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)

Myosin has been isolated from the clonal lines of murine neuroblastoma and rat glioma cells. Partial characterization of the two cellular myosins indicates that both possess the following properties: (1) the same elution position as rabbit skeletal muscle myosin by Sepharose 4B chromatography; (2) the presence of heavy (molecular weight about 200,000) and light subunit polypeptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis; (3) EDTA and Ca2+ activated but Mg2+-inhibited ATPase activity in 0.6 M KCl; and (4) binding to rabbit skeletal muscle F-actin which is inhibited by Mg2+-ATP. For both mouse neuroblastoma and rat glioma cells, approximately 0.5-1.5% of the total cell protein is present as myosin. Cellular myosin appears to be indistinguishable in quantity and biochemical properties regardless of whether it is isolated from monolayer or suspension neuroblastoma cells.
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PMID:Isolation and characterization of myosin from cloned rat glioma and mouse neuroblastoma cells. 13 25

Synthesis and turnover of the main structural protein (P73) of intracisternal A-particles were studied in mouse neuroblastoma cells in tissue culture. Triton X-100:EDTA-insoluble pellets containing 95% of the A-particle antigen in the cells were prepared and analyzed by electrophoresis in Na dodecyl-SO4-minus polyacrylamide gels. A 73,000 molecular weight component was prominent in pellets from three lines of neuroblastoma which contain numerous A-particles and this component was identified as the A-particle structural protein P73. It was absent in pellets prepared from cells which do not contain A-particles. Incorporation of labeled amino acids into P73 represented approximately 1.2% of total cell incorporation and this proportion did not change when the cell growth changed from log phase to stationary phase. Label appeared P73 within 2 min after radioactive amino acids were added to the medium. Pulse-chase and inhibitor studies confirmed antigenic measurements in demonstrating that the pool of P73 not assembled into A-particles was small. Turnover studies showed that P73 gained and lost label more rapidly than the average cell protein. In one cell line which was thoroughly characterized, approximately 60% of the main A-particle protein was estimated to turn over in a 24-hour period. Although the cells released approximately 10% of the proteins synthesized into the culture fluid, A-particle protein did not appear to be released. Analysis of culture fluid failed to reveal A-particles, soluble A-particle proteins, or A-particle antigen. It appears, therefore, that the particles are relatively rapidly synthesized and degraded, and that turnover occurs entirely intracellularly.
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PMID:Synthesis and turnover of intracisternal A-particle structural protein in cultured neuroblastoma cells. 16 1

Treatment of neuroblastoma cells with dibutyryl-adenosine 3':5'-monophosphate or adenine induced axon formation and a three-fold increase in the polyadenylate, poly(A), content of the polysomal mRNA. The extracted poly(A) contained 90% adenylic acid and showed a mobility of 6--7 S in dodecylsulfate-polyacrylamide gel electrophoresis. Treatment with dibutyryl-adenosine 3':5'-monophosphate or adenine, also induced a 4--6 fold increase in a nuclear enzymic activity that incorporated [3H]ATP to an acid-insoluble polymer in a cell-free system. This polymer, like poly(A) extracted from the polysomal mRNA, was bound at high salt concentration to nitrocellulose filters. [3H]ATP incorporation was Mg2+-dependent, sensitive to ribonuclease and EDTA and resistant to deoxyribonuclease and actinomycin D. There was no incorporation of [3H]UTP or [3H]dTTP and addition of TUP, CTP and GTP did not increase the incorporation of [3H]ATP. 5-Bromodeoxyuridine induced axon formation of neuroblastoma cells and poly(A) polymerase activity, without increasing the poly(A) content in the polysomal mRNA. The results indicate that induction of axon formation of neuroblastoma cells is associated with an increase in the activity of poly(A) polymerase. It is suggested that the induction of this enzyme may be generally involved in cell differentiation.
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PMID:Induction of polyadenylate polymerase and differentiation in neuroblastoma cells. 17 99

The regulation of cyclic adenosine 3:5-monophosphate (cyclic AMP) phosphodiesterase activity in homogenates of malignant and cyclic AMP-induced "differentiated" neuroblastoma cells was studied. Neuroblastoma cells of at least three mouse and one human clone had both the low (2 to 4 muM) and the high (66 to 106 muM) Km phosphodiesterase. In cyclic AMP-induced differentiated cells the values of Km were decreased, whereas the values of Vmax appeared to be slightly increased. Magnesium and manganese stimulated phosphodiesterase activity. Calcium, zinc, copper, mercury, ethylenediaminetetraacetic acid, and imidazole completely inhibited phosphodiesterase activity in malignant cells, whereas the above agents, except ethylenediaminetetraacetic acid, only partially inhibited enzyme activity in differentiated cells. Ethylenediaminetetraacetic acid completely reduced phosphodiesterase activity in differentiated cells. The pH optimum for phosphodiesterase activity was about 8 in both malignant and differentiated cells. The present studies show that the values of Km and Vmax and the sensitivity of phosphodiesterase activity to divalent ions change in cyclic AMP-induced differentiated neuroblastoma cells, and therefore we propose that the reverse may be true during malignant transformation of nerve cells.
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PMID:Cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in malignant and cyclic adenosine 3':5'-monophosphate-induced "differentiated" neuroblastoma cells. 23 30

