Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In adult mammalian CNS, axons mostly fail to regenerate after injury, while in the PNS they often succeed in reaching their previous targets. Crucial differences are present in the local tissue microenvironment of CNS and PNS. To investigate the substrate properties of nervous tissue for neuronal adhesion and fiber growth, we used frozen sections of rat CNS and PNS as culture substrates for neuroblastoma cells and for sympathetic and dorsal root ganglia. The results showed that CNS white matter from adult rat spinal cord, cerebellum, forebrain, or optic nerve did not allow cell adhesion and axonal elongation. In contrast, gray matter areas, sciatic nerve, and also trout CNS white and gray matter were permissive substrates. To delineate the tissue components of white matter involved in this nonpermissive substrate effect, newborn rats were injected for 13 d with the antimitotic agent 5-azacytidine. This treatment strongly reduced the oligodendrocyte population and the myelin content of the spinal cord. The immunoreactivity for specific oligodendrocyte and astrocyte markers confirmed the selective suppression of oligodendroglia in these rats. Neuroblastoma cells plated on spinal cord sections taken from these animals were no longer exclusively localized on the gray matter but were also found on regions normally rich in myelin. A significant reduction of the white matter nonpermissive substrate effect was also obtained by the monoclonal antibody IN-1 directed against 2 defined myelin proteins with inhibitory substrate properties (Caroni and Schwab, 1988b). Our results, therefore, show that, in the adult mammalian CNS, cell adhesion and axonal elongation are prevented by white matter components, which are, at least in part, associated with oligodendrocytes and myelin.
 ...
PMID:Rat CNS white matter, but not gray matter, is nonpermissive for neuronal cell adhesion and fiber outgrowth. 246 69

The relative levels of the central nervous system myelin marker enzyme 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37, CNPase) were determined in neuroblastoma, astrocyte, oligodendrocyte and Schwann cell cultures and in freshly isolated human lymphocytes and platelets. The highest specific activities were associated with the cells that elaborate myelin membrane in the central and peripheral nervous system, oligodendrocytes and Schwann cells, respectively. Antiserum to bovine CNPase recognized both CNP1 and CNP2 in CNS myelin and human oligodendroglioma. In addition, a 53,000 dalton protein was evident on autoradiographs of immunoblotted PNS myelin and human oligodendroglioma proteins. Cultured rat oligodendrocyte, C6 and mouse NA neuroblastoma CNPase appear to share common determinants with the corresponding normal rat CNS enzyme.
 ...
PMID:Differential expression of 2':3'-cyclic nucleotide 3'-phosphodiesterase in cultured central, peripheral, and extraneural cells. 299 54

The identification and molecular characterization of Brn-3.2 has revealed a family of Brn-3-related mammalian POU proteins that share homology with the C. elegans developmental regulator Unc-86 and extended similarity with the Drosophila neurodevelopmental gene I-POU, which defines a novel POU-IV box. Brn-3.2 exhibits DNA binding properties similar to those of Brn-3.0, but its expression is uniquely regulated by retinoic acid in teratocarcinoma and neuroblastoma cells. In the developing PNS and retina, the expression pattern of Brn-3.2 is similar to that of Brn-3.0. In the caudal CNS (spinal cord, hindbrain, and midbrain) Brn-3.2 and Brn-3.0 are initially coexpressed, but diverge later in development. Rostral to the midbrain, Brn-3.2 and Brn-3.0 exhibit nonoverlapping patterns of expression, suggesting divergence of gene function in more recently evolved structures. Our analysis suggests that in the CNS Brn-3.2 is selectively expressed in postmitotic neurons, implying a role in specifying terminally differentiated neuronal phenotypes.
 ...
PMID:Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid. 790 22

