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 (N1E-115) cells in culture rapidly incorporated exogenous fatty acyl chains suspended as albumin complexes in the medium. The essential fatty acids, linoleic (18:2(n - 6)) and linolenic (18:3(n - 3)) acids, were converted to polyunsaturated acids by delta 6 and delta 5 desaturation and chain elongation. The major end products (20:4 from 18:2(n - 6) and 20:5 and 22:5 from 18:3(n - 3)) were preferentially esterified to phospholipids, whereas intermediates were esterified primarily or equally to triacylglycerol. The effects of unlabeled exogenous fatty acids (eg. 40 microM 18:2(n - 6), 18:3(n - 6), 18:3(n - 3), 20:3(n - 6), 20:4(n - 6), trans-18:2(n - 6), 18:1(n - 9), trans-18:1(n - 9), or 16:0) on the conversion of 2 microM [1-(14)C]18:2(n - 6), 18:3(n - 3), 20:3(n - 6), 20:4(n - 6), or 16:0 and on accumulation of products and unaltered substrates in phospholipids and triacylglycerol were examined after incubations of 2-24 h. With [1-(14)C]18:2, formation and esterification of 20:4 to phospholipids was (i) stimulated 4-8-fold by 18:2(n - 6), 20:3(n - 6), or 20:4(n - 6), (ii) inhibited by 18:3(n - 3) or trans-18:2(n - 6), or (iii) unaffected by 18:3(n - 6), 18:1(n - 9), trans-18:1(n - 9), and 16:0. Specific but less marked effects were observed with the other 1-(14)C-substrate acids. Thus, various fatty acids influenced the metabolism of essential fatty acids both at the level of conversion by desaturation and elongation and at esterification to complex lipids by mechanisms specific to individual acids. Product inhibition was not a major feedback mechanism; however, the complement of available fatty acids evidently modulates the acyl chain composition of membrane phospholipids through processes in addition to acyltransferase selectivity. The data support a closely coordinated or concerted enzyme system for directed synthesis of esterified polyunsaturated acyl chains.
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PMID:Concerted stimulation and inhibition of desaturation, chain elongation, and esterification of essential fatty acids by cultured neuroblastoma cells. 686 55

The effect of human albumin on neuronal voltage-dependent Na+ channels was studied in NH15-CA2 neuroblastoma x glioma hybrid cells. At an albumin concentration of 32 g/l, the transient Na+ currents, elicited at 1 Hz and recorded with the whole-cell technique, were increased to 125% the control value. The effect was complete within 2-4 s of extracellular albumin application; 35 s after washout of the protein it was not yet fully abolished. The albumin effect is mediated by a shift of the voltage dependence of steady-state inactivation of the Na+ channels towards more positive potentials. The activation of the channels is not noticeably influenced.
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PMID:Human serum albumin enhances sodium currents in NH15-CA2 neuroblastoma x glioma hybrid cells. 747 4

Exogenous gangliosides have been shown to exert a regulatory influence on the proliferation and differentiation of several cell lines in tissue culture. The effect of ganglioside GM3 on C-1300 murine neuroblastoma (MNB) cell proliferation and the modulating action of fetal calf serum (FCS) concentration in the culture media have been investigated. MNB cells were cultured in DMEM containing 1, 2.5, 5 or 10% FCS, and incubated with GM3 at concentrations ranging from 1.95 to 500 microM. Cell proliferation was assayed 4 days after the addition of GM3 using the CellTiter 96 Non-Radioactive Cell Proliferation Assay. GM3 inhibited MNB cell proliferation in a dose-dependent manner regardless of the FCS concentration in the culture media. However, the magnitude of this inhibitory effect was inversely proportional to the FCS concentration in the culture media. The addition of albumin to MNB cells cultured in DMEM containing 1% FCS exerted no effect on the antiproliferative action of GM3. FACS cell cycle analyses demonstrated that MNB cultured in DMEM containing 1% FCS had a higher proportion of cells in the G0/G1 compartment when compared to those cultured in 10% FCS. The enhanced response of MNB cells to GM3 observed in 1% FCS, may be due to a preferential action on cells in the G0/G1 stage of the cell cycle. These studies have demonstrated that the ganglioside GM3 inhibited MNB cell proliferation in tissue culture and this effect was modulated by FCS concentration in the culture media. Since protein-binding of GM3 by FCS does not appear to be the primary mechanism by which FCS exerts its antagonistic effects, we hypothesize that this may be due to the opposing action of stimulatory growth factors present in FCS.
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PMID:Inhibitory action of ganglioside GM3 on murine neuroblastoma cell proliferation: modulating effect of fetal calf serum. 764 39

