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)

Our studies demonstrate that rat anterior pituitary cells (GH3) are capable of synthesizing and secreting tissue kallikrein together with prolactin and growth hormone. The secretion of prolactin and growth hormone in GH3 cells was measured by two newly developed sensitive radioimmunoassays (RIA), using the polyethylene glycol separation technique. In the direct radioimmunoassay for rat tissue kallikrein, using a polyclonal antiserum which recognizes both active and prokallikrein, the GH3 kallikrein displays parallelism with standard curves of rat urinary kallikrein. The production of immunoreactive kallikrein, prolactin, and growth hormone is time-dependent, and the levels after a 72 h incubation in serum-free media are approximately 12.2 +/- 4.4 ng, 272.2 +/- 33.0 ng, and 475.6 +/- 4.8 ng per 10(6) cells per ml (mean +/- SD, n = 3), respectively. In Western blot analyses, a specific monoclonal antibody to tissue kallikrein (V4D11) identifies GH3-secreted kallikrein as a approximately 39,000 Da protein, slightly larger than approximately 38,000 Da kallikreins of submandibular gland, mouse anterior pituitary cells (AtT 20) or rodent neuroblastoma X glioma hybrid cells (NG108). Kallikrein mRNA in GH3 cells was identified in Northern blot analyses, using a tissue kallikrein cDNA probe. In a RIA using a kallikrein monoclonal antibody (V1C3) recognizing only active kallikrein, kallikrein could not be detected in the media incubated up to 48 h with GH3 cells. However, after trypsin treatment, a time-dependent increase of immunoreactive kallikrein (using monoclonal antibody V1C3), Tos-Arg-OMe esterase, and kinin-releasing activities can be measured in the conditioned media. The activated esterase activity was inhibited by aprotinin and by affinity-purified kallikrein monoclonal antibody (V4D11) in a dose-dependent manner. The data indicated that rat anterior pituitary GH3 cells secrete latent tissue kallikrein, which can be converted to active kallikrein by trypsin. These hormonally responsive cells co-synthesize kallikrein with prolactin and growth hormone and provide a model system for studying the regulation of kallikrein gene expression.
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PMID:Identification of latent tissue kallikrein, prolactin and growth hormone secretion in GH3 pituitary cells using modified radioimmunoassays. 336 Feb 6

The study of the autologous immune response to cancer avoids the difficulties encountered in the use of xenoantisera and may identify antigens of physiological relevance. However, the low titer and incidence of autologous antibody to melanoma have hampered further evaluation. By utilizing acid dissociation and ultrafiltration of serum, we have been able to augment the detectable autologous immune response to melanoma in the majority of patients studied. In autologous system Y-Mel 84:420, serum S150 demonstrated a rise in titer from 1:32 in native sera to 1:262,044 after dissociation. The antigen detected by S150 was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma, and head and neck carcinoma cell lines. It did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, or autologous cultured lymphocytes. Using polyacrylamide gel electrophoresis, S150 detects a 66,000-mol wt antigen in spent tissue culture media and serum ultrafiltrate. In cell lysate two bands between 20,000 and 30,000 mol wt are detected by S150. The 66,000-mol wt antigen is sensitive to trypsin digestion and but is resistant to pepsin and heat inactivation. Exposure of spent media to trypsin results in the development of a 24,000-mol wt band that appears to correspond to the antigen detected in the cell lysate. The difference between the antigens detected in the cell lysate as compared with spent media and serum ultrafiltrate may be due to degradation during cell lysis. We conclude that melanoma-associated antigens are present in the serum of patients with melanoma and are shed or secreted by their tumor cells.
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PMID:Isolation and partial characterization of melanoma-associated antigens identified by autologous antibody. 338 49

Ciliary neurotrophic factor (CNTF) is a protein supporting the in vitro survival of a characteristic spectrum of embryonic chicken and rat peripheral neurons. High-speed supernatants of extracts from two neuroblastoma (NB) cell lines--the mouse C 1300 N2a and the human IMR 32--mimic the effects of CNTF on identical target neurons. Promotion of survival is dose-dependent with an ED50 of 80 micrograms (IMR 32) and 140 micrograms (C 1300 N2a) of protein per ml and saturable at plateau values for surviving neurons identical to those achieved with purified CNTF. Small amounts of a CNTF-like material are also detectable in medium conditioned by NB cells. The activity is destroyed by heat and trypsin and not blocked by antibodies to (mouse) nerve growth factor. Unlike the neurite-promoting and neuronal-survival modulating agent laminin, it cannot be depleted on poly(L-alpha-ornithine)-coated plastic surfaces. NB IMR 32 cell extracts were electrophoresed using NaDodSO4/PAGE and transferred to nitrocellulose. Ciliary ganglion neurons seeded on the blotting paper in culture medium lacking CNTF ("cell blot") exclusively survive on two distinct bands with apparent molecular masses of 24 and 48 kDa. Twenty-four kilodaltons is the molecular mass of a CNTF purified from rat sciatic nerve. These results suggest that NB cells may contain a CNTF-like protein and provide further evidence that neurons may store neurotrophic factors. Purified (chicken) CNTF failed to affect proliferation and neurite growth of NB cells. The biological relevance of CNTF for NB cells, therefore, remains to be elucidated.
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PMID:Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor. 347 25

