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)

At 2 degrees, murine C1300 neuroblastoma cells bound NGF-coated sheep erythrocytes and formed rosettes. When the temperature was raised to 37 degrees, the neuroblastoma cells underwent a rapid transformation characterized by microtubule formation, which occurred under the membrane surface close to the points of contact with the attached red cells. Cytoplasmic processes filled wit- microtubules were then emitted by the cell body and surrounded the red cells. Within 20 to 30 min, the attached erythrocytes were phagocytized. Interiorization of membrane-bound erythrocytes-antibody-complement complexes by neuroblasto-a cells could be similarly induced at 37 degrees. In both cases, the extent of phagocytosis was decreased when microtubule formation was blocked with colchicine or vinblastine. Complete inhibition was obtained only by pretreatment of cells with cytochalasin B, a strong inhibitor of microfilament contraction. The role played by the microtubules and the microfilaments in promoting the phagocytosis of the attached erythrocytes is discussed.
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PMID:Phagocytosis of nerve growth factor-coated erythrocytes in neuroblastoma rosette-forming cells. 111 48

Gene expression of nerve growth factor receptor (NGFR), epidermal growth factor receptor(EGFR), chromogranin A (CGA) and neuropeptide Y (NPY) in 4 neuroblastoma cell Lines without N-myc amplification was studied by using Northern blot technique. N type cells expressed more NGFR mRNA than S type cell's and have only little or no EGFR expression. S type cells had stronger expression of EGFR mRNA than that of N type cells accompanying with only less or even no NGFR expression. The results indicated that difference of gene expression of these growth factor receptors might be due to the various directions of tumor cell differentiation. Cells differentiating toward neurons gave more NGFR expression and cells prepared to be differentiating toward other direction might give more EGFR gene expression. Various gene expression of CGA and NPY in neuroblastoma cell lines might be due to the presence of different stages of tumor cell differentiation and NGF only induced differentiation of those neuroblastoma cells ready to be differentiating to neurons afterwards.
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PMID:[Gene expression of NGFR, EGFR, CGA, NPY in 4 neuroblastoma cell lines]. 132 22

The human neuroblastoma cell line IMR-32 exhibits both cholinergic and adrenergic properties. We have used IMR-32 cells to study the effects of CDF (CAT development factor) and bFGF (basic fibroblast growth factor) on the development of neurotransmitter properties. CDF treatment increases CAT activity in a dose-dependent manner, independent of cell density. Time course studies show that there is a threefold increase in the specific CAT activity in IMR-32 cells treated with CDF for 6 d. CDF does not, however, affect the level of tyrosine hydroxylase (TH) activity, or the rate of cell proliferation. bFGF, on the other hand, induces TH activity and decreases CAT activity in a dose-dependent manner. bFGF's effect on TH is enhanced by increasing cell density, while its reduction of specific CAT activity is independent of cell density. Time course studies show a 30-fold increase in TH activity per cell and a threefold decrease in CAT activity per cell, after treatment with bFGF for 6 d. In contrast to the effects of CDF, bFGF enhances cell proliferation in IMR-32 cells. Double-labeled immunofluorescence studies showed that 95% of the cells stain for CAT and 65% stain for TH following treatment with CDF and bFGF, respectively. When these factors are combined, approximately 75% of the cells express both CAT and TH, demonstrating that IMR-32 cells are bipotential with regard to neurotransmitter-associated enzyme expression. We also show that insulin-like growth factor I and NGF selectively induce CAT activity and cell proliferation, respectively, whereas epidermal growth factor has no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of neurotrophic factors on neurotransmitter development in the IMR-32 human neuroblastoma cell line. 134 44

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

Nuclear receptors for the thyroid hormone triiodothyronine (T3) have been identified in vivo in brain tissues and in vitro in mouse and rat neuroblastoma and glioma cells. The present study characterizes nuclear T3 receptors in human neuroblastoma SH-SY5Y cells and compares their level before and after differentiation. Undifferentiated cells, grown in DME/HAM F-12 medium supplemented with 10% fetal calf serum, show an abundant single type of nuclear receptor, indicated by a straight Scatchard plot, with a Kd of 0.11 nmol/l. After treatment with sodium butyrate (0.5 mM for 4 days) or NGF (2 nM for 6 days), the cells showed neuronal-like patterns (extension of neurites, slowing of growth, increased tyrosine hydroxylase activity), with a decrease in the number of nuclear T3 receptors. As sodium butyrate and NGF treatments differentiate neuroblastoma SH-SY5Y cells, these data suggest a down-regulation of T3 receptors with cell maturation.
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PMID:Characterization of nuclear T3 receptors in human neuroblastoma cells SH-SY5Y: effect of differentiation with sodium butyrate and nerve growth factor. 167 4