The 3-5 year survival rates of patients with disseminated Ewing's sarcoma (ES) or the closely related peripheral primitive neuroectodermal tumors (PNET) remain low, even under aggressive treatment involving highly toxic multidrug chemotherapeutic regimens. ES and PNET are sensitive to doxorubicin, but may escape treatment by expression of the multidrug-resistant phenotype and/or other mechanisms. In this study, we have identified albumin as growth supporting factor for ES and PNET cells in IGF-I-supplemented serum-free tissue culture medium. To investigate the specificity and toxicity of albumin-based drug conjugates, doxorubicin was coupled to bovine serum albumin (BSA) by either a two step glutaraldehyde or carbodiimide-C4-spacer technique, yielding monomeric DOX-albumin conjugates with conjugation numbers ranging from 3-20 moles DOX/mole BSA. Cellular uptake of fluorescein-isothiocyanate-(FITC)-labeled albumin and DOX-albumin conjugates could be demonstrated by flow cytometric measurements of cell-associated fluorescence and confocal microscopy. The cytostatic activity of these conjugates against ES/PNET cell lines, a neuroblastoma (LAN-1) and prostate cancer carcinoma cell line (PC-3) and normal lymphoblasts was tested in short-term proliferation assays (48 h). The results show a high selectivity of the DOX-albumin conjugates for ES/PNET cell lines, with highest growth inhibition by conjugates with low DOX conjugation numbers (n = 3) in serum-supplemented medium (17-32 fold loss of activity compared to free DOX), followed by 20-DOX-C4-albumin in serum-free medium and low activity of the other conjugates. In conclusion, DOX-albumin conjugates inhibit the growth of ES/PNET cell lines selectively, showing low activity against the unrelated carcinoma line PC-3 and sparing normal lymphoblasts. The inverse correlation of activity and conjugation number demonstrates a low cytotoxic activity of DOX in acid-stable binding to monomeric albumin, pointing to a selective cytostatic activity of the modified albumin against ES and PNET cells, even in the presence of a 100 fold excess of unmodified serum albumin.
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PMID:In vitro antiproliferative effects of albumin-doxorubicin conjugates against Ewing's sarcoma and peripheral neuroectodermal tumor cells. 784 32

The patterned covalent surface addition of a monoamine to fluorinated ethylene propylene films (FEP) controls both cellular attachment and differentiation in defined media conditions. A radio frequency glow discharge (RFGD) process was used to replace FEP surface fluorine atoms with hydroxyl groups. The primary amine was then covalently attached by polymerizing aminopropyl-triethoxysilane (APTES) via the hydroxyl functionalities. The selective attachment of cells to the APTES regions was determined to be dependent upon the initial adsorption of albumin to the patterned FEP membrane. Albumin was determined to enhance cellular attachment to the APTES regions and prevent attachment to the unmodified FEP areas for both an NB2a neuroblastoma cell line and primary rat endothelial cells. If albumin were not preadsorbed onto the membrane, selective attachment to the modified regions would not occur. Radiolabeling albumin with 125I demonstrated the preference of albumin for adsorption onto the monoamine surface where the cells preferentially attached. Both hydrophobic and ionic forces contributed to the adsorption process. Although selective cellular attachment to the patterned APTES regions could be achieved by albumin preadsorption to the surface, the neuroblastoma cells did not significantly differentiate unless additional serum components were supplemented to the media.
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PMID:Selective neuronal cell attachment to a covalently patterned monoamine on fluorinated ethylene propylene films. 836 Feb 19

