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)

Three human neuroblastoma cell lines were shown to have markedly different contents of catecholamines and serotonin. Two of the cell lines (CHP-134 and IMR-5) have higher levels of dopamine and its metabolites, while CHP-404 cells have higher levels of serotonin and its metabolites. Each cell line responded to the addition of D,L-2-amino-5-phosphonovalerate, an agent which increases plasma membrane permeability to Ca2+ (Pastuszko and Wilson, 1988; with striking changes in the metabolism of the neurotransmitters. These changes were dependent on the extracellular calcium concentration and include activation of dopamine synthesis (tyrosine hydroxylase), increased levels of dihydroxyphenylacetic acid and increased formation of N-methylated dopamine derivatives. Catabolism of serotonin to 5-hydroxyindole acetic acid was inhibited while that to 5-hydroxytryptophol was stimulated. These data clearly identify several important sites for regulation of neurotransmitter metabolism by calcium. The mechanisms, direct or indirect, by which the enzyme activities are modulated by calcium remain to be established.
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PMID:Calcium dependent regulation of catecholamine and serotonin metabolism in human neuroblastoma cells. 290 75

The susceptibility of human neuroblastoma cells to direct cellular cytotoxicity has not been previously established. This is of particular interest because of their aggressive growth and low HLA expression. Neuroblastoma lines CHP 100 and CHP 126 were found to be excellent targets in 4-hr CML assays. Natural killer (NK) cells from fresh PBL and from an NK clone, 3.3, have high lytic activity against both cell lines. We also studied mixed lymphocyte culture-generated cytotoxic lines containing allo-specific cytotoxic T lymphocytes (CTL) directed against HLA antigens present on the neuroblastoma target cell lines. These lines did show excellent lytic activity, but cold target competition studies indicated that all of the lysis resulted from NK activity. This was verified by using inhibition studies with the use of monoclonal antibodies. OKT 3 and anti-HLA antibodies that block CTL function caused no reduction in kill. In contrast, anti-lymphocyte function antigen-1 (anti-LFA-1), which blocks both NK and CTL function, significantly inhibited lysis. These results serve as a functional confirmation of earlier findings of a very weak expression of HLA-A,B,C and beta 2-microglobulin on neuroblastoma cells.
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PMID:Human neuroblastoma cell lines are susceptible to lysis by natural killer cells but not by cytotoxic T lymphocytes. 315 2

Polysialic acid-containing glycoproteins consisting of extended chains of at least 55 sialyl residues (DP55, where DP represents degree of polymerization) are expressed on human neuroblastoma cells, CHP-134. The strategy used for detecting these unique carbohydrate structures was based on the use of two highly specific prokaryotic-derived enzyme systems and an anti-polysialosyl antibody (H.46). These probes were developed for the detection of polysialic acid on neural cell adhesion molecules (Troy, F. A., Hallenbeck, P. C., McCoy, R. D., and Vimr, E. R. (1987) Methods Enzymol. 138, 169-185). Proof for the presence of long chain multimers of sialic acid was based on two types of experiments which utilized: 1) a glycopeptide fraction of CHP-134 cells, labeled metabolically with D-[3H]GlcN and 2) a membrane fraction from CHP-134 cells which served as an exogenous acceptor of [14C] NeuNAc residues in an Escherichia coli K1 sialyltransferase assay. In vitro, this enzyme CMP-NeuNAc:poly-alpha-2,8-sialosyl sialyltransferase catalyzes the transfer of [14C]NeuNAc from CMP-[14C]NeuNAc to exogenous acceptors containing at least 3 sialyl residues. In the first series of experiments, endo-N-acetylneuraminidase (Endo-N), a bacteriophage-derived enzyme specific for hydrolyzing poly-alpha-2,8-sialosyl chains containing a minimum of 5 sialyl residues was used. Limit Endo-N digestion of the 3H-glycopeptides from the [3H] GlcN-labeled cells released short [3H]sialyl oligomers [( 3H]DP1-6) which were degraded to [3H]NeuNAc by exosialidase. Partial Endo-N digestion released a series of [3H]sialyl oligomers extending up to DP55. The longer (DP20-55) and intermediate sized (DP10-20) oligomers were isolated and converted to short oligomers ((3H]DP1-6) by retreating with Endo-N, thus confirming their identity as homo-oligomers of alpha-2,8-linked [3H]NeuNAc residues. In the second series of experiments, a membrane fraction of CHP-134 cells was radiolabeled in vitro with [14C]NeuNAc by E. coli K1 sialyltransferase. The membrane fraction had a major portion of radioactivity that was high Mr and polydisperse (Mr 100,000-250,000) as demonstrated in sodium dodecyl sulfate-polyacrylamide gels. Using Western blotting, pre-existing material of similar size was shown to react with antibody H.46.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extended polysialic acid chains (n greater than 55) in glycoproteins from human neuroblastoma cells. 328 35

