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)

A method for the on-line determination of oxygen-18, at a naturally occurring level, in organic material is presented. After pyrolysis of the samples to form carbon monoxide, which is performed at 1300 degrees C in a vitreous carbon tube, the pyrolysis products are transported by a stream of helium gas. Using an open split, a small part of the effluent is transferred to the ion source of an isotope ratio mass spectrometer. The ratio is obtained from a measurement of the ion current intensities at m/z 30 and 28 (12C18O and 12C16O). The method was tested with the secondary water standard GISP (Greenland Ice Sheet Precipitation) and the carbonate standard NBS 19. The values obtained were -24.8/1000 and 27.3/1000 vs. VSMOW (Vienna Standard Mean Ocean Water) (LAEA reference values are -24.8/1000 and 28.7/1000 vs. VSMOW). The potential of the method was demonstrated by measuring the 18O content of samples of beet and cane sucrose and also samples of vanillin extracted from vanilla pods or of synthetic origin.
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PMID:Isotope ratio mass spectrometric method for the on-line determination of oxygen-18 in organic matter. 900 72

Administration of a tumour-seeking compound labeled with a low-energy isotope and intraoperative screening with the gamma probe (radioguided surgery, RGS) could be useful in reoperations for advanced neuroblastoma when the normal anatomy is altered. A pilot study was performed to test the feasibility of this technique. Five patients underwent six relaparotomies for recurrent stage III or IV neuroblastoma. All had been treated with intensive chemotherapy and/ or metaiodobenzylguanidine (MIBG)-I131 with or without hyperbaric oxygen. Reoperation was performed to achieve near-total (greater than 95%) excision. In all instances, active tumour was seen on the preoperative MIBG scan. Before the operation, a tracer dose of MIBG-I123 was given. At laparotomy, a search was made with the gamma probe for areas of increased activity. The gamma probe correctly identified active neuroblastoma tissue that was seen on the preoperative MIBG scan. There appeared to be a relationship between intensity of radioactivity and degree of maturation on histologic examination. This pilot study shows that RGS with MIBG and intraoperative use of the gamma probe is able to identify recurrent neuroblastoma. Whether this method is able to detect occult tumour and whether RGS will result in better outcome are the subjects of ongoing research.
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PMID:Intraoperative search for neuroblastoma by MIBG and radioguided surgery with the gamma detector. 902 10

Enhanced oxidative stress has been suggested to be involved in the degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease. The high turnover rate of dopamine and/or unsequestered dopamine may cause an increase of formation of hydrogen peroxide via either oxidative deamination of dopamine by monoamine oxidase or autoxidation. Hydrogen peroxide would be converted to more toxic hydroxyl free radicals. L-beta-3,4-Dihydroxyphenylalanine hydrochloride (L-DOPA), the most useful drug in the symptomatic treatment of Parkinson's disease, has been considered to possess deteriorating degenerative side-effects. The catecholaminergic neuroblastoma SH-SY5Y cells were chosen to investigate the cytotoxic effect of dopamine and L-DOPA. Both dopamine and L-DOPA were found to be cytotoxic towards SH-SY5Y cells. Such toxic effects were accompanied by an increase of oxidative stress in the cell cultures and could be reversed effectively by catalase and to a lesser extent by superoxide dismutase. The non-enzymatic antioxidants L-ascorbic acid, glutathione, N-acetyl-L-cysteine, but not (+)-alpha-tocopherol, also completely protected SH-SY5Y cells against the cytotoxic effects induced by dopamine and L-DOPA. Antioxidative factors, namely free radical scavengers (including N-tert-butyl-alpha-phenylnitrone, salicylic acid, and D-mannitol) and a strong iron chelator, deferoxamine, however, did not protect the SH-SY5Y cells against dopamine and L-DOPA. The generation of reactive oxygen species and the resulting enhanced oxidative stress was clearly involved in the dopamine- and L-DOPA-induced cytotoxic effects. Hydrogen peroxide played the most important role related to cytotoxicity of dopamine and L-DOPA.
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PMID:Dopamine- and L-beta-3,4-dihydroxyphenylalanine hydrochloride (L-Dopa)-induced cytotoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells. Effects of oxidative stress and antioxidative factors. 906 40