While PBSC collection has become a safe procedure for adults, only a few reports exist about its efficacy, safety and feasibility in paediatric patients, especially extremely low-weight infants. We describe successful PBSC collection in three infants of less than 10 kg body weight (BW; range: 6.92-9.4 kg) suffering from stage IV neuroblastoma. Harvest of PBSC started after mobilisation with high-dose chemotherapy and G-CSF, as soon as 1.0% CD34+ cells were detected. Collections were performed using a Baxter CS-3000 Plus separator primed with a mixture of irradiated, white cell-depleted and CMV-negative packed red cells resuspended in 5% human albumin and diluted with saline to match the patient's haematocrit. Performing a median of four, (4-7, median, range) procedures we collected at least 4 x 10(8)/kg BW nucleated cells (NC) from all three patients. The infants were not sedated and showed no serious side-effects. All three children were successfully transplanted with myeloid engraftment in 8 (7-9) days, independence from red cell support was achieved in 15 (10-20) days and from platelet transfusions in 25 (14-29) days after PBSC infusion. We conclude that PBSC harvesting using continuous flow cell separators is safe, even in low-weight infants of less than 7 kg BW.
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PMID:Peripheral blood stem cell (PBSC) collection in extremely low-weight infants. 883 90

Nine children from 10 to 76 months (median 28.0), weighing 8.5 to 19.7 kg (median 13.0 kg) underwent peripheral blood stem cell separation (PBSCS) or peripheral blood mononuclear cell separation (PBMNCS), after insertion of a double-lumen central venous catheter (8-10 French). Separations were performed with a continuous flow blood separator (Fen-wall CS 3000 plus), running a specially adopted separation-program. In 7 children (5 with neuroblastoma IV, 1 with multifocal Ewing's sarcoma, and 1 with rhabdomyosarcoma IV), stem cells were mobilized by application of G-CSF at a dosage of 15-27.7 micrograms/kg body weight (median 16.25) subcutaneously following high-dose chemotherapy, according to the disease-related protocols, whereas 2 children had PBMNCS to induce graft vs. leukemia (GvL)-reaction in the HLA-identical sibling suffering from relapsed chronic myelogenous leukemia (CML: n = 1), or chronic myelomonocytic leukemia (CMML: n = 1) after allogeneic BMT. In all cases, the collecting procedure was performed after filling the cell separator with priming solution consisting of 2 U of irradiated and washed packed red cells, 250 ml human albumin, and 0.9% NaCl. In the 7 patients with solid tumors between 0.45 and 62.7 x 10(6) CD-34 positive cells/kg body weight were separated; the patient who had the lowest yield was separated twice after another mobilizing course. Three patients (2 with neuroblastoma IV and 1 with multifocal Ewing's-sarcoma) underwent a double transplantation with 1-3 portions of the collected stem cells within a 5- to 6-week interval. Two children had a rapid engraftment on both peripheral blood stem cell transplantations (PBSCTs). The third child, who had the lowest yield and was separated twice had prompt engraftment at the first PBSCT but delayed and incomplete engraftment at the second PBSCT. One patient after adoptive immunotransfer with PBMNCs for relapsed CML is now 40 months in complete cytogenetic and molecular biological remission, whereas the other patient treated for relapsed CMML did not respond to the PBMNC-transfusion. The results indicate that PBSCS and PBMNCS can be performed in children with a body weight below 20 kg.
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PMID:Feasibility of peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMNC) separation in children with a body weight below 20 KG. 918 Sep 13

Human macroaggregated albumin (MAA), which is currently labeled with technetium-99m (99mTc) and 99mTc-MAA, is used clinically as a pulmonary perfusion agent and was directly labeled with yttrium-90 (90Y)-acetate. This study evaluated whether 90Y-MAA could be potential radiotherapeutic agent for regional radiotherapy against malignant tumors. MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 90Y-acetate and purified in order to get rid of unstable binding of 90Y by electrophoresis. The radiochemical purity of 90Y-MAA in normal human serum was estimated by an agarose electrophoresis method and was more than 94% over 168 h in vitro. Following the intratumoral administration of 90Y-MAA, the time course of tumor radioactivity and the biodistribution in nude mice bearing human neuroblastoma were investigated up to 168 h. More than 93% of the radioactivity of the injected dose was found on the subcutaneous tumor over 168 h. The bone radioactivity was shown as 0.06 +/- 0.03% injection dose/gram tissue (% ID/g) (n = 5) at 24 h, 0.73 +/- 0.20% ID/g at 72 h, 0.92 +/- 0.16% ID/g at 120 h, and 2.51 +/- 0.59% ID/g at 168 h. A slight increase in radioactivity was noted in the liver, kidneys, and spleen over the 168-h periods. In conclusion, 90Y-MAA may be a potential agent for regional radiotherapy (brachytherapy) because of the sufficient persistence in the tumor following an intratumoral administration.
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PMID:Preparation of yttrium-90-labeled human macroaggregated albumin for regional radiotherapy. 929 84

