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)

Dissociated fetal mouse brain cells are allowed to reassociate in rotation culture to form aggregates. After several weeks these reaggregated brain cell cultures show markedly increased specific activities of monoamine oxidase, lactate dehydrogenase, and the brain-specific protein S-100, while catechol-O-methyltransferase activity increases slightly. Similar changes in these activities are found during mouse brain maturation. The amounts of monoamine oxidase, catechol-O-methyltransferase, and S-100 were also determined in surface cultures of fetal mouse brain cells, as well as glioma and neuroblastoma cell lines. The fetal brain and glial cell cultures possess much higher activities than the cultured neuroblastoma cells. However, lactate dehydrogenase activity was highest in the glioma and lowest in the surface cultures of fetal brain cells.
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PMID:Expression of differentiated activities in reaggregated brain cell cultures. 114 Dec 38

In 211 patients with neuroblastoma, serum vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were determined and correlated to stage, histological differentiation, ferritin, neuron-specific enolase, lactate dehydrogenase (LDH) and outcome. Elevated serum VMA and/or HVA levels were found 16% less frequently than elevated urine levels. The incidence of the elevated serum levels increased with stage (stages I-III 58%, IV 78%, IVS 100%). Increased VMA/HVA ratios were not associated with a higher grade of tumour differentiation. Serum ferritin and neuron-specific enolase showed no correlation, and LDH a borderline non-random correlation with the serum catecholamine metabolites. Using age-related reference values a quotient of serum VMA/HVA (P = 0.061) < 0.7 indicated a poorer event-free survival (48 +/- 10%) than ratios > or = 0.7 (event-free survival 81 +/- 6%) for children with localised neuroblastoma (P = 0.0004). No correlation with prognosis was detected for patients with stage IV and stage IVS disease. We conclude that serum VMA and HVA determinations may be useful as tumour markers for 71% of neuroblastoma patients, and aid in estimating the prognosis in children with localised disease.
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PMID:Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma. 141 87

On the basis of an extensive recursive partitioning analysis of 668 patients with newly diagnosed neuroblastoma registered on Pediatric Oncology Group (POG) studies between October 1981 and May 1987, four major subsets of patients were created. Important prognostic factors included the patient's stage of disease, age, and level of serum lactate dehydrogenase (LDH). After adjusting for these factors, no other clinical prognostic factors were significant. The implications for protocol design are that (a) fine tuning of current therapy should be sought for the two favorable disease patient subsets, while (b) novel aggressive therapies are needed for the two unfavorable disease patient subsets where the overwhelming majority are dying. This article may serve as a model for others investigating prognostic factors. The data were divided into two subsets: one was used for an exploratory analysis; the other was used to confirm the exploratory findings. Despite spite the large number of statistical tests performed, the likelihood that the findings can be attributed to chance can be dismissed as virtually zero.
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PMID:Serum lactate dehydrogenase in childhood neuroblastoma. A Pediatric Oncology Group recursive partitioning study. 151 25

The properties and bimodal distribution of phosphatidic acid phosphohydrolase (PAP) were investigated in neuroblastoma X glioma hybrid NG108-15 cells. Two PAP activities distinguished by their differential sensitivity to Mg2+ and Triton X-100 were identified in the cytosolic and microsomal fractions. A digitonin permeabilization method was employed to study the basal distribution of the cytosolic PAP and its redistribution upon cell exposure to amphiphilic lipids. Under conditions which release 100% of the cytosolic marker enzyme lactate dehydrogenase, only 60% of total cellular PAP activity was released into the medium through the digitonin-induced membrane pores, suggesting that about 40% of the total are membrane associated. Elevated plasma-membrane levels of phosphatidic acid, accomplished by incubating cells with Streptomyces chromofuscus phospholipase D, did not affect the distribution of cytosolic PAP. In contrast, oleic acid induced a marked concentration-dependent redistribution of the cytosolic enzyme to the particulate fraction. PAP redistribution was completely abolished in the presence of the sphingoid base sphingosine, previously shown to inhibit PAP activity in vitro (Lavie, Y., Piterman, O. & Liscovitch, M. (1990) FEBS Lett. 277, 7-10). Thus, the distribution of cytosolic PAP is reciprocally regulated by a long-chain (fatty) acid and a long-chain (sphingoid) base which are breakdown products of phospholipids and sphingolipids, respectively. These effects might influence PAP function in glycerolipid metabolism and signal transduction under physiological and pathophysiological conditions.
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PMID:Bimodal distribution of phosphatidic acid phosphohydrolase in NG108-15 cells. Modulation by the amphiphilic lipids oleic acid and sphingosine. 154 Dec 71

