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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The techniques of somatic cell hybridization allow a genetic analysis of differentiated functions of mammalian cells in vitro. Clonal lines of mouse neuroblastoma cells expressing a variety of differentiated neuroectodermal functions have been fused to L cells not expressing these functions. The resulting NL hybirds, on a clonal basis, express a variety of parental and non-parental phenotypes. Some hybrid clones inherit the ability to synthesize the neurotransmitter acetylcholine (Ach) (expression of high levels of choline acetyltransferase, CAT) while others do not. The ability to synthesize Ach and the ability to degrade this neurotransmitter (high levels of acetylcholinesterase activity, AChE) appear to segregate independently in NL hybrid progeny.--When a a variety of clonal cell lines replicating in culture are fused to cells freshly derived from the embryonic nervous system, interesting phenotypes result in the hybrid progeny. Neuroblastoma x rodent nervous tissue hybrids express AChE and in a few instances have developed the ability to synthesize CAT. Transformed human fibroblasts fused to normal rodent nervous tissue yield hybrid progeny that retain human and segregate mouse chromosomes and isozymes. No expression of differentiated functions has yet been found in these latter hybrids but they are useful for mapping mouse genes.
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PMID:Expression of phenotypes in hybrid somatic cells derived from the nervous system. 115 88

Several neuroblastoma clones and the same clones adapted to proliferation in a medium containing 15 mug/ml of 8-azaguanine and 6-thioguanine are characterized with respect to their morphology, acetylcholinesterase activity, catecholamine content and chromosomal pattern. Interclonal as well as intraclonal heterogeneity was found for the cell parameters studied. A reduction in the number of catecholamine-containing cells was observed in the azaguanine and thioguanine resistant adrenergic (M1, N115) cells compared with their parental lines. An increase of choline acetyltransferase activity was found in the M5 cholinergic clone, and a decrease of the same activity in the S21 cholinergic line selected in the medium with the purine analogues. Furthermore, a striking change in the distribution of chromosomes and chromosomal markers appeared in the resistant cells of all clones.
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PMID:Morphological, histochemical and chromosomal patterns of neuroblastoma parental and purine resistant lines. 120 69

1. The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of acetylcholinesterase, neuron-specific enolase, catecholamines and related neurotransmitters, vasointestinal peptide, and substance P were evaluated after induction. 2. Cell morphology was strongly affected by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The main effects of retinoic acid and gamma-interferon were the loosening of cell clusters and the extension of long neurites; cytosine arabinoside induced cell body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13-acetate treatment, the cells became small, round, and neuritic. Conversely, modifications induced by nerve growth factor and tumor necrosis factor were mild. Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase activity was significantly stimulated by retinoic acid and by gamma-interferon. Neuron-specific enolase activity was unaffected by all treatments except 12-O-tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular catecholamine and related metabolite content was lowered by retinoic acid and gamma-interferon, while cytosine arabinoside and, even more, 12-O-tetradecanoylphorbol 13-acetate showed a stimulatory activity on their intracellular accumulation. 5. Finally, the cell-associated vasointestinal peptide level was strikingly increased by gamma-interferon and, to a lesser extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. 6. It is concluded that the most relevant biochemical changes associated with LAN-5 cells differentiation involve the repertoire of neurotransmitters and neuropeptides. These events vary in quality and in quantity, likely due to the pattern complexity of gene expression triggered by each inducer in determining the diversity of neuronal phenotypes.
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PMID:A combined evaluation of biochemical and morphological changes during human neuroblastoma cell differentiation. 135 48

Radio-frequency electromagnetic radiation (RFR) at 915 and 147 MHz, when sinusoidally amplitude modulated (AM) at 16 Hz, has been shown to enhance release of calcium ions from neuroblastoma cells in culture. The dose-response relation is unusual, consisting of two power-density "windows" in which enhanced efflux occurs, separated by power-density regions in which no effect is observed. To explore the physiological importance of these findings, we have examined the impact of RFR exposure on a membrane-bound enzyme, acetylcholinesterase (AChE), which is intimately involved with the acetylcholine (ACh) neurotransmitter system. Neuroblastoma cells (NG108), exposed for 30 min to 147-MHz radiation, AM at 16 Hz, demonstrated enhanced AChE activity, as assayed by a procedure using 14C-labeled ACh. Enhanced activity was observed within a time window between 7.0 and 7.5 h after the cells were plated and only when the exposure occurred at power densities identified in a previous report as being effective for altering the release of calcium ions. Thus RFR affects both calcium-ion release and AChE activity in nervous system-derived cells in culture in a common dose-dependent manner.
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PMID:Dose dependence of acetylcholinesterase activity in neuroblastoma cells exposed to modulated radio-frequency electromagnetic radiation. 151 Jul 40