We studied (a) the distribution and properties of fast and slow 125I-nerve growth factor (125I-NGF) binding sites in cultured human neuroblastoma (NB) cell lines that were categorized as responsive (N+) or unresponsive (N-) to NGF by neurite outgrowth, (b) whether fast or slow sites mediate actions of NGF, and (c) whether NGF-mediated conversion of fast to slow sites occurs in human NB and pheochromocytoma PC 12 cells. In human NB SH-SY5Y cells, the slow sites were trypsin resistant and binding was of high affinity. Loss of binding to the slow sites had a half-time of 25 to 30 min at 37 degrees C and was very slow at 4 degrees C. In contrast, the fast sites were trypsin sensitive and binding was of lower affinity; its dissociation half-time was less than 1 min at 4 degrees C and 37 degrees C. The association rate constants of both sites were about 0.8 to 1.2 X 10(7) M-1 sec-1. Some human NB cells had both fast and slow sites. The N+ human NB lines SH-SY5Y and LA-N-5 had only slow sites. Despite the virtual elimination of fast sites by trypsin in NB MC-IXC cells, remaining slow sites could still efficiently bind 125I-NGF. These observations showed that fast sites are not required for slow site binding, neurite outgrowth, or other demonstrated actions of NGF in some NB cells. In PC 12 cells, 125I-NGF initially bound to fast sites was not directly transferred to slow sites as required for NGF-mediated conversion. The association rate constants of fast and slow sites in PC12 cells were both about 2 X 10(7) M-1 sec-1. The association kinetics were consistent with simple bimolecular reactions in both NB and PC12 cells. The combined evidence in NB and PC12 cells did not support the hypothesis of NGF-mediated conversion of fast to slow sites.
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PMID:Fast and slow nerve growth factor binding sites in human neuroblastoma and rat pheochromocytoma cell lines: relationship of sites to each other and to neurite formation. 402 Apr 17

It was recently reported (Endoh et al. 1981, Exp Cell Biol 49:272-277) that conditioned medium of neonatal mouse brain (CM-NB) inhibited the growth of mouse neuroblastoma cells. In this work we fractionated CM-NB by size exclusion high performance liquid chromatography, and separated two active principles (28,000 and 62,000 daltons) Each or a combination of the 28,000 and 62,000 dalton fractions showed a differential inhibitory effect on DNA synthesis or clonal growth of the three human lung cell lines: the normal diploid fibroblast WI38 cells were less susceptible than their simian virus 40-transformed VA13 cells and carcinoma A549 cells. This preferential growth-inhibition of malignant cells was also observed for rat fibroblast 3Y1 and its simian virus 40-transformed W3Y cells, and for two other normal and five other malignant cell lines. The growth-inhibitory activity of CM-NB or the 28,000 and 62,000 dalton fractions was lost by pronase, trypsin, tetrahydrofuran, acetonitrile, or dithiothreitol in the presence of guanidine, and also labile to heat, vigorous agitation, or freeze-thawing. The activity was also found in the conditioned medium of prenatal mouse brain, but not in either the conditioned medium of the adult brain and of the secondary culture of the neonatal brain, or in the homogenate and rinsing fluid of the neonatal brain. Thus the mouse brain at the terminal stage of ontogenesis liberates proteinaceous factors, which exhibit a preferential growth-inhibition of tumor or transformed cells and act on malignant cells of human and rodent origin.
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PMID:Inhibition of tumor cell growth by protein factors derived from the developing mouse brain. 407 18

Murine C 1300 neuroblastoma cells bind with high avidity on their membrane surface the nerve growth factor (NGF), a protein capable of inducing differentiation of sympathetic nerve cells. The total binding capacity of NGF by the cells was quantitatively measured by a radioimmunoassay technique, using (125)I-labeled NGF. An average number of about 10(6) molecules of NGF could be bound, at saturation, by each cell with an average relative association constant of about 10(7) liters/mol. Using synchronized cells, it was found, however, that either the number of molecules of ligand bound or the avidity of the binding interaction between NGF and cells varied depending upon their growth cycle, the maximal-binding occurring during the G(1) and early S phase. Binding of [(125)I]NGF was suppressed by trypsin treatment of the cells, however new receptor sites were rapidly replaced onto the membrane surface within 1-2 h. Cells exposed to 3 M KCl released into the supernate a protein product exhibiting similar high avidity for NGF. Acrylamide gel electrophoresis suggested a restricted molecular heterogeneity of this product, with a major component in the 52,000 mol wt region. Antibodies made specific to this protein were capable, in the absence of the complement, of inhibiting the binding of [(125)I]NGF by the cells and in the presence of the complement they killed them.
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PMID:Specific binding of nerve growth factor (NGF) by murine C 1300 neuroblastoma cells. 421 Oct 21

