1 potentiated these actions. Transmission electron microscopy revealed numerous microtubules and neurofilaments in neurites and microfilaments with the spine-like processes along fine neuritic branches and in the filopodia of growth cones. Neuritic varicosities and growth cones contained a variety of vesicles. All of these structures were increased in the presence of GM1 and were increased further by extracellular Ca2+ or A23187. The ability of GM1 to enhance neuritogenesis was diminished by EGTA or Ruthenium red. Similarly, the effect of GM1 was diminished or abolished by Ca2+ channel blockers such as CdCl2 or LaCl3. X-ray microprobe analysis revealed that GM1 alone enhanced intracellular levels of total ionic and membrane bound Ca2+, perhaps accounting for the increased neuritogenesis observed under conditions in which Ca2+ was manipulated. The present study suggest that the neuritogenic action of GM1 is Ca2+ dependent.
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PMID:Calcium regulation of neuronal differentiation: the role of calcium in GM1-mediated neuritogenesis. 170 40

1. The effects of gamma-interferon (gamma-IFN), retinoic acid (RA), and cytosine arabinoside (ARA-C) on the growth, morphology, and phenotype of the human neuroblastoma (NB) cell lines, LAN-1 and GI-ME-N, have been extensively tested. 2. RA, gamma-IFN, and ARA-C induced a dose-dependent morphological differentiation and growth inhibition, without affecting cell viability. Cells exposed to 10(-6) M RA or 1000 U/ml gamma-IFN significantly decreased their growth rate within the first 24 and 48 hr of culture, respectively. Cells became smaller and polygonal and sprouted long cellular processes with varicosities along their courses. In contrast, ARA-C-differentiated cells were larger and flattened, with few elongated dendritic processes. 3. Analysis of membrane and cytoskeletal markers by immunofluorescence and Western blot showed several changes in NB-specific antigen expression after 5 days of treatment with all inducing agents. Analysis of labeled phosphatidylinositol metabolites from prelabeled cells showed, within 1 min of treatment with RA, a rapid decrease in inositol 1,4,5-trisphosphate and of 1,2-diacylglycerol levels. No changes in inositol phospholipid metabolism were observed in gamma-IFN- or ARA-C-treated cells. 4. We conclude that RA-induced decrease in phosphatidylinositol (PI) hydrolysis is not likely to be a consequence of the acquisition of a different phenotype, as its changes precede the acquisition of neuronal markers. In addition, gamma-IFN and ARA-C, both inducing a mature phenotype, did not affect PI hydrolysis. 5. Decreased PI hydrolysis seems to be sufficient, although not necessary, to commit NB cells to neuronal differentiation. Analysis of molecular mechanisms associated with NB cell differentiation may be helpful to clarify the potential of various biological agents in affecting the development of the neural cell.
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PMID:Gamma-interferon, retinoic acid, and cytosine arabinoside induce neuroblastoma differentiation by different mechanisms. 175 63

The synapsins are a family of closely related phosphoproteins (termed synapsins Ia, Ib, IIa and IIb) associated with synaptic vesicles and implicated in the short-term regulation of neurotransmitter release from nerve endings. During development, expression of the synapsins correlates temporally with synapse formation, but there has been no direct evidence that they are involved in synaptogenesis. Here we report that overexpression of synapsin IIb in the neuroblastoma x glioma hybrid clonal cell line NG108-15 leads, during cell differentiation, to marked increases in the number of neuritic varicosities and in the numbers of small clear vesicles and large dense core vesicles per varicosity, as well as to the appearance of synapse-like cell-cell contacts. Thus, synapsin IIb may be involved in the regulation of synapse formation and, as a result, in long-term neuronal signalling.
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PMID:Induction of formation of presynaptic terminals in neuroblastoma cells by synapsin IIb. 189 14

A number of recent studies have suggested a relationship between Ewing's sarcoma (ES) and other small round cell tumours of childhood such as peripheral neuroepithelioma (PN). We report scanning electron microscopic studies on the character of induced neural differentiation in ES, neuroblastoma, PN, osteosarcoma and colon carcinoma. We found evidence of neural differentiation in both neural lines and in one of two Ewing's lines before treatment. After differentiation, both Ewing's and neural lines developed neuritic processes with varicosities and little arborization, except for the initially undifferentiated Ewing's line (A4573) which displayed extensive lateral sprouting from neuritic processes after differentiation. Neither treated nor untreated osteosarcoma or colon carcinoma displayed any evidence of neural differentiation. Further, neuroblastoma cells are easily distinguished from ES and PN by virtue of their single, unbranched neurites and lack of lateral sprouting or filopodia. These results provide further evidence for the neural character and close relationship between ES and PN.
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PMID:Scanning electron microscopic evidence for neural differentiation in Ewing's sarcoma cell lines. 210 25

