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)

Neutral endopeptidase-24.11 (EC 3.4.24.11) (NEP) is a transmembrane metallo-endopeptidase that has been shown to be involved in the degradation of several mammalian neuropeptides, including enkephalins. The enzyme has recently been found to be specifically associated with the axonal and synaptic membranes of neurons in the globus pallidus of the pig brain. This result suggests that neurons must possess mechanisms for targeting NEP to particular membrane domains. Study of these mechanisms would greatly benefit from the existence of an established neuron-like cell line capable of expressing and targeting NEP to specific membrane domains. For this reason we have used a retroviral vector containing the cDNA for rabbit kidney NEP to express this enzyme in a mouse neuroblastoma cell line (Neuro2A). Labelling of the cell surface with an antibody coupled to colloidal gold particles and examination of the cells by electron microscopy revealed a non-uniform distribution of NEP at the surface of the cells, the protein being preferentially associated with the membrane of neurites compared with the cell body. This observation suggests that Neuro2A cells possess a mechanism for targeting NEP to specific domains of the plasma membrane. This cell line could thus constitute a good model for studying the mechanisms responsible for targeting this enzyme to specialized regions of the plasma membrane.
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PMID:Recombinant neutral endopeptidase-24.11 expressed in mouse neuroblastoma cells is associated with neurite membranes. 233 3

Neuroblastoma (NB) is a solid tumor of childhood with a relatively bad prognosis, with the exception of young infants (less than 1 year), in whom spontaneous regression of tumor burden occurs. The reasons for this are still unknown but immune mechanisms may be involved. In this study, we have examined the ability of several monoclonal antibodies (MoAbs), which recognize markers predominantly expressed on human haematopoietic cells, to react with four human neuroblastoma cell lines (UKF-NB 1-4) and SK-N-SH as control cell line. In order to define the phenotype of NB cells, we used a large panel of MoAbs consisting of 2 major groups: a) well characterized MoAbs raised against antigens of neuroectodermal origin from the Kemshead-serie (e.g. UJ 13A, UJ 127.II, UJ 167.11, UJ 181.4, UJ 223.8, A2B5), b) monoclonal antibodies which have been considered to react with haematopoietic cells (HLA-DR and anti-CD-molecules CD1, CD7, CD9, CD10, CD13, CD16, CD19, CD20, CD24, CD57). The phenotypic analyses were performed at various times of culture by an immunoenzymatic procedure (APAAP-technique). Most of the MoAbs used against neuroblastoma cells showed a strong reactivity pattern with the NB cell lines. None of the antibodies against T-lymphocytes bound to any of the NB cells assayed in our study, with the exception of anti-CD 1. On the contrary, B-cell markers BA-2 (CD9) and BA-1 (CD24) cross-reacted with the NB cells just as well as the marker for NK-cells (CD57), but they did not express reactivity with Leu-11b (CD16), anti-CALLA (CD10) and anti-HLA-DR.
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PMID:Expression of markers shared between human haematopoietic cells and neuroblastoma cells. 238 85

The ability of normal human fibroblast-derived chromosomes to suppress tumorigenicity in nude mice and in vitro growth properties of various tumor cell lines was examined. Normal human chromosomes tagged with pSV2neo gene by DNA transfection were transferred to the following human tumor cell lines by microcell-fusion: SiHa (uterine cervical carcinoma), A204 (rhabdomyosarcoma), SK-NEP-1 (Wilms' tumor), HHUA (uterine endometrial carcinoma), SK-N-MC (neuroblastoma), YCR (renal cell carcinoma), HT1080 (fibrosarcoma), and CC1 (chorionic carcinoma). The results indicate the presence of a putative tumor-suppressor gene(s) in multiple chromosomes, and suggest that multiple genes may normally be involved in suppressing the transformed phenotypes at different stages in some tumors. Thus, the microcell transfer of chromosomes to specific tumor cell lines is a useful technique to demonstrate the presence of tumor-suppressor genes on individual chromosomes, and may also be useful in cloning of tumor-suppressor genes as well as elucidating their function in cell-growth and differentiation.
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PMID:Multiple chromosomes carrying tumor suppressor activity, via microcell-mediated chromosome transfer, for various tumor cell lines. 248 35

