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)

During a Phase I study of intravenous vitamin E-free alcohol (all-rac-alpha-tocopherol or Ephynal) in patients with neuroblastoma, we noticed a bleeding diathesis in two patients receiving 2300 mg/m2 daily for four or more days in succession. Both blood prothrombin time and accelerated partial thromboplastin times were prolonged. These spontaneously returned to normal levels three days after interrupting vitamin E infusions. It was also noted that factors VII, IX and X were decreased, which corresponded with the prolonged PT and APTT. It was found that by infusing menadiol sodium diphosphate just prior to the vitamin E, these inhibiting effects on procoagulant factors could be abrogated and high dosages of vitamin E-free alcohol safely given.
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PMID:The effect of intravenous vitamin E and menadiol sodium diphosphate on vitamin K dependent clotting factors. 647 8

d- and dl-alpha-tocopheryl succinate inhibited growth and caused morphological changes in mouse melanoma (B-16), mouse neuroblastoma (NBP2), and rat glioma (C-6) cells in culture. To study whether the effects of alpha-tocopheryl (vitamin E) succinate on tumor cells are mediated by antioxidant mechanisms, the effects of lipid-soluble antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) were compared with those of vitamin E succinate. Results showed that these antioxidants produced alterations on the growth and morphology of neuroblastoma, melanoma, and glioma cells which are similar to those produced by vitamin E succinate; however, the extent of the effect depended upon the type of antioxidant and the form of tumor cells. These data suggest that the effects of vitamin E succinate on tumor cells may be mediated, in part, by antioxidant mechanisms.
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PMID:Study on the specificity of alpha-tocopheryl (vitamin E) acid succinate effects on melanoma, glioma and neuroblastoma cells in culture. 663 22

The effect of dl-alpha-tocopheryl (vitamin E) succinate in modifying the radiation response of mouse neuroblastoma (NBP2) and mouse fibroblast (L-cells) cells in culture was studied on the criterion of growth inhibition (due to cell death and inhibition of cell division). Results show that vitamin E succinate markedly enhanced the effect of 60CO-gamma-irradiation on NB cells, but it did not significantly modify the effect of irradiation on mouse fibroblasts. Sodium succinate plus ethanol (0.25% final concentration) did not modify the radiation response of NB cells or fibroblasts. Butylated hydroxyanisole, a lipid soluble antioxidant, also enhanced the effect of irradiation on NB cells, indicating that the effect of vitamin E in modifying the radiation response may be mediated, in part, by antioxidation mechanisms.
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PMID:dl-alpha-Tocopheryl succinate enhances the effect of gamma-irradiation on neuroblastoma cells in culture. 669 72

Levodopa, at concentrations of 0.25 x 10(-4) M or larger, is toxic for the human neuroblastoma cell NB69. Toxicity is associated with high levels of quinones, increased activity of complex II-III, and lack of changes of complex I of the mitochondrial respiratory chain. Deprenyl, which does not alter the production of quinones, has a partial protective effect. Tocopherol, 23 or 115 x 10(-6) M, lacks significant preventive effect on levodopa toxicity, but ascorbic acid, 10(-3) M, prevents levodopa toxicity and quinone formation. Deprenyl, 10(-4) M, provides additional protection in cultures treated with levodopa and ascorbic acid. Our results indicate that ascorbic acid and deprenyl prevent levodopa neurotoxicity by unrelated mechanisms. Both compounds should be considered as complementary drugs to test for slowing the progression of Parkinson's disease.
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PMID:Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine-rich human neuroblastoma cell line. 834 Dec 91

Buthionine sulphoximine (BSO) selectively inhibits glutathione (GSH) synthesis and may enhance the antineuroblastoma activity of melphalan (L-PAM). We determined the cytotoxicity of BSO (dose range 0-1000 microM) alone and in combination with L-PAM (dose range 0-0 microM) in a panel of 18 human neuroblastoma cell lines. BSO alone was highly cytotoxic with 16/18 neuroblastoma cell lines having IC90 values (range 2.1- > 1000 microM) below the clinically achievable steady-state plasma level of 500 microM BSO. Maximal cell killing correlated with GSH levels decreased to less than 10% baseline, and was partially reversed by the addition of exogenous anti-oxidants (GSH, vitamin E and ascorbate). Fluorocytometric analysis of DNA fragments by the Tunnel method detected 92% of a BSO sensitive cell line in apoptosis after a 48 h exposure to 500 microM BSO. The combination of L-PAM and BSO synergistically enhanced the cell killing of L-PAM alone by > 1-3 logs (combination index < 1). We conclude that BSO has significant single-agent cytotoxicity against neuroblastoma and enhances cell killing when combined with L-PAM.
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PMID:Buthionine sulphoximine alone and in combination with melphalan (L-PAM) is highly cytotoxic for human neuroblastoma cell lines. 951 45

Beta-amyloid (betaA) toxicity in culture is accompanied by multiple events culminating in apoptosis. Calcium influx may represent the initial event, since calcium chelation prevents all subsequent events, while subsequent events include increased generation of reactive oxygen species (ROS) and hyperphosphorylation of tau. In the present study, we undertook to determine whether ROS generation or tau hyperphosphorylation mediate betaA-induced apoptosis. The anti-oxidant vitamin E or the kinase inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenslfonamide (W7) was added following brief treatment of differentiated SH-SY-5Y human neuroblastoma cells with 22 microM betaA. Under these conditions, vitamin E prevented ROS generation and apoptosis, but did not prevent intracellular calcium accumulation or tau phosphorylation. W7 prevented tau phosphorylation but did not block betaA-induced calcium influx, ROS generation or apoptosis. While these studies do not address the long-term consequences of PHF formation, they indicate that ROS generation, rather than tau hyperphosphorylation, leads to apoptosis following betaA-induced calcium influx into cultured cells.
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PMID:Beta-amyloid-induced calcium influx induces apoptosis in culture by oxidative stress rather than tau phosphorylation. 1076 16

