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)

Neuroblastoma cells (N1E-115) and glial cells possess aminopeptidases, dipeptidyl carboxypeptidases and dipeptidyl aminopeptidases, which are located in the plasma membranes. Neuronal cells possess angiotensin-converting enzyme (ACE), which splits the Gly-Phe bond and generates Tyr-Gly-Gly from enkephalin. They have no enkephalinase A. In contrast, glial cells possess enkephalinase A but no ACE. Not only the dipeptidyl carboxypeptidases on neuronal and glial cells are different. These cells have aminopeptidases which have to be distinguished as well. This differentiation is made by using bestatin as an aminopeptidase inhibitor and reveals peptidases of high and poor bestatin-sensitivity.
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PMID:Angiotensin-converting enzyme, enkephalinase A and aminopeptidases in the breakdown of enkephalin--studies in cell cultures. 609 67

A dimeric pentapeptide enkephalin (DPE2) consisting of two molecules of [D-Ala 2, Leu 5] enkephalin linked at C-terminal leucine with ethylenediamine, (H-Tyr-D-Ala-Gly-Phe-Leu-NH-Ch2)2 is a bivalent ligand for the delta enkephalin receptors of rat brain and neuroblastoma-glioma hybrid (NG108-15) cells. This new enkephalin analog shows dramatically increased affinity in radioligand assays using whole brain membranes when delta but not mu specific radioligands are employed. When membranes from NG108-15 cells are used, the dimer shows greatly increased activity irrespective of the mu or delta specificity of the tracer. The dimer DPE2 shows a four-fold, "sodium shift" in its IC50 for competition with [3H]naloxone, suggestive of agonist behavior. Agonist activity was confirmed by demonstrating that DPE2 inhibits cyclic AMP production in prostaglandin E1 stimulated NG108-15 cells, and by demonstrating very high potency in the mouse vas deferens bioassay. DPE2 binds to the same delta sites as the delta-selective monomer [D-Ala2, D-Leu5] enkephalin, since the two ligands show complete crossdisplacement. Radiolabeled 3H-DPE2 shows a five-fold higher affinity constant, a 2.5-fold higher association rate constant, and a two-fold lower dissociation rate than the monomer. These results are consistent with the hypothesis that the dimeric pentapeptide enkephalin can bridge two delta receptors. This enkephalin dimer provides a valuable new probe of opiate receptors and their organization in cell membranes.
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PMID:Dimeric pentapeptide enkephalin: a novel probe of delta opiate receptors. 629 43

It is generally assumed that enkephalinase A, a highly thiorphan-sensitive dipeptidylcarboxypeptidase cleaving the Gly-Phe bond during enkephalin degradation, is bound to the neuronal membrane. To clarify the localization of the enzyme, we used three neuron-like models (neuroblastoma cells N1E-115, bulk prepared neurons and neurons in primary culture) and three glial models (astrocytes from rat brain and from chick embryo brain in primary culture and bulk prepared glial cells). After incubating membranes and cells with (Leu5)-enkephalin, we found that, contrary to the present opinion, the enkephalinase A is located on the glial cells, whereas the neuronal cells possess angiotensin-converting enzyme.
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PMID:No evidence for enkephalinase A on neuronal cells. 636 50

Ten children with recurrent metastatic (stage IV) neuroblastoma received local radiation therapy, supralethal chemotherapy, and total-body irradiation. Rescue with infusions of either allogeneic (four patients) or autologous (six patients) bone marrow followed. The drugs given to the first two patients were individualized combinations based on previous tumor responses. Both patients died with recurrent tumor three and nine months posttransplant. The eight remaining patients were treated more uniformly with local irradiation, VM-26, doxorubicin, melphalan (L-phenylalanine mustard), and 1,000-rad total-body irradiation in three fractions. Two of these patients had cardiac dysfunction and received no doxorubicin. Three children died in the immediate posttransplant period with disseminated fungal infections. A fourth relapsed and died nine months posttransplant. As of December 1, 1983, two children who received allogeneic marrow grafts have survived in complete remission for 54 and 36 months, and two children who received autologous marrow grafts have survived in complete remission for 35 and 22 months. These results suggest that relapsed metastatic neuroblastoma can be controlled by supralethal combinations of chemotherapy and irradiation coupled with bone-marrow rescue.
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PMID:Treatment of advanced neuroblastoma with supralethal chemotherapy, radiation, and allogeneic or autologous marrow reconstitution. 637 56

Human retinoblastoma contains clusters of cells immunoreactive for methionine-enkephalin and methionine-enkephalin-arginine-phenylalanine. Some tumour cells also exhibited methionine-enkephalin-arginine-glycine-leucine-like immunoreactivity. The results are in agreement with those obtained with similar testing of neuroblastoma cell cultures. It is concluded that some human retinoblastoma cells are capable of synthesizing preproenkephalin A or parts of this molecule.
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PMID:Immunohistochemical evidence for preproenkephalin A synthesis in human retinoblastoma. 638 22

