Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Synapsin I is a phosphoprotein localized to the cytoplasmic surface of synaptic vesicles and is one of the best characterized neuron-specific proteins. Synaptophysin is an integral membrane glycoprotein, also located on presynaptic vesicles, which has been shown to be a useful immunohistochemical marker for neuroendocrine/neuronal differentiation in tumor diagnosis. The sensitivity and specificity of immunohistochemical staining for these two proteins in formalin-fixed, paraffin-embedded tissues was studied in a series of 67 neuroectodermal, neuroendocrine, and non-neural tumors. Intense immunoreactivity for both synapsin I and synaptophysin was observed in tumors containing well-differentiated neurons (gangliocytoma, ganglioglioma, neurocytoma). In these tumors, immunostaining was primarily concentrated along the outer surface of the cell membrane of the neuronal cells. Primitive neuroectodermal tumors (PNETs) (cerebral PNET, medulloblastoma, neuroblastoma) and most neuroendocrine tumors generally showed less intense and more variable immunoreactivity for these proteins. In most cases, immunostaining for synapsin I was sharper and often more intense than for synaptophysin. Some PNETs and neuroendocrine tumors that were immunoreactive for synapsin I did not stain for synaptophysin. We conclude that synapsin I is a reliable, sensitive immunohistochemical marker for neuronal/neuroendocrine differentiation in human neoplasms and may offer some advantages over synaptophysin when applied to formalin-fixed, paraffin-embedded tissues, particularly in the evaluation of primitive neuroectodermal tumors and neuroendocrine tumors.
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PMID:Immunohistochemistry of synapsin I and synaptophysin in human nervous system and neuroendocrine tumors. Applications in diagnostic neuro-oncology. 828 27

Multifactorial resistance is the main mechanism of chemotherapy failure in cancers. Multidrug resistance (MDR) is related to the expression of a 170 kDa membrane glycoprotein, the so-called P-glycoprotein (P-gp). This protein is able to extrude drugs of various structures and mechanisms out of the cytoplasm. P-gp is a pronostic value in hemopathy as well as in child sarcoma, osteosarcoma and neuroblastoma. Modulator agents of different generations are capable of inhibiting P-gp. MDR modulation is obtained in hemopathies and is associated with an eradication of the P-gp (+) cell clones. In solid tumors, clinical trials using verapamil or cyclosporin are not so convincing. It is likely that other mechanisms of resistance are responsible for tumor progression, such as the MRP system, glutathion and topoisomerases. A better knowledge of multifactorial resistance and drug synthesis counteracting these resistance mechanisms will allow to elaborate new therapeutic basis for cancer therapy.
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PMID:[MDR (Multiple Drug Resistant) type of resistance to chemotherapy in clinical practice]. 886 40

Paranodin/contactin-associated protein (caspr) is a transmembrane glycoprotein of the neurexin superfamily that is highly enriched in the paranodal regions of myelinated axons. We have investigated the role of its association with F3/contactin, a glycosylphosphatidyl inositol (GPI)-anchored neuronal adhesion molecule of the Ig superfamily. Paranodin was not expressed at the cell surface when transfected alone in CHO or neuroblastoma cells. Cotransfection with F3 resulted in plasma membrane delivery of paranodin, as analyzed by confocal microscopy and cell surface biotinylation. The region that mediates association with paranodin was mapped to the Ig domains of F3 by coimmunoprecipitation experiments. The association of paranodin with F3 allowed its recruitment to Triton X-100-insoluble microdomains. The GPI anchor of F3 was necessary, but not sufficient for surface expression of paranodin. F3-Ig, a form of F3 deleted of the fibronectin type III (FNIII) repeats, although GPI-linked and expressed at the cell surface, was not recovered in the microdomain fraction and was unable to promote cell surface targeting of paranodin. Thus, a cooperative effect between the GPI anchor, the FNIII repeats, and the Ig regions of F3 is required for recruitment of paranodin into lipid rafts and its sorting to the plasma membrane.
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PMID:The glycosylphosphatidyl inositol-anchored adhesion molecule F3/contactin is required for surface transport of paranodin/contactin-associated protein (caspr). 1076 38

During myelination, membrane-specialized domains are generated by complex interactions between axon and glial cells. The cell adhesion molecules caspr/paranodin and F3/contactin play a crucial role in the generation of functional septate-like junctions at paranodes. We have previously demonstrated that association with the glycosylphosphatidylinositol-linked F3/contactin is required for the recruitment of caspr/paranodin into the lipid rafts and its targeting to the cell surface. When transfected alone in neuroblastoma N2a cells, caspr/paranodin is retained in the endoplasmic reticulum (ER). Using chimerical constructs, we show that the cytoplasmic region does not contain any ER retention signal, whereas the ectodomain plays a crucial role in caspr/paranodin trafficking. A series of truncations encompassing the extracellular region of caspr/paranodin was unable to abolish ER retention. We show that N-glycosylation and quality control by the lectin-chaperone calnexin are required for the cell surface delivery of caspr/paranodin. Cell surface transport of F3/contactin and caspr/paranodin is insensitive to brefeldin A and the two glycoproteins are endoglycosidase H-sensitive when associated in complex, recruited into the lipid rafts, and expressed on the cell surface. Our results indicate a Golgi-independent pathway for the paranodal cell adhesion complex that may be implicated in the segregation of axonal subdomains.
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PMID:The paranodal complex of F3/contactin and caspr/paranodin traffics to the cell surface via a non-conventional pathway. 1297 10

