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 tumors have only the fifth isozyme band (A(4)) of lactate dehydrogenase, whereas this band is missing in the brain which contained four other bands of lactate dehydrogenase. The alpha-esterase isozyme patterns of tumors, kidney, and brain are similar except that there is an additional slowest-moving form of esterase in all tumor tissues. The malate dehydrogenase pattern is not altered in any of the tissues.
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PMID:Esterase, malate, and lactate dehydrogenases activity in murine neuroblastoma. 471 10

The activity of the neutral, Mg2+-stimulated sphingomyelinase of cultured neuroblastoma cells (N1E-115) is enriched in the plasma membrane fraction and is reduced following treatment of intact or broken cells with trypsin, alpha-chymotrypsin, papain, and protease. Two protease-sensitive enzymes of the cell interior (lactate dehydrogenase and NADPH-cytochrome c reductase) are not affected by protease treatment of intact cells. These results indicate that the neutral, Mg2+-stimulated sphingomyelinase is oriented externally on the plasma membrane of the cultured neuroblastoma cell.
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PMID:Evidence that neutral sphingomyelinase of cultured murine neuroblastoma cells is oriented externally on the plasma membrane. 609 59

The specific activity of lactate dehydrogenase (LDH; EC 1.1.1.27) is induced two-fold by l-norepinephrine (NE) in C6TK- rat glioma cells, but not in NA mouse neuroblastoma cells or various other nonglial cells. Previous reports have shown that the induction is mediated by cyclic AMP (cAMP) and possibly protein phosphorylation, and that it requires RNA and protein synthesis. To study the block to LDH induction in nonglial cells, we hybridized C6TK- cells with NA cells and isolated a hybrid clone in which LDH is inducible by NE. Mouse and rat LDH from hybrid cells were separated by electrophoresis and quantitated by two independent methods, and it was found that mouse and rat LDH were induced equally when cells were exposed to NE. The results suggest that inducibility of LDH is not determined by a cis-acting control at the gene level, but rather by the presence or absence of an earlier component in the cAMP-mediated induction system, and that the induction system acts indiscriminately on all active LDH gene copies in the cell.
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PMID:Induction of both rat and mouse lactate dehydrogenase in hybrids between inducible rat glioma and uninducible mouse neuroblastoma cells. 625 3

Dibutyryl cyclic AMP and butyrate inhibited growth of S-20 (cholinergic) and NIE-115 (adrenergic) neuroblastoma clones. Both these drugs resulted in a parallel increase of choline acetyltransferase and ATP-citrate lyase activities in S-20 neuroblastoma cells. On the other hand, the increase in tyrosine hydroxylase activity in NIE-115 caused by these drugs was not accompanied by a significant change in ATP-citrate lyase activity. Both dibutyryl cyclic AMP and butyrate caused a decrease in fatty acid synthetase activity in both cell lines. The activities of pyruvate dehydrogenase, citrate synthase, choline acetyltransferase, and lactate dehydrogenase in both S-20 and NIE-115 cells were not significantly influenced by the drugs. ATP-citrate lyases from S-20 and NIE-115 had similar kinetic and immunological properties, and their subunits had the same molecular weight as the rat liver enzyme. These data indicate that the differential regulation of ATP-citrate lyase activity in cholinergic and adrenergic cells does not result from the existence of different molecular forms of the enzyme in these cell lines. They also provide further evidence to support the hypothesis that ATP-citrate lyase activity increases during maturation of normal cholinergic neurons and decreases in noncholinergic cells of the brain.
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PMID:The enzymes of acetyl-CoA metabolism in differentiating cholinergic (s-20) and noncholinergic (NIE-115) neuroblastoma cells. 630 53