We have used three continuous human neuroblastoma cell lines to establish patterns of in vitro drug sensitivities, as judged by clonogenic assay. We evaluated 12 'standard' antitumor drugs already in clinical usage, and tested four newer analogues, one of cisplatin and three of doxorubicin, and the investigational agent desferrioxamine. A certain heterogeneity of drug sensitivities was noted amongst these three cell lines, but a few general conclusions can be drawn. Responses of all lines tested were similar for actinomycin D, dibromodulcitol, doxorubicin, 5-fluorouracil, melphalan and VM 26. However, line CHP 100 proved hypersensitive to amsacrine, bleomycin, methotrexate and vincristine yet refractory to cisplatin, carboplatin and VP-16, compared with the other two lines. This emphasizes the necessity for using a panel of cell lines for this type of drug screening programme. A comparison of IC50 drug concentrations, derived from these in vitro tests, with plasma levels achievable clinically, indicate that VP-16, VM 26, doxorubicin and cisplatin appear to be the most effective agents in this tumor type. This finding is consistent with clinical experience. The newer doxorubicin analogues proved 2-5 fold more cytotoxic than doxorubicin itself. However, these differences also appear to be reflected in the lower dose ranges now being tested in phase I/II clinical trials. Desferrioxamine, which proved cytotoxic against all three neuroblastoma cell lines, exerted comparable cytotoxicity against two of the three non-neuroblastoma human tumor cell lines evaluated. Therefore we suggest that attempts to identify any specific antineuroblastoma activities by new investigational agents using this type of model systems require evaluation against panels of both neuroblastoma and non-neuroblastoma lines.
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PMID:Use of human neuroblastoma continuous cell lines for in vitro drug sensitivity screening. 341 Jun 62

A protocol for the rapid cloning of many DNA fragments from an amplified genomic region is described. The procedure is based on a modification of the phenol-emulsion reassociation technique (PERT) previously used to clone DNA fragments missing from a chromosomal deletion [Kunkel et al., Proc. Natl. Acad. Sci. USA 82 (1985) 4778-4782]. The procedure was used to construct recombinant libraries in the plasmid pBR322 which were highly enriched for amplified sequences from two neuroblastoma cell lines, CHP-126 and IMR-32. Many new amplified DNA fragments were isolated from these libraries, indicating that the PERT methodology should be of general use in isolating amplified DNA from other cell lines and tumors.
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PMID:Rapid cloning of multiple amplified nucleotide sequences from human neuroblastoma cell lines by phenol emulsion competitive DNA reassociation. 359 38

The presence of fucosyl residues linked alpha 1----3(4) to N-acetylglucosamine was demonstrated on the oligosaccharides from glycoproteins of 11 human neuroblastoma tumors from ten different patients. This finding is in complete agreement with the previous report that human neuroblastoma cell lines contained an unusually large proportion of metabolically incorporated L-[3H]fucose in this specific linkage (U. V. Santer and M. C. Glick, Cancer Res., 43:4159-4166, 1983). Furthermore, the glycopeptides derived from the neuroblastoma tumors had a low percentage of fucose-containing biantennary oligosaccharides as determined by affinity to concanavalin A-Sepharose and in this characteristic were similar to glycopeptides from virus transformed and other tumor cells. To obtain these results, the tumor cells were labeled metabolically for 48 h with L-[3H]fucose. The cells were harvested and digested with Pronase, and the glycopeptides were isolated and treated with alpha-L-fucosidase from almonds, specific for the release of fucose linked alpha 1----3(4) to N-acetylglucosamine. A portion of the glycopeptides was characterized by serial affinity chromatography on immobilized concanavalin A and lentil lectin. The phenotypic similarity of the tumor cells to the cell lines, particularly CHP-134, included the paucity of biantennary oligosaccharides and the presence of fucosyl residues on the multiantennae of the glycopeptides.
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PMID:Similarities in glycosylation of human neuroblastoma tumors and cell lines. 370 96

