UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five children with neural crest tumors (two ganglioneuromas, one ganglioneuroblastoma, and two neuroblastomas) were investigated regarding neuropeptide Y-like immunoreactivity (NPY-LI) in tumor tissue and plasma at diagnosis and during surgery. Radioimmunoassay of extracted plasma revealed higher NPY-LI at diagnosis of neuroblastoma (640 and 230 pmol/L resp) than ganglioneuroblastoma or ganglioneuroma (74, 45, and 26 pmol/L resp). During surgery of neuroblastoma plasma NPY-LI increased two- to four-fold while no peroperative increase was seen in the other children. NPY-LI was considerably higher in neuroblastoma tissue (220 pmol/g and 144 pmol/g) than in ganglioneuroblastoma (40.2 pmol/g), ganglioneuroma (0.6 and 4.4 pmol/g), or healthy adrenal tissue (5.5 pmol/g). The highest NPY-LI concentration was found in neuroblastoma metastasis, 3,091 pmol/g. Gel-permeation chromatography of a neuroblastoma tumor showed that a majority of NPY-LI was representing intact NPY (NPY 1-36) while metastasis and plasma from the same child mainly contained smaller immunoreactive fragments. High concentrations of systemic NPY in neuroblastoma patients are of tumoral origin. Plasma levels of NPY and its fragments can be useful in diagnosing and monitoring neuroblastoma, and for early detection of relapse or metastatic disease. A possible involvement of NPY in neuroblastoma tumor growth and spread deserves further investigation.
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PMID:Neuropeptide Y in neuroblastoma: increased concentration in metastasis, release during surgery, and characterization of plasma and tumor extracts. 849 45

The processing of two homologous precursors, pro-neuropeptide Y (pro-NPY) and pro-pancreatic poly-peptide (pro-PP), was studied in four neuroendocrine cell lines after transfection: CA-77 medullary thyroid carcinoma cells, AtT-20 corticotrope pituitary cells, RIN2A-19 pancreatic endocrine cells, and NB1 neuroblastoma cells. Northern blot analysis indicated that the AtT-20 cells only expressed precursor convertase 3; in contrast, NB1 cells only expressed precursor convertase 2, whereas the RIN2A-19 and CA-77 cells expressed both enzymes. Despite these differences in expression pattern of precursor convertases the four cell lines were, surprisingly, indistinguishable in respect to their processing of pro-PP and pro-NPY. In all four cell lines, pro-NPY was almost completely converted to NPY, and, in all four cell lines, only around 50% of the PP precursor was converted to PP. The relatively poor processing efficiency of pro-PP was rather similar to the processing efficiency of the endogenously produced precursors in the respective cell lines, pro-calcitonin (CA-77), proopiomelanocortin (AtT-20), proinsulin (RIN2A-19), and pro-vasoactive intestinal polypeptide (NB1). At least in the CA-77 cells, NPY and PP were apparently sorted to the regulated secretory pathway, as upon stimulation with secretagogue the release of the transfected peptides increased in parallel with the endogenously expressed peptide, calcitonin gene-related peptide. Mutagenesis studies showed that on the N-terminal side of the di-basic processing site, the otherwise important difference in structure between PP and NPY, a proline for glutamine in position 34, was not responsible for the difference in processing efficiency. On the C-terminal side of the processing site, the efficient processing of pro-NPY could not be transferred to pro-PP by exchanging the whole C-terminal domains of the precursors. It is concluded that pro-NPY is processed more efficiently than pro-PP in all neuroendocrine cell lines tested independent on their expression of the two main precursor convertases and that mutagenesis data indicate that the structural element responsible for the efficient processing of pro-NPY is not located on the N-terminal side of the dibasic processing site.
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PMID:Processing of two homologous precursors, pro-neuropeptide Y and pro-pancreatic polypeptide, in transfected cell lines expressing different precursor convertases. 851 71

Xenopus oocytes were injected with RNAs for the two inward-rectifier potassium channel subunits Kir3.1 (GIRK1) and Kir3.4 (rcKATP or CIR) in addition to RNA from the neuroblastoma cell line KAN-TS. Potassium currents were evoked by neuropeptide Y in oocytes injected with polyadenylated RNA or with cRNA from pools of a neuroblastoma (KAN-TS) cDNA library, and progressive subdivision of responding pools yielded a single cDNA. The encoded protein contains 381 amino acids, has the seven hydrophobic domains characteristic of G protein-coupled receptors, and is 31% identical to the Y1 receptor: potassium currents were induced by neuropeptide Y (EC50=60pm) and Y2-selective analogues. Coexpression with potassium channel subunits will be a generally useful method for the cloning of G protein-coupled receptors.
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PMID:Coexpression with potassium channel subunits used to clone the Y2 receptor for neuropeptide Y. 864 76