Since there is no nutritional requirement for the biopterin cofactor, we attempted to create a drug-induced deficiency in rats in order to study the role of tetrahydrobiopterin in regulating the biosynthesis of dopamine and serotonin. The hypothesis that dihydrofolate reductase (EC 1.5.1.3) mediates the final step in the de novo synthesis of tetrahydrobiopterin was tested by treating rats with methotrexate along with leucovorin as a protective agent; there was no reduction in total biopterin or in the fraction present as tetrahydrobiopterin in adrenal medulla, adrenal cortex, pituitary, brain, or pineal glands. Similar results were obtained with metoprine, a lipid-soluble inhibitor of dihydrofolate reductase which readily enters the central nervous system. Treatment with loading doses of phenylalanine along with methotrexate reduced the level of tetrahydrobiopterin in liver. Neuroblastoma N115 cells growing in medium supplemented with thymidine and hypoxanthine continued to form normal amounts of tetrahydrobiopterin in the presence of concentrations of methotrexate which completely inhibited dihydrofolate reductase; higher concentrations of methotrexate increased the tetrahydrobiopterin content of the cells 2-fold and the total biopterin in the medium 3-fold. Although attempts to create a drug-induced deficiency were unsuccessful, the evidence indicates that the de novo synthesis of tetrahydrobiopterin proceeds by a pathway independent of dihydrofolate reductase and that folate antagonists, such as methotrexate are unlikely to impair the hydroxylation of tyrosine and tryptophan, which is dependent upon the availability of the biopterin cofactor.
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PMID:Biosynthesis of tetrahydrobiopterin in the presence of dihydrofolate reductase inhibitors. 686 19

Phe-tRNA from normal rat liver (designated Phe-tRNAN) and the under-modified, tumor specific, Phe-tRNAs from mouse neuroblastoma (designated Phe-tRNANB) and rat lymphoma (designated Phe-tRNARL) recognize the phenylalanine codons, UUU and UUC in a ribosome binding assay, but not other codons that differ from UUU and UUC in a single base at either the 5' or 3' position. Phe-tRNANB was incorporated into protein more extensively than either Phe-tRNARL or Phe-tRNAN in wheat germ extracts programmed with globin mRNA. The utilization level of each Phe-tRNA was correlated with its rate of deacylation in wheat germ extracts, i.e., Phe-tRNANB deacylated less rapidly than Phe-tRNARL or Phe-tRNAN. Phe-tRNA, from which the Y base was chemically excised (designated Phe-tRNA-Y), did not respond to UUU or UUC in the ribosomal binding assay, nor did it transfer its phenylalanine to protein in wheat germ extracts programmed with globin mRNA.
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PMID:Comparison of the codon recognition properties and of the utilization of normal and tumor specific Phe-tRNAs in protein synthesis. 691 Oct 52

In the present study we investigated uptake of the nitric oxide (NO) synthase inhibitors NG-methyl-L-arginine and NG-nitro-L-arginine by the mouse neuroblastoma x rat glioma hybrid cell line NG108-15. Uptake of NG-methyl-L-arginine was characterized by biphasic kinetics (Km1 = 8 mumol/L, Vmax1 = 0.09 nmol x mg-1 x min-1; Km2 = 229 mumol/L, Vmax2 = 2.9 nmol x mg-1 x min-1) and was inhibited by basic but not by neutral amino acids. Uptake of NG-nitro-L-arginine followed Michaelis-Menten kinetics (Km = 265 mumol/L, Vmax = 12.8 +/- 0.86 nmol x mg-1 x min-1) and was selectively inhibited by aromatic and branched chain amino acids. Further characterization of the transport systems revealed that uptake of NG-methyl-L-arginine is mediated by system y+, whereas systems L and T account for the transport of NG-nitro-L-arginine. In agreement with these data on uptake of the inhibitors, L-lysine and L-ornithine antagonized the inhibitory effects of NG-methyl-L-arginine on bradykinin-induced intracellular cyclic GMP accumulation, whereas L-tryptophan, L-phenylalanine, and L-leucine interfered with the effects of NG-nitro-L-arginine. These data suggest that rates of uptake are limiting for the biological effects of NO synthase inhibitors.
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PMID:Characterization of neuronal amino acid transporters: uptake of nitric oxide synthase inhibitors and implication for their biological effects. 753 32

In addition to the mu- and delta-opioid receptors previously reported, the SH-SY5Y human neuroblastoma cell line has high levels of kappa 3 receptors, accounting for 40% of total opioid binding, as measured with [3H]-diprenorphine binding. Competition studies reveal binding profiles for all three receptor classes that are similar to those observed in brain membranes. Differentiation with retinoic acid increases the levels of opioid receptor binding in the cell line, with the largest elevations in kappa 3 binding. Fully 75% of the increased binding corresponds to kappa 3 sites, which represent 50% of total opioid receptor binding in differentiated cells. Morphine inhibits forskolin-stimulated cyclic AMP accumulation, and this effect is readily blocked by the mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Naloxone benzoylhydrazone, a kappa 3 agonist, inhibits forskolin-stimulated cyclic AMP accumulation more potently than morphine and is not reversed by CTAP. These studies indicate that SH-SY5Y cells contain high levels of functional kappa 3 receptors.
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PMID:Demonstration of kappa 3-opioid receptors in the SH-SY5Y human neuroblastoma cell line. 779 Aug 58

Phenylacetate, a natural metabolite of phenylalanine which was originally described as a plant growth hormone, has recently gained attention as a possible differentiation inducer for a variety of human tumor cell types. This interest prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the differentiation of human neuroblastoma cells, both alone and in combination with retinoic acid (RA), a known inducer of neuroblastoma differentiation and maturation. Using the LA-N-5 cell line, we have determined that NaPA can stimulate the differentiation of neuroblastoma cells, as evidenced by dose-dependent inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity and reduction of N-myc expression. Furthermore, NaPA and RA synergized in inducing differentiation, in that combination treatment resulted in cessation of cell growth along with morphologic and biochemical changes indicative of the loss of malignant properties. We have determined that NaPA can markedly enhance mRNA levels of the nuclear RA receptor-beta (RAR beta) in LA-N-5 cells prior to morphologic or other phenotypic changes induced by this compound. This effect appeared to be distinct from the ability of NaPA to alter tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among its varied effects on LA-N-5 cells, NaPA appears to interact with the RA pathway at the nuclear level by up-regulating RAR beta expression.
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PMID:Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells. 782 65


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