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

Sodium butyrate produces reversible changes in morphology, growth rate, and enzyme activities of several mammalian cell types in culture. Some of these changes are similar to those produced by agents which increase the intracellular level of adenosine 3',5'-cyclic monophosphate (cAMP) or by analogs of cAMP. Sodium butyrate increases the intracellular level of cAMP by about two fold in neuroblastoma cells; therefore, some of the effects of sodium butyrate on these cells may in part be mediated by cAMP. Sodium butyrate appears to have properties of a good chemotherapeutic agent for neuroblastoma tumors because the treatment of neuroblastoma cells in culture causes cell death and "differentiation"; however, it is either innocuous or produces reversible morphological and biochemical alterations in other cell types.
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PMID:Effect of sodium butyrate on mammalian cells in culture: a review. 0 48

A variety of compounds were assessed for their ability to induce morphological differentiation and to affect the synthesis of RNA in uncloned mouse neuroblastoma cells in culture. The stimulation of morphological differentiation in uncloned cells after exposure for 48 hours to concentrations of 3 times 10-7 to 3 times 10-4 M papavarine or 10-9 to 10-3 M dibutyryl adenosine 3':5'-monophosphate (dibutyryl-cAMP) was associated, in part, with a concentration-dependent decrease in incorporation of [5-3H]uridine into ribosomal RNA (rRNA) and heterogeneous RNA (HnRNA). The latter effect on cellular RNA produced by papavarine occurred within 1 hour after its addition to the medium and was associated with impaired uptake of radioactive precursor into uridine nucleotides and reduction in the intracellular concentration of uridine 5'-triphosphate (UTP). Dibutytyl-cAMP produced a decreased in the specific radioactivity of UTP without affecting the concentration of UTP in the tumor cells. The effects of papavarine and dibutyryl-cAMP could be distinguished further by the 50% reduction of acetylcholinesterase activity produced by papavarine, but not by dibutyryl-cAMP. Papavarine did not, however, reduce the cellular level of the soluble enzyme, adenine phosphoribosyltransferase. Sodium butyrate, while producing morphological effects similar to those of papavarine and dibutyryl-cAMP at equimolar concentrations, caused no significant changes in the incorporation of [5-3H]uridine into rRNA and HnRNA; however, acetylcholinesterase activity was stimulated 6- to 7-fold above control levels. In contrast to the other differentiating agents examined, addition of 10-9 to 3 times 10-4 M concentrations of cAMP to the tissue culture medium enhanced morphological differentiation of nueroblastoma cells, and caused a 10- to 20-fold stimulation of the incorporation of [5-3H]uridine into rRNA and HnRNA at concentrations of 10-4 M and higher. This effect observed only at high concentrations of cyclic nucleotide was accompanied by an elevation in the specific acitivty of UTP, These studies suggest that the morphological response of neuroblastoma cells is not necessarily associated with concomitant alterations in the synthesis of RNA with agents other than cAMP. Observed changes in incorporation of [5-3H]uridine into RNA appear in most instances to be due to alterations in the uptake of uridine, and in the pool size and specific radioactivity of UTP.
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PMID:Effects of adenosine 3':5'-monophosphate and related agents on ribonucleic acid synthesis and morphological differentiation in mouse neuroblastoma cells in culture. 16 51

Sodium butyrate, X-irradiation, chemotherapeutic agents and cyclic AMP-stimulating agents cuased reduction in the cell number (due to cell death and reduction in cell division) when added individually to mouse neuroblastoma cells in culture. However, the combination of sodium butyrate with X-irradiation, chemotherapeutic and cyclic AMP-stimulating agents produced a greater reduction in the cell number than that produced by the individual agents.
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PMID:Effect of sodium butyrate in combination with X-irradiation, chemotherapeutic and cyclic AMP stimulating agents on neuroblastoma cells in culture. 22 92

The inhibitors of cyclic AMP phosphodiesterase (papaverine and 4-(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone), serum-free medium, and x irradiation caused cell death and neurite formation in human neuroblastoma cells in culture (IMR-32), whereas theophylline was ineffective. Prostaglandin (PG) E1, N6O'2-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) induced neurites without causing cell lethality. Inhibitors of phosphodiesterase and PGE1 increased the intracellular level of cAMP by about 2- and 4-fold respectively, whereas serum-free medium and x irradiation did not. The combination of PGE1 and phosphodiesterase inhibitor was more effective in causing morphological differentiation and in increasing the cAMP level than the individual agent. Sodium butyrate induced cell death and neurites, probably in part by increasing the cAMP level. cAMP, guanosine 3',5'-cyclic monophosphate, and adenosine had no detectable effect on the growth or morphology of neuroblastoma cells in culture. Adenosine 5'-monophosphate produced cell death without causing neurite formation. DbcAMP, and to a much lesser degree, sodium butyrate increased the tyrosine hydroxylase activity.
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PMID:Role of cyclic AMP in differentiation of human neuroblastoma cells in culture. 24 May 3