In vitro, we were able to induce a differentiation of human (SK-N-MC, IMR-32, Leo-2) and murine neuroblastoma cells (NA-2, C-1300, NIE-115) with dibutyryl cyclic 3'5'-adenosine monophosphate (dbcAMP), hypothalamic factor (HF), and somatostatin. As morphological criteria of cellular differentiation we used the decrease in cell proliferation and the formation of neurites. Functional parameters were the increase of A cholinesterase activity, cAMP level, and protein content, and the decrease of cGMP level. After application of dbcAMP and HF, the effects were stronger than after somatostatin. We believe that the action of HF and somatostatin is caused by an increase in cAMP levels. In the in vivo experiments, human and murine neuroblastoma cells (NA-2, C-1300, and Leo-2) were transplanted into nude/nude mice. After HF treatment of 14 mice with NA-2 tumors, 4 of the mice were tumor-free, and mean tumor weight was reduced to one-third of the controls. Of the animals with C-1300 and Leo-2 tumors, half became tumor-free, and mean tumor weight was reduced to one-fourth. The results indicate that the induction of cellular differentiation by factors and hormones may in future become a method of therapy for human neuroblastoma.
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PMID:Research on the differentiation of human and murine neuroblastoma cells. 167 82

Site-directed mutagenesis was used to study the cysteine residue involved in the assembly of human acetylcholinesterase (HuAChE) catalytic subunits. Substitution of the cysteine at position 580 by alanine resulted in impairment of interchain disulfide bridge formation; the mutagenized enzyme (C580A) was secreted from recombinant cells in the monomeric form and failed to assemble into dimers. The mutant monomeric HuAChE did not differ from the native oligomeric enzyme neither in rate of catalysis nor in affinity to acetylthiocholine. Mutant monomers were also shown to retain the acetylcholinesterase characteristic sensitivity to high substrate concentrations. The mutation did not seem to affect the efficiencies of either synthesis or secretion of recombinant HuAChE polypeptides, as was demonstrated in cell lines derived from human embryonic kidney (293 cells) as well as from a human neuroblastoma (SK-N-SH). Furthermore, the mutation did not lead to an increase in accumulation of intracellular HuAChE polypeptides, suggesting that export of acetylcholinesterase from cells may not be coupled to subunit assembly.
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PMID:The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. 174 70

The antineoplastic drug 4'-iodo-4'-deoxydoxorubicin (IDX), a new halogenated anthracycline (1), was examined as a differentiation inducing agent on the human neuroblastoma cell lines TS12 and SK-N-MC. IDX induced morphological and biochemical differentiation and growth inhibition. The effect of a combined treatment of IDX with retinoic acid (RA) and with nerve growth factor (NGF) respectively was then investigated. The responses of neuroblastoma cells to IDX alone and to these combined treatments were compared, with respect to neuritic outgrowth, acetylcholinesterase activity and cellular growth. The data obtained indicate that the combination of differentiation-inducing drugs may be able to enhance the effects of the same drugs given alone.
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PMID:Neuronal cell differentiation of human neuroblastoma cells by inducing agents in combination. 176 60

