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)

Both lithium and valproate have been used in the treatment of manic-depressive illness with very limited understanding of their therapeutic mechanism of action. Recent literature suggests that blocking of potassium channels may be a common therapeutic mechanism of many antidepressant agents. To determine whether the commonly used antimanic agents could prevent potassium efflux-induced cell damage and apoptosis and the underlying mechanisms, we treated SH-SY5Y human neuroblastoma cells with the potassium ionophore, valinomycin (2-100 microM) and observed cell shrinkage, mitochondria damage, a significant increase in of lactate dehydrogenase (LDH) activity and caspase-3 protein expression. Cells treated with lithium (0.5-3 mM) or valproate (0.07-1.4 mM) alone produced no apoptotic morphological and biochemical changes while both mood stabilizers pretreatment reduced or prevented the apoptotic morphological changes. However, valinomycin-induced caspase-3 elevation was only prevented by lithium pretreatment while both lithium and valproate attenuated valinomycin-induced LDH release. Our results suggest that lithium and valproate share a common neuroprotective action against potassium efflux-induced cell apoptosis with different mechanisms.
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PMID:A novel evidence of different mechanisms of lithium and valproate neuroprotective action on human SY5Y neuroblastoma cells: caspase-3 dependency. 1107 36

Protective effects of CV-3611, a free radical scavenger, on retinal ischemic injury in the rat and on glutamate-induced cytotoxicity in a cell line were evaluated. Transient retinal ischemia was induced by raising intraocular pressure of rats to 110 mm Hg for 45 min, and the electroretinogram (ERG) was measured to evaluate retinal function. No ERG could be recorded immediately after reperfusion, and thereafter the ERG gradually recovered. Recovery of the a-wave latency and the amplitudes of the a and b waves in the CV-3611-treated (10 mg/kg, p.o.) group were significantly better than those in the control group up to 24 h after reperfusion. In both the control and CV-3611 group, the b wave showed better recovery than the a wave up to 6 h after reperfusion, while the relationship was reversed after 24-hour reperfusion. Glutamate (10 mM)-induced cytotoxicity in the N18-RE-105 cell, a neural retina-neuroblastoma hybridoma, was quantified by measuring lactate dehydrogenase. Three and 10 microM of CV-3611 significantly attenuated the glutamate-induced cytotoxicity in N18-RE-105 cells. Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity. These results suggest that oxygen free radicals play an important role in the early phase of retinal ischemic injury. Moreover, differential recovery processes of the a and b waves after ischemia suggest that the selective vulnerability of the retina to ischemia could change functionally during the period of reperfusion.
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PMID:Involvement of oxygen free radicals in experimental retinal ischemia and the selective vulnerability of retinal damage. 1146 71

Neuroblastoma treatment remains challenging but has been advanced by the establishment of clinical and biological variables that determine prognostic risk. Risk-based therapy currently is the hallmark of neuroblastoma treatment. Initially, stage and age were the prime determinants of survival used in clinical practice. The Shimada histopathologic classification added to the former 2 and biochemical markers like the serum ferritin, lactic dehydrogenase, and neuron-specific enolase also provided information regarding prognosis. The current era of neuroblastoma therapy has been influenced heavily by advances in molecular biology, most notably the identification of the MYCN oncogene and the application of recombinant DNA methods to identification of chromosomal deletions. Current risk assessment includes age, stage, histopathology, and biochemical markers but also analyses performed on DNA extracted from fresh tumors. This places the onus of obtaining an adequate quantity and quality of fresh neuroblastoma tissue directly on the pediatric surgeon who performs the initial biopsy.
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PMID:Surgical management of neuroblastoma. 1148 50

Lithium and nickel present low toxicity, but are able to cause alterations in different tissues. The toxic effects of lithium and nickel at different cellular levels were assessed using two inorganic chemical species: lithium chloride and nickel(II) chloride. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed to both compounds for 24 h. The cytotoxic effects evaluated were cell proliferation by quantification of total protein content, cytoplasmic membrane integrity to cytosolic lactate dehydrogenase leakage, and lysosomal hexosaminidase release. Metabolic markers were lactate dehydrogenase activity and mitochondrial succinate dehydrogenase activity. Lysosomal markers were relative neutral red uptake by lysosomes, and lysosomal hexosaminidase sphingolipid degradation activity. Acetylcholinesterase activity on intact cells was also quantified. Nickel was found to be 36 times more toxic than lithium to neuroblastoma cell proliferation (EC(50)= 0.29 and 10.5 mM, respectively), but the relative extent of other alterations differed. Lithium stimulated nearly all the indicators studied, particularly lactate dehydrogenase, mitochondrial succinate dehydrogenase and acetylcholinesterase activities, as well as hexosaminidase release. In contrast, nickel mainly stimulated hexosaminidase release and inhibited lactate dehydrogenase activity. The stabilization of the cytoplasmic membrane to lactate dehydrogenase leakage simultaneously with the secretion of lysosomal hexosaminidase for both compounds also shows that functional metabolic alterations produced by lithium and nickel are more important than cytoplasmic damage.
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PMID:In vitro effects of lithium and nickel at different levels on Neuro-2a mouse neuroblastoma cells. 1156 64

