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)

We previously cloned cDNAs encoding two different polysialic acid (PSA) synthases, ST8Sia II and IV, from mouse, and showed that both mouse ST8Sia II and IV can synthesize PSA on the neural cell adhesion molecule (NCAM) as well as other glycoproteins such as fetuin, at least in vitro (Kojima, N., Tachida, Y., Yoshida, Y., and Tsuji, S. (1996) J. Biol. Chem. 271, 19457-19463]. In the present study, to clarify how the two PSA synthases act differently in vivo, we first cloned PSA-expressing cell lines (N2a-II and N2a-IV) by stable transfection of the cDNA encoding either mST8Sia II or IV into mouse neuroblastoma Neuro2a cells, which do not express PSA but express NCAM, then compared the expression of the PSA and NCAM isoforms and de novo synthesis of PSA between N2a-II and N2a-IV. Western blotting with an anti-NCAM polyclonal antibody showed that NCAM was expressed as the polysialylated form in both ST8Sia II cDNA-transfected and ST8Sia IV cDNA-transfected Neuro2a cells, but that the polysialylated NCAMs expressed in ST8Sia IV cDNA-transfected clones migrated much slower on SDS-PAGE than those expressed in ST8Sia II cDNA-transfected clones. The slower migration of polysialylated NCAM of the ST8Sia IV cDNA-transfected clone (N2a-IV) than that of the ST8Sia II cDNA-transfected clone (N2a-II) was also observed when cells were metabolically labeled with [3H]glucosamine or pulse-chase labeled with [35S] methionine followed by immunoprecipitation with anti-PSA antibody or anti-NCAM monoclonal antibody. In addition, polysialylated N-glycans of PSA-carrying glycoproteins prepared from [3H] glucosamine-labeled N2a-IV by immunoprecipitation with anti-PSA monoclonal antibody were eluted at a much higher salt concentration than those from [3H] glucosamine-labeled N2a-II on an anion-exchange column. These results indicated that the degree of de novo polysialylation of NCAM by mST8Sia IV was much higher than that by mST8Sia II. In N2a-IV, NCAM-120, -140, and -180 were expressed as polysialylated forms, while polysialylation was restricted to NCAM-140 and -180, i.e., not NCAM-120, in N2a-ST8Sia II. Metabolic labeling of the cells with [3H] glucosamine, pulse-chase labeling with [35S] methionine followed by immunoprecipitation with anti-PSA antibody, and subsequent sialidase treatment revealed that NCAM-140 and -180 were specifically polysialylated in N2a-II, whereas not only NCAM but also other glycoproteins were de novo polysialylated in N2a-IV. The above results demonstrated that the two different PSA synthases, mST8Sia II and IV, synthesize PSA of different lengths on different substrate glycoproteins in vivo when the enzymes are expressed in neuroblastoma Neuro2a cells. These differences suggest that mST8Sia II and IV play different roles in the biosynthesis and expression of PSA.
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PMID:Two polysialic acid synthases, mouse ST8Sia II and IV, synthesize different degrees of polysialic acids on different substrate glycoproteins in mouse neuroblastoma Neuro2a cells. 949 75

Neuroendocrine-specific protein (NSP) reticulons are expressed in neural and neuroendocrine tissues and cell cultures derived therefrom, while most other cell types lack NSP-reticulons. Three major subtypes have been identified so far, designated NSP-A, NSP-B, and NSP-C. We have investigated the correlation between the degree of neuronal differentiation, determined by morphological and biochemical criteria, and NSP-reticulon subtype expression. For this purpose, several human neuroblastoma cell lines, exhibiting different degrees of neuronal differentiation, were examined immuno(cyto)chemically. It became obvious that the expression of NSP-C, as detected by immunofluorescence microscopy and Western blotting, is most prominent in cell lines with a high degree of neuronal differentiation, such as LA-N-5. Such highly differentiated cells also express other neural and neuroendocrine markers, such as neural cell adhesion molecule (NCAM), neurofilament proteins, synaptophysin, and chromogranin. NSP-A was observed in all cell lines to a different extent. However, no clear correlation was observed with the degree of neuronal differentiation as defined by other neuronal and neuroendocrine markers or morphology. NSP-B could not be detected. The induction of neuronal differentiation with nerve growth factor, dbcAMP, and retinoic acid in the rat pheochromocytoma cell line PC12 and the human teratocarcinoma cell line hNT2, respectively, induced the expression of NSP-A and NSP-C in these cell lines parallel to the induction of neurofilament protein expression. It is concluded that NSP-C expression, in particular, is strongly correlated with neuronal differentiation.
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PMID:Neuronal differentiation is accompanied by NSP-C expression. 956 Apr 66