Peripheral neuropathy following cisplatin treatment is a major limiting factor in cisplatin chemotherapy of cancer patients. We investigated the pathomechanism underlying cisplatin neuropathy using a mouse dorsal root ganglion neuron-neuroblastoma hybrid cell line (N18D3) developed in our laboratory. DNA fragmentation, a characteristic feature of apoptosis, was induced in hybrid neurons following treatment with cisplatin. Accumulation of p53, Fas, and Fas ligand (Fas-L) was also demonstrated in these neurons. Preincubation with N-acetylcysteine (NAC), a precursor of glutathione, blocked cisplatin-induced apoptosis completely, whereas Trolox, a vitamin E analogue, blocked it partially. Cisplatin-induced p53 accumulation was suppressed by NAC treatment, whereas p53 accumulation was retarded by Trolox treatment. In contrast, neither NAC nor Trolox showed any inhibitory effect on cisplatin-induced Fas/Fas-L accumulation. These results suggest that the neuroprotective effects of antioxidants against cisplatin-induced neurotoxicity in hybrid neurons are mediated mainly through the inhibition of p53 accumulation but not of Fas/Fas-L accumulation by these antioxidants.
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PMID:Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by antioxidants through suppression of cisplatin-mediated accumulation of p53 but not of Fas/Fas ligand. 1093 75

The cause of neuronal degeneration in Alzheimer's disease (AD) has not been completely clarified, but has been variously attributed to increases in cytosolic calcium and increased generation of reactive oxygen species (ROS). The beta-amyloid fragment (Abeta) of the amyloid precursor protein induces calcium influx, ROS and apoptosis. Homocysteine (HC), a neurotoxic amino acid that accumulates in neurological disorders including AD, also induces calcium influx and oxidative stress, which has been shown to enhance neuronal excitotoxicity, leading to apoptosis. We examined the possibility that HC may augment Abeta neurotoxicity. HC potentiated the Abeta-induced increase in cytosolic calcium and apoptosis in differentiated SH-SY-5Y human neuroblastoma cells. The antioxidant vitamin E and the glutathione precursor N-acetyl-L-cysteine blocked apoptosis following cotreatment with HC and Abeta, indicating that apoptosis is associated with oxidative stress. These findings underscore that moderate accumulation of excitotoxins at concentrations that alone do not appear to initiate adverse events may enhance the effects of other factors known to cause neurodegeneration such as Abeta.
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PMID:Homocysteine potentiates beta-amyloid neurotoxicity: role of oxidative stress. 1146 60

24-Hydroxycholesterol, the main cholesterol elimination product of the brain is increased in serum of Alzheimer patients. This oxysterol behaves neurotoxic towards the human neuroblastoma cell line, SH-SY5Y. Here we demonstrate, that 24-hydroxycholesterol-induced neurotoxicity in differentiated SH-SY5Y cells was due to apoptosis, as indicated by DNA-fragmentation, caspase-3 activation and a decrease of the mitochondrial membrane potential. Free radicals were generated, resulting in the death of 75% of the cells within 48h; neurotoxicity in differentiated SH-SY5Y cells was partially prevented by physiological concentrations of vitamin E (50-100 microM) in that 75% of the cells survived. Physiological concentrations of estradiol-17beta (1-100nM) elicited a protective effect in differentiated cells, which was not significant; however, in undifferentiated cells a significant protection was noted by this steroid hormone. Vitamin C and melatonin did not prevent 24-hydroxycholesterol-induced neurotoxicity. These in vitro data support the in vivo observed beneficial effects reported as circumstantial evidence of vitamin E and estradiol-17beta treatment in the prevention and therapy of neurodegenerative disease.
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PMID:Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17beta. 1147 14

Exposure of neurons to amyloid-beta (Abeta) is accompanied by a cascade of oxidative damage that initiates with lipid peroxidation followed by subsequent generation of cytosolic free radicals and reactive oxygen species (ROS). The antioxidant vitamin E has been utilized to counteract Abeta-induced oxidative stress. We considered herein whether or not the lipid-solubility of vitamin E limits its neuroprotection to membrane-related oxidative damage, and renders it relatively ineffective where prior lipid peroxidation has already generated cytosolic free radicals and ROS. To test this possibility, we treated differentiated SH-SY-5Y human neuroblastoma with vitamin E or a cell-permeant antioxidant, N-acetyl cysteine (NAC), simultaneously with or 15 min after the application of Abeta. Both vitamin E and NAC prevented Abeta-induced ROS generation when applied simultaneously with Abeta, but only NAC prevented Abeta-induced ROS generation when added to cultures that had previously been exposed to Abeta. These results support the hypothesis that vitamin E can quench Abeta-induced lipid peroxidation, but cannot effectively quench ROS generated by prior lipid peroxidation. These findings in cell culture may provide limited insight into why vitamin E is not fully effective against neurodegeneration in AD in clinical settings, since some neuronal populations are likely to already have been compromised by prior Abeta exposure before vitamin E treatment was initiated.
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PMID:Differential efficacy of lipophilic and cytosolic antioxidants on generation of reactive oxygen species by amyloid-beta. 1221 18


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