A new human neuroblastoma cell line (LS) that originated from an abdominal tumor of a 16-month-old girl is presented; it was classified, according to Evans, as being stage III. Morphological (dense-core particles) and biochemical characteristics (dopamine-beta-hydroxylase, acetylcholinesterase, neuron-specific-enolase) confirmed the diagnosis. In addition to a slightly variable modal chromosome number of 48 or 49 (because of marker-chromosomes and autosomal trisomies), cytogenetic analysis revealed two constantly appearing chromosomes with homogeneously stained regions (HSR's). The karyotype remained constant over 50 passages in vitro [49,XX, -12, +der5, + 17, + mar1, + mar2]. Double minutes were a rare phenomenon and appeared only in a few metaphases. In situ hybridization showed that some of the HSR's consisted of amplified N-myc copies. The distribution of the N-myc copies according to in situ hybridization signals along the HSR's was compared with the data of Southern and Northern blotting analyses.
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PMID:Cytogenetic and molecular characterization of a newly established neuroblastoma cell line LS. 202 21

The HT4 cell line was derived from infection of a mouse neuroblastoma cell line with a retrovirus that encoded the temperature-sensitive (ts) mutant of SV40 large T antigen. At nonpermissive temperature, HT4 cells differentiated with neuronal morphology, expressed neuronal antigens, synthesized nerve growth factor (NGF) mRNA, and secreted biologically active NGF in vitro. We sought to establish whether transplanted HT4 cells expressed class I major histocompatibility complex (MHC) antigens, a partial requirement for recognition by cytotoxic T lymphocytes (CTL), and thus be susceptible to xenograft rejection. Differentiated HT4 cells expressed marginally detectable levels of class I MHC antigens, but demonstrated higher levels of class I MHC expression after treatment with interferon-gamma. However, HT4 cells were resistant to direct lysis by perforin, the pore-forming protein of CTLs, and thus may have potential use in xenograft experiments. To address whether HT4 cells secrete NGF in vivo, HT4 cells were transplanted into adults rats with unilateral fimbria-fornix transections. A ts cell line derived from P4 cerebellum, BT1, that does not differentiate with neuronal phenotype or synthesize NGF in vitro, was transplanted as a control. Six weeks posttransplant. HT4 cells had integrated into host CNS without forming tumors. In BT1 transplants, the number of medial septal acetylcholinesterase (AChE)-positive cells was reduced to 26-39% of the contralateral control side, depending on the rostrocaudal level. In HT4 transplants, the number of cholinergic septal neurons was 58-78% of the contralateral side. This percentage was significantly (P less than 0.005) greater than that seen with BT1 transplants, indicating that transplanted HT4 cells secrete NGF in vivo and rescue cholinergic septal neurons following fimbria-fornix transection.
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PMID:Transplantation of a temperature-sensitive, nerve growth factor-secreting, neuroblastoma cell line into adult rats with fimbria-fornix lesions rescues cholinergic septal neurons. 203 46

Recent studies suggest that the nature of events leading to the formation, maintenance, and elimination of synapses may be regulated by cascade-type, locally expressed proteases and protease inhibitors acting on adhesive extracellular matrix components. We have identified a molecule in conditioned medium of murine skeletal muscle cells that in molecular weight, target protease inhibition, heparin-binding and cross-reactivity with authenic antisera is similar to the human serine proteinase inhibitor, protease nexin I. Protease nexin I is a 43-50 kDa glycoprotein of the serpin superfamily (arg-serpin class). Purified anti-protease nexin I antibody (anti-47 kDa) stains adult mouse skeletal muscle in discrete foci that precisely superimpose on synaptic neuromuscular junctions. Protease nexin I appears in patches on surfaces of cultured mouse skeletal myotubes, but not on myoblasts. These patches co-localize with acetylcholine receptor clusters and acetylcholinesterase staining during cellular maturation in culture. Evidence that protease nexin I is a synaptic, extracellular antigen is particularly intriguing since it has been shown to be identical, in structure and activity, with a factor released by glial cells, called glia-derived nexin that stimulates mouse neuroblastoma cell neurite outgrowth and inhibits granule cell migration. Protease nexin I inhibits both tumor cell and myoblast plasminogen activator-mediated destruction of extracellular matrix. Thus, such observations as presented in this report provide further evidence for involvement of cascade proteolytic systems, and their post-translational regulation by specific serpins, in the remodeling that occurs in synapse formation and elimination.
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PMID:Plasminogen activators and inhibitors in the neuromuscular system: III. The serpin protease nexin I is synthesized by muscle and localized at neuromuscular synapses. 203 25


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