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

The synthesis of acetylcholine, as well as catecholamines, was studied by assaying the activities of choline acetyltransferase (ChA) and tyrosine hydroxylase (TH) in the tumor tissues and the culture cells of human neuroblastoma. In the majority of 20 neuroblastomas of sympathetic origin, both ChA and TH activities were detected at a significantly high level. In the culture cells of five cell lines of human neuroblastoma, ChA activity was high, but TH was negative in four of the lines. However, it was observed that these enzyme activities changed significantly while in the long-term culture. ChA assay is a useful diagnostic test for neuroblastomas that synthesize acetylcholine. Future studies of neuroblastoma should consider cholinergic activity.
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PMID:Acetylcholine synthesis in sympathetic human neuroblastoma. 1 56

The stability of a clonal mouse neuroblastoma x rat glioma hybrid cell line was examined. Cell volume and cellular content of DNA and protein were measured as functions of the passage number. They decreased with the number of serial subcultivations. Cellular volume was linearly related to cellular DNA and protein. Thus, measurements of cell volume can be used to monitor the loss of DNA from hybrid cells. After about 60 passages a stable population of hybrid cells arose, as judged by the constancy of cellular volume and by the decreased coefficient of variation of the cell volume distribution. A mathematical model for the kinetics of the simultaneous loss of cellular volume, DNA and protein is introduced. Several neuronal properties were investigated. The specific activity of the neurotransmitter enzyme choline acetyltransferase decreased by more than 50% during 56 passages. After 70 subcultivations, the hybrid cells were still capable of extending processes, action potentials could still be elicited electrically or by iontophoretic application of acetylcholine, and the cells still responded to prostaglandin E1 as they do at low passage number.
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PMID:Influence of the time in culture on cellular and neuronal properties of neuroblastoma x glioma hybrid cells. With an appendix, mathematical description of the kinetics of the loss in cell volume. 59 72

The effect of bromoacetylcholine on mouse neuroblastoma C-1300 was investigated in cell culture as well as in A/J mice. In vitro, bromoacetylcholine (1 X 10(-5) M) was a potent cytolytic agent and produced an additive effect in combination with vincristine (3 X 10(-9) M). Since the choline acetyltransferase inhibitor, dimethylaminoethyl chloroacetate, does not inhibit neuroblastoma efficiently in vitro, the potent cytolytic action of bromoacetylcholine is probably not due to its choline acetyltransferase inhibitory action. Furthermore, the neuroblastoma inhibitory effect of bromoacetylcholine was not affected by atropine. Therefore, the inhibitory action is not related to the interaction of bromoacetylcholine with muscarinic receptors either. In in vivo experiments, 1, 10, or 30 mg/kg of bromoacetylcholine was injected directly into the tumors three times daily for 6 weeks. Bromoacetylcholine at 10 and 30 mg/kg gave significant protection of A/J mice from the death induced by neuroblastoma inoculation, and the lifespan was prolonged significantly with these bromoacetylcholine treatments.
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PMID:Cytolysis of neuroblastoma cells in vitro and treatment of neuronal tumors in vivo with bromoacetylcholine. 87 86

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

Two clonal immortalized neurons designated CL8c4.7 and CL8a5.2 were established by somatic cell fusion between a hypoxanthine phosphoribosyltransferase-(HPRT-) deficient neuroblastoma N18TG2 and newborn mouse cerebellar/brain stem neurons. In the serum-containing medium without extra differentiating agents, both clones exhibited a morphology of differentiated neurons. They contained high levels of glutamate but no gamma-aminobutyric acid (GABA). The CL8a5.2 clone synthesized choline acetyltransferase and serotonin. In immunocytochemical studies, both clones expressed 200 kD neurofilament protein, neuron-specific enolase, microtubule-associated protein 2 (MAP2), tau protein, neuronal cell adhesion molecule (N-CAM), HNK-1, Thy-1.2, saxitoxin-binding sodium channel protein, and glutamate. Synaptophysin immunoreactivity was identified in the neuritic terminals of CL8c4.7 cells. Most of these antigens were barely detectable on N18TG2 cells. Electrophysiologically, both clones generated action potentials in response to electrical stimuli. The hybrid clones that express characteristics of differentiated neurons derived from the cerebellar and brain stem regions might be invaluable for the study of the molecular basis of neuronal differentiation and degeneration in these regions.
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PMID:Establishment of mouse-immortalized hybrid clones expressing characteristics of differentiated neurons derived from the cerebellar and brain stem regions. 135 6

