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)

Two unique cisplatin-resistant neuroblastoma (NB) cell lines have been derived from the established lines IMR-32 and SK-N-SH by treatment with escalating doses of cisplatin. IMR/CP.20 was 6.6-fold and SK/CP.15 was 3.8-fold more resistant to the cytotoxic effects of cisplatin than the parent lines. The parent SK-N-SH cells were 16.6-fold more resistant to the effects of cisplatin than IMR-32 cells. The cisplatin-resistant cell lines demonstrated alterations to their morphology, but there was no change in the cell growth characteristics of the resistant compared to the sensitive lines. Cytogenetic analysis revealed that clonal selection of parental subclones had occurred with additional chromosomal changes in both resistant lines. Both IMR/CP.20 and SK/CP.15 lines were cross-resistant to aphidicolin and to L-phenylalanine mustard. The IMR/CP.20 line was 7.3-fold more resistant to mitomycin C than the parent line. Neither cisplatin-resistant NB line was cross-resistant to 5-fluorouracil, etoposide or doxorubicin. All NB lines had low levels of DNA repair compared to HeLa or CHO-K1 cells. However, the IMR/CP.20 cell line showed a significantly higher ability to effect DNA repair than the parent IMR-32 line, indicating that the increased resistance to cisplatin observed in this line may, in part, be due to an enhanced DNA repair capacity.
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PMID:Establishment of an in vitro model for cisplatin resistance in human neuroblastoma cell lines. 787 59

Mu and delta opiate receptor regulation by opiate agonists and antagonists was studied in the human neuroblastoma cell line SH-SY5Y. Morphine down-regulated both mu and delta receptors, but its effects on each subtype could be dissociated by use of specific antagonists. The selective mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Pen-Thr-NH2 (CTAP) blocked the down-regulation of mu, but not delta receptors. Conversely, the delta antagonist (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH([N,N-diallyl-Tyr1, Aib2,3]Leu- enkephalin)] ICI 174,864 blocked morphine-induced down-regulation of delta but not mu receptors. These selective antagonists also were studied alone for their effects on both receptors. CTAP alone at doses of 0.1 microM and higher up-regulated mu receptors. CTAP did not affect delta receptors at 0.3 microM or less, but it down-regulated them at doses of 1 microM or more, apparently due to its delta agonist activity at higher doses, which was reversed by ICI 174,864. ICI 174,864 alone also showed complex effects on the two subtypes, up-regulating both mu and delta sites. Its effects were most selective at a low dose (0.1 microM), which upregulated delta sites with minimal effects on mu sites. The nonselective antagonist naloxone provided a more robust upregulation (> 40%) of both mu and delta receptors than either selective antagonist alone or in combination. The mu-to-delta ratio (1.4 to 1) was not altered by differentiation of the cells with retinoic acid, which up-regulated both mu and delta receptors. Differentiation with the phorbol agent 12-O-tetradecanoyl-phorbol-13-acetate, however, up-regulated mu, but not delta receptors. The selective mu agonist Tyr-Pro-MePhe-D-Pro-NH2 (PL017) down-regulated mu receptors with a half-maximal effect at 180 nM, but was without effect on delta receptors at concentrations up to 10 microM. Conversely, the selective delta agonist Tyr-D-Pen-Gly-Phe-D-Pen([D-Pen2,5]-enkephalin) (DPDPE) potently down-regulated delta receptors, producing half-maximal decreases at 0.5 nM. At doses above those that reduced the maximum binding of [3H]pCl-DPDPE binding to the delta site, DPDPE also induced an apparent loss of affinity (increased Kd) at the delta site. It was without effect on mu receptors, however, at doses up to 10 microM. Thus, down-regulation of mu and delta receptors was homologous, because selective agonists down-regulated their respective receptors without effect on the heterologous opiate receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential regulation of mu and delta opiate receptors by morphine, selective agonists and antagonists and differentiating agents in SH-SY5Y human neuroblastoma cells. 793 56

The human neuroblastoma cell line SH-SY5Y was used to demonstrate morphine-induced down-regulation and naloxone-induced up-regulation of opiate receptors in a mu receptor containing neuronally derived preparation capable of desensitization to morphine. Chronic exposure to morphine decreased the number but not the affinity of mu opiate receptors in SH-SY5Y cells. Differentiation of the cells with retinoic acid or with the phorbol agent TPA (12-O-tetradecanoyl-phorbol-13-acetate) increased the number of mu receptors. Morphine-induced down-regulation, however, was observed in the absence of differentiation as well as after differentiation with retinoic acid or TPA. The decrease in the number of receptors was related to time of exposure, with a half-maximum disappearance time (T1/2) of about 3 hr during the initial phase. The receptor decrease was near maximum at 24 hr with no further significant change up to 72 hr. The loss of [3H] DAMGO ([3H]Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol) binding was also dose-dependent, with reductions occurring at 0.3, 1 and 10 microM. The loss of receptors was dependent on temperature, with reductions at 37 but not 23 degrees C. The down-regulation was blocked by naloxone and the mu-selective antagonist CTOP (D-Phe-Cys-Tyr-D(-Trp-)Orn-Thr-Pen-Thr-NH2), but not by the delta antagonist ICI 174864 ([N,N-diallyl-Tyr1,Aib2,3]Leu-enkephalin). Cholinergic ([3H]quinclidinyl benzilate) binding was not affected by the morphine treatment, indicating that the down-regulation was homologous for opiate receptors. In SH-SY5Y cells, unlike other cell models, the opiate antagonist naloxone upregulated mu receptors by more than 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mu opiate receptor down-regulation by morphine and up-regulation by naloxone in SH-SY5Y human neuroblastoma cells. 809 44