We studied the clinical significance of genomic amplification of N-myc in Stage IV-S neuroblastoma, with reference to spontaneous regression. Among 103 neuroblastomas in which N-myc was measured, ten were Stage IV-S (eight children were younger than and two were older than 1 year of age). The number of copies of N-myc was 1 to 3 in five patients, four to ten in one patient, and more than ten in four patients, and the survivors of each group were four, one, and one (recurrent), respectively. Of 41 patients younger than 1 year of age, N-myc amplification of more than three copies was found only in Stage IV-S neuroblastoma. Cure with a tendency to regress spontaneously was seen in five of eight patients younger than 1 year of age. However, two patients older than 1 year of age classified as Stage IV-S (one with N-myc amplification) died of progressive disease. In two patients (1 and 3 months of age) with a huge hepatic involvement and in whom the tumor had an amplified N-myc of more than ten copies, tumor regression occurred but there was a relapse to a progressive state later. The overexpression of N-myc mRNA occurred in nine of ten stage IV-S tumors and did not correlate with the prognosis. The vanillylmandelic acid (VMA) to homovanillic acid (HVA) ratio was low in tumors with an increased number of copies of N-myc. Serum lactate dehydrogenase (LDH) levels were increased in Stage IV-S patients with N-myc amplification but not in those with regressing tumors and without N-myc amplification. These data suggest that N-myc amplification may affect the final outcome in the patient classified as Stage IV-S, but tumor regression can occur early after birth and appears to be independent of N-myc amplification.
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PMID:N-myc oncogene and stage IV-S neuroblastoma. Preliminary observations on ten cases. 219 87

The toxic effects of physostigmine, an anticholinesterase drug, and its metabolite eseroline were investigated in three neuronal cell culture systems, mouse neuroblastoma N1E-115, rat glioma C6, and neuroblastoma-glioma hybrid NG 108-15. Physostigmine and eseroline (0.5 nM) elicited a time-dependent leakage of lactic acid dehydrogenase (LDH) from all three cell types. An increased release of [14C]adenine nucleotides was also detected from cells when they were prelabeled with [14C]adenine. Eseroline was comparatively more toxic than the parent compound, physostigmine. Eseroline elicited a dose- and time-dependent leakage of LDH and release of adenine nucleotides from the neuronal cells. A nonneuronal cell line, rat liver ARL-15, was comparatively the most resistant cell type to eseroline toxicity. The concentrations of eseroline needed for 50% release of adenine nucleotides or 50% leakage of LDH from NG-108-15 and N1E-115 cells in 24 hr ranged from 40 to 75 microM. The concentrations of eseroline needed to obtain similar responses in C6 and ARL-15 cells were much higher and ranged from 80 to 120 microM. Phase contrast microscopy showed extensive damage to three neuronal cell lines at concentrations of eseroline as low as 75 microM. The loss of ATP from N1E-115 cells exceeded 50% when they were treated with 0.3 mM eseroline for 1 hr--at which time the leakage of LDH was not detectable. It seems that eseroline causes neuronal cell death by a mechanism involving loss of cell ATP. Thus, the formation of eseroline may contribute to the toxic effect of physostigmine.
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PMID:Eseroline, a metabolite of physostigmine, induces neuronal cell death. 225 81

As neuroblastoma, the most common solid tumour in childhood, may contain all the constituents of the catecholamine biosynthesis cascade, some of these constituents may be produced in excess in a varying mixture reflecting the wide variability in expression of differentiated features of the tumour. We have measured plasma levels of norepinephrine (NE), epinephrine (E), dopamine (DA) and 3,4-dihydroxyphenylalanine (DOPA), and plasma activities of dopamine beta-hydroxylase (DBH) and aromatic L-amino acid decarboxylase (ALAAD) in 18 patients with neuroblastoma, in 13 at various times during the course of their disease. Activities of serum lactic dehydrogenase (LDH), serum levels of ferritin (FER) and neuron-specific enolase (NSE), and urinary vanilmandelic acid (VMA) were also determined. NE, E and DBH were found not to reflect tumour activity. In untreated active neuroblastoma DOPA or ALAAD (10 out of 10) or both (six out of 10) were clearly elevated. In all 13 patients where samples were obtained during chemotherapy, ALAAD activities fell within the normal range, while DOPA decreased more slowly. During relapse, DOPA and, especially, ALAAD, rapidly increased; in all six patients who had a relapse both DOPA and ALAAD were elevated. In complete remission (eight patients), ALAAD was normal in all patients, but DOPA remained elevated in the one patient who later experienced a relapse. Our preliminary conclusion is that combined measurements of plasma ALAAD and DOPA may be useful markers for neuroblastoma activity at diagnosis, but even more so in indicating residual disease (DOPA) and in the early detection of relapse (ALAAD).
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PMID:Combined measurements of plasma aromatic L-amino acid decarboxylase and DOPA as tumour markers in diagnosis and follow-up of neuroblastoma. 250 83