The effect of merocyanine 540 (Mc 540) mediated photoirradiation on both neoplastic and normal hemopoietic progenitor cells was studied. Bone marrow (BM) cells from children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) at initial diagnosis, ALL in remission, neuroblastoma and normal children as well as cells of Reh-6 and HL-60 cell lines were incubated with Mc 540 in the presence of human albumin (HA) and exposed to different argon laser 514 nm doses. Cell survival was estimated using Trypan Blue supravital stain following a 24-h incubation and leukemic cell lines were studied in continuous cell cultures of 4 weeks duration. Our results showed that HA protects normal BM cells from Mc 540 mediated phototoxicity. A 99.9999% inhibition of Reh-6 and HL-60 was noted at irradiation doses where the corresponding mean survival of normal BM cells was 77.4 +/- 12 and 70.3 +/- 10%, respectively. BM leukemic cells from children with ALL and AML were also very sensitive to Mc 540 photoirradiation in contrast to neuroblastoma cells where only a three-fold reduction was observed. Finally, the survival of normal BM progenitors was 38% for colony forming unit erythroid CFU-E, 37% for burst forming unit erythroid BFU-E, 55% for CFU-GM and 29% for CFU-GEMM. In conclusion it seems that Mc 540 mediated photoirradiation in neoplastic cells exerts selective cytotoxicity and can be used in ex vivo purging of malignant cells in BM.
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PMID:Merocyanine 540 mediated photolysis of normal bone marrow, committed hemopoietic progenitors and neoplastic cells. implications for bone marrow purging. 930 85

Cell type-specific responses (microfilament stress fibers for fibroblasts or neurites for neuroblastoma cells) were evaluated in culture on inert and chemically-derivatized silane substrata adsorbed with fibronectin (Fn). Substrata of self-assembled monolayers contain a 14-17 carbon aliphatic chain terminating with different chemical endgroups -- [CH3], [C=C], [Br], [CN], [Diol], [COOH], [NH2], [SH], [SCOCH3], or [SO3H]. Fn adsorbed effectively to all derivatized surfaces. 3T3 fibroblasts or neuroblastoma cells attached equivalently to all surfaces preadsorbed with Fn, indicating availability of receptor binding sites on Fns. However, transmembrane signaling from Fn(adsorbed): receptor(cell) surface complexes yielded a range of abilities for generating F-actin stress fibers in fibroblasts or neurites in neuroblastoma cells. Efficiency for stress fiber formation was very different from that of neurite extension. The same chemical endgroups on glass, titanium, or germanium yielded the same patterns of cellular physiological responses, indicating that inert substrata do not act at a distance and that only chemical endgroups regulate Fn signaling functions. When adhesion-inert albumin is co-adsorbed with Fn, efficiency of neurite extension is improved on some surfaces or diminished on others. These results indicate that the conformation of Fn(adsorbed) changes in specific ways on derivatized substrata. Change in Fn conformation was confirmed by FTIR/ATR spectroscopy experiments of Fn(adsorbed). Overall, these studies indicate changes in Fn conformations on chemically-derivatized self-assembled monolayers leading to up- or down-regulation of cell type-specific physiological responses from receptors via their signaling pathways. They also offer predictability for regulating responses of specific cell types when these cells interact with biomaterial implants in vivo.
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PMID:Cell type-specific modulation of fibronectin adhesion functions on chemically-derivatized self-assembled monolayers. 986 Jan 78


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