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)

Normal mouse sera contain naturally occurring antibodies that are cytotoxic in the presence of rabbit complement for NB1, a cell line derived from a neuroblastoma adrenal metastasis of a spontaneous ovarian teratoma. The anti-NB1 antibodies can be specifically removed from normal mouse sera by absorption of the sera with homogenized brain tissue of mouse, rat, guinea pig, chicken, and man and by homogenized kidney tissue of mouse and man. The antigen recognized by anti-NB1 naturally occurring autoantibodies, designated mouse brain antigen-2 (MBA-2), is not present on other normal tissues or tumor cell lines tested. MBA-2 is distinct from previously described mouse brain antigens.
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PMID:Interspecies brain antigen detected by naturally occurring mouse anti-brain autoantibody. 4 48

Monoclonal antibodies (designated IIIG5, VIID1, VIIIC8, and XIF1) have been produced that bind to the human nerve growth factor receptor (NGF-R) as well as to a soluble, truncated form of the receptor (NGF-Rt). The antibodies were generated against partially purified NGF-Rt from the conditioned medium of E9b cells, a transfected mouse fibroblast cell line (Ltk-) that expresses large numbers of the low affinity form of the human NGF-R on its cell surface (Chao MV, Bothwell MA, Ross AH, Koprowski H, Lanahan AA, Buck CR, Sehgal A [1986]: Science 232:518-521). Hybridomas were screened by radiometric immunosorbent assay (RISA) and by immunoprecipitation of solubilized cell surface receptor covalently cross-linked to [125-I]-NGF. Four positive lines were cloned by limiting dilution and were found to secrete monoclonal antibodies of the IgGl,k subclass. All monoclonal antibodies bound to both NGF-R and NGF-Rt. Two monoclonal antibodies (VIID1, XIF1) immunoblotted the NGF-R from E9b cell preparations resolved on non-reducing sodium dodecyl sulfate (SDS)-polyacrylamide gels. The antibodies immunoprecipitated NGF-R from both E9b cells and from SH-SY5Y human neuroblastoma cells. The monoclonal antibodies bound to monkey (rhesis and cynomolgus) NGF-Rt, but did not cross-react with NGF-R from chick or rat. Results of antibody competition studies demonstrated that three antibodies bound to a similar or overlapping epitope on the NGF-Rt and one monoclonal antibody (IIIG5) recognized a distinct receptor epitope. Antibodies that bound to different sites on the receptor were used to develop a sensitive 2-site RISA. The 2-site RISA can be used to rapidly quantitate NGF-R and NGF-Rt in large numbers of biological samples in the absence of added [125-I]-labeled NGF.
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PMID:Monoclonal antibodies to the cell surface and a soluble form of the human nerve growth factor receptor. 170 84

Subclones of F11 neuronal hybrid cells (neuroblastoma x dorsal root ganglion neurons) have segregated differing and/or overlapping neuritogenic mechanisms on three substrata--plasma fibronectin (pFN) with its multiple receptor activities, cholera toxin B subunit (CTB) for binding to ganglioside GM1, and platelet factor-4 (PF4) for binding to heparan sulfate proteoglycans. In this study, specific cell surface receptor activities for the three substrata were tested for their modulation during neuritogenesis by several experimental paradigms, using F11 subclones representative of three differentiation classes (neuritogenic on pFN only, on CTB only, or on all three substrata). When cycloheximide was included in the medium to inhibit protein synthesis during the active period, neurite formation increased significantly for all subclones on all three substrata, virtually eliminating substratum selectivity for differentiation mediated by cell surface integrin, ganglioside GM1, or heparan sulfate proteoglycans. Therefore, one or more labile proteins (referred to as disintegrins) must modulate functions of matrix receptors (e.g., integrins) mediating neurite formation. To verify whether cycloheximide-induced neuritogenesis was also regulated by integrin interaction with cell surface GM1, two approaches were used. When (Arg-Gly-Asp-Ser)-containing peptide A was added to the medium, it completely inhibited cycloheximide-induced neuritogenesis on all three substrata of all subclones, indicating stringent requirement for cell surface integrin function in these mechanisms. In contrast, when CTB or a monoclonal anti-GM1 antibody was also added to the medium, cycloheximide-induced neuritogenesis was amplified further on pFN and sensitivity to peptide A inhibition was abolished. Therefore, in some contexts ganglioside GM1 must complex with integrin receptors at the cell surface to modulate their function. These results also indicate that (a) cycloheximide treatment leads to loss of substratum selectivity in neuritogenesis, (b) this negative regulation of neurite outgrowth is affected by integrin receptor association with labile regulatory proteins (disintegrins) as well as with GM1, and (c) complexing of GM1 by multivalent GM1-binding proteins shifts neuritogenesis from an RGDS-dependent integrin mechanism to an RGDS-independent receptor mechanism.
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PMID:Neurite outgrowth in dorsal root neuronal hybrid clones modulated by ganglioside GM1 and disintegrins. 182 96