Although infants (age less than 1 year) with neuroblastoma have a favorable overall prognosis, metastatic disease is associated with poorer treatment outcome. To assess the role of surgery in these patients, the authors reviewed survival data for 151 infants treated for neuroblastoma, focusing on patient and tumor characteristics, biological markers, and surgical management among the 99 patients with metastatic disease. Patients were divided into early (1961 to 1978) and contemporary (1979 to 1993) treatment eras. Potential prognostic factors were statistically tested to determine their significance in affecting survival. Five-year survival by Pediatric Oncology Group stage was: A, 100% (+/- 0%); B, 94% (+/- 6%); DS, 77% (+/- 9%); C, 73% (+/- 9%); and D, 61% (+/- 8%). Survival for infants with metastatic disease (stages C, D, and DS) was affected significantly by treatment era (P = .0001). Analyses restricted to patients treated during the contemporary era showed prognostic significance for DNA index (P = .02), N-myc copy number (P = .007), serum lactate dehydrogenase level (P = .001), and extent of resection (P = .01). A > or = 95% resection of the primary tumor was found to be associated with improved survival. Significantly more surgical complications were associated with resections performed at the time of diagnosis (P = .007), and delaying surgery until after several courses of chemotherapy did not decrease survival. In conclusion, multiple factors affect the outcome of treatment for infants with metastatic neuroblastoma, and whenever feasible, a > or = 95% resection of the primary tumor should be performed in this patient subgroup.
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PMID:Infants with metastatic neuroblastoma have improved survival with resection of the primary tumor. 747 48

It has been shown that nitric oxide (NO) regulates NO synthase (NOS) activity through negative feedback in cytosolic enzyme preparations in various cell types. We compared the effects of the NO-generating compounds S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) on NOS activity in intact neuroblastoma N1E-115 cells and in the cytosol obtained from the same cells. Enzyme activity was measured by the conversion of L-[3H]arginine into L-[3H]citrulline. At concentrations that elicit almost complete inhibition of NOS activity in cytosolic enzyme preparations of these cells, SIN-1 and SNP did not cause significant attenuation of enzyme activity measured at 45 min in intact cells. It is surprising that SIN-1 and SNP markedly stimulated L-[3H]citrulline formation in a time- and concentration-dependent manner when cells were incubated with the compounds for > 1.5 h. Neither inhibitory nor stimulatory effects of SNAP on NOS were observed in intact N1E-115 cells. This is in contrast to the inhibitory effects of SNAP in cytosolic preparations of the enzyme. The increased NOS activity by SIN-1 or SNP in intact cells was dependent on the presence of extracellular Ca2+, suggesting that it might be due to increased Ca2+ influx. On the other hand, measurements of the activity of lactate dehydrogenase showed that there was no generalized increase in cell permeability in response to SIN-1 or SNP. There was no agreement in the rank order of potencies of these compounds in activating guanylate cyclase and in affecting NOS activity, both in broken-cell preparations and in intact cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anomalous increase in nitric oxide synthase activity by certain nitric oxide-generating compounds in intact neuronal cells. 754 Jun 59

In neuroblastoma, N-myc amplification and loss of heterozygosity for the short arm of chromosome 1 (LOH 1p) are common genetic abnormalities. We have recently shown that the presence of additional material of the long arm of chromosome 17 (add.17q) also occurs relatively frequently. In the present study, we analyzed a series of 55 tumors for LOH 1p, N-myc amplification and add.17q, using Southern blot analysis with polymorphic DNA probes of pairs of tumor and constitutional DNA. We determined the correlation of these parameters with clinical variables, such as age, stage, serum lactate dehydrogenase (LDH) and ferritin and also with outcome. LOH 1p occurred in 20 out of 55 cases (36%) and was found more often in stage III/IV tumors and in the older age group, although both correlations were not statistically significant. N-myc amplification was only demonstrated in 12 tumors with concomitant LOH 1p and was not present in the 35 cases without LOH 1p. Add.17q was found in 20/53 (38%) informative cases. LOH 1p was shown to be the most significant predictor of a poor outcome (P < 0.00001), independent of age and stage. LOH 1p is also of prognostic value in those cases without N-myc amplification, indicating a stronger prognostic value for LOH 1p. Add.17q was also associated with an unfavourable prognosis, although this was less significantly then with LOH 1p (P = 0.00004).
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PMID:Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma. 770 Jan 65