The presence of neonatal (cord) lymphokine-activated killer (LAK) cell activity toward natural killer cell resistant Raji and Daudi cell lines has recently been reported from our laboratory. We investigated the future therapeutic use of LAK adoptive immunotherapy by examining LAK in vitro cytotoxicity from both neonatal and adult mononuclear cells against solid tumor cell lines of relevance to pediatric oncology: SH-SY5Y (neuroblastoma), SK-NM-C (neuroblastoma-neuroepithelioma), NEP-1 (Wilms' tumor), SK-ES-1 (Ewing's sarcoma), and A-204 (rhabdomyosarcoma). Cord and adult mononuclear cells were activated by recombinant IL-2 (100 mu/ml) for 5-7 days and added in an effector:target ratio of 40:1 to 51Cr-labeled target cells. Specific cell lysis was determined after a 4-h incubation. There was a significantly high level of cord and adult LAK cytotoxicity against Wilms' (76.4 +/- 9.8 versus 77.3 +/- 6.8%) and Ewing's (84.2 +/- 5.5 versus 71.1 +/- 6.5%) cell lines and significant but moderate LAK activity against neuroepithelioma (52.0 +/- 6.6 versus 55.4 +/- 4.5%) and rhabdomyosarcoma (46.6 +/- 5.7 versus 43.9 +/- 5.2%) cell lines. There was no difference between cord and adult LAK activity toward these targets. However, a differential response toward the more classical neuroblastoma cell line, SH-SY5Y, was noted with significantly more LAK cytotoxicity from cord mononuclear cells than adult mononuclear cells (51.2 +/- 6.9 versus 28.5 +/- 8.2%) (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lymphokine-activated killer cytotoxicity in neonatal mononuclear cells: in vitro responses to tumor cell lines from pediatric solid tumors. 253 88

Recently, great interest has been shown in the histological identification of small cell tumours of childhood--nephroblastoma (Wilms' tumour), neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma--using immunohistochemical methods. However, several antigens operationally specific for leucocyte typing in blood and marrow are also expressed on cells of epithelial and neural origin. We undertook phenotypic characterization of 17 non-haemopoietic small cell tumours of childhood using a panel of 30 monoclonal antibodies to leucocyte, epithelial and cytoskeletal antigens using a sensitive alkaline phosphatase-anti-alkaline phosphatase technique on cryostat sections of fresh tumour. Our results demonstrated frequent expression of the leucocyte-associated antigens CD10 (CALLA), CD9 (p24) and CDw32 (FcRII) in these small cell tumours and occasional expression of MHC class II (HLA-DR) and HNK-1 antigens. However, the leucocyte-associated antigens CD45 (leucocyte common), CD22 (pan B-cell), CD11b (C3bi receptor), CD15 (Lewisx) or CDw42 (platelet gp Ib) were not detected on any tumour. Aberrant expression of desmin, neurofilament and UJ13A antigen was found in nephroblastoma and of epithelial-associated markers (CIBr17 and 43-9F) in neuroblastoma. Our results also demonstrated broad reactivity in frozen section with two monoclonal antibodies specific for melanoma (NKI/C-3) or epithelial cells (OM-1) in paraffin sections. Hence, it is necessary to include monoclonal antibodies to CD45 and pan-epithelial antigens, e.g. LP34 (cytokeratin) or HEA125 for the precise immunohistochemical identification of small round cell malignancies of childhood.
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PMID:Phenotypic characterization of non-haemopoietic small cell tumours of childhood with monoclonal antibodies to leucocytes, epithelial cells and cytoskeletal proteins. 254

