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

We have used cDNA subtractive cloning to identify a group of human genes that are expressed in diverse differentiated derivatives of neural crest origin but not in neuroblastoma cell lines. One of these genes was identified as CD44, which encodes an integral membrane glycoprotein that serves as the principal receptor for hyaluronate and participates in specific cell-cell and cell-extracellular matrix interactions. The repression of CD44 expression in neuroblastoma cell lines might be relevant to their high metastatic potential. We have cloned full-length cDNAs corresponding to CD44 trancscripts and identified a novel splice variant of CD44 lacking 31 amino acids of the extracellular domain. As a first step toward analysis of CD44 downregulation in neuroblastoma cells, we have mapped the CD44 RNA initiation site and analyzed the structure of the upstream regulatory region. We constructed a series of plasmids containing different amounts of CD44 upstream regulatory region linked to the bacterial chloramphenicol acetyltransferase gene and then analyzed their ability to promote transcription in neuroblastoma and melanoma cells. We found that a DNA segment including about 150 bp of the CD44 upstream region and the 5' end of the gene itself was sufficient to induce substantial transcription of the chloramphenicol acetyltransferase gene in both neuroblastoma and melanoma cells. Several upstream cis-acting elements contribute to the downregulation of CD44 in neuroblastoma cells, the most prominent being a 120-bp DNA fragment located 450 bp upstream to the RNA initiation site. Our data suggest that multiple factors might be involved in downregulation of CD44 in neuroblastoma cells.
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PMID:Expression of CD44 is repressed in neuroblastoma cells. 192 57

Neural cell adhesion molecule (N-CAM) is a membrane glycoprotein expressed on neural and muscle tissues that is involved in homotypic adhesive interactions. We have demonstrated that N-CAM also is expressed on hematopoietic cells, and is recognized by the anti-Leu-19 mAb. Leu-19 is preferentially expressed on NK cells and T lymphocytes that mediate MHC-unrestricted cytotoxicity, but is also present on some myeloid leukemia cell lines. On NK cells, T cells, the KG1a.5 hematopoietic cell line, and a neuroblastoma cell line, Leu-19 is a approximately 140-kD polypeptide with N-linked carbohydrates and abundant sialic acid residues. Sequential immunoprecipitation and peptide mapping demonstrated that the Leu-19 and N-CAM molecules expressed on leukocyte and neuroblastoma cell lines are similar structures. These findings suggest that the Leu-19 antigen on leukocytes may be involved in cell adhesion, analogous to the function on N-CAM on neural cells.
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PMID:Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. 247 77

Laminin, a basement membrane glycoprotein promotes both cell attachment and neurite outgrowth. Separate domains on laminin elicit these responses, suggesting that distinct receptors occur on the surface of cells. NG108-15 neuroblastoma-glioma cells rapidly extend long processes in the presence of laminin. We report here that 125I-labeled laminin specifically binds to these cells and to three membrane proteins of 67, 110, and 180 kDa. These proteins were isolated by affinity chromatography on laminin-Sepharose. The 67-kDa protein reacted with antibody to the previously characterized receptor for cell attachment to laminin. Antibodies to the 110-kDa and 180-kDa bands demonstrated that the 110-kDa protein was found in a variety of epithelial cell lines and in brain, whereas the 180-kDa protein was neural specific. Antibodies prepared against the 110-kDa and 180-kDa proteins inhibited neurite outgrowth induced by the neurite-promoting domain of laminin, whereas antibodies to the 67-kDa laminin receptor had no effect on neurite outgrowth. We conclude that neuronal cells have multiple cell-surface laminin receptors and that the 110-kDa and 180-kDa proteins are involved in neurite formation.
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PMID:Laminin receptors for neurite formation. 296 41

Synaptophysin, an integral membrane glycoprotein of presynaptic vesicles, was tested as an immuno-histochemical marker for childhood neuroblastoma. Synaptophysin immuno-reactivity was found in all neuroblastomas (6/6), but not in the other small round-cell tumors to be considered in its differential diagnosis. Thus, rhabdomyosarcomas (0/5), lymphomas (0/4), or Ewing's sarcomas (0/2) were negative for synaptophysin. The results suggest that synaptophysin is a useful marker for neuroblastoma, and it should belong to the marker panel used for the differential diagnosis of small round-cell tumors of childhood.
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PMID:Synaptophysin--an immuno-histochemical marker for childhood neuroblastoma. 311 75

Synaptophysin, an Mr 38,000 integral membrane glycoprotein of neurotransmitter vesicles, has been identified in diverse primary neuroendocrine (NE) tumors of both neural and epithelial origin (Wiedenmann and co-workers, Proc Natl Acad Sci USA 1986; 83: 3500-3504). In the present study, metastases of several types of NE tumors, including medullary thyroid carcinoma, gastrinoma, insulinoma, small (oat) cell carcinoma of the lung, gastrointestinal carcinoid, and neuroblastoma, were examined for the presence of synaptophysin by immunocytochemistry, with the use of tissue sections as well as centrifuged cell suspensions and by immunoblotting of tumor proteins. The results show that expression of synaptophysin can be maintained during formation of metastases. Therefore, the authors propose that synaptophysin antibodies be used for the positive identification of metastatic NE tumors, notably in differential diagnosis. The possible implications of these findings for tumor diagnosis are discussed.
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PMID:Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting. 311 96