Cholinergic neurons in PNS and CNS are identified by the presence of choline acetyltransferase and the accumulation of choline by a high-affinity, sodium-coupled choline transporter to be used for acetylcholine synthesis. It appears that expression of choline acetyltransferase can be altered by several physiological conditions, including hormones and trophic factors, but little is known about control of expression of the sodium-coupled choline carrier or whether these two phenotypic markers are regulated similarly. In the present study, the cholinergic human neuroblastoma LA-N-2 was used to investigate regulation of expression of choline acetyltransferase and choline uptake activity associated with differentiation and neurite extension. Cells grown in serum-containing basal medium maintained a relatively undifferentiated morphology, expressed low levels of choline acetyltransferase activity, and accumulated choline by a sodium-dependent process followed by conversion to acetylcholine. Transfer of cells to an enriched, serum-free defined medium resulted in morphological and neurochemical differentiation, with an enhancement of cholinergic phenotype. Hemicholinium-sensitive choline uptake activity was increased about sixfold over a 4-day period, with no change in choline acetyltransferase or acetylcholinesterase specific activity. Acetylcholine synthesis was increased in parallel with the changes in choline accumulation; choline metabolism in the differentiated cells differed significantly from that observed in the undifferentiated cells, with proportionally less converted to phosphorylcholine and proportionally more remaining as unmetabolized choline and converted to acetylcholine. The enhanced choline accumulation appeared to be mediated by an increased number of choline carriers, demonstrated by increased binding of the affinity ligand [3H]-choline mustard to the transporter and by an increased Vmax for the uptake process. The increased expression of the transport function appeared to be under transcriptional control, as the enhancement of uptake was blocked by the RNA polymerase II inhibitor alpha-amanitin as well as by the protein synthesis inhibitor cycloheximide. These results show that expression of sodium-coupled choline carriers and choline acetyltransferase may be regulated separately in the differentiating neuroblastoma LA-N-2 and that neurotransmitter synthesis is controlled by provision of precursor rather than at the level of the biosynthetic enzyme.
 ...
PMID:Regulation of expression of cholinergic neuronal phenotypic markers in neuroblastoma LA-N-2. 837 93

Extracellular ATP has neurotransmitter-like properties in the CNS and PNS that are mediated by a cell-surface P2 purinergic receptor. In the present study, we have extensively characterized the signal transduction pathways that are associated with activation of a P2U receptor in a cultured neuroblastoma x glioma hybrid cell line (NG108-15 cells). The addition of > or = 1 microM ATP to NG108-15 cells caused a transient increase in [Ca2+]i that was inhibited by 40% when extracellular calcium was chelated by EGTA. ATP concentrations > or = 500 microM also elicited a sustained increase in [Ca2+]i that was inhibited when extracellular calcium was chelated by EGTA. The increase in [Ca2+]i elicited by ATP occurred concomitantly with the hydrolysis of [32P]-phosphatidylinositol 4,5-bisphosphates and an increase in the level of inositol 1,4,5-trisphosphate. ATP also caused a time- and dose-dependent increase in levels of [3H]inositol monophosphates in lithium-treated cells. Separation of the inositol monophosphate isomers by ion chromatography revealed a specific increase in the level of inositol 4-monophosphate. The magnitude of the increase in [Ca2+]i elicited by ATP correlated with the concentration of the fully ionized form of ATP (ATP4-) in the medium and not with the concentration of magnesium-ATP (MgATP2-). Similar to ATP, UTP also induced polyphosphoinositide breakdown, inositol phosphate formation, and an increase in [Ca2+]i. ADP, ITP, TTP, GTP, ATP gamma S, 2-methylthio ATP, beta, gamma-imidoATP or 3'-O-(4-benzoyl)benzoylATP, but not CTP, AMP, beta, gamma-methylene ATP, or adenosine, also caused an increase in [Ca2+]i. In cells labeled with [32P]P(i) or [14C]-arachidonic acid, ATP caused a transient increase in levels of labeled phosphatidic acids, but had no effect on levels of arachidonic acid. The increase in phosphatidic acid levels elicited by ATP apparently was not due to activation of a phospholipase D because ATP did not induce the formation of phosphatidylethanol in [14C]myristic acid-labeled cells incubated in the presence of ethanol. These findings support the hypothesis that a P2 nucleotide receptor in NG108-15 cells is coupled to a signal transduction pathway involving the activation of a phospholipase C and a plasma membrane calcium channel, but not the activation of phospholipases A2 and D.
 ...
PMID:Signal transduction pathways coupled to a P2U receptor in neuroblastoma x glioma (NG108-15) cells. 838 62