The prognosis for patients with neuroblastoma is related to the age and stage at time of presentation, as well as to the presence or absence of biological markers such as N-myc amplification and the degree of DNA ploidy. However, previous studies have shown that neuroblastoma in the thoracic site also is a favorable prognostic indicator, in that children with mediastinal neuroblastoma have a better survival rate, regardless of age or stage at time of presentation. This study was designed to evaluate the biological differences between thoracic and nonthoracic neuroblastoma with respect to N-myc amplification, DNA index as a measure of DNA ploidy, serum lactate dehydrogenase levels, and serum ferritin levels. Patients enrolled in the Pediatric Oncology Group study protocols for neuroblastoma were evaluated retrospectively, and log-rank analysis allowed the impact of each biological variable on survival to be determined for each cohort of patients. There were 1,335 neuroblastoma patients in the data base; 227 had thoracic-site neuroblastoma. Through analysis, it was apparent that patients with thoracic neuroblastoma have better survival rates than do their nonthoracic counterparts (P < .0001), and they are less likely to have N-myc amplification (P = .001), more likely to have an LDH level of less than 1,500 (P < .0001), and usually have a DNA index of greater than 1 (P < .003). Both thoracic and nonthoracic patients have low serum ferritin levels (86% of thoracic versus 83% of nonthoracic patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biological variables in thoracic neuroblastoma: a Pediatric Oncology Group study. 773 54

The toxic effects of arsenic at different cellular levels were assessed using two inorganic chemical species: sodium arsenite and sodium arsenate, representing the trivalent and pentavalent states of arsenic, respectively. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed for 24 h, and cytotoxic effects evaluated were: cell proliferation by quantification of total protein content; cytoplasmic membrane integrity to cytosolic lactate dehydrogenase leakage; lysosomal hexosaminidase release; lactate dehydrogenase activity; mitochondrial succinate dehydrogenase activity; relative neutral red uptake by lysosomes; lysosomal hexosaminidase sphingolipid degradation activity; and acetylcholinesterase activity. As(III) was found to be five times more toxic than As(V) to neuroblastoma cell proliferation, but the relative extent of other alterations differed. Special sensitivity was detected for lactate dehydrogenase inhibition. Hexosaminidase activity was also very susceptible, being inhibited at low concentrations and stimulated at high concentrations. Less sensitive were the inhibition of cell proliferation, relative neutral red uptake, and acetylcholinesterase activity. As(III) was lysosomotropic, with secretion of hexosaminidase, but the release was decreased by As(V). Mitochondrial succinate dehydrogenase was inhibited by As(III) and stimulated by As(V). Minor sensitivity to cytoplasmic lactate dehydrogenase leakage for both compounds also shows that functional metabolic alterations produced by arsenic are more important than structural damage.
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PMID:Comparative in vitro effects of sodium arsenite and sodium arsenate on neuroblastoma cells. 794 May 56

The sesquiterpene endoperoxide antimalarial agents arteether and artemether have been reported to cause neurotoxicity with a discrete distribution in the brain stems of rats and dogs after multiple doses. The nature and distribution of the brain lesions suggest a specific neuronal target, the identity of which is unknown. In order to further investigate artemisinin analog-induced neurotoxicity, we evaluated several in vitro models: fetal rat primary neuronal cultures, fetal rat secondary astrocyte cultures, and transformed neuronal cultures (rat-derived neuroblastoma NG108-15 and mouse-derived neuroblastoma Neuro-2a). Results indicate that toxicity was specific for neuronal cell types but not glial cells. Neurotoxicity, as indexed by liberation of lactate dehydrogenase and/or inhibition of radiolabelled-leucine uptake, was seen in all three neuronal culture types, implicating a common target. In vitro neurotoxicity was dose and time dependent. Acute exposure to drug results in delayed, but not immediate, manifestations of cell toxicity. Structure-activity comparisons indicate that substitutions at positions 9 and 10 and stereoisomerism at position 10 of the artemisinin backbone influence the degree of toxicity. The endoperoxide is necessary but not sufficient for toxicity. Sodium artesunate and dihydroartemisinin, a metabolite common to all artemisinin analogs currently being developed for clinical use, are the most potent of all analogs tested. These results are consistent with a specific neuronal target, but the identity of the target(s) remains unknown.
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PMID:Neurotoxicity of artemisinin analogs in vitro. 798 12


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