Glycoproteins from mammalian brain tissues contain unique N-linked oligosaccharides terminating with beta-N-acetylglucosamine residues. Lectin blot analysis of membrane glycoprotein samples from human neuroblastoma SH-SY5Y cells showed that several protein bands bind to Psathylera velutina lectin (PVL), which interacts with beta-N-acetylglucosamine-terminating oligosaccharides. No lectin positive bands were detected by digestion with jack bean beta-N-acetyl-hexosaminidase or N-glycanase before incubation with the lectin, indicating that the cells contain beta-N-acetylglucosamine-terminating N-linked oligosaccharides. When cells were cultured in dishes with different concentrations of PVL, the cell proliferation was inhibited in a dose-dependent manner. Similarly, the neurite extension, which was stimulated with nerve growth factor, was also inhibited in a manner dependent on the lectin dose. Cell proliferation and neurite extension were recovered by the addition of 10 mM N-acetylglucosamine into the medium. Immunoblot analysis of the activation of mitogen-activated protein (MAP) kinases and protein kinase C revealed that phosphorylation of 42-kDa and 44-kDa MAP kinases and 80-kDa protein kinase C are inhibited when SH-SY5Y cells are cultured in PVL-coated dishes, but are restored by the addition of the haptenic sugar into the medium, indicating that MAP kinase and protein kinase C pathways are inhibited by interaction with immobilized PVL. These results indicate that beta-N-acetylglucosamine-terminating N-linked oligosaccharides expressed on neural cells can induce intracellular signals upon binding to extracellular receptors, and are important for growth regulation of neural cells.
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PMID:Suppression of proliferation and neurite extension of human neuroblastoma SH-SY5Y cells on immobilized Psathyrella velutina lectin. 1474 51

Exposure to nicotine has a broad range of physiological and psychological effects that can be long lasting and contribute to nicotine dependence. On a time course longer than that needed to activate nicotinic acetylcholine receptor (nAChR) function, nicotine exposure induces functional inactivation of nAChR, upregulation of nAChR radioligand binding sites, and other alterations of cellular functions. To identify possible mechanisms underlying nicotine-induced changes in nAChR numbers and function, we defined changes in gene expression in neuron-like, SH-SY5Y human neuroblastoma cells following 24 h of continuous exposure to 1 mM nicotine. This treatment condition produces both functional inactivation and upregulation of nAChR. Repeat and cross-controlled microarray ( approximately 5000 genes queried) analyses revealed 163 genes whose expression was consistently altered at the p<0.01 level following nicotine treatment. Quantitative, real-time, reverse transcription-polymerase chain reaction analyses confirmed altered expression of thirteen out of fourteen of these genes chosen for further study, including contactin 1, myozenin 2, and ubiquitin-conjugating enzymes E2C and E2S. Inhibition or reversal of these effects by the general nAChR antagonist, d-tubocurarine, indicated that gene expression changes are dependent on nAChR activation. Studies using other nAChR subtype-selective antagonists identified gene expression changes that required activation of both alpha7- and alpha3*-nAChR, alpha7-nAChR alone, or either alpha7- or alpha3beta4*-nAChR, suggesting some convergent and some divergent pathways of gene activation coupled to these nAChR subtypes. These results suggest that longer-term physiological and psychological effects of nicotine exposure and changes in nAChR expression may be due in part to effects on gene expression initiated by interactions with nAChR.
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PMID:Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. 1694 57

Neuroblastoma (NBL) is the most common solid tumor in children. Tumors in advanced stage or with positive risk factors still have a poor prognosis. Thy1 (CD90) is a membrane glycoprotein expressed in thymus, retinal ganglionic cells, and several types of stem cells. The aim of this study was to assess Thy1 expression in NBL and analyze the correlation with clinical outcome. Sixty-three specimens of NBL were stained for Thy1 on a tissue microarray by immunohistochemistry. Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for Thy1-mRNA expression was performed. Patients' survival data were correlated with Thy1 status using a log rank test and a Cox regression multivariate analysis. Thy1 was expressed on 51 (81%) of the tumors. Kaplan-Meier survival analysis showed a significantly impaired survival in patients with NBL missing Thy1 (P < 0.005 by log-rank test). A multivariate Cox regression showed an independent prognostic value of Thy1 status for overall survival (P < 0.05). In addition, the frequency of events and deaths was significantly higher in the group of patients with Thy1 negative tumors, as assessed by ANOVA analysis (P < 0.05 by F-test). The data showed that Thy1-negative NBL patients have a significantly impaired overall survival compared with Thy1-positive NBL patients. Thus, Thy1 seemed to be a marker with a specific prognostic value in NBL patients. Future studies are aiming at the biological role of this marker in the tumor cell differentiation.
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PMID:Lack of Thy1 (CD90) expression in neuroblastomas is correlated with impaired survival. 1795 44