Neuroblastoma adenylate cyclase is activated by 2-chloroadenosine, prostaglandin E1, and 5'-guanylylimidodiphosphate [GMP-P(NH)P]. However, the process of activation by the first two compounds is different from that induced by the third. Prostaglandin E1 and 2-chloroadenosine activation is rapid, producing elevated activities which are constant throughout a 20-min assay. In contrast, GMP-P(NH)P activation is slow and although the activity is elevated within 1 min, it continues to increase for up to 12 min before attaining a maximal constant value. Activation is more rapid when either prostaglandin E1 or 2-chloroadenosine is present with GMP-P(NH)P. Activation of the enzyme by GMP-P(NH)P appears to be retarded by endogenous nucleotides as suggested by the following observations: (a) if the enzyme is incubated at 30 degrees with 5 mM MgCl2 for 5 to 7 min, GMP-P(NH)P then produces maximal activation without a detect able lag; (b) if, during this incubation, nucleotides, a nucleotide regenerating system, or EDTA (instead of MgCl2) are present, subsequent GMP-P(NH)P activation is slow; and (c) in the assays which contain a nucleotide regenerating systm and MgATP as substrate, the Km for GMP-P(NH)P is 6 +/- 2 muM. However, in the assays using MgAMP-P(NH)P as substrate but no nucleotide regenerating system, the Km is 0.5 +/- 0.2 muM. GPD and GTP do not replace GMP-P(NH)P as an enzyme activator in any of our assays systems, and in fact, are potent inhibitors of GMP-P(NH)P enzyme activation. Prostaglandin E1 and 2-chloradensine do not alter significantly the Km for GMP-P(NH)P but do decrease the ensyme's sensitivity of GDP. Proposed is a hysteretic model of neuroblastoma adenylate cyclase, which shows the enzyme responding slowly to rapid changes in GMP-P(NH)P concentration due to the slow displacement of the tightly bound endogenous guanine nucleotides by GMP-P(NH)P. Additionally, prostaglandin E1 and 2-chloroadenosine increase the rate of GMP-P(NH)P activation by decreasing the enzyme's affinity for these endogenous guanine nucleotides.
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PMID:Neuroblastoma adenylate cyclase. Role of 2-chloroadenosine, prostaglandin E1, and guanine nucleotides in regulation of activity. 93 91

ANP-R1 receptors for atrial natriuretic peptide (ANP) showed the following rank order of affinity in intact human neuroblastoma cells NB-OK-1: human ANP-(99-126) approximately human ANP-(102-126) approximately rat ANP-(99-126) (K1 17-32 pM) > human ANP-(103-126) > porcine brain natriuretic peptide (BNP). Analogues truncated at the C-terminal extremity or devoid of a disulphide bridge, such as rat ANP-(103-123), rat C-ANP-(102-121), rat ANP-(111-126), rat ANP-(99-109) and rat [desCys105,Cys121]ANP-(104-126) and chicken C-type natriuretic peptide, were not recognized. The occupancy of these high affinity ANP-R1 receptors led to marked cyclic GMP accumulation in the presence of 3-isobutyl 1-methylxanthine. An ectoenzymic activity, partly shed in the incubation medium, provoked the stepwise release of Phe-Arg-[125I]Tyr, Arg-[125I]Tyr and [125I]Tyr from rat [125I]ANP-(99-126), at an optimal pH of 7.0. Its inhibition by 1,10-phenanthroline, EDTA and bacitracin but not by thiorphan suggests the contribution of at least one neutral metalloendopeptidase, distinct from EC 3.4.24.11, for which ANP showed high affinity.
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PMID:Atrial natriuretic peptide binds to ANP-R1 receptors in neuroblastoma cells or is degraded extracellularly at the Ser-Phe bond. 133 13