Cystathioninuria is a frequent and highly specific marker of neuroblastoma, but the etiology of this abnormality has not been well studied. To investigate this phenomenon, we analyzed 27 human neuroblastoma tissue specimens for the presence of cystathionine synthase and cystathionase. Levels of cystathionine synthase varied from undetectable to 622 pmol/mg protein, but no specimen had cystathionase measurable by rocket radioimmunoassay or catalytic assay. In addition, we assayed neuroblastoma cell lines exposed to a variety of differentiating agents: butyric acid, dimethyl sulfoxide, serum-free medium, or sodium citrate to induce differentiation. In each case we were unable to demonstrate cystathionase induction. These data are consistent with the hypothesis that neuroblastomas have a biochemical block in the transsulfuration enzymes at the level of cystathionase and that expression of cystathionine synthase in the absence of cystathionase may account for the presence of cystathioninuria in patients with neuroblastoma.
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PMID:Cystathionine metabolism in neuroblastoma. 338 29

The effect of dl-alpha-tocopheryl (vitamin E) succinate in combination with Prostaglandin A2 (PGA2) and sodium butyrate on mouse neuroblastoma cells (NBP2) in culture, according to the criteria of growth inhibition and morphological differentiation (neurite formation), was studied. Results showed that PGA2 and sodium butyrate inhibited the growth of NB cells in a dose-dependent manner. The combined effects of vitamin E succinate with PGA2 or sodium butyrate, according to the criterion of growth inhibition, were additive. Vitamin E succinate by itself did not induce morphological differentiation, but it enhanced PGA2-induced morphological differentiation. Sodium butyrate alone or in combination with vitamin E succinate did not significantly increase the level of morphological differentiation. Sodium succinate and an equal amount of solvent (ethanol) failed to modify the effect of PGA2 or sodium butyrate. This suggests that the effect of vitamin E succinate in modifying the response of PGA2 and sodium butyrate on NB cells is due to the effect of vitamin E rather than to that of succinate.
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PMID:Effects of dl-alpha-tocopheryl succinate in combination with sodium butyrate and cAMP stimulating agent on neuroblastoma cells in culture. 609 78

Cellular differentiation of the neuroblastoma X glioma hybrid cell line NG108-15 was measured and correlated with quantitative changes in the cells' ganglioside composition. The degree of differentiation was measured using an enzymatic marker, choline acetyltransferase (CAT), which is responsible for neurotransmitter synthesis in this cell line. Differentiation of these cells is commonly induced by agents such as dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP). However, in our studies, we observed that these cells "self-differentiated," in the absence of chemical inducers, when the cells became dense in culture. The differentiation marker, CAT specific activity, rose from 150 to more than 400 pmol/min/mg of protein as cell density increased, attaining a level higher than that achieved by treatment with Bt2cAMP. Differentiation of sparse cultures could be induced by conditioned medium removed from dense cultures. This effect was not due to depletion of a serum component from the medium by the cells, since it was not mimicked by serum depletion or inhibited by addition of fresh serum to the conditioned medium. These data suggest that cell density-dependent differentiation was caused by release of a factor from the cells which induced differentiation in a concentration-dependent manner. Gangliosides, therefore, were purified from sparse control cultures, dense cultures, and cultures treated with the differentiating agents Bt2cAMP, prostaglandin E1 (plus theophylline), or butyric acid. Quantitative thin layer chromatography revealed that all of the cultures contained the four gangliosides GM3, GM2, GM1, and GD1a. The concentration of one of the gangliosides, GM2, increased markedly (up to 12-fold) during differentiation. The GM2 concentration correlated closely with the level of CAT activity in the different cultures (r = 0.99). These data demonstrate that the ganglioside concentration in these cells is regulated during differentiation, a finding consistent with a possible role for gangliosides in the differentiated phenotype.
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PMID:Ganglioside composition is regulated during differentiation in the neuroblastoma X glioma hybrid cell line NG108-15. 630 Mar 57