A mounting body of evidence suggests that cell adhesion molecules (CAMs) play important roles in morphogenetic patterning of the nervous system. The combined factors that control the expression of CAMs during early neural development are, however, largely unknown. We have hypothesized that the coordinate expression of homeobox (Hox) and paired box (Pax) proteins in the neural axis leads to the differential expression of particular CAM genes. Following this hypothesis, we have characterized the promoters and identified cis-regulatory sequences that bind to and respond to Hox and Pax proteins in the genes for three neurally expressed CAMs - the neural cell adhesion molecule, N-CAM, the neuron-glia cell adhesion molecule, Ng-CAM, and L1. Experiments on transgenic mice carrying N-CAM promoter/lacZ reporter gene constructs indicated that mutation of either the HBS or the PBS disrupted patterning of N-CAM expression in the embryonic spinal cord. To examine the factors that restrict the expression of certain CAMs to the nervous system, we identified regulatory elements that block expression of the Ng-CAM and L1 genes in non-neural cells. We characterized a 310 base pair region of the first intron of the Ng-CAM gene containing five neural restrictive silencer elements (NRSEs) and a binding site for the Pax-3 protein. These elements silenced activity of the Ng-CAM promoter in NIH3T3 fibroblasts, but had no effect on its activity in N2A neuroblastoma cells line. Similar analyses of the L1 gene revealed a single NRSE within the second intron that was important for silencing in this cellular transfection system. To analyze the role of the NRSE in vivo, we prepared transgenic mice containing two L1 gene/lacZ constructs, one containing the NRSE and another in which the NRSE was deleted. The wild type L1lacZ transgene showed a neurally restricted pattern of expression, whereas the NRSE-mutated L1 construct showed extensive extraneural expression of the L1 gene. Thus, neural specificity of CAM expression is controlled by the NRSE. The general significance of these observations is that they connect the expression of important families of transcriptional regulators with gene products capable of direct cellular mechanochemistry.
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PMID:Gene regulation of cell adhesion: a key step in neural morphogenesis. 965 50

Neuroblastoma cells express the polysialylated form of the neural cell adhesion molecule (NCAM), which normally becomes restricted to a few neural tissues after embryogenesis. In this study, we investigated serum levels of polysialylated NCAM in 14 children with different grades and stages of neuroblastoma using an immunoluminescence assay, and compared the results to 269 healthy control subjects. Simultaneously, the polysialylated NCAM content of the tumours was determined by immunohistochemistry. Serum levels were dramatically elevated (more than sixfold) in children with advanced stages and fatal courses of disease, whereas children with differentiated tumour types and limited disease had low or normal levels. Serum concentrations correlated with the polysialylated NCAM content of the tumours, and they decreased during successful therapy. We therefore suggest polysialylated NCAM to be a useful marker monitoring childhood neuroblastoma.
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PMID:Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma. 966 59