The mechanisms by which insulin-like growth factors (IGFs) reduce IGF-binding protein-4 (IGFBP-4) levels in cellular conditioned media are poorly understood. The effect of IGFs on IGFBP-4 levels in fibroblast conditioned media is not mediated via the type 1 or type 2 cellular IGF receptors, and the IGFs exert little or no effects on IGFBP-4 messenger RNA levels in human adult fibroblasts or in rat neuroblastoma cells. To determine whether the effects of IGFs on IGFBP-4 might be exerted through alterations in IGFBP-4 degradation, we incubated cell-free, fibroblast-conditioned media from either sheep or human dermal fibroblasts with or without IGF-I, IGF-II (each 1 microgram/ml), or insulin (10 micrograms/ml) for 72 h at 37 C. Samples were then analyzed by Western ligand blot using radiolabeled IGFs and by immunoblotting using a polyclonal antisera to human IGFBP-4. In the absence of IGFs, no apparent changes in the basal concentrations of the various IGFBPs were observed. In contrast, incubation of media with IGFs caused a 70-80% reduction in levels of both sheep and human IGFBP-4, whereas incubation with insulin was without effect. Similarly, incubation of cell-free conditioned media containing recombinant human IGFBP-4 with IGF-I caused a reduction in detectable levels of the 28K protein. The decrease in IGFBP-4 levels was accompanied by the appearance of an immunoreactive approximate 17-20K fragment that did not bind radiolabeled IGFs by ligand blot. The IGF-dependent decrease in IGFBP-4 was prevented by coincubation of the media with serine protease inhibitors, EDTA, or 1,10-phenanthrolene, suggesting that IGFs may activate an IGFBP-4 specific metallo-serine protease present in fibroblast conditioned media. Alternatively, binding of IGF-I or -II to IGFBP-4 may enhance the susceptibility of IGFBP-4 to proteolytic degradation. The demonstration that IGF-I and IGF-II can promote directly the proteolytic degradation of IGFBP-4 into fragments that do not bind IGFs provides a novel mechanism by which the IGFs may increase their own availability and/or activity in biological fluids.
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PMID:Evidence for a novel insulin-like growth factor (IGF)-dependent protease regulating IGF-binding protein-4 in dermal fibroblasts. 138 96

Studies on the involvement of protein kinase C in retinoic acid-induced differentiation of human neuroblastoma were carried out with two variants of the SK-N-SH cell line namely the SH-F subline, which differentiates to give a fibroblast-like phenotype, and the SH-N subline, which develops into the typical neuronal phenotype. In SH-F, a substantial increase in protein kinase C activity accompanied morphological differentiation. Accordingly, after 7 days of retinoic acid treatment, EDTA-extracted, cytosolic protein kinase C activity increased by slightly more than 2-fold over vehicle-treated controls. Again, detergent-extracted activity, representing membrane-bound or total protein kinase C, showed a similar 2.6- to 5.1-fold increase in treated cells. A time-course study revealed an earliest increase in total activity after two days of retinoic acid treatment which continued linearly for the first 6 to 8 days, and then levelled off. A study of the effect of retinoic acid on the protein kinase C in vitro with SH-F cell extracts showed only a slight increase in activity (of 25%) at the relatively high concentration of 10(-4) M; however, no significant differences were observed at lower concentrations. In contrast, the SH-N cell line responded to retinoic acid by a 45% decrease in EDTA-extractable, and a 63% decrease in detergent-extractable protein kinase C activity. Added to SH-F cell cultures, 15 nM staurosporine was found to inhibit protein kinase C in vivo and to a lesser extent, the protein kinase A. Present together with retinoic acid, staurosporine not only prevented the augmentation but caused a marked decrease of protein kinase C activity in this cell line. Morphological studies indicated that when SH-N cells are treated with staurosporine, or staurosporine and retinoic acid together, a neuronal phenotype similar to that produced by retinoic acid alone is observed. In contrast, when the SH-F cell line is treated with staurosporine or staurosporine and retinoic acid together, the flattened fibroblast-like cell type normally induced by retinoic acids is not observed. Instead, these cells display much smaller cell bodies and elaborate extensions resembling the neuronal phenotype produced by retinoic acid induced differentiation of the SH-N variant. These results suggest that changes in the protein kinase C activity may be involved in regulating the expression of the phenotype during cell differentiation.
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PMID:Effects of retinoic acid and staurosporine on the protein kinase C activity and the morphology of two related human neuroblastoma cell lines. 211 83

We have treated human neuroblastoma cells with various complexes of aluminium, over a range of concentrations, and have measured the amount of aluminium entering the cells after one week, using atomic absorption spectroscopy. We have found that the cells incorporate much higher levels of the element after treatment with aluminium-EDTA than with aluminium-citrate or aluminium-maltol. With aluminium-EDTA, initially the uptake increases with increasing concentration in the medium but eventually reaches a plateau; the concentration within the cells is then higher than that in the medium. No obvious change in morphology of the cells occurs after treatment. The number of cells present after a week's treatment with aluminium-EDTA is lower than that of untreated cells but does not vary over a wide range of aluminium concentrations.
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PMID:Uptake of aluminium by human neuroblastoma cells. 213 36

Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500 mg m-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60 mg m-1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial 51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following 'megatherapy' given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2,000 Hz in 37% of children but at or below 2,000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate.
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PMID:Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group. 238 51


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