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

We have been investigating the use of three culture types for both screening and mechanistic neurotoxicology in vitro. These are the neuroblastoma cell lines (IMR32 - human; C-1300 - mouse), primary mixed monolayer cultures of the rat and chick embryonic midbrain ('micromass' systems) and organotypic whole rat brain reaggregate cultures. The performance of these models for neurotoxicity resting has been investigated with ethylcholine mustard aziridinium (ECMA), vincristine, aluminium, glutamate receptor antagonists, MPTP, and 'hypothyroidism'. From a 'screening' viewpoint, in vitro exposure through a tiered testing system (ranging from simple cytotoxicological parameters in the neural cell lines to neurotransmitter measurements in the organotypic cultures) may permit detection of CNS neurotoxicity and delineation of possible mechanisms. The type of developmental neurotoxicological information gained is highlighted in the cases of aluminum and the glutamate receptor antagonists. High concentrations of aluminum caused significant neural cell death in differentiated neuroblastoma cell lines after approximately two weeks exposure in vitro. In contrast, cell death was detected in the developing midbrain cultures as early as 24 - 48 hr. Studies in whole brain reaggregates suggest that cholinotoxicity may occur in a similar time-frame and is consistent with some of aluminium's effects in vivo. Preliminary experiments have shown that exposure of immature developing midbrain rat primary cultured neurones to the glutamate receptor antagonists, AP3 and MK-801 induces neural cell death which may relate to control of NGF by glutamate cells. Developing neural culture systems may prove useful for testing agents which cause neurotoxicity through disturbances of neurotrophic function.
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PMID:Models for the in vitro assessment of neurotoxicity in the nervous system in relation to xenobiotic and neurotrophic factor-mediated events. 150 34

The authors have investigated the relationship between oncogene (N-myc and c-src) expression and major histocompatibility complex (H-2 in the mouse) antigen gene expression at the molecular levels, by using mouse neuroblastoma sublines (NB-1 and NB-V). Fluorescence-activated cell sorter analysis showed that NB-1 cells exhibited positive expression to H-2 Kk, H-2 Dd, and beta-2-microglobulin, while NB-V cells were negative to all three antigens. It was found that dimethyl sulfoxide (DMSO) had a capacity to increase an H-2 class I antigen expression on NB-1 cells, whereas no change was observed on NB-V cells after DMSO treatment. Molecular analysis with deoxyribonucleic and ribonucleic acid (RNA) blot hybridization and immunoprecipitation revealed that the enhancement of H-2 antigen expression on NB-1 cells was modulated at the transcriptional control of the H-2 gene. In contrast, negative H-2 antigen expression on NB-V cells was caused by block at the level of glycosylation of the H-2 heavy chain, although an increase in messenger RNA of the H-2 gene was induced after DMSO treatment. There was neither amplification nor rearrangement of N-myc and c-src oncogenes in either neuroblastoma subline. Nuclear run-on transcription assay revealed that the N-myc gene was post-transcriptionally down-modulated by DMSO, whereas the c-src gene was transcriptionally up-regulated. It was thus suspected that N-myc and c-src might be directly associated with cellular proliferation and differentiation in neuronal tumors and that in vivo tumorigenicity could be regulated by the control mechanism of oncogene expression in relation to H-2 gene expression on tumor cells.
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PMID:[Molecular analysis of relationship between oncogene (N-myc and c-src) expression and major histocompatibility complex antigen gene expression in mouse neuroblastoma lines]. 170 53

Human neuroblastomas show a high incidence of deletions in the distal region of the short arm of chromosome 1. In pursuit of a molecular analysis of these deletions, we have generated a microclone bank from microdissected 1p35-pter chromosomal fragments. To allow a rapid localization of the microclones, we have also generated a panel of (human x mouse) hybrid cell lines through microcell-mediated chromosome transfer. The hybrid cells contained different portions of the human chromosome 1 on a murine background. A total of 20 randomly chosen single or low-copy microclones were localized by Southern analysis on DNA of the hybrid panel: All probes were derived from chromosome I. Sixteen mapped in region 1p36.1-pter, two in 1p22-p36.1, and another two in 1cen-qter. The mapping of ten of these microclones was further refined by in situ hybridization. Cells of the neuroblastoma line GI-ME-N carry two types of chromosome 1, one cytogenetically normal and another with a translocation reported to be in 1p36.2, i.e., a t(1;?) (p36.2;?) marker. Using cell hybridization, we separated the two chromosome 1 types of GI-ME-N into different hybrid cell clones. Southern hybridization of three microclones from distal Ip to DNA of the hybrid cell clones revealed that the breakpoint in the translocated chromosome I was located in 1p36.1.
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PMID:Chromosome 1 deletions in human neuroblastomas: generation and fine mapping of microclones from the distal 1p region. 253 35