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

A method for the purification of full-length nerve growth factor receptor (NGFRc) using membranes from three different cell lines was developed. We emphasized recovery of NGFRc that retained specific binding activity. Lipids were required to preserve binding activity during solubilization and throughout the purification procedure. Phosphatidylcholine was used for this purpose. Lectin affinity chromatography followed by high-resolution anion-exchange chromatography was used, and a 3000-fold increase in specific binding activity was obtained for NGFRc from human melanoma A875 membranes. Seven percent of the original binding activity was recovered as pure NGFRc. NGFRc binding activity eluted at 0.35 M NaCl in anion-exchange chromatography of solubilized A875, rat pheochromocytoma PC12, and human neuroblastoma MC-IXC membranes. Eight and three percent of the original binding activity were recovered as highly enriched NGFRc from membranes prepared from PC12 and MC-IXC cells, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of highly enriched, 125I-labeled NGFRc revealed several protein species. After chromatography, identification of proteins as NGFRc was verified both by immunoprecipitation using receptor-specific monoclonal antibodies and by covalent cross-linking to 125I-NGF using N-hydroxysuccinimidyl-4-azidobenzoate. Predominantly, NGFRc was recovered as a mixture of species of 80 and 160-180 kDa. Small amounts of larger species as well as smaller species were observed, consistent with minor amounts of receptor aggregation and proteolysis occurring during purification.
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PMID:Two-step purification of full-length nerve growth factor receptor and maintenance of receptor-specific binding activity. 196 21

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

Neuroblastoma may arise from the blockage of differentiation of neuroblast along the neuronal pathway. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study the gene regulation during differentiation, we hybridized several cDNA probes with RNA extracted from different cell lines before and after NGF treatment, and found that c-myc oncogene was down-regulated in NGF-induced differentiated cells in comparison with the control samples. The time course of c-myc down-regulation was concordant with the appearance of morphological changes of differentiation. No significant change was found in the expression of other oncogenes like K-ras and N-ras in the neuroblastoma cell lines before and after NGF treatment. The results indicate that down-regulation of c-myc oncogene may be one of the important events during NGF-induced differentiation and over expression of c-myc oncogene may, at least partly, be responsible for the development of neuroblastoma.
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PMID:[Gene regulation during NGF--induced differentiation of neuroblastoma cells]. 206 83

We hypothesized that defects in the nerve growth factor receptor (NGFR) pathway may play a role in maintenance of the undifferentiated state of neuroblastomas. To test this hypothesis, we examined the structure and function of the NGFR in a panel of 10 neuroblastoma cell lines. Southern blot analysis showed that all 10 cell lines possess apparently normal NGFR genes. Northern blot and ligand binding/immunoprecipitation assays revealed four receptor-positive cell lines (NGP, NLF, SK-N-SH and, LA-N-6), with NGFR mRNA and protein of expected sizes (3.8 kb and approximately 75 kD respectively). NGF binding assays and Scatchard analyses were performed on these four lines. The NGP line possesses only low affinity receptor (Kd approximately 3.5 x 10(-9] while the other three lines express both low- and high-affinity forms (Kd approximately 10(-9) and Kd approximately 10(-11), respectively). However, none of the 10 lines exhibited an early or late response to NGF treatment as assayed by c-fos mRNA induction (45 min) and neurite extension (8-10 days). These results demonstrate at least three distinct defects in the NGFR pathway in these tumor lines: 1) absence of NGFR mRNA or protein expression, 2) expression of only low-affinity receptor, and 3) inability of high affinity receptor to mediate a response to NGF. Such defects may play an important role in the initiation or maintenance of the undifferentiated state of neuroblastoma.
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PMID:Multiple defects of the nerve growth factor receptor in human neuroblastomas. 206 40


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