Previous studies demonstrated expression of GM1 ganglioside in the nuclear envelope of differentiating neuroblastoma cells and cultured cerebellar granule cells from neonatal rat brain. In the present study, relatively few of the latter cells were shown to possess a nucleus with appreciable GM1 during the first few days in culture, but increasing numbers of such cells possessed GM1-expressing nuclei as morphological differentiation progressed. This phenomenon reached a plateau by the 8th day in culture, approximately 90% of observed nuclei showing cytochemical evidence of GM1 at that time. Cerebral cortical neurons from embryonic rat brain in culture also gave clear evidence of GM1 in the nuclear membrane. Similar results were obtained with cultured neurons from the superior cervical ganglion from embryonic rats, demonstrating developmental appearance of GM1 in the nuclear envelope of PNS neurons. Cytochemical evidence for GM1 in purified nuclei from freshly isolated cortical neurons of neonatal rat brain indicated that expression of nuclear GM1 is not an artifact of cell culture. Study of NG108-15 neuroblastoma x glioma hybrid cells showed upregulation of nuclear GM1 to lag somewhat behind neurite outgrowth, suggesting nuclear GM1 to have a functional role subsequent to onset of morphological differentiation.
 ...
PMID:Developmental appearance of nuclear GM1 in neurons of the central and peripheral nervous systems. 1040 37

The neuropeptide vasoactive intestinal peptide (VIP) is expressed in several distinct sites in the CNS, in cholinergic and enteric ganglia, and in a small subpopulation of neurons within sympathetic ganglia. Previous studies on the human VIP gene indicate that transcription in neural crest-derived neuroblastoma and pheochromocytoma cell lines is controlled in part by multiple regulatory elements located along 4.5 kb of upstream 5' flanking sequence. In the current studies, transgenic mice were created with a chimeric gene consisting of 16.5 kb of the mouse VIP gene fused to the beta-galactosidase reporter. In situ hybridization analysis in adult mice indicated that reporter gene expression was correctly targeted to neurons in the esophagus, stomach, small intestine, and colon. No expression was observed in the brain, including regions that contain abundant VIP-expressing cells, such as the thalamus, amygdala, cerebral cortex, hippocampus, and suprachiasmatic nucleus. Analysis of transgene expression in neonatal and embryonic day 13.5 mice revealed a near perfect correlation between VIP and beta-galactosidase gene expression in cranial cholinergic ganglia and the superior cervical ganglia, and lack of transgene expression in sensory ganglia and in nonneuronal tissue. Potential ectopic transgene expression was observed in neonates, in the cerebellar external granule layer and in a small subpopulation of neurons in the olfactory epithelium. We conclude that the 16.5 kb of VIP gene used in these studies contains sequences sufficient for directing expression specifically to VIP neurons in the PNS, and that sequences located elsewhere on the gene are required for proper CNS expression. The VIP gene sequences used here should be capable of targeting other gene products to specific populations of embryonic and adult peripheral neurons without causing significant expression in the CNS.
 ...
PMID:Targeting of embryonic and postnatal autonomic and enteric neurons with a vasoactive intestinal peptide transgene. 1050 Dec 23