Propyl-4-yn-valproic acid (2-propyl-4-pentynoic acid), an analogue of valproic acid with a triple bond in one alkyl side chain, potently induces exencephaly in mice. Given that propyl-4-yn-valproic acid is a branched chain carboxylic acid, we synthesized a series of analogues with n-alkyl side chains of increasing length and correlated their potential to induce neural tube defects and to inhibit proliferation and induce differentiation in cells of neural origin, the latter being crucial to the orderly structuring of the embryo. All analogues significantly increased the incidence of neural tube defects in the embryos of dams exposed to a single dose of 1.25 mmol/kg on day 8 of gestation. This effect occurred in a dose-dependent manner and the rate of exencephaly increased with the progressive increase in n-alkyl side chain length. Moreover, increasing chain length resulted in a dose-dependent inhibition of C6 glioma proliferation rate over a concentration range of 0-3 mM and this was independent of the cell type employed and mode of estimating proliferative rate. The antiproliferative action of these analogues was associated with profound shape change in neuro-2A neuroblastoma involving extensive neuritogenesis and an associated increase in neural cell adhesion molecule (NCAM) prevalence at points of cell-cell contact, the latter exhibiting a dose-dependent increase when the n-alkyl chain was extended to five carbon units. These results suggest an interaction with a specific site in which the n-alkyl side is proposed to serve as an 'anchor' within a hydrophobic pocket to facilitate the ionic and/or H-bonding of the carboxylic acid and high electron density of the carbon-carbon triple bond.
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PMID:Studies on the teratogen pharmacophore of valproic acid analogues: evidence of interactions at a hydrophobic centre. 975 31

To develop a specific chemotherapy modality for the perineural invasion of neural cell adhesion molecule (NCAM) positive biliary tract cancer, an anticancer drug, mitomycin C (MMC), was covalently bound to anti-NCAM monoclonal antibody (anti-NCAM MoAb) to form a conjugate using the cyanogen bromide method. The substitution ratio of the conjugate determined spectrophotometrically was 3.5 (MMC mol/immunoglobulin G mol). The cytotoxic activity of the conjugate, which was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test in the growth inhibition of the neuroblastoma cell line with NCAM expression, was maintained at 65.8% to 94.5% compared with the same concentration of MMC solution. The binding activity of the conjugate to the NCAM-positive bile duct cancer was examined by immunohistochemical staining and proved to be the same level as that of free anti-NCAM MoAb. The conjugate prepared in this study therefore appeared to be a potentially useful tool for immunotargeting specific chemotherapy against biliary tract cancer with NCAM expression.
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PMID:Preparation of a conjugate of mitomycin C and anti-neural cell adhesion molecule monoclonal antibody for specific chemotherapy against biliary tract carcinoma. 985 39

Serum concentrations of polysialylated neural cell adhesion molecule (PSA-NCAM), a developmentally regulated form of the NCAM, have been recently described to be elevated in children with rhabdomyosarcoma and neuroblastoma, proving PSA-NCAM to be a tumor marker of diagnostic relevance to these malignancies. The present investigation was undertaken to define age-dependent reference intervals in normal children. Serum concentrations of polysialylated NCAM were determined in 366 children aged newborn to 17 y and in 18 adult patients by an immunoluminescence assay using the polysialic acid-specific MAb 735. Serum levels in newborn children were 51.7 kU/L (mean +/- 12.0 kU/L SD), whereas in adult patients they were 9.9 kU/L (mean +/- 3.5 kU/l SD). Assigning the patients to 14 different age groups, a gradual decay of PSA-NCAM serum concentrations was observed, and therefore, mean levels and empirical interpolated percentiles were determined for every age group. Applying specially fitted logistic functions, two different sigmoid graphs were obtained describing the age-dependent decrease of serum PSA-NCAM during the neonatal period and during childhood. The age at which the levels reach half the initial value was located at 3.1 d (mean +/- 2 d SE) and 14 y (mean +/- 1 y SE), respectively. There was no difference between male and female individuals. Repeated measurements revealed variations below 10%. For the first time, our study describes serum levels of PSA-NCAM in children of different age and their gradual decay until adulthood.
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PMID:Polysialylated neural cell adhesion molecule serum levels in normal children. 985 27