Chondroitin sulfate (CS) plays critical roles in central nervous system development and regeneration, and individual modifications of CS form a "sulfation code" that regulates growth factor signaling or neuronal growth. Although we have shown that CS-E polysaccharide, but not CS-A or -C polysaccharide, has an inherent ability to promote neurite outgrowth toward primary neurons, its molecular mechanism remains elusive. Here, we show the involvement of a plasma membrane-tethered cell adhesion molecule, contactin-1 (CNTN-1), in CS-E-mediated neurite extension in a mouse neuroblastoma cell line and primary hippocampal neurons. CS-E, but not CS-A, -C, or heparan sulfate, engaged CNTN-1 with significant affinity and induced intracellular signaling downstream of CNTN-1, indicating that CS-E is a selective ligand for a potential CS receptor, CNTN-1, leading to neurite outgrowth. Our data provide the first evidence that biological functions of CS are exerted through the CS receptor-mediated signaling pathway(s).
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PMID:Contactin-1 is a functional receptor for neuroregulatory chondroitin sulfate-E. 1907 12

The prion protein (PrP) is a glycosylphosphatidylinositol-anchored membrane glycoprotein that plays a vital role in prion diseases, a class of fatal neurodegenerative disorders of humans and animals. Approximately 20% of human prion diseases display autosomal dominant inheritance and are linked to mutations in the PrP gene on chromosome 20. PrP mutations are thought to favor the conformational conversion of PrP into a misfolded isoform that causes disease by an unknown mechanism. The PrP mutation D178N/Met-129 is linked to fatal familial insomnia, which causes severe sleep abnormalities and autonomic dysfunction. We showed by immunoelectron microscopy that this mutant PrP accumulates abnormally in the endoplasmic reticulum and Golgi of transfected neuroblastoma N2a cells. To investigate the impact of intracellular PrP accumulation on cellular homeostasis, we did a two-dimensional gel-based differential proteomics analysis. We used wide range immobilized pH gradient strips, pH 4-7 and 6-11, to analyze a large number of proteins. We found changes in proteins involved in energy metabolism, redox regulation, and vesicular transport. Rab GDP dissociation inhibitor alpha (GDI) was one of the proteins that changed most. GDI regulates vesicular protein trafficking by acting on the activity of several Rab proteins. We found a specific reduction in the level of functional Rab11 in mutant PrP-expressing cells associated with impaired post-Golgi trafficking. Our data are consistent with a model by which mutant PrP induces overexpression of GDI, activating a cytotoxic feedback loop that leads to protein accumulation in the secretory pathway.
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PMID:Mutant prion protein expression is associated with an alteration of the Rab GDP dissociation inhibitor alpha (GDI)/Rab11 pathway. 1999 23

The neural cell adhesion molecule L1 (CD171) is a multidomain type 1 membrane glycoprotein of the immunoglobulin superfamily important in the nervous system development, kidney morphogenesis, and maintenance of the immune system. Recent studies reported CD171 expression being associated with adverse clinical outcome in different types of cancer and there has been a growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. Nevertheless, conflicting results regarding the prognostic value of CD171 expression in renal cell carcinomas and gastrointestinal stromal tumors were published. In this study, CD171 expression was immunohistochemically analyzed in 5155 epithelial, mesenchymal, melanocytic, and lymphohematopoietic tumors to assess its utility in diagnostic pathology and to pinpoint potential targets for CD171-targeting therapy. A newly developed anti-CD171 rabbit monoclonal antibody, clone 014, was selected from the panel of commercially available CD171 antibodies. Immunohistochemistry was performed using Leica Bond Max automation and multitumor blocks containing up to 60 tumor samples. CD171 was constitutively and strongly expressed in neuroectodermal tumors such as schwannoma, neuroblastoma, and paraganglioma, whereas other mesenchymal tumors including schwannoma mimics showed only rarely CD171 positivity. Frequent CD171-expression was also detected in ovarian serous carcinoma, malignant mesothelioma, and testicular embryonal carcinoma. CD171 immunohistochemistry may have some role in immunophenotypic differential diagnosis of neurogenic tumors and pinpointing potential candidates for anti-CD171 therapy. Though, because of its rare expression and lack of predictive value, CD171 is neither a diagnostic nor prognostic marker for gastrointestinal stromal tumors.
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PMID:Expression of neural cell adhesion molecule L1 (CD171) in neuroectodermal and other tumors: An immunohistochemical study of 5155 tumors and critical evaluation of CD171 prognostic value in gastrointestinal stromal tumors. 2741 70


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