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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DOPA-content in neuroblastoma clone N1E-115 is higher than the dopamine or noradrenaline content. Blockade of tyrosine hydroxylase by alpha-methyl-p-tyrosine (1 X 10(-3) M) resulted in a decrease of cellular DOPA-content to 24.9% after 4 hr. The accumulation of DOPA in these cells which is probably due to limited activity of l-aromatic amino acid decarboxylase led us to use DOPA-content as a measure of tyrosine hydroxylase (TH) activity. Dopamine and especially apomorphine were effective at low concentrations (dopamine IC50 1 X 10(-5) M, apomorphine 2 X 10(-7) M); lisuride had no effect on TH-activity. The low effective dose of apomorphine and the failure of lisuride to influence TH-activity are comparable to the observations in striatal synaptosomal preparations and make the N1E-115 clone a suitable model for studying the mechanism of TH-regulation. However, since haloperidol (1 X 10(-5) M) did not reverse the apomorphine-induced blockade of TH, a receptor-mediated blockade of TH seems to be improbable.
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PMID:Mouse neuroblastoma clone N1E-115: a suitable model for studying the action of dopamine agonists of tyrosine hydroxylase activity. 612 55

The neuroblastoma line SK-N-SH-SY5Y (SY5Y) is a thrice subcloned nearly diploid clonal line of human origin. When grown in 15% fetal calf serum in Ham's F-12 medium as herein described, SY5Y has neuroblast-like properties in its undifferentiated state. Treatment with nerve growth factor results in morphological and physiological differentiation not unlike that elicited by nerve growth factor in sympathetic ganglia primary cultures. Careful examination of catecholamine synthesizing enzyme specific activities and catecholamine concentrations in nerve growth factor-treated SY5Y cells showed a small elevation of tyrosine hydroxylase, no change in dopamine-beta-hydroxylase or in dopamine or norepinephrine intracellular concentrations. This is consistent with the interpretation that nerve growth factor acts as a permissive or trophic factor, and not necessarily as an instructive or specifying factor in this system.
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PMID:Effect of nerve growth factor on catecholamine metabolism in a human neuroblastoma clone (SY5Y). 613 Sep 33

Two neurotransmitter-synthesizing enzymes, tyrosine hydroxylase (TH) and choline acetyltransferase (CAT), were assayed in neuroblastoma tissues from 24 children, in human neuroblastoma tissues serially transplanted in nude mice, and in human neuroblastoma cells in culture. Among tissues from 24 children, five showed an adrenergic pattern with significant TH activity alone, seven showed a cholinergic pattern with significant CAT activity alone, and the remaining 12 specimens showed a "both-active" pattern with both TH and CAT activity. Enzymatic activities were maintained through many serial passages in vitro and in nude mice. All four specimens from children under one year of age exhibited the adrenergic pattern. In general, enzymatic activity was not correlated with degree of differentiation histologically. Among four cases of paravertebral dumb-bell type in this series, two were cholinergic, one was adrenergic, and the last was both-active. These results suggest that dumb-bell type tumors may arise from either sympathetic ganglia or dorsal root ganglia. This study supports the concept that neuroblastomas are a composite of adrenergic and cholinergic cells. Significant changes in the relative proportions of these two cell types were observed with time, and after extensive therapy. Different metastatic sites often exhibited important differences in enzymatic activity. These results help to account for clinical discrepancies between urinary VMA levels and tumor growth. Assays for TH and CAT can be useful for confirming a diagnosis of neuroblastoma, and have important potential for helping to clarify the natural history of neuroblastoma.
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PMID:Tyrosine hydroxylase and choline acetyltransferase activity in human neuroblastoma. Correlations with clinical features. 613 77

This study was undertaken to determine whether the two type of cells (one neuroblast-like and the other epithelial in appearance) of the human neuroblastoma line SK-N-SH in culture undergo morphological interconversion, whether conversion is bidirectional, and whether there are coordinate neurochemical changes. Phenotypic analysis of serially isolated neuroblast clones (SH-SY, SH-SY5, SH-SY5Y) revealed conversion to epithelial-like cells. Conversely, conversion also was promoted from an epithelial-like clone (SH-EP) to neuroblastic subclones. Cell origin could be verified because of a marker chromosome specific to SH-EP. Only neuroblastic subclones of SH-EP contained activities for tyrosine hydroxylase and dopamine-beta-hydroxylase, enzymes unique to catecholamine neurons; epithelial-like cells lacked activities for these enzymes. These findings indicate a coordinate morphological and biochemical interconversion of neuroblastoma SK-N-SH cells and reveal a plasticity in phenotypic expression in malignant neuronal cells.
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PMID:Coordinate morphological and biochemical interconversion of human neuroblastoma cells. 613 86