In membranes from SH-SY5Y human neuroblastoma cells differentiated with retinoic acid, the mu-selective agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) inhibited cAMP formation with an IC50 of 26 nM. Two separate antibodies raised against distinct regions of the Go alpha sequence attenuated the effect of DAMGO by 50-60%, whereas antibodies to Gi alpha 1,2 or Gi alpha 3 reduced the mu-opioid signal insignificantly or to a lesser extent. In contrast, inhibition of adenylyl cyclase by the delta-opioid agonist Tyr-D-Pen-Gly-Phe-D-Pen-OH (DPDPE; Pen = penicillamine) was very sensitive to the Gi alpha 1,2 antibody. In membranes from rat brain striatum, coupling of the mu opioid receptor to adenylyl cyclase was also maximally blocked by antibodies to Go alpha. After long-term treatment of the cells with DAMGO, the content of Go alpha was reduced by 26%, whereas the levels of Gi alpha 1,2, Gi alpha 3, and Gs alpha were unaltered. Addition of Go, purified from bovine brain, to membranes from pertussis toxin-treated SH-SY5Y cells restored the inhibition of adenylyl cyclase by DAMGO to 70% of that in toxin-untreated cells. To comparably restore the effect of DPDPE, much higher concentrations of Go were required. By demonstrating mediation of cAMP-dependent signal transduction by Go, these results describe (i) an additional role for this G protein present at a high concentration in brain, (ii) preferential, although not exclusive, interaction of mu and delta opioid receptors with different G protein subtypes in coupling to adenylyl cyclase, and (iii) reduced levels of Go following chronic opioid treatment of SH-SY5Y cells with mu opioids.
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PMID:Go mediates the coupling of the mu opioid receptor to adenylyl cyclase in cloned neural cells and brain. 809 84

Gestational exposure to ethanol causes defects in neuronal migration, fasciculation, and synaptogenesis, developmental events that depend on the patterned expression and function of cell adhesion molecules (CAMs). Recombinant human osteogenic protein-1 (hOP-1) increases cell-cell adhesion and promotes cell clustering in proliferating neuroblastoma x glioma hybrid NG108-15 cells by strongly inducing N-CAM and L1. Here we show that concentrations of ethanol achieved during social drinking inhibit hOP-1-induced cell clustering without affecting cell proliferation, the induction and cell surface expression of N-CAM and L1, or the alternative splicing and sialylation of N-CAM. This inhibition was reproduced by other alcohols in proportion to their chain length, but not by teratogenic anticonvulsants or phenylalanine. Ethanol inhibition of hOP-1 morphogenesis was inversely proportional to the concentration of hOP-1 and, hence, to the levels of N-CAM and L1. Low concentrations of ethanol (IC50 5-10 mM) inhibited cell-cell adhesion in hOP-1-treated cells, and this action too was reproduced more potently by propanol and butanol. Ethanol may perturb brain and skeletal development by inhibiting CAM-mediated cell-cell interactions.
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PMID:Ethanol inhibits neural cell-cell adhesion. 813 68

To study the putative binding sites of the neurotrophic peptide Org 2766, an analogue of ACTH(4-9) [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH], biotinylated forms of the peptide were used. After fixation, cultures of rat spinal cord and dorsal root ganglia were incubated with 4-10 microM of biotinyl-Org 2766 (b-Org 2766). Binding of both N- and C-terminally biotinylated Org 2766 was seen to phase-bright, round cells with thin processes, but not to flat, orthogonal-shaped cells with tapering processes. The b-Org 2766 binding was displaceable by an excess of nonbiotinylated Org 2766. Light and electron microscopy showed that the biotinylated peptide binds to a cytoplasmatic component as well as to the cell membrane. Double-labeling experiments with b-Org 2766 and an antibody (RT-97) to a high molecular weight neurofilament protein in dorsal root ganglion cultures showed, using fluorescence and confocal scanning laser microscopy, that all b-Org 2766 binding cells were neurofilament positive. Biotinylated Org 2766 did also bind to the neuronally differentiated cells in cultures of the human neuroblastoma cell line SK-N-SH, but not to those differentiated into epithelial cells. The present data suggest that the neurotrophic peptide Org 2766 binds specifically to cell types with neuronal characteristics.
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PMID:Binding of a biotinylated neurotrophic ACTH(4-9) analogue, Org 2766, to neurofilament-positive cells in primary or cell line cultures. 813 2