A membrane glycoprotein, Mr = 20,000, has been purified from human neuroblastoma cells (IMR-5) with the use of monoclonal antibody selected for binding capacity to human neuroblastoma cell lines. The antigen was extracted with 0.5% Nonidet P-40 from cells metabolically labeled with L-[3H]fucose or D-[3H]glucosamine. A double antibody affinity column was used to purify the membrane glycoprotein. Goat anti-mouse IgM was coupled to cyanogen bromide-activated Sepharose 4B. The absorption of the monoclonal antibody contained in ascites fluid completed the affinity column. Appropriate controls of similar material from other cell types and another monoclonal antibody demonstrated the specificity of the affinity column. Glycopeptides from the surface of human neuroblastoma cells, IMR-5 and CHP-134, had antigenic activity, as radioactive pronase-digested material bound to the affinity column and inhibited complement-mediated cytolysis. Glycolipids extracted from the cells had no antigenic activity. It was concluded that the carbohydrate residues of the glycoprotein conferred the antigenic specificity. Three methods were devised to aid in detection and purification of the antigen. These were: 1) an assay for the detection of complement-mediated cytolysis by measuring the enzyme creatine phosphokinase in the nonlysed target cells; 2) precipitation of the antigen . antibody complex with 4% polyethylene glycol; and 3) removal of the antibody by a wheat germ agglutinin-agarose column.
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PMID:A membrane glycoprotein from human neuroblastoma cells isolated with the use of a monoclonal antibody. 616 Jan 55

Interactions between neural cell surfaces seem to be of prime importance during neuroontogenesis, and responsible for the guidance of migrating neuroblasts and growing axons and for the formation of synapses. Little is known about the underlying molecular mechanisms, but most hypotheses imply the existence of cell-surface molecules that mediate the formation of transient or permanent bonds between neural cells. Recently, a membrane glycoprotein called neural cell adhesion molecule (N-CAM) has been characterized in chick and rodent nervous tissue that appears to act as a ligand in adhesion among neural cell bodies or neurites. We have identified a mouse neural surface glycoprotein, named BSP-2 (ref. 7), which by criteriaof electrophoretic migration, developmental changes, amino acid and sugar composition seems to be closely related or identical to N-CAM. Both BSP-2 (refs 8, 9) and N-CAM undergo conversion from an embryonic to an adult form during brain development and it has been suggested that this transition changes the adhesive properties or the binding specificity of the molecule. Using a neuroblastoma line to study functional differences between embryonic and adult BSP-2/N-CAM molecules, we show here that liposomes bearing adult BSP-2 but not those bearing the embryonic form adhere to neuroblastoma cells, demonstrating that the two forms do indeed possess different binding properties.
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PMID:Adult and embryonic mouse neural cell adhesion molecules have different binding properties. 687 55

Receptor-type protein tyrosine phosphatase beta (RPTP beta) is expressed in the developing nervous system and contains a carbonic anhydrase (CAH) domain as well as a fibronectin type III repeat in its extracellular domain. Fusion proteins containing these domains were used to search for ligands of RPTP beta. The CAH domain bound specifically to a 140 kDa protein expressed on the surface of neuronal cells. Expression cloning in COS7 cells revealed that this protein is contactin, a GPI membrane-anchored neuronal cell recognition molecule. The CAH domain of RPTP beta induced cell adhesion and neurite growth of primary tectal neurons, and differentiation of neuroblastoma cells. These responses were blocked by antibodies against contactin, demonstrating that contactin is a neuronal receptor for RPTP beta. These experiments show that an individual domain of RPTP beta acts as a functional ligand for the neuronal receptor contactin. The interaction between contactin and RPTP beta may generate unidirectional or bidirectional signals during neural development.
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PMID:The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a functional ligand for the axonal cell recognition molecule contactin. 762 14

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.
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PMID:[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study]. 780 68

We have prepared a monoclonal antibody, Neuro-1, that recognizes the human homolog of the chicken contactin/F11 and mouse F3 cell adhesion molecules. The Neuro-1 antigen, structurally characterized as a 135 kDa glycosylphosphatidylinositol-linked glycoprotein, was immunoaffinity purified and partially sequenced. Comparison of an internal peptide sequence to that predicted from the chicken contactin/F11, mouse F3 and human contactin (reported herein) cDNA sequence identifies the Neuro-1 antigen as human contactin. Moreover, a polyclonal antisera generated against the purified Neuro-1 antigen was immunoreactive with a fragment of human contactin expressed in bacteria. The complete coding and deduced amino acid sequences of human contactin were determined and are 86% and 95% identical to the respective mouse F3 sequences. Structural features shared with contactin/F11/F3 include six immunoglobulin type C2 and four fibronectin type III-like domains, multiple sites for asn-linked glycosylation and a COOH-terminal signal peptide presumably removed during the generation of a phosphatidylinositol cell surface linkage. The potential for glycosylation and GPI-linkage is also consistent with protein chemical studies of human contactin. Contactin mRNA expression was characterized using Northern blot analyses of human tissues and cell lines. High level expression of a single contactin transcript in adult brain, and low level expression of multiple transcripts in lung, pancreas, kidney and skeletal muscle are observed. Highly expressed multiple transcripts, similar in pattern to that of pancreas, lung, kidney and skeletal muscle, are also observed in human neuroblastoma and retinoblastoma cell lines.
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PMID:Identification and characterization of the human cell adhesion molecule contactin. 816 10


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