In this paper we report the effects of the combination of MIBG (a structural analogue of norepinephrine, used in its radio iodinated form for the diagnosis and therapy of neuroblastoma) and hyperbaric oxygen on the human neuroblastoma cell line SK-N-BE(2c). Exposure of the neuroblastoma cells to hyperbaric oxygen conditions enhanced the effects of MIBG on cell proliferation, lipid peroxidation and energy metabolism of the cell line. Cell proliferation and energy metabolism were further decreased and lipid peroxidation further increased. Enhancement of the effects of MIBG by HBO may provide an explanation for the positive effects on the cumulative survival curve observed when stage IV neuroblastoma patients were treated with the combination of [131I] MIBG and HBO.
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PMID:Hyperbaric oxygen enhances the effects of meta-iodobenzylguanidine (MIBG) on energy metabolism and lipid peroxidation in the human neuroblastoma cell line SK-N-BE(2C). 906 62

Dibucaine, a local anesthetic known to interact with cell membranes, induced apoptosis in SK-N-MC human neuroblastoma cells in a dose-dependent manner. Apoptosis was demonstrated by direct visualization of morphological nuclear changes using a DAPI staining technique and confirmed by the production of characteristic ladder patterns of DNA fragmentation on gel electrophoresis. At concentrations which induced apoptosis, dibucaine significantly altered membrane fluidity, indicating that fluidity may be a major target for the cytotoxic action of dibucaine. Also, dibucaine increased intracellular calcium levels more effectively in calcium-containing Krebs-Ringer buffer than in calcium-free Krebs-Ringer buffer. Removal of extracellular calcium or addition of antioxidants or protein synthesis inhibitor effectively blocked dibucaine-induced apoptosis. These results suggest that membrane damage, intracellular calcium levels, and oxygen free radicals may be involved in the apoptosis induced by dibucaine.
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PMID:Induction of apoptotic cell death in a neuroblastoma cell line by dibucaine. 908 63

Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) inactivates experimental leukemia, lymphoma, and neuroblastoma cells by a singlet oxygen-mediated mechanism but is relatively well tolerated by normal pluripotent hematopoietic stem cells and granulocyte/macrophage progenitors (CFU-GM). MC540 is currently undergoing phase I clinical testing for the extracorporeal purging of autologous bone marrow and peripheral blood stem cells. We report here that performing MC540-mediated PDT at 4.7 degrees C (hypothermia) instead of at ambient temperature enhanced the photoinactivation of L1210 cells and CFU-GM but left the photoinactivation of K562 cells unchanged. Hypothermia reduced dye binding in K562 but not in L1210 cells, whereas the photogeneration of lipid hydroperoxides (LOOH) was affected in neither cell line. Post-PDT incubation at 4 degrees C delayed the decay of LOOH and enhanced the photoinactivation of CFU-GM as well as L1210 and K562 cells. Taken together, these results suggest that hypothermia interfered with the repair of potentially lethal photodynamic damage. They stress the importance of temperature control during and immediately after the photochemical purging of autologous bone marrow and peripheral blood stem cells.
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PMID:Effect of hypothermia on the merocyanine 540-mediated purging of hematopoietic cells. 911 16

In this paper we report the effects of Hyperbaric Oxygen (HBO) exposure on the uptake and retention of meta-Iodobenzylguanidine (MIBG) in human platelets and two neuroendocrine cell lines. The combination of [131I] MIBG and HBO is used for therapy of neuroblastoma. Exposure to HBO can cause oxidative stress, which is potentially capable of affecting uptake and storage of MIBG in both neuroendocrine cells and platelets. Oxidative stress generated by menadione decreased both the uptake and retention of MIBG in the platelets and the cell lines. HBO did not affect these processes, indicating that the HBO induced oxidative stress is not high enough to affect the MIBG uptake and storage pathways in these cells. This suggests that the positive effects observed by the treatment of neuroblastoma patients with the combination of HBO and [131I] MIBG are most likely not due to improved uptake or retention of MIBG in the neuroblastoma. Neither can reduced cytotoxicity (trombocytopenia) be expected due to decreased uptake/retention of [131I] MIBG in platelets or their precursor cells.
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PMID:HBO and the uptake and retention of [125I] MIBG in human platelets and two neuroendocrine cell lines. 913 73

