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)

Prostaglandin E1 (PGE1)-mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E-115). PGE1 increased intracellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca2+]i). PGE1 transiently increased inositol 1,4,5-trisphosphate formation, peaking at 20 s. There was more than a 10-fold difference between the ED50 for PGE1 at cyclic AMP formation (70 nM) and its ED50 values at IP accumulation (1 microM), cyclic GMP formation (2 microM), and [Ca2+]i increase (5 microM). PGE1-mediated IP accumulation, cyclic GMP formation, and [Ca2+]i increase depended on both the concentration of PGE1 and extracellular calcium ions. PGE1 had more potent intrinsic activity in cyclic AMP formation, IP accumulation, and cyclic GMP formation than did PGE2, PGF2 alpha, or PGD2. A protein kinase C activator, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, had opposite effects on PGE1-mediated IP release and cyclic GMP formation (inhibitory) and cyclic AMP formation (stimulatory). These data suggest that there may be subtypes of the PGE1 receptor in this clone: a high-affinity receptor mediating cyclic AMP formation, and a low-affinity receptor mediating IP accumulation, cyclic GMP formation, and intracellular calcium mobilization.
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PMID:Two possibly distinct prostaglandin E1 receptors in N1E-115 clone: one mediating inositol trisphosphate formation, cyclic GMP formation, and intracellular calcium mobilization and the other mediating cyclic AMP formation. 165 30

Mouse neuroblastoma x rat glioma hybrid NG108-15 cells form cholinergic synapses with rat or mouse muscle cells in culture. The rate of synapse formation is greatly dependent on intracellular cyclic AMP concentrations. The synapse formation is lower in the presence of glia maturation factor, a partially purified brain extract. Once the synapse between NG108-15 cells and myotubes has been formed, this synapse is stable for days. Extracellular application of serotonin, PGF2 alpha, PGD2, neurotensin and bradykinin on NG108-15 cells increases synaptic transmission. Since bradykinin increases the level of intracellular inositol 1,4,5-trisphosphate (InsP3), bradykinin-induced facilitation is due to InsP3-dependent elevation of intracellular Ca concentrations.
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PMID:Cholinergic synapse formation between NG108-15 and muscle cells and modulation of transmission. 217 13

To determine the role of adenosine 3'5'-cyclic monophosphate (cAMP) in the antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1), we studied 2 cell lines of human neuroblastoma; i.e. GOTO and SK-N-DZ. PGE1 or E2 at 30 micrograms/ml and PGD2 or PGA1 at 5 micrograms/ml were cytotoxic to these neuroblastoma cells. In both cell lines, increase of intracellular cAMP was closely associated with E-type PGs cytotoxicity, however, in PGD2, or PGA1 cytotoxicity, cAMP increase was observed only in GOTO cells. Pretreatment of GOTO cells with 5 micrograms/ml PGE2 for 24 hr caused a desensitization of cAMP responses to PGE1, PGD2 or PGA1 only in association with a reduced cytotoxicity of PGE1. On the other hand, PGE2-pretreated SK-N-DZ cells resulted in a desensitization in response to PGE1, but not to other PGs, without affecting the cytotoxicity of these PGs. A decreased [3H]PGE1 binding similarly occurred in either the PGE2-pretreated GOTO or SK-N-DZ cells. However, cholera toxin- or forskolin-induced cAMP production was suppressed only in the pretreated GOTO cells. cAMP response by forskolin rather increased in the pretreated SK-N-DZ cells. These results indicate that antineoplastic effect of E type PGs mediates through cAMP, but not that of PGD2 and PGA1 and that PGE2 pretreatment may cause a down regulation of PGE1 receptor site in both cell lines. It is also suggested that PGE2 pretreatment results in a heterologous desensitization in GOTO and a homologous desensitization in SK-N-DZ cells.
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PMID:Role of adenosine 3'5'-cyclic monophosphate in antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1) on human neuroblastoma cells. 284 1