In order to stabilize the C-terminal dodecapeptide of neuropeptide Y (NPY) we replaced Leu28 and Thr32 by Lys and Glu, respectively, and subsequently linked these residues by lactamization. This peptide analog of NPY shows a more than 100-fold increase in affinity compared to the C-terminal linear dodecapeptide in receptor binding studies performed at human neuroblastoma cells SMS-KAN, which exclusively express the Y2 receptor subtype. Signal transduction was investigated by measuring Ca2+ current inhibition in human SH-SY5Y cells and cyclic [Lys28-Glu32] NPY Ac-25-36 and NPY were shown to be equipotent in this assay. Thus, this molecule is the smallest Y2 receptor selective full agonist of NPY. Using 2D-NMR experiments and molecular modelling techniques, the structures of the linear and cyclic peptides have been investigated and significant differences have been found, which may explain the improvement in biological activity. Thus, a model of the bioactive conformation of NPY at the human Y2 receptor is suggested.
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PMID:Modified, cyclic dodecapeptide analog of neuropeptide Y is the smallest full agonist at the human Y2 receptor. 884 57

A novel type of C-terminally modified analogs of the 36-mer peptide hormone neuropeptide Y has been synthesized, characterized and tested with respect to receptor affinity and biological activity in various systems. The compounds were obtained by synthesizing the fully protected peptide fragment NPY 1-35 or analogs of this, and coupling it in solution to various amines, alcohols, and modified tyrosine residues. It could be confirmed, that the C-terminal tyrosineamide of NPY is essential for its affinity to the Y1 receptor subtype. Obviously, the amino group of the amide part is more important than the oxygene atom of the carbonyl group, as NPY 1-35-tyrosinol has a lower affinity than NPY 1-35-tyrosinethioamide. NPY 1-35-tyramide could be shown to act as an antagonist in a Ca2+ release assay in human neuroblastoma cells. Analogs of NPY 1-35-tyramide showed the same structure-affinity relationships as NPY itself, suggesting, that there exists the same binding mode for the agonist and the antagonist.
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PMID:Structure-affinity studies of C-terminally modified analogs of neuropeptide Y led to a novel class of peptidic Y1 receptor antagonist. 887 37

The prognosis of children with neuroblastoma (NB) is dependent upon the patient's age at diagnosis, the location of the primary tumor, and histologic tumor cell differentiation. These characteristics, as well as the presumption that NB results from clonal expansion of primitive cells involved in sympathetic nervous system (SNS) development, predict that a model of tumorigenesis based upon normal fetal SNS histogenesis might indicate tumor progenitor status and define biologic and clinical behavior. Immunohistochemistry and in situ hybridization were used to examine a panel of marker gene products predicted or shown to be expressed during SNS development in the normal human fetal SNS from 8 to 24 weeks' gestational age. A similar analysis was performed in a selection of clinical NB tumors, and the results were compared. In a subset of differentiating, often extra-adrenal NB tumors in patients who frequently had a favorable outcome; advancing morphologic tumor cell differentiation spatially paralleled an advancing fetal extra-adrenal chromaffin marker gene expression phenotype (ie, increasing TrkA, TrkC, TH, IGF-2, and neuron-specific enolase expression but a lack of phenylethanolamine N-methyltransferase expression). In these tumors, expression of gene products associated with normal fetal sympathetic ganglionic differentiation (ie, Bcl-2, HNK-1, and neuropeptide Y) was lost with morphologic tumor cell differentiation. In contrast, undifferentiated tumors, the majority of which were high stage, adrenal in origin, and prognostically unfavorable, displayed marker expression characteristics mirroring that of an early fetal ganglionic lineage. Thus, we show that morphologic differentiation in stroma-poor NB tumors, long held as an important prognostic feature in tumor grading systems, often corresponds to an extra-adrenal chromaffin rather than a ganglion cell or adrenal medullary chromaffin phenotype. Understanding the biology of extra-adrenal chromaffin tissues may provide an explanation for the clinically less aggressive nature of differentiating NB tumors and suggest potential mechanisms for spontaneous regression and/or treatment response.
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PMID:A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage. 894 Dec 12