The product of the choline acetyltransferase (ChAT) gene is the enzyme that synthesizes the neurotransmitter acetylcholine. A 14.4-kb portion of the human ChAT gene contains 7 exons, which are estimated to comprise approximately one-third of the human protein coding sequence by comparison with porcine ChAT mRNA. Two of the exons were used to identify polyadenylated human ChAT gene transcripts on Northern blots. An exon with 84% identity to the region of porcine ChAT mRNA that codes for the amino terminus of the corresponding protein detected 6,000- and 2,300-nucleotide mRNAs in RNA isolated from human CHP134 neuroblastoma cells. Only the 2,300-nucleotide mRNA was detected by a second probe containing an exon with 96% identity to porcine ChAT mRNA in the domain that encodes amino acids 204-263 of the predicted porcine ChAT protein. Further evidence that two species of human mRNA are produced from the human ChAT gene was obtained from nuclease protection assays using an antisense RNA probe prepared from a human ChAT cDNA clone. Total RNA isolated from either CHP134 cells or adult human nucleus basalis protected 525- and 400-nucleotide fragments of this probe, confirming the presence of two species of RNA that differ by the inclusion of an internal exon. cDNA clones of each of these transcripts have been isolated. Their sequences suggest that the 2,300-nucleotide mRNA encodes enzymatically active human ChAT, while translation of the 6,000-nucleotide mRNA would be terminated prematurely by a shift in the reading frame. These results indicate that a complex pattern of transcription produces two mRNAs with different coding potentials from the human ChAT gene.
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PMID:Two mRNAs are transcribed from the human gene for choline acetyltransferase. 138 31

We have developed a series of mouse-mouse neural hybrid cell lines by fusing the aminopterin-sensitive neuroblastoma N18TG2 with motor neuron-enriched embryonic day 12-14 spinal cord cells. Of 30 neuroblastoma-spinal cord (NSC) hybrids displaying a multipolar neuron-like phenotype, 10 express choline acetyltransferase, and 4 induce twitching in cocultured mouse myotubules. NSC-19, NSC-34, and their subclones express additional properties expected of motor neurons, including generation of action potentials, expression of neurofilament triplet proteins, and acetylcholine synthesis, storage, and release. In addition, NSC-34 cells induce acetylcholine receptor clusters on cocultured myotubes, and undergo a vimentin-neurofilament switch with maturation in culture, similar to that occurring in neuronal development. NSC cell lines appear to model selected aspects of motor neuron development in an immortalized clonal system.
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PMID:Neuroblastoma x spinal cord (NSC) hybrid cell lines resemble developing motor neurons. 146 57

Neuroblastoma x glioma hybrid NG108-15 cells and mouse neuroblastoma N18TG-2 and N1E-115 cells were transiently transfected with the sense cDNA coding for rat choline acetyltransferase (ChAT). All transfected cell lines showed a high level of ChAT activity. ACh secretion was monitored by recording miniature end-plate potentials (MEPPs) in striated muscle cells that had been co-cultured with transfected cells. The number of muscle cells with synaptic responses and the MEPP frequency were higher in co-culture with transfected NG108-15 cells than with control or mock cells. No synaptic response was detected in muscle cells co-cultured with transfected N18TG-2 or N1E-115 cells. The results show that ACh secretion into the synaptic cleft was enhanced due to ChAT overexpression in NG108-15 hybrid cells but not in neuroblastoma cells.
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PMID:Enhanced acetylcholine secretion in neuroblastoma x glioma hybrid NG108-15 cells transfected with rat choline acetyltransferase cDNA. 146 77

Differentiation-promoting effects of interferon-gamma (IFN-gamma), both alone and in combination with retinoic acid (RA), were studied on the human neuroblastoma cell line, LA-N-5. The results show that IFN-gamma inhibited the growth and induced morphological differentiation in a dose- and time-dependent manner with measurable effects appearing at 20-40 IU/ml after 3 to 4 days of treatment in vitro. Acetylcholinesterase activity, used as a biochemical index of neuroblastoma differentiation, increased up to 2.5-fold in the presence of IFN-gamma with a half maximal concentration of approximately 100 IU/ml. Concomitantly, modest IFN-induced increases (less than or equal to 2-fold) in choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) activities were seen. Combination treatment of cells with IFN-gamma and RA resulted in synergistic effects on morphological differentiation, growth inhibition and induction of ChAT. Reversal of IFN-gamma's ability to influence neuroblastoma cell growth as well as potentiate the anti-tumor effects of RA was obtained in the presence of an antibody against the IFN-gamma receptor, implying receptor-mediated physiological events. Taken together, these data confirm the differentiating effects of IFN-gamma on human neuroblastoma cells and suggest that combination therapy with RA may be beneficial in the treatment of this disease.
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PMID:Effects of interferon-gamma and its interaction with retinoic acid on human neuroblastoma differentiation. 167 49


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