MYCN belongs to the MYC family of proto-oncogenes, which encode for transcription factors of the basic-helix-loop-helix-zipper (bHLHZ) class and is fundamental in the development of the peripheral and central nervous systems (PNS and CNS). While Myc is ubiquitous, MYCN has a very restricted expression pattern: it is mainly expressed during embryonic development, but then becomes downregulated, while in adults it is usually detected in B-cell development. Identification of selective inhibitors of MYCN and its mRNA and protein could be important for the development of more specific, effective and less toxic therapeutic agents for tumors of the PNS and CNS. In children, the most common tumors of the PNS and CNS are neuroblastomas and medulloblastomas, respectively. About 30% of neuroblastoma (NB) tumors present MYCN amplification/over-expression, which is associated with rapid progression and poor prognosis. N-Myc is essential during neurogenesis for the rapid expansion of progenitor cells in the brain. MYCN amplification and over-expression has been reported in medulloblastoma, and especially in the desmoplastic type. Other tumors associated with MYCN overexpression include retinoblastoma, small cell lung carcinoma, glioblastoma and certain embryonal tumors. A cell-based, N-Myc-dependent luciferase reporter gene assay to identify specific N-Myc small-molecule inhibitors has allowed identification of five compounds showing significant activity. Antisense oligodeoxynucleotides have been shown to inhibit N-Myc production and anti-tumoral activity in vitro and in vivo for NB. Peptide nucleic acids (PNA), which belong to the most recent (third) generation of nucleic acid therapeutics, form highly stable duplexes with DNA and RNA, and are resistant to degradation by nucleases and proteases. Encouraging results have been reported utilizing a PNA-based antisense strategy for inhibition of N-Myc expression in neuroblastoma.
 ...
PMID:The MYCN oncogene as a specific and selective drug target for peripheral and central nervous system tumors. 1597 48

The deposition of transthyretin (TTR) amyloid in the PNS is a major pathological feature of familial amyloidotic polyneuropathy. The aim of the present study was to examine whether TTR could disrupt cytoplasmic Ca(2+) homeostasis and to determine the role of TTR aggregation in this process. The aggregation of amyloidogenic TTR was examined by solution turbidity, dynamic light scattering and atomic force microscopy. A nucleation-dependent polymerization process was observed in which TTR formed low molecular weight aggregates (oligomers < 100 nm in diameter) before the appearance of mature fibrils. TTR rapidly induced an increase in the concentration of intracellular Ca(2+) ([Ca(2+)](i)) when applied to SH-SY5Y human neuroblastoma cells. The greatest effect on [Ca(2+)](i) was induced by a preparation that contained the highest concentration of TTR oligomers. The TTR-induced increase in [Ca(2+)](i) was due to an influx of extracellular Ca(2+), mainly via L- and N-type voltage-gated calcium channels (VGCCs). These results suggest that increasing [Ca(2+)](i) via VGCCs may be an important early event which contributes to TTR-induced cytotoxicity, and that TTR oligomers, rather than mature fibrils, may be the major cytotoxic form of TTR.
 ...
PMID:Transthyretin oligomers induce calcium influx via voltage-gated calcium channels. 1707 59

Esthesioneuroblastoma (olfactory neuroblastoma) is an uncommon neuroectodermal tumor. Its biological activity ranges from indolent growth to local recurrence and rapid widespread metastasis. Treatment options consist of surgical resection followed by radiation therapy for primary lesions and the addition of chemotherapy for advanced, recurrent, or metastatic lesions. Patients often present with nasal obstruction, rhinorrhea, recurrent epistaxis, hyposmia, or anosmia. We report a case of esthesioneuroblastoma involving bilateral nasal cavity leading to bilateral nasal obstruction, epistaxis and proptosis of the right eye associated with decreased visual acquity on that eye and loss of smell. A diffuse nontender, 6x6 cms swelling with illdefined margins was seen over the nasal bridge, extending superiorly to glabella and laterally to right maxillary region. X-ray PNS showed soft tissue mass in the nasal cavity with destruction of nasal septum, intense periosteal reaction with destruction of right maxillary wall and extension to right orbit. CT scan of paranasal sinuses showed 8.5 x 4.9 x 7.8 cms irregularly marginated heterogeneous iso- to hyper dense soft tissue mass lesion with extensive adjacent bony destruction and spiculated periosteal reaction involving bilateral nasal cavity and anterior cranial fossa. Biopsy from right nasal mass showed neuroblastoma. The patient received radiotherapy and chemotherapy. The modified Kadish staging system, lymph node status, treatment modality, and age are useful predictors of survival in patients who present with esthesioneuroblastoma. Excellent outcomes for esthesioneuroblastoma are achievable. Long-term follow-up is necessary because of the extended interval for recurrent disease; unlike most sinonasal malignancies, surgical salvage is possible.
 ...
PMID:Esthesioneuroblastoma: a case report. 2122 14


1 2 Next >>