Stimulation of human SH-SY5Y neuroblastoma cells by a muscarinic receptor agonist, carbachol (CCh; 1 mM), elevated levels of free intracellular calcium and subsequently increased the production of reactive oxygen species (ROS). Quinuclidinylbenzilate (QNB) binding increased at 1 h after CCh, but returned back to the control level at 3 h. Production of ROS increased, however, during the 3 h time period. CCh also increased the translocation of protein kinase C (PKC) to the membrane. ROS production was completely blocked by atropine and a PKC inhibitor, Ro 31-8220. These results show that increased ROS production was a result of muscarinic receptor stimulation, and that PKC had an active role in this cellular stimulation. ROS production upon cellular stimulation by CCh was completely inhibited also by superoxide dismutase, and partially by catalase, indicating that the formation of superoxide anion dominated in cholinergic-induced generation of ROS in human neuroblastoma cells. These results also show that muscarinic stimulation causes sustained ROS production in human neuroblastoma cells. The slow increase in ROS production by CCh suggest a stepwise cascade of events leading to oxidative stress with a triggering role of cholinergic muscarinic receptors in this process.
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PMID:Cholinergic-induced production of reactive oxygen species in human neuroblastoma cells. 915 1

Alzheimer's disease (AD) is associated with defects in mitochondrial function. Mitochondrial-based disturbances in calcium homeostasis, reactive oxygen species (ROS) generation, and amyloid metabolism have been implicated in the pathophysiology of sporadic AD. The cellular consequences of mitochondrial dysfunction, however, are not known. To examine these consequences, mitochondrially transformed cells (cybrids) were created from AD patients or disease-free controls. Mitochondria from platelets were fused to rho0 cells created by depleting the human neuroblastoma line SH-SY5Y of its mitochondrial DNA (mtDNA). AD cybrids demonstrated a 52% decrease in electron transport chain (ETC) complex IV activity but no difference in complex I activity compared with control cybrids or SH-SY5Y cells. This mitochondrial dysfunction suggests a transferable mtDNA defect associated with AD. ROS generation was elevated in the AD cybrids. AD cybrids also displayed an increased basal cytosolic calcium concentration and enhanced sensitivity to inositol-1,4, 5-triphosphate (InsP3)-mediated release. Furthermore, they recovered more slowly from an elevation in cytosolic calcium induced by the InsP3 agonist carbachol. Mitochondrial calcium buffering plays a major role after this type of perturbation. beta-amyloid (25-35) peptide delayed the initiation of calcium recovery to a carbachol challenge and slowed the recovery rate. Nerve growth factor reduced the carbachol-induced maximum and moderated the recovery kinetics. Succinate increased ETC activity and partially restored the AD cybrid recovery rate. These subtle alterations in calcium homeostasis and ROS generation might lead to increased susceptibility to cell death under circumstances not ordinarily toxic.
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PMID:Calcium homeostasis and reactive oxygen species production in cells transformed by mitochondria from individuals with sporadic Alzheimer's disease. 916 22

Oxidative stress has been implicated in the mechanism of aging and neurodegenerative disorders such as Alzheimer's disease (AD). Menadione causes oxidative stress by generating reactive oxygen species through its redox cycling and these free radicals are detoxified subsequently at the expense of intracellular thiol homeostasis. In non-neuronal cells, the cytoskeleton is a prime target of menadione-induced thiol oxidation. We used cultured human neuroblastoma MSN cells in this study to determine how tau proteins in neuronal cells are affected by menadione exposure. Menadione caused a dose-dependent thiol oxidation in these cells just like their non-neuronal counterparts. A prominent consequence of such oxidative insult in these neuronal cells was tau dephosphorylation. This dephosphorylation resulted in disappearance of phosphorylated 57-kDa tau with a concomitant emergence of 53-kDa tau whose full-length nature is indicated by its reactivity with antibodies Alz 50, Tau-1 and Tau-46. Immunochemical analyses using phosphorylation-dependent immunoprobes Tau-1 and PHF-1 with the aid of alkaline phosphatase demonstrated that 53-kDa tau was derived from dephosphorylation of 57-kDa tau. Despite its effect on thiol oxidation, menadione treatment did not lead to cytoskeletal changes reminiscent of the neurofibrillary tangles of AD. The data thus indicate that tau dephosphorylation constitutes a major feature of the menadione-induced oxidative injury in these neuronal cells.
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PMID:Menadione-induced tau dephosphorylation in cultured human neuroblastoma cells. 923 26


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