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)

The status of the neural cell adhesion molecule NCAM gene which is mapped to human chromosome 11q23-24 has been investigated in Ewing-tumor-derived cell lines which present the t(11;22)(q23-24;q12) translocation characteristic of this malignancy. No rearrangement was detected when 2 different non-overlapping probes to mouse NCAM were used. The expression of the NCAM gene was analysed at both the protein and messenger levels in material extracted from Ewing cell lines, human neuroblastoma cell line and fetal mouse brain. Immune blot and immunoprecipitation studies showed that the neuroblastoma cell line contained more NCAM material than the Ewing lines. In neuroblastoma but not in Ewing, the NCAM material had the electrophoretic characteristics of molecules with long polysialic acid chains. After treatment with endosialidase, the diffusely migrating neuroblastoma material was resolved into 3 discrete bands of 120, 140 and 180 kDa. In Ewing extract, high-molecular-weight NCAM species were also detected with a 3-band pattern more reminiscent of mature brain. Endoglycosidase F treatment of Ewing NCAM indicated that all 3 species were largely N-glycosylated. Northern blot analysis confirmed that NCAM was expressed more abundantly in neuroblastoma than in Ewing cell lines. Among the 4 NCAM messengers (7.0, 6.5, 4.3 and 4.1 kb) detected in the neuroblastoma, the 6.5 kb species was largely predominant. The Ewing messenger RNA pattern was clearly different as the largest 7.0-kb species was virtually absent and the other bands were of similar intensities.
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PMID:Characterization of neural cell adhesion molecules (NCAM) expressed by Ewing and neuroblastoma cell lines. 303 23

We evaluated the utility of an immunocytochemical technique employing the commercially available anti-CD56 monoclonal antibody, NKH 1. The utility and sensitivity of this technique in the detection of invasive neuroblastoma (NB) cells in the bone marrow were compared with those of Wright-Giemsa staining. The correlation coefficient for the percent NB cells detected using Wright-Giemsa staining with the percent NKH 1 immunoreactive cells was 0.78. In the analysis of specificity, this monoclonal antibody showed slight cross-reactivity with normal bone marrow cells, including macrophages, lymphocytes and osteoblasts. In the evaluation of the sensitivity of the NKH 1 immunocytochemical technique, SK-N-DZ and SK-N-SH NB cell lines were added to morphologically normal bone marrow mononuclear cells from patients without NB to the final NB cell line at concentrations of 2%, 1% and 0.1%. NB cells at the final concentration of 0.1% could be detected by the immunocytochemical technique. We conclude that the NKH 1 immunocytochemical staining technique is useful in the detection of metastatic NB cells in bone marrow.
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PMID:Immunocytochemical detection of bone marrow-invasive neuroblastoma cells. 752 90

In this report, we show that the overexpression of tissue transglutaminase (tTG) in the human neuroblastoma cell line SK-N-BE(2) renders these neural crest-derived cells highly susceptible to death by apoptosis. Cells transfected with a full-length tTG cDNA, under the control of a constitutive promoter, show a drastic reduction in proliferative capacity paralleled by a large increase in cell death rate. The dying tTG-transfected cells exhibit both cytoplasmic and nuclear changes characteristic of cells undergoing apoptosis. The tTG-transfected cells express high Bcl-2 protein levels as well as phenotypic neural cell adhesion molecule markers (NCAM and neurofilaments) of cells differentiating along the neuronal pathway. In keeping with these findings, transfection of neuroblastoma cells with an expression vector containing segments of the human tTG cDNA in antisense orientation resulted in a pronounced decrease of both spontaneous and retinoic acid (RA)-induced apoptosis. We also present evidence that (i) the apoptotic program of these neuroectodermal cells is strictly regulated by RA and (ii) cell death by apoptosis in the human neuroblastoma SK-N-BE(2) cells preferentially occurs in the substrate-adherent phenotype. For the first time, we report here a direct effect of tTG in the phenotypic maturation toward apoptosis. These results indicate that the tTG-dependent irreversible cross-linking of intracellular protein represents an important biochemical event in the induction of the structural changes featuring cells dying by apoptosis.
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PMID:Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells. 793 79