In the pursuit of potent analogues of neuropeptide Y (NPY) that are selective for the Y1 receptor subtype, two lactam bridge scans of a centrally truncated parent compound were synthesized. A single lactam bridge (gamma-carboxyl of Glu to epsilon-amino of Lys) extending from residues i to i + 3 or i to i + 4 of the proposed alpha-helical region (residues 25-31 of NPY) was introduced in des-AA7-24[Gly6]NPY. Cyclogues (contraction of cyclic analogues), which were approximately one-half the size of native NPY, were initially screened for binding affinity at two discrete NPY receptor types using human neuroblastoma cell membranes, SK-N-MC and SK-N-BE2. Exploitation of the subtle differences present on each receptor type allowed for the identification of cyclogues which bound specifically to Y1 receptors with increased affinity when compared to the corresponding linear parent analogue, while one short Y1 specific cyclogue, des-AA2,3,5,7-24cyclo-(26/29)[Gly6,Glu26,Lys2 9,Pro34]NPY, bound with Ki = 16 nM. Other cyclogues showed distinct preference for Y2 receptors and bound in the low-nanomolar range. Functionally, the compounds inhibited the norepinephrine-stimulated accumulation of cAMP indicating that all acted as agonists with varying potencies.
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PMID:Identification of high-potency neuropeptide Y analogues through systematic lactamization. 900 19

We previously isolated a 1.3-kb genomic fragment in the 5'-flanking region of the murine neuropeptide Y (NPY) Y1 receptor gene, which is able to drive the expression of LacZ reporter gene in neuronal cells. We determined the ability of deletion mutants of this region to modulate transcription of the heterologous luciferase gene in the Y1 receptor-expressing neuroblastoma/ glioma NG108-15 cells and the Y1 receptor-deficient 293 cells. Results suggest the presence of a cell type-specific core promoter (-399 to -218 from the initiator ATG) and, upstream, of two positive and two negative regulatory elements. Sequence analysis of the Y1 receptor promoter identified two decameric sequences corresponding to consensus binding sites for nuclear factor-kappa B/Rel proteins. Gel shift analysis indicated that a 29-bp oligonucleotide comprising the two putative kappa B sites, which we refer to as Y1-kappa B sequence, specifically binds kappa B-related complexes in nuclear extracts from rat brain areas, NG108-15 cells, and the murine T cell clone A.E7. In nuclear extracts from A.E7 and NG108-15 cells, the Y1-kappa B sequence specifically binds an additional complex whose molecular nature remains to be elucidated. Through transient transfection studies, we also demonstrated that the Y1-kappa B sequence acts as an enhancer element, inferring its potential role in regulation of the Y1 receptor gene expression.
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PMID:Regulation of mouse neuropeptide Y Y1 receptor gene transcription: a potential role for nuclear factor-kappa B/Rel proteins. 901 43

The modulatory effects of neuropeptide Y (NPY) on ATP-induced increases in cytosolic free-calcium concentration ([Ca2+]i) were investigated in the CHP-234 human neuroblastoma cell line. Pretreatment of cells with 100 nM NPY potentiated the increase in [Ca2+]i evoked subsequently by 20 microM ATP, compared with initial application of ATP in a control experiment, whereas a similar pretreatment with 1 microM NPY attenuated the subsequent response to ATP. Both actions of NPY were completely blocked by H-89 [N-[2-((3-(4-bromo-phenyl)-2-propenyl)-amino)-ethyl]-5 isoquinoline sulphonamide dihydrochloride], a selective antagonist of protein kinase A. The effects of 100 nM NPY were mimicked by H-89, while forskolin and 8-Br-cAMP mimicked the effects of 1 microM NPY. Both basal and forskolin-stimulated cAMP levels were inhibited by 100 nM NPY and by 100 nM NPY(13-36), a selective agonist of the NPY Y2-receptor subtype. In contrast, at 1 microM such inhibition was not observed for either NPY or NPY(13-36). It is concluded that NPY has a biphasic modulatory effect on increases in [Ca2+]i produced by ATP, which probably involves the cAMP/protein kinase A cascade.
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PMID:Neuropeptide Y modulates ATP-induced increases in internal calcium via the adenylate cyclase/protein kinase A system in a human neuroblastoma cell line. 902 Aug 78