We have studied the cellular pharmacokinetics of carboplatin (CBDCA), as part of the evaluation of the antitumor activity of CBDCA in cancers limited to the peritoneal cavity in comparison with cisplatin (cDDP). The uptake of CBDCA into L1210 (lymphosarcoma), CC531 (colonic carcinoma), COV413.B (human ovarian carcinoma) and NB1 (human neuroblastoma) cells was 1.5 to 13 times lower than the uptake of cDDP. The uptake of CBDCA into human ovarian carcinoma cells, taken directly from patients, was also 8-20 times lower than cDDP. Platinum concentrations, expressed as a percentage of the total intracellular Pt concentration, were similar for CBDCA and cDDP in cytosol and nucleus/membrane fractions. A second major difference between the drugs was their binding to DNA. Less CBDCA-DNA than cDDP-DNA adducts were formed after incubation at equimolar amounts of drug with isolated salmon sperm DNA (5-25 times less). A 16-69 times higher concentration of CBDCA than cDDP was needed to induce similar changes in cell growth activity (50% [3H]thymidine inhibition) in CC531 and COV413.B cells, indicating that equitoxicity can only be achieved when tumor cells are exposed to higher concentrations of CBDCA than cDDP. Similar toxicity was achieved in CC531 cells after incubation with a 16-fold higher CBDCA dose than cDDP. Comparable intracellular platinum concentrations, however, were obtained with a 10-fold higher CBDCA dose, suggesting that cellular pharmacokinetics of the drugs are different. Regarding drug uptake and pharmacokinetics the mechanism of action of CBDCA differed from cDDP at a cellular level.
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PMID:Cellular pharmacokinetics of carboplatin and cisplatin in relation to their cytotoxic action. 185 50

Sodium nitroprusside (SNP) stimulates cGMP formation to a greater extent in 20,000 g supernatant fractions of the human neuroblastoma clones NB1-G and SH-SY5Y than in the human astrocytoma clone D384. This suggests that these cell lines contain the soluble form of guanylate cyclase. Arachidonic, 8,11,14- and 11,14,17-eicosatrienoic acids inhibit SNP (10(-4) M)-stimulated cGMP formation more potently than the C18 unsaturated fatty acids linolenic and linoleic acids in D384 and NB1-G. In contrast the C20 saturated fatty acid, arachidic acid had little effect even at 10(-4) M concentration. In addition arachidonic and 8,11,14-eicosatrienoic acids inhibited basal guanylate cyclase activity, in NB1-G, over the same concentration range as they inhibited SNP-stimulated cGMP formation. No evidence could be obtained for the stimulation of guanylate cyclase by arachidonic acid in either NB1-G or D384. These results provide further support for suggestions that arachidonic acid or its metabolites may be important regulators of cGMP formation in the nervous system.
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PMID:The effect of unsaturated fatty acids on sodium nitroprusside stimulation of guanylate cyclase in the human astrocytoma clone, D384, and the human neuroblastoma clone, NB1-G. 196 40

This study aims to select the radiopharmaceutical vehicle for targeted radiotherapy of neuroblastoma which is most likely to penetrate readily the centre of micrometastases in vivo. The human neuroblastoma cell line NB1-G, grown as multicellular spheroids, provided an in vitro model for micrometastases. The radiopharmaceuticals studied were the catecholamine analogue metaiodobenzyl guanidine (mIBG), a specific neuroectodermal monoclonal antibody (UJ13A) and beta nerve growth factor (beta NGF). Following incubation of each drug with neuroblastoma spheroids, autoradiographs of frozen sections were prepared to demonstrate their relative distributions. mIBG and beta NGF were found to penetrate the centre of spheroids readily although the concentration of mIBG greatly exceeded that of beta NGF. In contrast, UJ13A was only bound peripherally. We conclude that mIBG is the best available vehicle for targeted radiotherapy of neuroblastoma cells with active uptake mechanisms for catecholamines. It is suggested that radionuclides with a shorter range of emissions than 131I may be conjugated to benzyl guanidine to constitute more effective targeting agents with potentially less toxicity to adjacent normal tissues.
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PMID:The distribution of alternative agents for targeted radiotherapy within human neuroblastoma spheroids. 200 81

