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)

Methods were developed to test angiogenic response to human tumor implants and various biologic agents in the cornea of rabbits and non-human primates (Macaca arctoides). Crude PDGF preparations were found to have significant angiogenic effect. Purified, recombinant PDGF preparations were also effective inhibitors (e.g. pentoxifylline (Px) (which also were found to release PgI2 and t-PA) inhibited human tumor implant induced angiogenesis and reduced spontaneous metastases in 3 transplantable murine tumors (Furth-Columbia Wilms' tumor in Furth-Wistar rats, C-1300 neuroblastoma in A/J mice and HM-Kim mammary carcinoma in Wistar rats) but not in the NIH adenocarcinoma in Balb/c mice. Sodium diethyldithiocarbamate (DDTC), a metal complexing agent with special affinity to copper and anti-thyroid as well as, immune stimulating activity was shown to be anti-angiogenic and to potentiate the effect of Px. The anti-fibrinolytic agents epsilon amino caproic acid (EACA) and tranaxamic acid (t-AMCHA) were anti-angiogenic. DDTC and Px were synergistic from this point of view.
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PMID:Studies on tumor induced angiogenesis. 137 68

The heparin-binding p30 protein amphoterin is proposed to mediate adhesive interactions of the advancing plasma membrane in migrating and differentiating cells. Since the NH2-terminal part of amphoterin is exceptionally rich in lysine residues, we have studied its interactions with plasminogen and tissue plasminogen activator (t-PA). On immunostaining of N18 neuroblastoma cells, amphoterin and t-PA showed a close co-localization in the filopodia of the leading membrane and in the substrate-attached material. In purified systems, both t-PA and plasminogen bound to immobilized amphoterin, and their binding was inhibited by the lysine analogue epsilon-aminocaproic acid. Plasminogen bound to immobilized amphoterin was activated by t-PA, and this resulted in effective degradation of the immobilized amphoterin. Correspondingly, amphoterin-bound t-PA activated plasminogen. In solution amphoterin accelerated t-PA-catalyzed plasminogen activation maximally 46-fold. The results indicate that t-PA and plasminogen form through their lysine-binding sites a complex with amphoterin, which results in acceleration of plasminogen activation and effective degradation of amphoterin. We suggest that local acceleration of t-PA-catalyzed plasminogen activation by amphoterin at the leading membrane enhances the penetration of growing cytoplasmic processes through extracellular materials during cell migration, differentiation and regeneration. The amphoterin-mediated adhesion at the leading membrane may be transient in nature, because the protein also enhances its own breakdown by accelerating t-PA-catalyzed plasminogen activation.
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PMID:Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin. 190 31

Recent studies suggest that the nature of events leading to the formation, maintenance, and elimination of synapses may be regulated by cascade-type, locally expressed proteases and protease inhibitors acting on adhesive extracellular matrix components. We have identified a molecule in conditioned medium of murine skeletal muscle cells that in molecular weight, target protease inhibition, heparin-binding and cross-reactivity with authenic antisera is similar to the human serine proteinase inhibitor, protease nexin I. Protease nexin I is a 43-50 kDa glycoprotein of the serpin superfamily (arg-serpin class). Purified anti-protease nexin I antibody (anti-47 kDa) stains adult mouse skeletal muscle in discrete foci that precisely superimpose on synaptic neuromuscular junctions. Protease nexin I appears in patches on surfaces of cultured mouse skeletal myotubes, but not on myoblasts. These patches co-localize with acetylcholine receptor clusters and acetylcholinesterase staining during cellular maturation in culture. Evidence that protease nexin I is a synaptic, extracellular antigen is particularly intriguing since it has been shown to be identical, in structure and activity, with a factor released by glial cells, called glia-derived nexin that stimulates mouse neuroblastoma cell neurite outgrowth and inhibits granule cell migration. Protease nexin I inhibits both tumor cell and myoblast plasminogen activator-mediated destruction of extracellular matrix. Thus, such observations as presented in this report provide further evidence for involvement of cascade proteolytic systems, and their post-translational regulation by specific serpins, in the remodeling that occurs in synapse formation and elimination.
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PMID:Plasminogen activators and inhibitors in the neuromuscular system: III. The serpin protease nexin I is synthesized by muscle and localized at neuromuscular synapses. 203 25