To determine the mechanism of the antineoplastic effect of PGD2, we studied the intracellular adenosine 3',5'-cyclic monophosphate (cAMP), cell growth and the kinetics of a human neuroblastoma (NCG line) in culture. Cells were maintained in RPMI 1640 with 10% FCS. cAMP level was determined for the cells, which were incubated for 10 min. with and without PGD2 (1 microgram/ml) in the presence of 100 microM papaverine. Growth inhibition was examined by counting viable cells after treatment with PGD2 (0-100 micrograms/ml) for 4 consecutive days starting at Day 4 after subculture. Effects on cell kinetics were examined for similarly treated cells by DNA cytofluorometry combined with 3H-thymidine autoradiography. In response to PGD2, the NCG line failed to increase its cAMP; however, cell growth was inhibited (IC50 13 micrograms/ml), accompanied by the marked decrease of S phase cells. The results indicate that PGD2 exerts its cytotoxic effect by a probable G1 block of the cell cycle and not through cAMP action.
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PMID:Cell kinetic studies of PGD2 cytotoxicity on the in vitro growth of human neuroblastoma. 301 53

To study the precise mechanism of cytotoxic activity of PGD2 or delta 12-PGJ2 (a biologically active metabolite of PGD2), we examined the effect of various compounds on PGD2 or delta 12-PGJ2 cytotoxicity, using a human neuroblastoma cell line (NCG). Cycloheximide (CHM) specifically protected PGD2 cytotoxicity on NCG cells. When delta 12-PGJ2 was tested, CHM exhibited a similar rescue effect. Puromycin, mitomycin C, and alpha-amanitin did not affect PGD2 or delta 12-PGJ2 cytotoxicity. Emetine showed a variable and no consistent rescue effect CHM may have been active at the primary site where PGD2 or delta 12-PGJ2 exerts its cytotoxicity. This is the first report indicating that CHM reduces the cytotoxicity induced by PGD2 or delta 12-PGJ2.
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PMID:Cycloheximide reduces PGD2 or delta 12-PGJ2 cytotoxicity on NCG cells. 309 33

Addition of linoleic acid (50 microM) to culture medium significantly increases levels of polyunsaturated fatty acids (PUFA) in membrane phospholipids of NIE-115 neuroblastoma. Basal levels of cyclic AMP are elevated significantly in supplemented cells. Exogenous prostaglandins (PG) PGE1 and PGD2 stimulate cAMP formation in NIE-115 neuroblastoma. Supplemented cells produce higher levels of PGE and PGD than do control cultures. Inclusion of cyclooxygenase inhibitors in culture medium does not block elevation of cyclic nucleotide in supplemented cells. Endogenous PG production and receptor activation cannot account for increased cAMP in EFA-supplemented neuroblastoma.
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PMID:Increasing membrane polyunsaturated fatty-acid content augments cyclic AMP formation and prostaglandin production in NIE-115 neuroblastoma. 609 86

The effect of prostaglandin (PG) D2 on neuronal functions was investigated in neuroblastoma X glioma NG108-15 hybrid cells. PGD2 caused a sustained increase in miniature end-plate potentials (MEPPs) recorded from cultured striated muscle cells which had formed junctions with NG108-15 cells. PGD2 initially hyperpolarized and then depolarized NG108-15 cells. The time course of depolarization fitted well to the facilitative phase of MEPPs. The same action on synaptic transmission and membrane potentials was detected with PGF2 alpha but not with PGE1. PGD2 (10(-4)M) produced a 3-fold increase of adenylate cyclase activity in NG108-15 cell homogenates through its receptors that are distinct from those of PGE1 and PGI2. These results show that PGD2 facilitates MEPP frequency from NG108-15 cells due to depolarization, and suggest that PGD2 may act as a physiological neuromodulator for synaptic transmission in vivo.
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PMID:Facilitation of synaptic transmission by prostaglandin D2 at synapses between NG108-15 hybrid and muscle cells. 632 47