The cytotoxicity against neuroblastoma cells of IL-2-activated peripheral blood (PBL) and tumor-infiltrating lymphocytes (TIL) was evaluated in seventeen patients with neuroblastoma. Regional lymph node lymphocytes (LNL) were similarly studied in some patients. Three allogeneic neuroblastoma cell lines, LA2D2, LA2B4 and SIFA, established from the different metastases of the same patient were used as targets. Of the three neuroblastoma lines, LA2D2, with low CD56 expression, was the most susceptible to IL-2-activated lymphocytes, while SIFA, with high CD56 expression, was resistant in the greatest degree. LA2B4 showed moderate susceptibility. Although TIL (73.9 +/- 2.1%), LNL (81.0%) and PBL (76.2 +/- 3.1%) revealed similar cytotoxic activity to K562, they demonstrated distinct cytotoxic activities to each neuroblastoma cell line, as follows: against LA2D2: TIL 56.3 +/- 4.2%, LNL 52.1%, PBL 33.6 +/- 4.9% (P < 0.01); against LA2B4: TIL 47.3 +/- 3.3%, LNL 37.8%, PBL 33.7 +/- 4.8% (P < 0.05); against SIFA: TIL 27.0 +/- 6.2%, LNL 20.7%, PBL 13.9 +/- 2.4% (P = 0.056). TIL always showed higher cytotoxic activity against neuroblastoma cells than those of LNL and PBL, whereas LNL were more cytotoxic than PBL. This data showed that TIL from neuroblastoma patients preferentially killed neuroblastoma cells. It was suggested that lymphocytes in the tumor site and regional lymph node could have been sensitized with neuroblastoma-related antigens and exert preferential killing activity against neuroblastoma cells. Phenotypical analysis revealed that TIL had a larger population of CD56+ cells than PBL. Conversely, PBL had a higher population of CD16+ cells than TIL. The cytotoxic activity of TIL significantly decreased by the depletion of CD56+ cells (10.9 +/- 6.2 from 49.9 +/- 5.9% against LA2D2, P < 0.001). These results indicated that CD56+ cells were most responsible for the killing of neuroblastoma cells, and that TIL, with a high proportion of CD56+ cells with strong activity, would be the best source for the immunotherapy of neuroblastoma. Additionally, since neuroblastoma cell lines used in the present study were derived from the different metastases of the same patient, heterogeneity in the susceptibility to lymphocytes might result from the differential expression of tumor-related antigens on these cell lines.
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PMID:Distinct cytotoxicity against neuroblastoma cells of peripheral blood and tumor-infiltrating lymphocytes from patients with neuroblastoma. 840 93

Amplification of the N-myc oncogene is associated with progression of neuroblastoma in humans. Previous studies indicated that neuroblastoma cell lines which are amplified for the N-myc gene and over-express N-myc exhibit enhanced tumorigenic properties when injected into athymic nude mice. In addition, neuroblastoma cells which over-express N-myc (IMR32 cells) expressed little or no beta 1, alpha 2, or alpha 3 integrin subunits, as compared with cells which do not express N-myc (SKNSH cells). In order to probe the possible relationship between N-myc and beta 1 integrin gene expressions more directly, transfection experiments were performed in which an N-myc cDNA (on the episomal expression vector pREP4; high-level constitutive expression is driven by an RSV-LTR promoter) was introduced into SKNSH cells. Expression of N-myc produced significant morphological alterations in transfected cells; one subpopulation of cells remained spread on tissue culture substrata, while a second subpopulation became rounded and grew as multi-cellular aggregates. Spread (attached) cells expressed low levels of N-myc and high levels of beta 1 integrin, while rounded (loose) cells expressed relatively high levels of N-myc and low levels of beta 1 integrin. Maintenance of transfected cells in higher concentrations of selective agent produced a higher proportion of loose cells, which expressed even greater amounts of N-myc and even less beta 1 integrin; a similar effect was observed in attached cells. Interestingly, loose cell populations expressed elevated levels of the neural cell adhesion molecule [NCAM]. The results presented here infer that N-myc regulates the expression of the beta 1 integrin and NCAM cell-surface receptors responsible for cell:extracellular cellular matrix interaction and possibly cell:cell adhesion.
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PMID:Over-expression of transfected N-myc oncogene in human SKNSH neuroblastoma cells down-regulates expression of beta 1 integrin subunit. 854 17