A new human cell line, TR14 , has been established in tissue culture from biopsy material of a primary neuroblastoma tumor. Most TR14 cells have short processes and grow mainly in clumps adhering to cells attached to the substratum. TR14 cells form colonies in soft agar demonstrating anchorage independence of growth and produce tumors in nude mice with histologies similar to that of the patient's tumor. The neurotransmitter-synthesizing activity of these cells is predominantly cholinergic with only a minor adrenergic component, since the activity of choline acetyltransferase is about 20-fold greater than that of tyrosine hydroxylase. Treatment with N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate induces TR14 neuroblastoma cells to extend fine, long processes or neurites. This morphological change is accompanied by elevated numbers of cytoplasmic dense-core vesicles observed by electron microscopy and an increase in the activities of neurotransmitter-synthesizing enzymes. Differentiation therefore occurs at the levels of cellular morphology, ultrastructure, and biochemistry. Prostaglandin E1 and cholera toxin can also induce differentiation, but a range of other agents including dimethyl sulfoxide, nerve growth factor, butyrate, corticosteroids, and 5-bromodeoxyuridine is ineffective. The concomitant induction of both morphological and biochemical differentiation therefore appears to be exclusively a cyclic adenosine 3':5'-monophosphate-mediated event in this cell line.
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PMID:Characteristics of a new human neuroblastoma cell line which differentiates in response to cyclic adenosine 3':5'-monophosphate. 614 83

The inhibitory effect of apomorphine on tyrosine hydroxylase (TH) was tested using enzyme preparations from rat striatum, neuroblastoma clone N1E-115 and pheochromocytoma clone PC-12. When the striatal enzyme preparation was incubated at pH 7.2 with (6R,S)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as cofactor (100-1,000 mumol/l), the IC50 for apomorphine was found to be in the 0.1-1 mumol/l range depending on the BH4-concentration used. Changing the incubation medium to pH 6.0 yielded an IC50 of about 2.5 mumol/l (BH4 = 100 mumol/l). Apomorphine was even less effective when 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine (100 mumol/l) was used as cofactor (IC50 approximately 10 mumol/l). Similar results were obtained with the enzyme preparations of the two cell clones. These experiments show that, even in low concentrations, apomorphine inhibits TH directly, provided more physiological test conditions are used. The relevance of these results for the autoreceptor-mediated mechanism of the apomorphine action on catecholamine synthesis is discussed.
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PMID:Inhibition of striatal tyrosine hydroxylase by low concentrations of apomorphine. 614 68

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

In three patients with neuroblastoma and high circulating levels of dopamine and dopa, we interfered pharmacologically with catecholamine biosynthesis either at the tyrosine hydroxylase or dopa decarboxylase step in an attempt to 1) improve the efficacy of antitumor therapy and 2) avoid the potential arrythmogenic interaction between elevated circulating catecholamines and an halogenated hydrocarbon anesthetic during surgery. Biochemical evidence indicated that inhibition of catecholamine biosynthesis had occurred but there was no associated significant change in clinical status or response to other therapy.
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PMID:Inhibition of catecholamine biosynthesis by carbidopa and metyrosine in neuroblastoma. 642 94

We show here that cells dissociated from fetal mouse hypothalamus and cerebral hemispheres can be grown in primary culture in a serum-free medium (SFM). We describe several properties of these cultures and compare them to those in serum-supplemented medium (SSM). The SFM used is a modification of that described for neuroblastoma cells: neuronal survival is improved when 17 beta-estradiol is added. Initial events in culture development were similar to those observed in SSM. However, after 1 week, several differences could be noted: in SFM, the proportion of neuron-like cells was increased while the basal glial layer was noticeably reduced, and the neurite network remained less developed than in SSM. These findings demonstrate that the use of SFM permits manipulation of the types and proportions of cells in these primary cultures. This point has been already made. Several neuronal activities were studied. In cultures from both hypothalamus and cerebral hemispheres, thyroliberin (TRH)-immunoreactive cells were visualized by immunohistochemistry, and TRH was radioimmunoassayed in cell extracts and in the medium. In hypothalamic cultures, tyrosine hydroxylase was shown to remain stable for 1 week, and then declined. Glutamic acid decarboxylase disappeared very quickly in vitro, whereas choline acetyltransferase activity increased more rapidly in SFM than in SSM. It is concluded that the use of an SFM for growing normal fetal hypothalamic cells offers a promising model for studying neuroendocrine regulatory mechanisms in culture.
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PMID:Differentiation of fetal mouse hypothalamic cells in serum-free medium. 678 65

Murine neuroblastoma cells have been widely used as a model system for neuronal cells as they can be induced to differentiate in culture by various stimuli, such as dibutyryl cyclic AMP (dbcAMP), prostaglandin, and serum starvation. The cells respond with assembly of microtubules, leading to neurite outgrowth, with increased activity of neuronal-specific enzymes, tyrosine hydroxylase, choline acetyltransferase and acetylcholine-esterase, and synthesis of neurotransmitters. The differentiated cells lose tumorigenicity. Cell-to-substratum adhesion is evidently crucial for neurone extension in vitro. Neurite outgrowth is induced by treatments that increase cell-to-substratum adhesion in some neuronal cell cultures. We have now identified the major high molecular weight proteins synthesized and secreted by murine C1300 neuroblastoma cells as fibronectin, laminin and type IV procollagen, of which the latter two were also found to be deposited in pericellular matrix form.
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PMID:Basal lamina glycoproteins are produced by neuroblastoma cells. 743 74


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