After in vitro microtubule assembly of mouse neuroblastoma crude extracts, six protein species migrate in the tubulin region of two-dimensional electrophoregrams. The evolution of these forms after morphological cell differentiation of the clone NIE115 shows two major modifications. Form 5 decreased drastically while form 6 increases during neurite formation. Peptide mapping analysis reveals that forms 5 and 6 are vimentin, a component of intermediate filaments, and beta-tubulin subunit, respectively. Sodium butyrate treatment of NIE115 cells or serum starvation of NIA103 cells, conditions blocking cell division and failing to induce morphological differentiation, prevent any modifications in the relative proportion of these proteins. It is concluded that the changes in the distribution of the tubulin isoforms and vimentin are directly related to neurite formation.
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PMID:Changes in some cytoskeletal proteins during neuroblastoma cell differentiation. 706 11

Immortalized hybrid cells were generated by somatic cell fusion of 18-d-old embryonic corpus striatum of the mouse strain C57BL/6J with the N18TG2 neuroblastoma. One of the cell populations obtained was treated with a combination of 1 mM n-butyric acid and 10 microM SKF 38393 (a specific D1 agonist), and a surviving cell population (E1X) was subcloned. Twenty-seven monoclonal cell lines were obtained and screened for the expression of striatal-specific characteristics including gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), acetylcholine (ACh), mRNA for specific dopamine receptors, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein, M(r) 32,000 (DARPP-32), and functional D1 and D2 dopamine receptors. Neither the parent hybrid cell population (E1X) nor any of the monoclonal cell lines examined expressed GABA levels significantly different than that of the N18TG2 parent neuroblastoma cells (1.36 +/- 0.07 micrograms/mg protein). The range of ChAT activity in the monoclonal hybrid cell lines was 5.5 +/- 0.3 to 921.3 +/- 97.4 pmol/min/mg protein. Two of the cell lines expressing ChAT activity (X52 and X58) contained ACh (49.64 +/- 4.23 and 1.78 +/- 0.07 ng/mg protein, respectively). The neuronal origin of four of the monoclonal hybrid lines was shown by their immunoreactivity, following differentiation with 10 microM forskolin, to neurofilament protein, a neuron-specific marker. The monoclonal hybrid cell lines, but not the N18TG2 neuroblastoma, were shown to express an array of D1, D2, and D5 receptor mRNA as well as DARPP-32 mRNA. Two monoclonal cell lines expressed D1 receptor binding sites (X57, 29.2 +/- 4.5 fmol/mg protein and X62, 43.8 +/- 6.8 fmol/mg protein) which mediated the stimulation of adenylate cyclase activity. One cell line, X58, expressed only D2 dopamine receptors (80.9 +/- 9.8 fmol/mg protein) which were negatively coupled to adenylate cyclase activity. These findings suggest that the immortalized monoclonal hybrid cell lines are of neuronal origin and have incorporated elements of the medium spiny and cholinergic neurons of the developing striatum.
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PMID:Immortalized murine striatal neuronal cell lines expressing dopamine receptors and cholinergic properties. 782 71

The interaction of Adriamycin and pivaloyloxymethyl butyrate (AN-9) was investigated in IMR-32 neuroblastoma and MCF-7 breast adenocarcinoma cells. Adriamycin is a widely used anticancer drug, whereas AN-9 is an anticancer agent presently undergoing Phase II clinical trials. The anticancer activity of AN-9 has been attributed to its ability to act as a butyric acid prodrug, although it also releases formaldehyde and pivalic acid. Adriamycin and AN-9 in combination display synergy when exposed simultaneously to cells or when AN-9 treatment is up to 18 h after Adriamycin administration. However, the reverse order of addition results in antagonism. These interactions have been established using cell viability assays and classical isobologram analysis. To understand the molecular basis of this synergy, the relative levels of Adriamycin-DNA adducts were determined using various treatment combinations. Levels of Adriamycin-DNA adducts were enhanced when treatment combinations known to be synergistic were used and were diminished using those treatments known to be antagonistic. The relative timing of the addition of Adriamycin and AN-9 was critical, with a 20-fold enhancement of Adriamycin-DNA adducts occurring when AN-9 was administered 2 h after the exposure of cells to Adriamycin. The enhanced levels of these adducts and the accompanying decreased cell viability were directly related to the esterase-dependent release of formaldehyde from AN-9, providing evidence for the formaldehyde-mediated activation of Adriamycin.
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PMID:Molecular basis for the synergistic interaction of adriamycin with the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate (AN-9). 1171 50


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