Membranes from the neuroblastoma x embryonic retina cell hybrid cell line, N18-RE-105, bind L-[3H]glutamate with a pharmacologic profile consistent with a 'quisqualate-type' brain L-glutamate receptor. We describe here the cytotoxic effect of L-glutamate receptor agonists on intact N18-RE-105 cells. Cytotoxicity was quantitated by measurement of the release of the cytosolic enzyme, lactate dehydrogenase, into the culture medium after addition of L-glutamate and its analogs to the cell culture medium. L-Glutamate (10 mM) and its confirmationally restricted analogs, quisqualate (1 mM) and ibotenate (10 mM), caused cell lysis. In contrast, similar analogs which do not bind to N18-RE-105 cell membranes (kainic acid, N-methyl-D,L-aspartic acid and gamma-aminobutyric acid) were not cytotoxic. L-Glutamate-induced cytotoxicity was eliminated when calcium-free medium was used. Addition of inorganic or organic calcium channel antagonists also reduced the cytotoxicity of L-glutamate, even when 1.8 mM calcium was present in the medium. Cadmium chloride (10 microM) completely blocked L-glutamate toxicity, whereas manganese chloride (150 microM) and lanthanum chloride (25 microM) reduced toxicity by greater than 50%. Dihydropyridine voltage-sensitive calcium channel agonists or antagonists, had little or no significant effect on L-glutamate-induced toxicity. In contrast, the verapamil derivatives, D600 and D888, and the diltiazem derivative, MDL 12,330A reduced L-glutamate toxicity by greater than 50%. These results suggest that a subtype of voltage-sensitive calcium channels is involved in the mechanism of L-glutamate receptor mediated cytotoxicity in this cell line.
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PMID:Calcium-dependent glutamate cytotoxicity in a neuronal cell line. 289 63

This study was designed to establish an in vitro model with biochemical and morphological similarities to the human neurodegenerative disease GM1 gangliosidosis. Utilizing a specific inactivator of the lysosomal enzyme GM1-ganglioside beta-galactosidase (beta-D-galactopyranosylmethyl-p-nitrophenyltriazene [beta-GalMNT]) and neuroblastoma X glioma hybrid cells (NG108-15), we suppressed beta-galactosidase activity for up to 72 hours. Coincidental with suppression of this enzyme to levels less than 1% of control, we found up to a nine-fold accumulation of its substrate, the GM1-ganglioside, and the ultrastructural appearance of membranous cytoplasmic bodies. beta-GalMNT treatment suppressed growth but had little effect on the specific activity of choline acetyltransferase, lactate dehydrogenase, or other lysosomal enzymes including galactosylceramidase. This model should permit studies of the neurophysiological effects of increased ganglioside accumulation and their reversibility.
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PMID:Inactivation of GM1-ganglioside beta-galactosidase by a specific inhibitor: a model for ganglioside storage disease. 303 98

Cellular and humoral markers of malignancy play several roles at many levels in the evaluation and staging of children with cancer. Cytogenetic analysis of constitutional cells can be used to determine the genetic risk of developing certain cancers, such as retinoblastoma and Wilms' tumor in high-risk families. Urinary metabolites of neuroblastoma have been studied not only for accurate diagnostic ability in children with "small round cell" tumors, but as a screen for the presence of the tumor in large normal populations. Markers are valuable as prognostic factors at the time of cancer diagnosis; for example, the use of cell surface antigens and cytogenetics in leukemia phenotyping, leading to alterations in initial therapy. Once found at diagnosis, both specific and nonspecific markers can then be utilized to follow the regression and recurrence of a malignancy, such as serum ferritin in neuroblastoma or lactate dehydrogenase in non-Hodgkin's lymphoma. Presence of cell surface antigens to which monoclonal antibodies can be directed are becoming increasingly helpful in both tumor localization, such as in radioisotope scanning, and in therapeutic intervention, such as in purging autologous bone marrow of malignant cells prior to use as a rescue after massive cytoreduction. Finally, cellular markers have lead to a better understanding of the basic biology of particular neoplasms; for example, gene rearrangements in lymphoma, which will ultimately lead to better diagnostic and therapeutic ability.
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PMID:The use and significance of biologic markers in the evaluation and staging of a child with cancer. 371 38


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