Human SH-SY5Y neuroblastoma cells treated with retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or nerve growth factor differentiated morphologically to neuronlike cells with increased amounts of neurofilament protein and mRNA. All three effectors induced an increase in the amount of relative molecular weight (Mr) 70,000 tissue-type plasminogen activator (t-PA) and its mRNA, as determined by immunocapture, enzyme activity, and Northern blotting analyses. About 90% of the t-PA activity was secreted to the culture medium. In contrast, of the three effectors studied, only TPA induced transcription of the proto-oncogene c-fos, studied as a control gene responsive to various stimuli, and induced a rapid increase in urokinase-type PA (u-PA). Most of the u-PA activity induced by TPA remained cell-associated. Because induction of differentiation correlated closely with induction of t-PA, and not u-PA, the authors propose that t-PA may have a functional role in the morphological differentiation of neuronal cells.
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PMID:Induction of morphological differentiation of human neuroblastoma cells is accompanied by induction of tissue-type plasminogen activator. 250 35

The fibrinolytic enzyme profile of SMS-KAN human neuroblastoma cells was found to vary dramatically during the differentiation process. Five maturational agents--retinoic acid, dibutyryl cAMP, 5-bromodeoxyuridine, sodium butyrate and phorbol myristate acetate were tested for their effects on cellular morphology, DNA synthesis, plasminogen activator (PA) and PA inhibitor (PAI) activity. SMS-KAN cells secrete urokinase (UK) and tissue PA (tPA) as well as a possibly unique PAI. Treatment of cells with 1 microM RA resulted in an inhibition of proliferation, extension of neurite-like processes indicative of differentiation, as well as a switch from secretion of UK to tPA and a reduction in PAI secretion. Other agents which caused neural process formation and decreased cell proliferation also induced alterations in PA/PAI while agents which had no detectable effect on cell growth induced little change in the fibrinolytic enzyme profile.
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PMID:Alterations in plasminogen activator and inhibitor activity during the differentiation of a human neuroblastoma cell line, SMS-KAN. 253 81

The relationship between plasminogen activator (PA)/plasminogen activator inhibitor (PAI) activity and morphological differentiation was investigated in human neuroblastoma (NB) cells treated with retinoic acid (RA). Conditioned medium from nine NB cell lines and one closely related neuroepithelioma line was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and zymography. All NB cell lines were shown to secrete urokinase (UK)-type PA (mol. wt., 52 kDa), and all except two produced tissue PA (mol. wt., 65 kDa). Identification of the PAs was made based on molecular weight and sensitivity to inhibition by anti-UK and anti-tPA antibodies. Several cell lines expressed PA inhibitory molecules; two molecular-weight forms were observed (35 and 40 kDa) in different cell lines. Complex formation with [125]I-labelled proteases revealed specific binding with UK and trypsin but not thrombin, plasmin, or kallikrein. After treatment for 6 days with 1 microM RA, six of the cell lines exhibited an increase in cell-associated and/or secreted tPA activity, corresponding to morphological differentiation of the cells as manifested by extensive neurite outgrowth. A decrease in UK and UK-complex secretion was observed in several of these cell lines. Three cell lines exhibiting no detectable morphological alterations with RA treatment also showed no dramatic changes in PA/PAI activity. These results suggest that morphological differentiation of NB cells may be associated with alterations in the regulation of PA activity.
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PMID:Effect of retinoic acid on human neuroblastoma: correlation between morphological differentiation and changes in plasminogen activator and inhibitor activity. 259 Sep 98