The cytotoxic action of prostaglandin (PG) D2, E1 and F2 alpha was examined on human neuroblastoma cells (NB-1 cell line), and PGD2 was found to be the most effective. PGE1, thought to be the most effective among all PGs in the therapy of neuroblastoma, was much less effective than PGD2. PGF2 alpha did not show any inhibitory effect on the proliferation of NB-1 cells. When PGD2 was added, the cytoplasma became microscopically larger, then the cells gradually died off. PGD2 also exerted a dose-dependent inhibition of DNA and RNA syntheses. These results strongly suggest an antineoplastic activity of PGD2 for human neuroblastoma.
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PMID:Prostaglandin D2 inhibits the proliferation of human neuroblastoma cells. 657 53

Addition to the culture medium of prostaglandin (PG) D2 resulted in the degeneration in a dose- and time-dependent manner of N18TG-2 cells cloned from mouse neuroblastoma. The ED50 for PGD2-induced cytotoxicity was about 10 microM. The degenerative changes were irreversible when the cells were exposed for more than 10 h. Scanning and transmission electron microscopic examination revealed that treatment with PGD2 resulted in appearance of numerous blebs of various sizes along the cell surface and also in destruction of surface membrane and of cytoplasmic organelles. Tumor weight of N18TG-2 neuroblastoma inoculated subcutaneously on the backs of A/J mice was about 35-70% less than that of controls after 14 days of single daily i.p. or s.c. injections of 0.5-1 mg/kg of PGD2. The results indicate that PGD2 has growth-inhibitory effects on mouse neuroblastoma cells in vitro and in vivo.
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PMID:Cytotoxic action of prostaglandin D2 on mouse neuroblastoma cells. 657 94

Combination of dibutyryl adenosine 3', 5'-cyclic monophosphate or prostaglandin E1 (PGE1) and papaverine effectively induced differentiation of neuroblastoma in mice. Two cases of human neuroblastoma with stage III and IV were administered intraaortic PGE1 infusion combined with oral papaverine and conventional chemotherapy. There were no noticeable side effects and the treatment was effective in decreasing tumor size and promoting tumor maturation in the infused area. However, distant osseous metastases were developed in both cases, during and after the PGE1 administration. They survived 30 and 17 months, respectively, from the initiation of therapy. (Jpn J Cancer Chemother 10(9): 1936-1943, 1983) These results prompted us to study the metastatic potentials of neuroblastoma. In vitro studies demonstrated that cultured human neuroblastoma cells (NB-1, GOTO, SK-N-DZ, SJ-N-KP, SJ-N-CG and SK-N-FI) aggregate human platelets with maximum aggregation ranging from 28% to 51%. Addition of PGE1 or PGD2 to PRP effectively inhibited the tumor-cell-platelet interaction, with IC50 approximately 100 nM for PGE1 and 10 nM for PGD2, respectively. In addition, 50 microM PGE1 or PGD2, 5 microM PGI2 reversed neuroblastoma-induced platelet aggregation in 4 out of 5 cell lines were studied. These findings indicate a the possible role of PGs in effective inhibition of neuroblastoma metastases in vivo. However, two cell lines (SK-N-DZ and SJ-N-CG), which had been exposed to 8.5 microM PGE1 or PGD2 for 90 min and 72 hr, respectively, retained the platelet aggregating activity which was not significantly different from that of untreated cells. We conclude that clinical application of intraaortic PGE1 in the treatment of advanced neuroblastoma has advantage in potentiation of tumor cell kill and in inducing maturation. Administered PGE1 may exert its action in two ways: in preventing tumor metastasis or possibly in enhancing the metastatic potential of neuroblastoma cells. Further refinement of these modalities including other PGs such as PGD2 or PGI2 and more detailed studies on optimal PG administration to prevent metastasis should be evaluated in future.
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PMID:[Differentiation induction and potentiation of chemotherapy by PGE1 infusion in patients with neuroblastoma--effect of PGE1 on metastatic potential of neuroblastoma]. 658 82


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