Sequential removal of surface glycopeptides was achieved by subjection of mouse neuroblastoma cells to a two-step trypsin treatment under different conditions. The glycopetides released by each trypsinization step were digested by Pronase and examined on columns of Sephadex G-50. Different chromatographic patterns were found for the two digests. Thus, several groups of glycopeptides can be distinguished by the trypsinization procedure. One group is readily removed and appears to be at a more accessible location on the cell surface. Among the four neuroblastoma clones examined, the glycopeptide patterns from axon-forming cells differed from those of axon-minus cells.
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PMID:Glycopeptides from surface membranes of neuroblastoma cells. 451 27

The activity of alpha-thrombin and chemically modified derivatives of this enzyme in stimulating cGMP formation in murine neuroblastoma clone N1E-115 cells is reported. The rank order potency of the compounds falls into three classes: 1) alpha-thrombin is the most potent and effective; 2) the catalytically active enzymes gamma-thrombin, trypsin, and nitro-alpha-thrombin are approximately 50-fold less potent than alpha-thrombin; and 3) active site blocked derivatives of alpha-thrombin are 100 to 1000-fold less potent than alpha-thrombin. Native alpha-thrombin consistently produces the most effective response, usually 1.5 to 3-fold greater than any of the other compounds tested. Preincubation of cells with quinacrine, an inhibitor of phospholipase A2, or with the lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid or nordihydroguaiaretic acid prior to thrombin challenge resulted in a concentration-dependent attenuation of the response. Indomethacin was without effect in modifying the response. These results suggest that thrombin stimulation of neuroblastoma cells involves the release of arachidonic acid and its metabolism by lipoxygenase. These results clearly demonstrate the activity of alpha-thrombin in stimulating a receptor-mediated response in cultured nerve cells. The results are discussed in relation to the interaction of endogenous alpha-thrombin with nerve cells following invasive trauma and to the possible presence of endogenous proteinases with a neurotransmitter-like function.
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PMID:Activation of cyclic nucleotide formation in murine neuroblastoma N1E-115 cells by modified human thrombins. 608 21

The activity of the neutral, Mg2+-stimulated sphingomyelinase of cultured neuroblastoma cells (N1E-115) is enriched in the plasma membrane fraction and is reduced following treatment of intact or broken cells with trypsin, alpha-chymotrypsin, papain, and protease. Two protease-sensitive enzymes of the cell interior (lactate dehydrogenase and NADPH-cytochrome c reductase) are not affected by protease treatment of intact cells. These results indicate that the neutral, Mg2+-stimulated sphingomyelinase is oriented externally on the plasma membrane of the cultured neuroblastoma cell.
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PMID:Evidence that neutral sphingomyelinase of cultured murine neuroblastoma cells is oriented externally on the plasma membrane. 609 59

Confluent cultures of a human neuroblastoma cell line (CHP100) were incubated for 48 h with D-[1-3H]glucosamine and sodium [35S]sulphate. Radioactive glycosaminoglycans were analysed in the growth medium, rapid trypsin digest of the cell monolayer and a 1% (w/v) Triton/0.5 M NaOH extract of the final cell pellet. Sulphated glycosaminoglycans co-chromatographed when eluted by NaCl gradient from DEAE-cellulose. The medium contained mainly chondroitin sulphates, whereas the cell surface was enriched in heparan sulphate. Heparan sulphate was isolated as chondroitinase ABC-resistant material and treated with nitrous acid. Analysis of the scission products on Bio-Gel P-10 yielded fragments varying in size from single disaccharides to glycans consisting of nine disaccharide units. Cell-surface and medium heparan sulphate had respectively 52% and 54% N-sulphated glucosamine residues distributed in similar patterns along the polymer chain. The N:O-sulphate ratio of neuroblastoma heparan sulphate was 1.1:1. Analysis by high-voltage electrophoresis of di- and tetrasaccharide products produced by nitrous acid treatment showed that the distribution of 'O'-sulphate groups differed strikingly between heparan sulphates from the medium and cell-surface compartments. A di-O-sulphated tetrasaccharide was identified in both heparan sulphate species. The absence of detectable amounts of 35[S]sulphate associated with fragments larger than tetrasaccharide supports the close topographical association of N-sulphate and O-sulphate groups.
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PMID:Differences in the distribution of O-sulphate groups of cell-surface and secreted heparan sulphate produced by human neuroblastoma cells in culture. 622 67


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