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)

Mouse neuroblastoma (NB) cells in culture were more sensitive to sodium L-ascorbate than were rat glioma cells by the criterion of growth inhibition (due to cell death and reduction in cell division). Sodium L-ascorbate at nonlethal concentrations potentiated the effect of 5-fluorouracil (FUra), x-irradiation, bleomycin, RO20-1724, prostaglandin E1, and sodium butyrate on NB cells but did not produce such an effect on glioma cells. Sodium L-ascorbate did not enhance the effect of vincristine, 6-thioguanine, or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) except at higher drug doses and it reduced the cytotoxic effect of methotrexate and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) on NB cells. Sodium D-ascorbate produced effects similar to those produced by sodium L-ascorbate on NB cells. L-Ascorbic acid-2-sulfate (barium salt) affected neither the growth rate nor the effect of 5-FUra on NB cells. Glutathione, a reducing agent, was more toxic to NB cells in comparison to D- OR L-ascorbate; however, at a similar concentration it failed to potentiate the effect of 5-FUra on NB cells.
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PMID:Sodium ascorbate potentiates the growth inhibitory effect of certain agents on neuroblastoma cells in culture. 28 5

A commercially available enzyme immunoassay was used to determine ferritin content and subsequently the loading and release of iron from ferritin in neuroblastoma cells. LS cells were incubated with 59Fe for 24 h, lysed, and the cytoplasmic ferritin was bound to monoclonal antibodies coupled to globules. After determination of the ferritin content the same globules with bound radioactive ferritin were measured in a gamma-counter. To illustrate the applicability of this test system, increased iron loading of cellular ferritin could be demonstrated in cycloheximide-treated cells; furthermore, release of iron was documented after incubation of LS cells with a combination of 6-hydroxydopamine and ascorbate. The assay turned out to be a simple method for determination of changes in 59Fe content of ferritin in neuroblastoma cells.
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PMID:A simple assay for determination of iron release from ferritin in neuroblastoma cells. 143 Jul 87

Clonal lines of murine neuroblastoma (NBP2) and rat glioma (C6) were used to investigate the effects of methylmercuric chloride (CH3HgCl). Glioma cells were more sensitive to CH3HgCl than NB cells on the criterion of growth inhibition, but these cells were equally sensitive to inorganic mercury (HgCl1), Tri-n-butyl lead acetate and acrylamide on the same criterion. Alpha-tocopherol, alpha-tocopheryl++ succinate and inhibitors of cAMP phosphodiesterase protected glioma cells against the growth-inhibitory effect of CH3HgCl, but they failed to protect NB cells in culture. Glioma factors, sodium ascorbate, non-inhibitory concentrations of prostaglandins E1 (PGE1), and glutamate enhanced the growth-inhibitory effect of CH3HgCl on both NB and glioma cells in culture. The levels of certain specific cAMP-dependent and -independent protein phosphorylations appear to be very sensitive to CH3HgCl, and can be altered in both cell types by concentrations of CH3HgCl which do not affect growth or morphology of these cells.
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PMID:New opportunities with neuronal cultures to study the mechanisms of neurotoxic injuries. 174 37

Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method.
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PMID:High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma. 190 68

Neuroblastoma cells accumulate ascorbic acid and iron. It was hypothesized that these features could be exploited for sensitizing neuroblastoma cells for therapy in combination with reactive oxygen intermediates. In the present study the effects of 6-hydroxydopamine (6-OHDA) and H2O2 on metabolic parameters critical for cell survival were investigated in cells with low and high ferritin content in the presence and absence of ascorbate. Human neuroblastoma SK-N-SH cells were pretreated with 100 microM FeSO4 and 10 microM desferrioxamine, respectively, for 24 h yielding cells with different ferritin contents. The effects of 6-OHDA and H2O2 (25 microM-250 microM) in the absence and presence of 1 mM ascorbic acid on DNA strand break formation, activation of poly(ADP-ribose) polymerase, and finally decrease in NAD+ and ATP concentration were investigated. All these parameters were influenced by 6-OHDA and H2O2 in a concentration-dependent manner in a similar way. The effects were most pronounced in ferritin-rich cells and in the presence of ascorbic acid. Using isolated CCC PM2 DNA, 6-OHDA and ascorbic acid caused strand breaks that were prevented in the presence of mannitol or desferrithiocine. H2O2-mediated strand breaks were observed only in the presence of ascorbic acid. Based on these data and data published by others a model explaining the deleterious effects of ascorbic acid on neuroblastoma cells is presented. It is suggested that continuous application of a high dosage of ascorbic acid might be a useful approach in neuroblastoma therapy.
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PMID:Ascorbic acid enhances the effects of 6-hydroxydopamine and H2O2 on iron-dependent DNA strand breaks and related processes in the neuroblastoma cell line SK-N-SH. 193 70