Ciliary neurotrophic factor (CNTF) is a protein supporting the in vitro survival of a characteristic spectrum of embryonic chicken and rat peripheral neurons. High-speed supernatants of extracts from two neuroblastoma (NB) cell lines--the mouse C 1300 N2a and the human IMR 32--mimic the effects of CNTF on identical target neurons. Promotion of survival is dose-dependent with an ED50 of 80 micrograms (IMR 32) and 140 micrograms (C 1300 N2a) of protein per ml and saturable at plateau values for surviving neurons identical to those achieved with purified CNTF. Small amounts of a CNTF-like material are also detectable in medium conditioned by NB cells. The activity is destroyed by heat and trypsin and not blocked by antibodies to (mouse) nerve growth factor. Unlike the neurite-promoting and neuronal-survival modulating agent laminin, it cannot be depleted on poly(L-alpha-ornithine)-coated plastic surfaces. NB IMR 32 cell extracts were electrophoresed using NaDodSO4/PAGE and transferred to nitrocellulose. Ciliary ganglion neurons seeded on the blotting paper in culture medium lacking CNTF ("cell blot") exclusively survive on two distinct bands with apparent molecular masses of 24 and 48 kDa. Twenty-four kilodaltons is the molecular mass of a CNTF purified from rat sciatic nerve. These results suggest that NB cells may contain a CNTF-like protein and provide further evidence that neurons may store neurotrophic factors. Purified (chicken) CNTF failed to affect proliferation and neurite growth of NB cells. The biological relevance of CNTF for NB cells, therefore, remains to be elucidated.
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PMID:Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor. 347 25

Neuroblastoma Cell line NG108 (a hybrid from Chinese hamster and mouse) produces high levels of enolase. Using ion-exchange chromatography and gel filtration, we have purified the enzyme (about 19 fold purification) and characterized it. The purified enzyme is a dimer of 90,000 m.wt. and is stable at room temperature. At higher temperatures (e.g., 50 degrees, 60 degrees C etc.) it gets inactivated. Enolase requires Mg++ for its activity and is resistant to urea. The optimum pH for the enzyme is 7, and Km values for Mg++ and 2-phosphoglycerate were found to be 3.1 and 1.1 mM, respectively. Fluorophosphate is a strong inhibitor of the enzyme. The clinical applications of the enzyme have been discussed.
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PMID:Purification and characterization of enolase from neuroblastoma cell line NG108. 380 Oct 33

A potent interferon (IFN) inducer, 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP), induced hyporeactivity in mice, and so IFN induced by subsequently administered ABPP was reduced even 120 hr after the first administration of ABPP. This hyporeactivity was counteracted by the injection of IFN (10,000 IU or more) 3 hr before the subsequent administrations of ABPP. Since the injection of more than 5,000 IU/mouse of IFN 3 hr before an administration of ABPP enhanced the circulating IFN titer, the priming effect in vivo by IFN may result in the reduction of hyporeactivity. Administrations of ABPP (200 mg/kg or 500 mg/kg) at intervals of 2 days and the injection of IFN (25,000 IU/mouse) 3 hr before each administration of ABPP to neuroblastoma-bearing A/J mice reduced the mortality and completely cured 40% of the mice in each combined therapy group. These results suggest that the combined use of the IFN inducer with IFN may be available for patients with neoplasm or viral infection.
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PMID:Interferon counteracts pyrimidinone-induced hyporeactivity and the combined treatment has antitumor effect in mice. 620 30

The in vitro sensitivities to differentiating agents of a murine neuroblastoma cell line (N18) and a selected variant cell line (N18-LM5) were examined. In addition, the sensitivities to differentiating agents of cells from spontaneous metastases produced by N18 cells were examined. When N18 cells (1 X 10(5) cells/mouse) were injected into the lateral tail vein of syngeneic A/J mice, only a few metastatic nodules formed in the liver and lung, while similar injection of N18-LM5 cells produced larger numbers of metastatic nodules. Exposure of N18 cells to differentiating agents, such as dibutyryl cyclic 3':5'-AMP (db-cAMP), prostaglandin E1, and dexamethasone, resulted in induction of differentiation in terms of neurite extension. N18-LM5 cells responded to differentiating agents to a greater extent than N18 cells, and most of the cells extended neurites when they were exposed to 1 mM db-cAMP for 3 days. On the other hand, not all cell lines from spontaneous metastases produced by N18 cells responded to db-cAMP. These results suggest that the colonizing potential of neuroblastoma cells is not necessarily correlated with loss of responsiveness to differentiating agents and that various spontaneous metastases show heterogeneity in responsiveness to differentiating agents.
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PMID:Differences in inducibility of morphological differentiation of parental cells, selected variant cells and cells from spontaneous metastases of mouse neuroblastoma cells. 630 60