The expression and activity of factors influencing early neuronal development are altered by ethanol. Such factors include growth factors, for example, platelet-derived growth factor and basic fibroblast growth factor (for cell proliferation), and cell adhesion molecules (for neuronal migration). One agent, transforming growth factor beta1 (TGFbeta1), may affect both events. We tested the hypothesis that ethanol alters myriad TGFbeta1-mediated activities [i.e., cell proliferation and neural cell adhesion molecule (N-CAM) expression] using B104 neuroblastoma cells. TGFbeta1 inhibited the proliferation of B104 cells as evidenced by decreases in cell number and [3H]thymidine ([3H]dT) incorporation. TGFbeta1 induced sustained activation of extracellular signal-regulated kinases (ERKs), which are part of the family of mitogen-activated protein kinases (MAPKs). Treatment with PD98059 (a MAPK kinase blocker) abolished TGFbeta1-regulated inhibition of [3H]dT incorporation. TGFbeta1-mediated growth inhibition was potentiated by ethanol exposure. Ethanol also produced prolonged activation of ERK, an effect that was partially eliminated by treatment with PD98059. On the other hand, TGFbeta1 up-regulated N-CAM expression, and this up-regulation was not affected by treatment with PD98059. Ethanol inhibited the TGFbeta1-induced up-regulation of N-CAM expression in a concentration-dependent manner. Thus, TGFbeta1 affects ERK-dependent cell proliferation and ERK-independent N-CAM expression in B104 cells. Both activities are sensitive to ethanol and may underlie the ethanol-induced alterations in the proliferation and migration of CNS neurons.
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PMID:Transforming growth factor beta1-regulated cell proliferation and expression of neural cell adhesion molecule in B104 neuroblastoma cells: differential effects of ethanol. 1034 37

Retinoic acid (RA) has been shown to induce human neuroblastoma SKNBE cell differentiation into a neuronal phenotype. Whether this neuronal differentiation is associated with modulation of matrix gelatinase [matrix metalloproteinase (MMP)-2 and MMP-9] expression was investigated in SKNBE cell cultures exposed to RA for 14 days. Their differentiation into a neuronal phenotype was typified by neural cell adhesion molecule and growth-associated protein-43 expression. Gelatinase expression was assessed by gel zymography, quantitative RT-PCR, and immunocytochemistry. Neuronal markers were located in neurites and ganglion-like clusters of neuronal cells induced upon RA exposure. MMP-2 expression was constitutive and remained unchanged at both the mRNA and protein levels in response to RA, tumor necrosis factor-alpha (TNFalpha), or phorbol 12-myristate 13-acetate (PMA) treatment. In contrast, MMP-9 was inducible by RA, TNFalpha, or PMA. MMP-9 was progressively enhanced by RA as a function of time exposure until day 14. The addition of TNFalpha or PMA potentiated RA-induced MMP-9 expression with a synergic maximal effect at day 14 of RA exposure. Immunoreactive MMP-9 was located early in outgrowing neurites, but only at day 14 of RA exposure in extensive neuritic networks. Taken together, the correlation between the MMP-9 expression by SKNBE cells and the time scale of their differentiation into a neuronal phenotype allowed us to propose that MMP-9 could participate in the neurite growth process and cell migration and organization into ganglion-like clusters.
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PMID:Induction of matrix metalloproteinase MMP-9 (92-kDa gelatinase) by retinoic acid in human neuroblastoma SKNBE cells: relevance to neuronal differentiation. 1064 1

Non-small-cell lung cancer (NSCLC) is currently one of the most prevalent malignant tumors. It displays a wide variety of phenotypes which includes neuroendocrine markers commonly found on small-cell lung cancers (SCLC) such as the neural cell adhesion molecule (NCAM) and in particular its highly polysialylated isoform, embryonic NCAM (eNCAM). NSCLC with neuroendocrine differentiation may represent a subset of tumors whose cells have a more aggressive biological behavior. A tumor marker that distinguishes this latter sub-type could be of clinical relevance. Accordingly, we have raised a monoclonal antibody of the IgM type (JLP5B9) directed against capsular polysaccharides of N. meningitidis B which bears polysialic acid groups. We have demonstrated that JLP5B9 recognizes eNCAM with high affinity and that it is specifically directed against the polysialic acid moieties of NCAM. JLP5B9 was also found to react with human SCLC, NSCLC and neuroblastoma cell lines. We then used JLP5B9 as a specific probe for the detection of tissue eNCAM and found that it was expressed on up to 20% of tumor cells obtained from 5 out of 13 patients with NSCLC. This mAb deserves further investigation to evaluate its potential as a tool for serodiagnosis of lung cancer.
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PMID:JLP5B9: new monoclonal antibody against polysialylated neural cell adhesion molecule is of value in phenotyping lung cancer. 1064 52

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