Preincubation with receptor agonists or phorbol esters desensitized muscarinic-receptor-mediated [3H]cyclic GMP responses in mouse neuroblastoma N1E-115 cells. However, desensitization mediated by phorbol esters was heterologous, whereas that effected by receptor agonist was specific towards the muscarinic receptors. In addition, there was no loss of cell surface muscarinic receptors, as measured by the binding of the hydrophilic ligand [3H]N-methylscopolamine, when cells were treated with phorbol esters, but receptor-agonist-induced desensitization was accompanied by a decrease in cell surface receptor density. We examined the role of protein kinase C (PKC) in the desensitization of muscarinic receptors by employing a kinase inhibitor and by down-regulation of PKC by long-term incubation of cells with phorbol esters. Whereas these manoeuvres had marked effects on phorbol-ester-induced desensitization of muscarinic responses, they did not block agonist-induced down-regulation and desensitization of muscarinic receptors. In addition, when phosphoinositide hydrolysis was suppressed, the muscarinic agonist was still capable of mediating receptor sequestration and desensitization. These results suggest that the mechanisms for regulating muscarinic receptor sensitivity could be both PKC-dependent and PKC-independent, being mediated by phorbol esters and receptor agonists respectively.
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PMID:Protein kinase C is involved in desensitization of muscarinic receptors induced by phorbol esters but not by receptor agonists. 215 8

The properties of a new tumour cell line (NB1-G) derived from human neuroblastoma by xenografting in nude rats followed by adaptation to tissue culture are described. Studies using a panel of monoclonal antibodies demonstrate the neuro-ectodermal nature of the cells and support the diagnosis of the primary tumour as neuroblastoma. Cytogenetic studies have revealed a human karyotype with several chromosomal abnormalities. Genetic analysis by in situ DNA hybridization has demonstrated the presence of multiple copies of the N-myc gene. Approximately 20-30 fold amplification of the gene is observed on Southern blot analysis. The cell line has been adapted to growth as multicellular tumour spheroids as well as monolayer culture. Radiobiological studies on spheroids show the cells to be radiosensitive with low capacity for sub-lethal damage accumulation and repair. The cell line should be useful for fundamental studies of human neuroblastoma as well as experimental therapy in vitro.
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PMID:Biological properties of a tumour cell line (NB1-G) derived from human neuroblastoma. 243 46

A number of additives typically used in the formulation of poorly soluble drugs can be shown to influence drug transport across various physiological barriers. Multicellular spheroids from a human neuroblastoma cell line (NB1-G) were used to investigate the effect of etoposide in solution, as its commercial formulation, Vepesid, in the presence of a nonionic surfactant, Brij 30, and a hydrotropic agent, sodium salicylate. Enhanced growth delay, apparently related to increased drug uptake, was observed both with the Vepesid and the sodium salicylate formulations. Brij 30, however, showed no enhancement of growth delay or drug uptake at a concentration at which it was not in itself cytotoxic. Significant morphological changes in the spheroid were observed at higher concentrations of additives, particularly with Brij 30, emphasizing the fact that many formulation additives cannot be used with impunity in tissue culture systems. The enhanced uptake of drug into tumour cells and potential synergy between additive and drug is worthy of further investigation.
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PMID:Etoposide (VP-16) uptake by tumour spheroids and activity in the presence of Brij 30, formulation additives and sodium salicylate. 267 May 83

The ret transforming gene was activated by recombination between two unlinked segments of human DNA, most likely during transfection of NIH 3T3 cells. To further define this transforming gene, we isolated and sequenced ret cDNA clones. The nucleotide sequence indicates that the active ret transforming gene encodes a fusion protein with a carboxy-terminal domain which is 40 to 50% homologous to members of the tyrosine kinase gene family. This tyrosine kinase domain is preceded by a hydrophobic sequence characteristic of a transmembrane domain. Transcription of the ret tyrosine kinase sequence was detected in the SK-N-SH neuroblastoma, HL-60 promyelocytic leukemia, and THP-1 monocytic leukemia cell lines, but not in 25 other human tumor cell lines surveyed. The ret tyrosine kinase may thus represent a cell surface receptor which is expressed in a restricted range of human cells.
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PMID:ret transforming gene encodes a fusion protein homologous to tyrosine kinases. 303 15


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