Between 1980 and 1986, 44 children with acute lymphoblastic leukemia (ALL) or Stage IV neuroblastoma (NB) underwent allogeneic or autologous bone marrow transplantation (BMT). Twenty-nine of these patients were alive and in remission 3 months post BMT and were evaluable for this analysis of whom eleven have developed renal dysfunction. Six of 17 (35%) evaluable ALL patients developed renal dysfunction (3.5 to 6 months post BMT). This group was transplanted for CALLA positive ALL and received an autologous transplant. Preparation included tenopiside (VM 26) cytosine arabinoside, and cyclophosphamide followed by total body irradiation (TBI). One patient received 850 cGy in a single fraction, while all other patients received fractionated TBI (1200-1400 cGy in 6-8 fractions over 3-4 days). Five of 7 (71%) evaluable patients who received a BMT for NB have developed late renal problems (4-7 months after BMT). The preparation for NB patients included VM 26, cis-platinum, melphalan, cyclophosphamide, and fractionated TBI (1200-1296 cGy). All seven NB patients had received cis-platinum as induction treatment prior to transplantation. All patients presented with anemia, hematuria, and elevations of BUN and creatinine. Two patients underwent renal biopsies which were consistent with radiation nephropathy or hemolytic uremic syndrome. In conclusion, a high incidence of renal dysfunction has occurred 3 to 7 months after BMT for children with NB and ALL. The clinical and laboratory features are consistent with either acute radiation nephropathy or hemolytic-uremic syndrome. These patients were prepared for BMT with multiple chemotherapeutic agents as well as TBI. The relatively young age of these patients and conditioning with intensive multi-agent chemotherapy may decrease the tolerance of the kidney to radiation injury.
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PMID:Late onset of renal dysfunction in survivors of bone marrow transplantation. 296 67

The expression of common acute lymphoblastic leukemia antigen (CALLA) on a human neuroblastoma cell line, SJ-N-CG, was demonstrated by indirect membrane immunofluorescence, complement-dependent cytotoxicity, and quantitative absorption, using two monoclonal antibodies (J-5 and BA-3) directed against CALLA. Immunoprecipitation of solubilized 125I-labeled membrane proteins from SJ-N-CG cells with J-5 antibody revealed a protein with a molecular weight of 100,000 as determined on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Morphological differentiation of SJ-N-CG cells could be induced in the presence of 2.0 mM dibutyryl adenosine 3'-5'-cyclic monophosphoric acid for 10 days of culture. Changes in cell surface membrane antigens associated with morphological differentiation were studied by indirect immunofluorescence and complement-dependent cytotoxicity using a panel of seven monoclonal antibodies. Increases in the antigens recognized by BA-2 (detecting leukemia-associated antigen), anti-Thy-1, and antibody 390 (Thy-1 antigen) were found in "differentiated cells," while those detected by BA-1 (B-cell-associated antigen) and J-5 (CALLA) were unchanged. In contrast, the antitransferrin receptor defined by B3/25 was inhibited, and expression of B7/21-defined la-like antigen was not induced. Kinetic studies on antigenic alterations showed that the expression of BA-2-defined antigen rose on Day 2 and remained at the same level until Day 10. The expression of CALLA was not changed from Days 2 to 10. The augmentation of Thy-1 antigen was noted on Day 4 and reached the maximum on Day 10. These results show that dibutyryl adenosine 3'-5'-cyclic monophosphoric acid is capable of inducing phenotypic changes in SJ-N-CG cells. The changes of expression of some antigens on exposure of cells to dibutyryl adenosine 3'-5'-cyclic monophosphoric acid may enable us to have a greater understanding of the differentiation of neuroblastoma to a more mature ganglioneuroblastoma phenotype.
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PMID:Altered expression of cell surface membrane antigens in a common acute lymphoblastic leukemia-associated antigen-expressing neuroblastoma cell line (SJ-N-CG) with morphological differentiation. 298 Nov 59

Mouse Neuro-2a neuroblastoma and rat C6 glioma cloned cells were screened for neuropeptide-metabolizing peptidases using a kininase bioassay combined with a time-course bradykinin-product analysis, and a fluorimetric assay for prolyl endopeptidase. The complementary peptide products Arg1----Phe5/Ser6----Arg9 and Arg1----Pro7/Phe8-Arg9 were released during bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) inactivation by homogenates of Neuro-2a and C6 cells. The 1:1 stoichiometry of the complementary fragments and their high yields, at 10% bradykinin inactivation, demonstrated the sites of hydrolysis. The initial rate of Phe5-Ser6 bond cleavage was six-fold higher than that of the Pro7-Phe8 bond. These sites of cleavage can be attributed to enzymes similar to endopeptidase A (Phe5-Ser6) and prolyl endopeptidase (Pro7-Phe8) on the basis of the specificity and sensitivity to inhibitors of the kininase activity in Neuro-2a and C6 cell homogenates. Kininase and prolyl endopeptidase specific activities (fmol/min/cell) were 10.5 and 12.4 for Neuro-2a, and 1.5 and 2 for C6 homogenate, respectively. The recovery of kininase activity was 2.2-fold higher in the particulate than in the soluble (105,000 g for 1 h) neuronal fraction, whereas the amount of prolyl endopeptidase activity was about the same in both fractions. Kininase and prolyl endopeptidase activities in C6 cells were recovered mostly in the soluble fraction. Prolyl endopeptidase specific activity decreased 10-fold in serum-starved Neuro-2a cultured cells, with no change in activity in similarly treated C6 cells. In contrast, kininase specific activity in both cell types was essentially unaffected on serum-deprivation-induced differentiation.
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PMID:Neuropeptide-metabolizing peptidases in neuro-2a neuroblastoma and C6 glioma cells. 301 93