That ferritin, an iron storage protein, can be produced by neuroblastoma cells raises the possibility that iron may have some role in promoting tumor cell growth. To explore this possibility, we studied the effects of desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP 100, two human neuroblastoma cell lines. Cells (5 X 10(4)) were incubated with graded amounts of desferoxamine or ferrioxamine, an iron-saturated analogue of desferoxamine. Within 5 days of exposure to 60 microM desferoxamine, approximately 90% of cells from each of these cell lines were dead. This effect was dose dependent, was not seen with ferrioxamine, and could be prevented by coincubation with greater than stoichiometric amounts of ferric citrate. As determined by binding of OK-T9, desferoxamine also resulted in increased expression of receptors for transferrin, an iron transport protein. Desferoxamine had only minimal effects on viability of several non-neuroblastoma cell lines. These results suggest that iron is required for growth of neuroblastoma and that desferoxamine has potent, specific, antineuroblastoma activity in vitro.
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PMID:Antineuroblastoma activity of desferoxamine in human cell lines. 381 70

The Thy-1 antigen is a cell surface glycoprotein found in neural tissue of all mammalian species so far studied. The distribution and amount of this antigen has been measured on 4 human neuronal and 2 neuroglial cell lines and on fresh tumour cells of neuronal origin. In 3 out of 4 neuronal lines (LAN-1, TR14, CHP 212) more than 90% of cells were Thy-1+, however, LAN-1 cells showed only weak immunofluorescence and bore on average 2.4 times fewer molecules of Thy-1 per cell than those of either TR14 or CHP 212. The mean number of Thy-1 molecules per TR14 cell was shown to be approximately 2.25 x 10(5). In contrast, only 66% of cells in the fourth neuronal line (CHP 100) were Thy-1+, although these showed strong immunofluorescence. Both glial cell lines, UCH-203 and H314/123, showed strong Thy-1 immunofluorescence on more than 90% of cells. Similarly, with fresh neuronal tumour cells, although approximately 80% of tumours were Thy-1+ (essentially 100% of cells in these being positive) there were considerable differences in the intensity of labelling by immunofluorescence between different tumours. Such heterogeneity in cell lines and malignancy may reflect normal in vivo variation. Different phenotypes might therefore represent separate neural cell lineages, or simply differences in maturational status within a lineage. The very low frequency of Thy-1+ cells in normal bone marrow (less than 0.1% of nucleated cells) indicates that anti-Thy-1 antibodies may be valuable in both the diagnosis and subsequent treatment of neuroblastoma.
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PMID:Human Thy-1: expression on the cell surface of neuronal and glial cells. 612 10

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

We studied the effects of nerve growth factor (NGF) to determine whether neuroblastoma (NB) cells share the pattern of altered response to growth regulatory factors shown by various malignant transformed cells. NGF induces neurite outgrowth, arrests growth, and enhances survival in normal neurons and in the rat pheochromocytoma, a tumor cell closely related to NB. With respect to neurite outgrowth, lines SK-N-SH, SH-SY5Y, LA-N-5, and CHP-126 were sensitive, IMR-32 was resistant, and SH-EP1, SK-N-MC, MC-IXC, CHP-100, and CHP-134 were unresponsive. Conditioned media from unresponsive cells did not inhibit response in sensitive cells. Unexpectedly, NGF neither reduced the growth rate nor enhanced survival in any NB cell line. Conditioned medium from all NB cell lines enhanced 125I-NGF binding in embryonic sensory cells. Regulation of growth rate and neurite outgrowth, then, are separable. A fundamental defect in NB may be the acquisition of a capacity for growth and survival independent of NGF. 125I-NGF was bound to both Fast and Slow receptors in MC-IXC cells, but only to Slow receptors in NGF-responsive SH-SY5Y and LA-N-5 cells, showing Fast receptors are not required for neurite outgrowth. Independence from NGF-regulated growth and survival is unexplainable by an absence of NGF receptors.
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PMID:Nerve growth factor effects and receptors in cultured human neuroblastoma cell lines. 629 15


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