A method for the assay of CMP-NeuAc:(NeuAc alpha 2-->8)n (colominic acid) sialyltransferase activity was developed. Using a 1-day-old rat brain membrane fraction as an enzyme preparation optimal activity was obtained at pH 6.5, 0.3% Triton X-100, and 5 mM MnCl2. However, no absolute cation requirement was found as EDTA only partially inhibited the activity. Within a concentration range of 0.3-3 mg colominic acid (which consists of a mixture of oligomers of alpha 2-->8-linked sialic acid) per 50 microliters a V of 0.61 nmol per mg protein h-1 was estimated while a half-maximal reaction velocity was obtained at a concentration of 1.75 mg per 50 microliters. High performance anion-exchange chromatography of the radioactive products formed in the reaction showed that sialic acid oligomers ranging in size from a degree of polymerization (DP) of 2 up to at least DP 9 could serve as acceptor substrates. Comparison of the acceptor properties of DP 3 and DP 6 showed that the larger oligomer was acted upon with a 10-fold higher efficiency. Periodate oxidation of the products followed by reduction and hydrolysis yielded the C7 analogue of NeuAc as the only radioactive product, indicating that under the conditions of the assay only a single sialic acid residue was introduced into the acceptor molecules. Using the assay it appeared that in rat brain the activity of this sialyltransferase decreased six-fold during postnatal development to the adult stage. The assay method was also applied to lysates of several neuroblastoma and small cell lung tumour cell lines, which differ in the expression of polysialic acid as well as of the neural cell adhesion molecule NCAM, a major carrier of this polymer. Activity of the sialyltransferase appeared to be correlated with the expression of polysialic acid present on NCAM. These results indicate that this sialyltransferase might function in the process of poly-sialylation.
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PMID:CMP-NeuAc:(NeuAc alpha 2-->8)n (colominic acid) sialyltransferase activity in rat brain and in tumour cells that express polysialic acid on neural cell adhesion molecules. 874 61

We describe here a novel monoclonal antibody (mab H6) which recognizes CD9, an integral cell surface constituent previously described in cells of the hematopoietic lineage and involved in the aggregation of platelets. Mab H6 was raised against membranes of immature mouse astrocytes and reacted with a protein of 25-27 kD in detergent extracts of adult mouse brain membranes. Sequence analysis of the N-terminal amino acids revealed an identity of 96% with CD9 from mouse kidney. CD9 was localized in the central and peripheral mouse nervous systems: in the spinal cord of 11-day-old mouse embryos, CD9 was strongly expressed in the floor and roof plates. In the adult mouse sciatic nerve, myelin sheaths were highly CD9-immunoreactive. Mab H6 reacted with the cell surfaces of both glial cells and neurons in culture and inhibited migration of neuronal cell bodies, neurite fasciculation and outgrowth of astrocytic processes from cerebellar microexplants. Neurite outgrowth from isolated small cerebellar neurons was increased in the presence of mab H6 on substrate-coated laminin, but not on substrate-coated poly-L-lysine. Addition of mab H6 elicited an increase in intracellular Ca2+ concentration in these cells on substrate-coated laminin. Immunoprecipitates of CD9 from cultured mouse neuroblastoma N2A cells contained the alpha 6/beta 1 integrin. Moreover, preparations of CD9 immunoaffinity-purified from adult mouse brain using a mab H6 column contained the neural adhesion molecule L1, but not other neural adhesion molecules. CD9 bound to L1, but not to NCAM or MAG. Both the alpha 6/beta 1 integrin and L1 could be induced to coredistribute with CD9 on the surface of cultured neuroblastoma N2A cells. The combined observations suggest that CD9 can associate with L1 and alpha 6/beta 1 integrin to influence neural cell interactions in vitro.
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PMID:CD9 of mouse brain is implicated in neurite outgrowth and cell migration in vitro and is associated with the alpha 6/beta 1 integrin and the neural adhesion molecule L1. 883 70

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

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

Recently we were able to show that valproic acid (VPA) induces growth-arrest and differentiation of human neuroblastoma cells. Hence we investigated in vitro the antitumoral effects of VPA on malignant gliomas by determining cell proliferation and expression of CD56 and CD44 of human T98G, A172, 85HG66, 86HG39 and rat C6 cell lines. VPA at concentrations ranging from 0.1 to 1 mM strongly inhibited proliferation of A172, 86HG39, 85HG66 and C6 cells in a dose-dependent manner, whereas T98G cell growth remained unchanged. All human glioma cells were highly positive for CD44, whereas CD56 was differently expressed. After 7 days of incubation with 1mM VPA CD56 expression was markedly increased in T98G, A172 and 85HG66 cells, whereas CD44 expression was decreased in all human cell lines. These data suggest that VPA has antitumoral effects on malignant glioma cells. Therefore we consider VPA as a potent therapeutic agent for treatment of these tumors.
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PMID:Valproic acid inhibits proliferation and changes expression of CD44 and CD56 of malignant glioma cells in vitro. 985 43

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