Both the sulphated and non-sulphated forms of cholecystokinin (CCK) octapeptide are susceptible to hydrolysis by the cell-surface peptidases endopeptidase-24.11 (NEP), angiotensin converting enzyme and aminopeptidase N (AP-N). Indirect studies have previously implicated an elastase-like serine endopeptidase in CCK metabolism in brain. We have therefore compared the hydrolysis of CCK, in both sulphated and non-sulphated forms by solubilized membrane preparations from the human astrocytoma clone D384 and the neuroblastoma line SH-SY5Y. Selective peptidase inhibitors were used to elucidate the principal activities involved in CCK metabolism. In the glial cell line the hydrolysis of cholecystokinin octapeptide (CCK-8), sulphated or non-sulphated, was inhibited predominantly by the NEP inhibitor, phosphoramidon (PR). In contrast, in the neuroblastoma line, angiotensin converting enzyme (ACE) was seen to play a major role in metabolism of CCK-8 with a lesser effect attributable to NEP but with some differences between sulphated and non-sulphated forms reflecting the preference of ACE for CCK-8ns. In neither cell line was a significant effect of the serine peptidase inhibitor Dip-F seen on CCK metabolism arguing against the presence of a putative CCK-degrading serine peptidase in these cell lines. Both NEP and ACE remain as candidates for inactivation of CCK at the cell surface.
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PMID:Comparison of cholecystokinin metabolism by membrane preparations from the human astrocytoma clone D384 and the neuroblastoma line SH-SY5Y. 791 87

Normal and tumoral human pituitaries release in vitro SRIH and contain messenger RNAs encoding preproSRIH. In the present study, we document the presence and characterization of the SRIH precursor in both human normal pituitaries and in GH-secreting adenomas. Molecular sieve filtration of normal pituitary and adenoma acid extracts revealed the presence of three immunoreactive SRIH peaks, distinct from SRIH 1-28 and SRIH 1-14. Western blot analysis performed under both nonreducing and reducing conditions confirmed the presence of the three different immunoreactive forms with respective molecular masses estimated as 21, 17, and 12 kilodaltons. When analyzed in reverse phase high performance liquid chromatography, the three immunoreactive SRIH material contained in the three peaks coeluted with the proSRIH extracted from rat hypothalamus and from a neuroblastoma cell line (N2A) transfected with the human preproSRIH complementary DNA. None of these three forms could bind concanavalin A. Digestion of the three forms with a specific endopeptidase resulted in the generation of SRIH 1-14, indicating that they can be considered as SRIH precursor or related forms. Estimation of proSRIH amount after molecular sieve filtration indicated that normal human pituitaries (n = 4) contained proSRIH in variable amounts (from 26.5-303 pg/mg proteins), the 21-, 17-, and 12-kilodalton forms being always present, in addition to SRIH 1-28. In contrast, among the 21 adenomas tested, only 11 contained proSRIH material (from 9-4480 pg/mg proteins). Moreover, neither SRIH 1-28 nor SRIH 1-14 could be detected in these adenomas. These data demonstrate the presence of high molecular mass SRIH in normal pituitaries which represent unprocessed proSRIH material. This provides an additional argument for a local synthesis of SRIH. Additionally, the fact that only 50% of GH-secreting pituitary adenomas here studied contain exclusively proSRIH may reflect an alteration in messenger RNA translation or in proSRIH processing, or both, resulting in the absence of mature SRIH in these adenomas.
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PMID:Presence and characterization of the somatostatin precursor in normal human pituitaries and in growth hormone secreting adenomas. 809 21

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