The role of N-myc, c-src, and major histocompatibility complex (MHC, H-2 in the mouse) class I antigen gene expressions in dimethyl sulfoxide (DMSO)-induced differentiation and intracerebral tumorigenicity was examined using a mouse MNB85 neuroblastoma cell line. A fluorescence-activated cell sorter disclosed cell-surface MHC enhancement by DMSO, causing an increase in cytotoxic T-lymphocyte sensitivity. Southern blot analysis verified a single copy of the proto-oncogenes and MHC deoxyribonucleic acids in both untreated and DMSO-treated MNB85 cells. Northern blot analysis indicated that DMSO treatment induced a decrease in N-myc and an increase in c-src and MHC messenger ribonucleic acids. Nuclear run-off transcription assay revealed down-regulation of N-myc at a posttranscriptional level, contrasted with primary up-regulation of c-src at a transcriptional level. Immunoprecipitation after treatment with enzyme endo-beta-N-acetyl-glycoseamidase H proved that the terminal glycosylation of MHC heavy-chain gene products normally occurs in the Golgi apparatus of MNB85 cells. Intracerebral tumorigenicity assay showed that cells highly MHC-expressed by DMSO were less tumorigenic than untreated cells in association with DMSO-augmented cytotoxic T-lymphocyte susceptibility. These results suggest that proto-oncogenes may be linked to cellular differentiation, while cell-surface MHC gene expression influences intracerebral immunosurveillance.
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PMID:Role of histocompatibility antigen gene and protooncogene expressions in intracerebral tumorigenicity of mouse neuroblastoma. 845 Mar 36

Neem seed preparations contain not only azadirachtin as the active insect antifeedant or growth regulator but also a variety of their limonoids, some of which are cytotoxic to N1E-115 neuroblastoma (mouse), 143B.TK- osteosarcoma (human) and Sf9 (insect) cultured cell lines. The most potent of these limonoids is nimbolide with an IC50 ranging from 4 to 10 microM, and averaging 6 microM for the three cell lines. Other limonoids of decreasing potency and their average IC50 values (microM) are epoxyazadiradione 27 microM, salannin 112 microM, and nimbin, deacetylnimbin and azadirachtin each >200 microM (practically nontoxic). Nimbolide at 10 microM acts rapidly in the neuroblastoma cells to induce blebbing associated with disruption of plasma membranes almost instantaneously and 50% loss of cell viability with 30 min. At 5 microM nimbolide, the cells become elongated and assume a neuronal shape accompanied by spikes and lamellipodia within 1-2 hr followed shortly thereafter by extensive cytological changes and and vacuolization associated with irreversible processess leading to cell death. Calcium is apparently not involved the cytotoxic effect since a calcium-free medium, leading to profound morpholigical changes, does not alter the sensitivity to nimbolide. In contrast, epoxyazadiradione requires higher concentrations and a few hr for 50 % viability loss without major morphological changes, indicating a difference in mode of action for nimbolide and epoxyazadiradione. and epoxyazadiradione.
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PMID:Cytotoxicity of nimbolide, epoxyazadiradione and other limonoids from neem insecticide. 862 60

As a new treatment protocol for neuroblastoma, the chimeric (human/mouse) antiganglioside GD2 antibody chl4.18 is being clinically tested. To improve the therapeutic effect of the antibody alone, we are currently investigating the cytotoxicity of glucose-oxidase coupled to the antibody chl4.18 on spheroids of the neuroblastoma cell line SK-N-LO. The cytotoxic effect of glucose-oxidase is achieved by the production of hydrogenperoxide (H2O2) and probably by the following reaction of H2O2 with iron to form hydrogen radicals (OH.). The cytotoxicity of glucose-oxidase was measured by two viability tests (MTT and WST 1). After a 4 hour treatment of the spheroids with the immunoconjugate, a reduction of viability to 50% (MTT-test) and 25% (WST 1-test), respectively, was obtained. The difference between the results of these two tests, might be explained by the different measurement protocols.
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PMID:Cytotoxic effect of immunoconjugate composed of glucose-oxidase coupled to an anti-ganglioside (GD2) antibody on spheroids. 932 30


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