L-Ascorbic acid inhibits the growth of mouse neuroblastoma and human endometrial carcinoma cells at concentrations greater than 100 microM. Under the same concentrations used in cell culture study, normal human lung fibroblasts show less sensitivity to the antiproliferative effect of ascorbate than tumor cell lines. The antitumor activity of ascorbate can be greatly potentiated by the combination with copper ions or copper chelates. The exposure of normal and tumor cells to the mixtures of ascorbate and copper chelates, especially Cu2+-o-phenanthroline and Cu2+-2,9-dimethyl-o-phenanthroline complexes, resulted in the killing of a large proportion of cell populations whereas the organic ligand portion of metal complexes was much less toxic. These copper chelates in combination with ascorbate showed different degrees of DNA-scission activities which could not be correlated with their cytotoxicities in the cell culture study. It is suggested that the primary targets of these antiproliferative agents may be on the biological sites such as cell membrane other than DNA in the nucleus which has been commonly assumed as the critical target for most free radical-generating antitumor drugs.
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PMID:Antiproliferative and DNA-scission activities of L-ascorbic acid in the presence of copper chelates. 293 76

Fibronectin is a multifunctional glycoprotein which promotes the adhesion of a variety of cell types to extracellular matrices, including artificial tissue culture substrata. Biochemical analyses of substratum adhesion sites indicated important functions for cell-surface heparan sulphate proteoglycan (HS-PG) in directly mediating adhesive responses by the binding of heparan sulphate sequences to fibronectin. In addition, fibronectin has a binding domain for a cell surface 'receptor' (possibly a 140K glycoprotein) important in these responses. To differentiate the relative importance of these two binding activities, a proteolytically generated cell-binding fragment of fibronectin has been isolated which binds to the 140K 'receptor' but not to HS or to collagen. Platelet factor 4 (PF4), a tetravalent HS-binding protein, provides a model of the tetravalent HS-binding activity of fibronectin, as supported by affinity chromatography studies (these studies also reveal the complexity of HS-PG metabolism in adhesion sites). Responses are measured on substrata coated with the cell-binding fragment of fibronectin, intact fibronectin, or PF4, singly or in combination. Fibroblast-like BALB/c 3T3 cells form both close and tight-focal adhesive contacts with associated microfilament stress fibres on intact fibronectin. Whereas HS-PG binding appears to mediate the formation of close contacts and linear microfilament bundles, a cooperative relationship exists between the HS- and the cell-binding activities of the intact fibronectin molecule in the formation of focal contacts and stress fibres. Human dermal fibroblasts generate different adhesive responses on HS-binding or cell-binding substrata, which are dependent on whether cells have been grown in medium with ascorbate to maximize production of their own collagenous matrix. As with 3T3 cells, focal contact and stress fibre formations of dermal cells require both binding activities in the intact fibronectin molecule. A third system consists of neuroblastoma tumour cells which adhere and extend neurites on fibronectin. Cell-body adherence, but not neurite extension, occurs on HS-binding matrices whereas neurite extension requires only fibronectin's cell-binding activity; the responses of primary peripheral neurons were exactly the opposite and CNS neurons did not respond at all. These studies indicate the diversity of molecular mechanisms by which various cells interact with the multifunctional fibronectin molecule in order to perform specialized functions, as well as the independent or cooperative functions of heparan sulphate proteoglycan on the cell surface in mediating these responses.
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PMID:Heparan sulphate proteoglycan as mediator of some adhesive responses and cytoskeletal reorganization of cells on fibronectin matrices: independent versus cooperative functions. 294 46