A 58 kDa protein which was phosphorylated on tyrosine residues with morphine was found in human neuroblastoma cells (SK-N-SH cells) by immunoblot with monoclonal anti-phosphotyrosine antibody. The tyrosine phosphorylation was induced by morphine in 5 min in a dose-dependent manner and the increment was completely inhibited by naloxone. A Delta (d) agonist, [D-Pen2,Pen5]-enkephalin (DPDPE), but not a m agonist, [D-Ala2,N-Me-Phe,Gly5-ol]-enkephalin (DAGO), stimulated the phosphorylation and treatment of the cells with pertussis toxin inhibited the phosphorylation by morphine. These data suggest that d receptor-stimulation increases tyrosine phosphorylation of the 58 kDa protein through Gi protein in SK-N-SH cells.
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PMID:Tyrosine phosphorylation of a 58 kDa protein induced by morphine in SK-N-SH cells. 817 14

We have investigated the frequency of p53 gene mutations in Ewing's sarcoma (ES) and neuroblastoma (NB) by using polymerase chain reaction-single strand conformation polymorphism analysis for genomic DNA or complementary DNA generated from total RNA. Mutations of the p53 gene were found in six of seven ES cell lines: a missense mutation of TGC (Cys)-->TAC (Try) at codon 141 in one, a missense mutation of CGT (Arg)-->TGT (Cys) at codon 273 in one, a missense mutation of TGC (Cys)-->TTC (Phe) at codon 176 in three, and one base deletion of CGC-->CG at codon 283 in one. Further analysis of 14 ES and related primary tumors showed mutations of the p53 gene in only two: one base insertion of CCG-->CCCG at codon 152 in one and a missense mutation of GGC (Gly)-->GTC (Val) at codon 154 in the other. Both of the two tumors were obtained from patients with an advanced stage disease. Three of the eight ESs with mutations of the p53 gene showed the same missense mutation at codon 176, suggesting the mutational hot spot of the p53 gene in ESs. In contrast to ES, none of 6 NB cell lines or 48 NB tumors including advanced-stage ones with or without N-myc amplification showed any aberration of the p53 gene. Our findings suggest that mutations of the p53 gene in ES might represent late genetic events related to tumor progression, and that aberrations of the p53 gene might not be involved in the development or the progression of NB.
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PMID:Mutations of the p53 gene are involved in Ewing's sarcomas but not in neuroblastomas. 822 63

In differentiated SH-SY5Y human neuroblastoma cells, various opioids exhibited a wide range of potencies (Ki) in acutely inhibiting adenylate cyclase to different extents (Imax). After exposure of the cells to opioids for 24 hr, the initially reduced cAMP content of the cells recovered toward pre-exposure levels. Withdrawal of agonist from, or addition of antagonist to, the tolerant cells rapidly increased the cAMP content to 1.5 times the basal value. Long term treatment of the cells with agonists of high acute potency, such as Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and levorphanol, decreased the Bmax of the antagonist [3H]naltrexone by 80-95%, increased the Ks for GTPase stimulation 10-14-fold, and increased the Ki for adenylate cyclase inhibition 2-3-fold. On the other hand, these parameters were only marginally affected by agonists of lower acute potency, such as profadol and morphiceptin, regardless of their Imax in inhibiting adenylate cyclase. The reduction in the level of receptor binding was experimentally not dissociable from effector desensitization. Tyr-D-Ala-Gly-(Me)Phe-Gly-ol retained the characteristics of a potent agonist in inducing tolerance even under conditions of submaximal signal, produced by lower concentrations of the peptide or by pretreatment with pertussis toxin. Alkylation of receptors by beta-chlornaltrexamine, although it reduced [3H]naltrexone binding by 50%, did not significantly alter the rank order of opioid agonists based on their ability to acutely inhibit adenylate cyclase. These results show that in opioid-tolerant SH-SY5Y cells the concurrently occurring down-regulation of receptor and shifts in the concentration dependence of effector response correlate with the potency of a given opioid in producing its acute effect but not with the maximum extent of that effect.
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PMID:Receptor mechanisms of opioid tolerance in SH-SY5Y human neural cells. 838 4

Monoclonal antibodies (TB1 & TB2), which were obtained by immunization of 24 amino acids in BALB/c mice, bound specifically to the amyloid senile plaque and amyloid-angiopathic lesions of brain tissues of patients with Alzheimer's disease (AD) or with senile dementia of Alzheimer type (SDAT), and strongly reacted with the 1st part (Asp-Ala-Glu-Phe-Arg-His-Asp) of beta-protein. Western blotting and two-dimensional immunoelectrophoresis of cerebrospinal fluid (CSF) and serum revealed bands of 125 and 20 kilodaltons. The positive frequency of 125 and 20 KD bands detected by two-dimensional immunoelectrophoresis was higher in the serum of AD and SDAT patients (12 cases) than in that of normal control patients. ELISA employing various anti-amyloid precursor protein (APP) antibodies was performed using the extract of the human neuroblastoma cell line (NB39) which produces APP. In the near future, we hope to measure APP in CSF and sera from patients with Alzheimer's disease.
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PMID:[Immunological study on Alzheimer's disease using anti-beta-protein monoclonal antibodies]. 847 24


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