Between 1985 and 1999, 128 children with neuroblastoma were treated at the Royal Alexandra Hospital for Children. The objective of this retrospective study was to report on a single institution's experience with neuroblastoma and to evaluate clinical and biological prognostic factors using univariate and multivariate assessment. Fifty-two percent presented with localized disease, 41% had stage IV disease, and 7% had stage IVs disease. The 5-year overall survival rate was 65%. Significant prognostic factors in univariate analysis included stage, site, histology, N-myc amplification, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), and urinary dopamine. In multivariate assessment, the adjusted hazard ratio was 3.5 (95 %CI 1.4-8.5) for N-myc amplification, 8.7 (95% CI 3.0-25) for NSE > 300 ng/mL, and 3.6 (95% CI 1.3-10) for-LDH > 3000 U/L. This study confirmed that survival was heavily influenced by closely interrelated clinical and biological factors. Prospective studies including more recently identified molecular prognostic factors are warranted to predict the biological heterogeneity of neuroblastoma.
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PMID:Neuroblastoma: a single institution's experience with 128 children and an evaluation of clinical and biological prognostic factors. 1188 90

Freshly solubilized A beta peptides synergistically increase the magnitude of the constriction induced by endothelin-1 (ET-1), via the activation of a pro-inflammatory pathway. We report that mevinolin and mevastatin, two inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are able to completely abolish the vasoactive properties of A beta in rat aortae. Mevinolin also appears to oppose the increased vascular reactivity to ET-1 induced by interleukin 1-beta and phospholipase A(2) suggesting that statins display some anti-inflammatory properties. We show that freshly solubilized A beta stimulates prostaglandin E(2) and F(2 alpha) production (by 6 and 3.6 times, respectively) in isolated rat aortae and that mevinolin completely antagonizes this effect confirming the anti-inflammatory action of mevinolin ex vivo in rat aortae. In addition, we observed that A beta vasoactivity is not mediated nor modulated by mevalonic acid suggesting that the anti-inflammatory action of the statins are not related to an inhibition of HMG-CoA reductase activity. Differentiated human neuroblastoma cells (IMR32) were used to assess the neurotoxic effect of pre-aggregated A beta by quantifying the release of lactate dehydrogenase (LDH) in the cell culture medium. A beta appears to enhance LDH release by 30% in IMR32 cells, an effect that can be completely opposed by mevastatin. Taken together these data show that statins can antagonize the effect of A beta in different assays and provide new clues to understand the prophylactic action of the statins against Alzheimer's disease.
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PMID:Statins inhibit A beta-neurotoxicity in vitro and A beta-induced vasoconstriction and inflammation in rat aortae. 1188 11

Excitotoxic effects leading to neuronal cell degeneration are often accompanied by a prolonged increase in the intracellular level of Ca(2+) ions and L-glutamate-induced toxicity is assumed to be mediated via a Ca(2+)-dependent mechanism. Due to their buffering properties, EF-hand Ca(2+)-binding proteins (CaBPs) can affect intracellular Ca(2+) homeostasis and a neuroprotective role has been attributed to some of the family members including calretinin, calbindin D-28k and parvalbumin. We have stably transfected N18-RE 105 neuroblastoma-retina hybrid cells with the cDNAs for the three CaBPs and investigated the effect of these proteins on the L-glutamate-induced, Ca(2+)-dependent cytotoxicity. Several clones for each CaBP were selected according to immunocytochemical staining and characterization of the overexpressed proteins by Western blot analysis. In calretinin- and parvalbumin-expressing clones, expression levels were quantitatively determined by ELISA techniques. Cytotoxicity of transfected clones was quantified by measurement of the activity of lactate dehydrogenase (LDH) that was released into the medium after L-glutamate (10 mM) exposure as a result of necrotic cell death. In untransfected and parvalbumin-transfected cells, LDH released into the medium progressively increased (starting from the 20th hour) reaching maximum levels after 28-30 h of glutamate application. In contrast, LDH release in both, calretinin and calbindin D-28k-transfected clones, was not significantly different from unstimulated transfected or untransfected cells over the same period of time. The results indicate that the 'fast' Ca(2+)-buffers calretinin and calbindin D-28k, but not the 'slow' buffer parvalbumin can protect N18-RE 105 cells from this type of Ca(2+)-dependent L-glutamate-induced delayed cytotoxicity.
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PMID:Calretinin and calbindin D-28k, but not parvalbumin protect against glutamate-induced delayed excitotoxicity in transfected N18-RE 105 neuroblastoma-retina hybrid cells. 1212 80