The mouse neuroblastoma cell line N18TG2 synthesizes and secretes a VIP-like immunoreactive material. The majority of this VIP-like material from both cell and media extracts elutes on HPLC in the same position as porcine or rat VIP. Several additional peaks which appear in the media extracts may represent variant forms or degradation products of VIP. The synthesis and release of VIP was significantly enhanced by agents which elevate cAMP levels directly (dbcAMP and forskolin) or through a receptor mediated process (secretin). These agents are also known to promote differentiation of these cells. The synthesis and release of VIP was also enhanced by ascorbate (thought to be a co-factor for the enzyme which amidates the carboxyl-terminal of VIP) [11]. In the presence of forskolin, ascorbate had a synergistic effect on the release of VIP, suggesting that forskolin and ascorbate are elevating VIP levels by different mechanisms; forskolin through a possible effect on VIP mRNA synthesis or translation, and ascorbate by increasing the rate of VIP processing. These results suggest that VIP synthesis and release is controlled by more than one process, whose rate can be altered with pharmacological agents.
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PMID:Synthesis and release of vasoactive intestinal polypeptide (VIP) by mouse neuroblastoma cells: modulation by cyclic nucleotides and ascorbic acid. 301 Feb 55

Previous electron spin resonance studies have demonstrated that the decay of ascorbyl plus semiquinone radicals, produced in an aqueous mixture of ascorbate and 2,6-dimethoxy-p-quinone, is accelerated by ascites cells. This effect was concluded to involve a sulfhydryl-containing NAD(P)H-enzyme, and work on cultured cell lines showed that on neoplastic transformation the activity against the radicals was increased. We show here that at least three disulfide-oxidoreductases are able to quench the radicals in a similar way to that of viable cells. Glutathione reductase (EC 1.6.4.2) in the presence of NADPH and oxidised glutathione, and dihydrolipoamide dehydrogenase (EC 1.8.1.4) with NADH and lipoamide, are found to accelerate the radical decay by reducing the quinone or semiquinone. DT-diaphorase (EC 1.6.99.2) in the presence of NAD(P)H can also achieve this by reducing the quinone directly. Lipoamide dehydrogenase and glutathione reductase are also capable of reducing nitroxide spin labels, a finding considered of relevance to the reported reduction of such spin labels by neuroblastoma cells.
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PMID:Electron spin resonance studies of the interaction of oxidoreductases with 2,6-dimethoxy-p-quinone and semiquinone. 302 90

The patterns of the cytolytic effects of 6-hydroxydopamine (6-OHDA), with/without ascorbate, on C-1300 and three other cloned mouse neuroblastoma cell lines (N1E-115, NS-20, N-18) were studied in vitro. The sensitivity to 6-OHDA differed and the three cloned cell lines were more sensitive than the wild type C-1300 cell line. Ascorbate synergistically potentiated the cytolytic effect of 6-OHDA to all four cell lines. The 6-OHDA cytotoxicity was eliminated by the addition of exogenous catalase but not by addition of other oxygen free radical scavengers, thereby suggesting that the hydrogen peroxide formed might influence the cells, extracellularly. In addition, the critical time for tumor cell lysis was the first 60 min of the reaction. The cytotoxicity induced by the unmasked cyclophosphamide, 4-hydroperoxycyclophosphamide, was synergistically enhanced in the presence of a nontoxic concentration of 6-OHDA and ascorbate. These data suggest that reactive oxygen intermediates may prove to be a good tool for destroying neuroblastoma cells.
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PMID:Patterns of destruction of mouse neuroblastoma cells by extracellular hydrogen peroxide formed by 6-hydroxydopamine and ascorbate. 308 96


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