1. In this study we have investigated neuropeptide Y (NPY) and somatostatin (SRIF) receptor-mediated elevation of intracellular Ca2+ concentration ([Ca2+]i) in the human neuroblastoma cell line SH-SY5Y. 2. The Ca(2+)-sensitive dye fura 2 was used to measure [Ca2+]i in confluent monolayers of SH-SY5Y cells. Neither NPY (30-100 nM) nor SRIF (100 nM) elevated [Ca2+]i when applied alone. However, when either NPY (300 pM-1 microM) or SRIF (300 pM-1 microM) was applied in the presence of the cholinoceptor agonist carbachol (1 microM or 100 microM) they evoked an elevation of [Ca2+]i above that caused by carbachol alone. 3. The elevation of [Ca2+]i by NPY was independent of the concentration of carbachol. In the presence of 1 microM or 100 microM carbachol NPY elevated [Ca2+]i with a pEC50 of 7.80 and 7.86 respectively. 4. In the presence of 1 microM carbachol the NPY Y2 selective agonist peptide YY(3-36) (PYY(3-36)) elevated [Ca2+]i with a pEC50 of 7.94, the NPY Y1 selective agonist [Leu31, Pro34]-NPY also elevated [Ca2+]i when applied in the presence of carbachol, but only at concentrations > 300 nM. The rank order of potency, PYY(3-36) > or = NPY > > [Leu31, Pro34]-NPY indicates that an NPY Y2-like receptor is involved in the elevation of [Ca2+]i. 5. In the presence of 1 microM carbachol, SRIF elevated [Ca2+]i with a pEC50 of 8.24. The sst2 receptor-preferring analogue BIM-23027 (c[N-Me-Ala-Tyr-D-Trp-Lys-Abu-Phe]) elevated [Ca2+]i with a pEC50 of 8.63, and the sst5-receptor preferring analogue L-362855 (c[Aha-Phe-Trp-D-Trp-Lys-Thr-Phe]) elevated [Ca2+]i with a pEC50 of approximately 6.1. Application of the sst3 receptor-preferring analogue BIM-23056 (D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2, 1 microM) to SH-SY5Y cells in the presence of carbachol neither elevated [Ca2+]i nor affected the elevations of [Ca2+]i caused by a subsequent coapplication of SRIF. The rank order of potency, BIM-23026 > or = SRIF > > L-362855 > > > BIM-23026 suggests that an sst2-like receptor is involved in the elevation of [Ca2+]i. 6. Block of carbachol activation of muscarinic receptors with atropine (1 microM) abolished the elevation of [Ca2+]i by the SRIF and NPY. 7. Muscarinic receptor activation, not a rise in [Ca2+]i, was required to reveal the NPY or SRIF response. The Ca2+ channel activator maitotoxin (2 ng ml-1) also elevated [Ca2+]i but subsequent application of either NPY or SRIF in the presence of maitotoxin caused no further changes in [Ca2+]i. 8. The elevations of [Ca2+]i by NPY and SRIF were abolished by pretreatment of the cells with pertussis toxin (200 ng-ml-1, 16 h). This treatment did not significantly affect the response of the cells to carbachol. 9. NPY and SRIF appeared to elevate [Ca2+]i by mobilizing Ca2+ from intracellular stores. Both NPY and SRIF continued to elevate [Ca2+]i when applied in nominally Ca(2+)-free external buffer. Thapsigargin (100 nM), an agent which discharges intracellular Ca2+ stores, also blocked the NPY and SRIF elevations of [Ca2+]i. 10. Delta-Opioid receptor agonists applied in the presence of carbachol also elevate [Ca2+]i in SH-SY5Y cells. When NPY (30 nM) or SRIF (100 nM) was applied together with a maximally effective concentration of the delta-opioid receptor agonist DPDPE ([D-Pen2,5]-enkephalin) (1 microM), the resulting elevations of [Ca2+]i were not greater than those caused by application of DPDPE alone. 11. Thus, in SH-SY5Y cells, NPY and SRIF can mobilize Ca2+ from intracellular stores via activation of NPY Y2 and sst2-like receptors, respectively. Neither NPY nor SRIF elevated [Ca2+]i when applied alone. The requirements for the elevations of [Ca2+]i by NPY and SRIF are the same as those for delta- and mu-opioid receptor and nociceptin receptor mobilization of [Ca2+]i in SH-SY5Y cells.
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PMID:Neuropeptide Y Y2 receptor and somatostatin sst2 receptor coupling to mobilization of intracellular calcium in SH-SY5Y human neuroblastoma cells. 903 49

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