A missense mutation (N1411) in Presenilin-2 (PS-2) gene is associated with early-onset familial Alzheimer's disease. In this study, SK-N-SH human neuroblastoma cells were transfected with wild-type and mutant PS-2 gene to examine presenilin-2 effects on apoptosis. Serum deprivation resulted in enhanced apoptosis in mutant PS-2 comparing with wild-type PS-2. Similarly, mutant PS-2 induced lactate dehydrogenase release to greater extent than wild-type PS-2. Time course experiment demonstrated that the increase in caspase-3-like activity was more pronounced and accelerated in mutant PS-2, compared to wild-type PS-2. While a significant decrease in bcl-2, an anti-apoptotic molecule, occurred in the cells overexpressing mutant PS-2, no significant change was observed in bax, a pro-apoptotic molecule, as compared with the cells overexpressing wild-type PS-2. Our study demonstrated that mutant PS-2 induces apoptosis accompanied by increased caspase-3-like activity and decreased bcl-2 expression in neuronal cells after serum-deprivation.
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PMID:N141I mutant presenilin-2 gene enhances neuronal cell death and decreases bcl-2 expression. 1217 18

To investigate retrospectively the clinical and biological features that influence the outcome of infants with neuroblastoma (NB) detected by mass screening (NBMS), and to construct surgical strategies to deal with NBMS, 20 infants diagnosed as having either NB or ganglioneuroblastoma (GNB) between 1986 and 1998 were enrolled in a study. They comprised 15 boys and 5 girls ranging in age from 7 to 14 months. The following factors were analyzed by multivariate analysis: age, stage according to the Japanese staging system at the time of diagnosis, site of the primary tumor, histologic findings, preoperative urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels, VMA/HVA ratio, lactate dehydrogenase, neuron-specific enolase, Shimada's histologic classification, amplification of the N- myc oncogene by Southern blot analysis, nuclear content, and chromosomal abnormality. The 2-year survival was 95.0% (19/20). The site of the primary tumor was the adrenal gland in 12 cases, retroperitoneum in 6, and retrothoracic space in 2. Four infants had stage I, 6 stage II, 3 stage III, 3 stage IVB, and 4 stage IV disease. Complete resection was achieved in all cases except for 1 retroperitoneal GNB. Histologic examination showed that 8 patients had NB. Of the 12 GNBs, 8 were poorly-differentiated and 1 was well-differentiated. Only 1 of the 14 examined tumors showed amplification of N- myc (20 copies). The infant with N- myc-positive NB (stage II) died 23 months after surgery in spite of aggressive postoperative chemotherapy. Multivariate analysis revealed the plasma NSE level to be a significant predictor of survival (p < 0.0143). This suggests that N- myc amplification and plasma NSE level could be closely related to the survival of infants with NBMS. The N- myc-positive NB case implies that even in locoregional NB detected by NBMS, surgical excision should play a central role in the diagnosis of its oncogenic characteristics and indicate any subsequent therapy.
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PMID:Outcome of infants with neuroblastoma detected by mass screening and surgically treated in Shiga Prefecture, Japan: what is the role of surgery? 1241 40

Elevated production of hydrogen peroxide (H2O2) in the central nervous system has been implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, ischemic reperfusion, stroke, and Alzheimer's disease. Pyruvic acid has a critical role in energy metabolism and a capability to nonenzymatically decarboxylate H2O2 into H2O. This study examined the effects of glycolytic regulation of pyruvic acid on H2O2 toxicity in murine neuroblastoma cells. Glycolytic energy substrates including D-(+)-glucose, D-(-) fructose and the adenosine transport blocker dipyridamole, were not effective in providing protection against H2O2 toxicity, negating energy as a factor. On the other hand, pyruvic acid completely prevented H2O2 toxicity, restoring the loss of ATP and cell viability. H2O2 toxicity was also attenuated by D-fructose 1,6 diphosphate (FBP), phospho (enol) pyruvate (PEP), niacinamide, beta-nicotinamide adenine dinucleotide (beta-NAD+), and reduced form (beta-NADH). Both FBP and PEP exerted positive kinetic effects on pyruvate kinase (PK) activity. Interestingly, only pyruvic acid and beta-NADH exhibited powerful stoichiometric H2O2 antioxidant properties. Further, beta-NADH may exert positive effects on PK activity. Subsequent pyruvic acid accumulation can lead to the recycling of beta-NAD+ through lactate dehydrogenase and beta-NADH through glyceraldehyde-3-phosphate dehydrogenase. It was concluded from these studies that intracellular pyruvic acid and beta-NADH appear to act in concert through glycolysis, to enhance H2O2 intracellular antioxidant capacity in neuroblastoma cells. Future research will be required to examine whether similar effects are observed in primary neuronal culture or intact tissue.
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PMID:Cytoprotection of pyruvic acid and reduced beta-nicotinamide adenine dinucleotide against hydrogen peroxide toxicity in neuroblastoma cells. 1271 24


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