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 effects of gamma-interferon (gamma-IFN) on the growth, morphology, and phenotypic expression of the human neuroblastoma (NB) cell line, LAN-1, have been extensively tested. Low doses of gamma-IFN allowing more than 90% cell viability induce morphological differentiation and growth inhibition. Cells exposed to gamma-IFN significantly decreased their growth rate, became smaller and poligonal, and sprouted long cellular processes with varicosities along their course, typical of the neurites seen in differentiated NB cells; morphological changes appeared within 48 h of culture with 1,000 U/ml gamma-IFN. The new morphological aspect reached the maximum expression after 6 days of culture, becoming more evident when fresh drug was added after 2 days of culture. A decrease in [3H]thymidine incorporation was also observed within 24 h; cell growth was completely inhibited at the 6th day. Membrane immunofluorescence showed several changes in NB-specific antigen expression after 6 days of treatment with gamma-IFN. At the same time gamma-IFN also modulated cytoskeletal proteins. These findings suggest that noncytotoxic doses of gamma-IFN do promote the differentiation of LAN-1 neuroblastoma cells which is associated with the reduced expression of the malignant phenotype.
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PMID:Effects of gamma-interferon on the growth, morphology, and membrane and cytoskeletal proteins expression of Lan-1 cells. 251 15

Morphological characteristics of undifferentiated and differentiated human neuroblastoma cells were studied. Monolayer cultures of a human neuroblastoma, IMR-32 clone, were grown in Eagle's minimum essential medium with fetal calf serum in tissue culture dishes with polystyrene film liners. After 48 h, cultures were treated with either mitomycin C and 5-bromodeoxyuridine or prostaglandin E1 (PGE1) and dibutyryl adenosine 3',5'-cyclophosphate (cAMP). A third dish was untreated to study as an undifferentiated control. Three days later, all cultures were processed for acetylcholinesterase staining, scanning and transmission electron microscopy and high performance liquid chromatography. Treatment with mitomycin/5-bromodeoxyuridine and PGE1/cAMP inhibited growth as seen by the growth curves and caused morphological differentiation as seen by the extension of long neurites. The treated cells showed increased acetylcholinesterase staining compared to the controls. With the scanning electron microscope, the differentiated cells showed long neurites, processes with beaded varicosities and growth cones. By transmission electron microscopy, these cells contained a large number of neurosecretory granules in their cytoplasm and neurites. Specialized cell contacts were also observed between the treated cells. This is the first study demonstrating that both the treated and control cells of IMR-32 clone contain large quantities of serotonin and comparatively small amounts of norepinephrine and dopamine.
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PMID:Differentiation characteristics of human neuroblastoma cells in the presence of growth modulators and antimitotic drugs. 298 88

The histogenesis of Ewing's sarcoma remains unknown. Recent studies have suggested a relationship to an unusual form of childhood neural tumor, often termed peripheral neuroepithelioma or primitive neuroectodermal tumor. Five Ewing's sarcoma tumor cell lines were studied for evidence of a neural phenotype. Under normal culture conditions, no morphologic evidence of neural differentiation was detected. Treatment with retinoic acid, an agent known to induce marked neural differentiation in neuroblastoma, had no demonstrable effect. Treatment with either cyclic AMP or TPA, in contrast, induced pronounced morphologic evidence of neural differentiation. Cells developed elongate processes with varicosities by phase-contrast microscopy; filaments, microtubules, and uraniffin-positive dense core granules were present by electron microscopy. Three neural markers (NSE, NFTP, and cholinesterase) were absent or barely detectable in untreated cells, but became abundant after treatment. These results provide convincing evidence for a neural histogenesis of Ewing's sarcoma. They also suggest a close relationship between Ewing's sarcoma and peripheral neural tumors, including the chest wall tumor described by Askin, but only a distant relationship to neuroblastoma.
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PMID:Experimental evidence for a neural origin of Ewing's sarcoma of bone. 303 30


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