Five highly toxic phospholipases A2 (PLAs) (beta-bungarotoxin, caudoxin, Mojave toxin, notexin and a basic PLA from Naja nigricollis venom) were compared for their pharmacological actions. In the chick biventer cervicis nerve-muscle preparation, all PLA toxins except beta-bungarotoxin (beta-BuTX) inhibited the postsynaptic acetylcholine response and induced contracture of the muscle at a high concentration. Indirect hemolytic activity was found in all PLA toxins and some of the toxins (Naja nigricollis basic PLA and Mojave toxin) even showed a potent direct hemolytic action, while beta-BuTX was devoid of both direct and indirect hemolytic activities on the guinea-pig erythrocytes. All PLA toxins except beta-BuTX caused an increase in muscle tone in the guinea-pig ileum at a concentration as low as 0.05 microgram/ml, and an increase in the contractile force in the guinea-pig atrium at a concentration of 1.0 microgram/ml. In contrast, beta-BuTX had no stimulant effect at concentrations up to 10 micrograms/ml. On the cultured cells, beta-BuTX suppressed the proliferation of neuroblastoma cells, but did not cause lysis of non-neuronal cells of the rat brain. However, beta-BuTX uniquely maintained a high population of viable cells in the neuroblastoma cell cultures. From these results it was concluded that beta-BuTX is the most specific presynaptic neurotoxin among the PLA toxins so far tested.
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PMID:Differences in pharmacological actions between beta-bungarotoxin and other neurotoxic phospholipases A2 purified from snake venoms. 377 15

Brain cells and glioma cells in culture release a protein which induces neurite outgrowth in neuroblastoma cells. This neurite-promoting factor (NPF), which has been purified from serum-free glioma conditioned medium, has an apparent mol. wt. of 43 000. NPF inhibits urokinase as well as plasminogen activator-dependent caseinolysis or fibrinolysis. NPF and urokinase form an SDS-resistant complex. The fact that this glia-derived NPF is a potent protease inhibitor indicates that glial cells modulate the proteolytic activity associated with neuronal cells and suggests that this phenomenon is one of the biochemical events involved in the regulation of neurite growth.
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PMID:A glia-derived neurite-promoting factor with protease inhibitory activity. 406

The effect of the presence of one cell type on the plasminogen activator activity of another cell type was studied. The cell types, AC and D, were isolated from a rat neuroblastoma (I. Imada and N. Sueoka, Dev. Biol. 66:97-108, 1978). AC cells are stem cells capable of multipotential differentiation in vitro and have little or no cell-associated plasminogen activator activity. D cells are tumorigenic and have high levels of cell-associated plasminogen activator activity. When AC cells were cocultivated with D cells, the plasminogen activator activity of the D cells was dramatically inhibited. The presence of as few as 1,250 AC cells inhibited 70% of the plasminogen activator activity of 20,000 D cells, as determined by a highly quantitative assay. The amount of inhibition by AC cells was proportional to the number of AC cells present. At increasing numbers of AC cells and a constant number of D cells, the Vmax for the activation of plasminogen proportionately decreased and the Km remained constant, implying that AC cells did not alter the structure or concentration of plasminogen. Inhibition was not mediated by a soluble inhibitor secreted by AC cells. Rather, attachment of AC cells adjacent to D cells, i.e., cell-to-cell contact, seemed to be required for inhibition. The substratum-attached material of AC cells, that which remained on the microwell surface after removal of AC cells with EDTA, inhibited D cell plasminogen activator activity. If plasminogen activator activity is involved in metastasis, then regulation of the plasminogen activator activity of one cell type by another cell type may be involved in determining which cells in a tumor can metastasize and where secondary tumors can arise.
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PMID:Modulation of cell-associated plasminogen activator activity by cocultivation of a stem cell and its tumorigenic descendant. 653 59

The plasminogen activator liberated by cells of human neuroblastoma strain SK-N-SH was purified up to 400-fold, with a 40% recovery of activity, by a relatively simple procedure. This involved (NH4)2SO4 precipitation, followed by chromatography on both Affi-Gel Blue and p-aminobenzaminidine-Sepharose. The SK-N-SH activator was shown to differ from human urokinase with respect to immunological specificity, the molecular weights and isoelectric points of their enzymatically active species, the ability to be activated by fibrin and their relative sensitivities to inactivation by diisopropyl fluorophosphate. The average molecular weights of the enzymatically active species derived from strain SK-N-SH were shown to be 66,500, 64,500, 60,500 and 37,500. In the presence of fibrin, the SK-N-SH plasminogen activator appeared to be stimulated approximately 16-fold, with no apparent stimulation of urokinase activity. Urokinase is inactivated by diisopropyl fluorophosphate at a rate 6.4-fold faster than that of the SK-N-SH activator.
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PMID:Characterization and partial purification of the plasminogen activator from human neuroblastoma cell line, SK-N-SH. A comparison with human urokinase. 705 33


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