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)

Antiproliferative effects of interferon alpha, beta and gamma were investigated on several human neuroblastoma cell lines using the soft agar colony forming assay and the MTT-test. Investigations were carried out in order to prove whether there is any relationship between antiproliferative effects, inhibition of N-myc expression and the 2-5A system. Growth of neuroblastoma cells was inhibited by all three kinds of interferons in a concentration-dependent manner, however, rather high concentrations were necessary in some cell lines. Expression of N-myc oncogen was not inhibited by interferon-beta and no relationship between antiproliferative effects and the 2-5A system was observed. A vector containing a small N-myc fragment in antisense direction was constructed and transferred into the interferon insensitive human neuroblastoma cell line LS. After transformation, LS cells became sensitive to interferon beta: Proliferation as well as N-myc expression were inhibited and these processes are most probably associated with activation of the 2-5A system.
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PMID:[The role of interferons in neuroblastoma. 1: Antiproliferative effects]. 169 35

A survey of in vitro cytotoxic effects of camptothecin in human epitheliod sarcoma, colon, breast and ovarian carcinomas, glioblastoma, and neuroblastoma (PNET) cell lines, was done. We chose the MTT assay to measure survival and observed that 24 h exposures to camptothecin caused consistently greater toxicity than 1 h exposures. The LD50 for camptothecin was in the 12.5-25 ng/ml range. There was a 10-fold range of growth rates measured by OD after 5 days exposure and varied expression of MDR1 in these cell lines--none of which could be correlated with tumor sensitivity to drug. The most sensitive cell lines were colon and glioblastoma, and the most resistance were ovarian, breast and epithelioid sarcoma.
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PMID:Camptothecin cytotoxic effects in vitro: dependency on exposure duration and dose. 757 68

Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter 90Y were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the 90Y magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with 90Y-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as 90Y-microspheres show great promise for regional or intracavitary radiotherapy.
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PMID:Effective targeting of magnetic radioactive 90Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results. 776 7

The cytotoxic effects of taxol at concentrations of 0.001-1.0 microgram/ml were determined in two human glioblastoma multiforme, two neuroblastoma and two primitive neuroectodermal tumor cell lines. The neuroectodermal cell lines were established from previously treated patients, while the glioblastomas were from untreated patients. At exposure durations of 1, 4 and 24 h there was an inverse taxol concentration-survival relationship for all six cell lines as measured by the MTT method. Significant differences in sensitivity to taxol among these cell lines were observed; the most resistant cell line SK-N-FI is characterized by very high levels of MDR1 expression and the most sensitive SK-N-AS by very low levels. An additional level of complexity concerns a saturation threshold for taxol-induced cytotoxic effects which when reached precludes additional effects of prolonged or additional exposure. Tumors of the brain and peripheral nervous system appear to be sensitive to taxol. However, dosage necessary to maximize cytocidal effects in tumors requires knowledge of at least the range of each tumors constitutive sensitivity to taxol and a way to optimize drug delivery.
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PMID:A saturation threshold for taxol cytotoxicity in human glial and neuroblastoma cells. 810 44

Acute intermittent porphyria (AIP) or precursor syndrome is a well described neuropathic clinical entity with incompletely known etiology. The most prominent biological abnormalities associated with this syndrome are elevations in serum and hepatic delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). We determined the impact of ALA and PBG on human neuroblastoma and glioblastoma tumor cell survival as measured by the MTT assay. ALA proved to be cytotoxic in neuroblastoma cells, while PBG lacked cytotoxic effects. This cytotoxic effect of ALA could be enhanced by deferoxamine and diminished by heme, presumably through modulation of ALA synthesis. In conclusion, ALA excess may prove to be associated with the development of neuropathy in AIP.
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PMID:delta-Aminolevulinic acid effects on neuronal and glial tumor cell lines. 827 91

Growth factor-dependent neurons die when they are deprived of their specific growth factor. This "programmed" cell death (PCD) requires macromolecular synthesis and is distinct from necrotic cell death. To investigate the mechanisms involved in neuronal PCD, we have studied the sequence of events that occur when a neuronal cell line (F-11: mouse neuroblastoma X rat dorsal root ganglia) is deprived of serum in a manner analogous to growth factor deprivation from neurons. Protein synthesis was inhibited within the first 8 h of serum deprivation, while DNA cleavage into nucleosome ladders was prominent by 24 h. The DNA cleavage could be inhibited by cycloheximide, consistent with a requirement for protein synthesis. In contrast, mitochondrial function was not compromised by serum deprivation. Rather, the cells appeared to be metabolically activated after serum removal as shown by an increased reduction of MTT by mitochondrial dehydrogenases and an increase in cellular autofluorescence, which is thought to be due to elevated levels of NADH and flavoproteins. Assessment of cell viability by propidium iodide staining showed no indication of cell death within 24 h. After 48 h of serum deprivation, cells decreased in size and increased propidium iodide uptake. Thus, serum deprivation activates PCD in F-11 cells and may be a useful model to study the intracellular events responsible for PCD.
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PMID:Induction of programmed cell death in a dorsal root ganglia X neuroblastoma cell line. 851 49

1. A class of compounds, 9-aminoacridines, have long been known to be reversible inhibitors of acetylcholinesterase (AChE-EC 3.1.1.7), the most familiar of which is 9-amino-1,2,3,4-tetrahydroacridine (Tacrine). 2. A novel aminoacridine was synthesised: -2-tertiary-butyl-9-amino-1,2,3,4- tetrahydroacridine (2tBuTHA). 3. In vitro comparisons of the acetylcholinesterase inhibitory potential and neurotoxicity compared to Tacrine were performed using a chemically differentiated neuroblastoma cell line (Neuro 2A). 2tBuTHA, but not Tacrine, was cytotoxic to the neural cell following 20 h exposure, despite being the least potent AChE inhibitor (IC80 AChE 12.53 microM +/- 1.14 s.e.m., Neutral Red Uptake IC50 9.53 microM +/- 0.98 s.e.m., MTT Reduction IC80 14.6 microM +/- 1.43 s.e.m.). 4. In vivo studies used a novel application of a five arm radial maze to assess neuropharmacological effects on working memory in control and Scopolamine (1 mg kg-1 i.p.) treated mice. There was an impairment of short term cognitive function with 2tBuTHA (15 mg kg-1 i.p.), but not Tacrine (10 mg kg-1 i.p.) which improved the Scopolamine deficit as expected. 5. This combined in vitro and in vivo data infers a neurotoxic property for the novel compound 2tBuTHA, a close structural analogue of Tacrine.
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PMID:Potential neurotoxicity of a novel aminoacridine analogue. 851 21

Haloperidol has recently been found to be metabolized to its pyridinium ion (HP+). This conversion of haloperidol to HP+ appears to be similar to the activation of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to N-methyl-4-phenyl pyridinium ion (MPP+). MPP+ is responsible for the damage of striatal dopaminergic neurons induced by MPTP in humans and animals. It seemed sensible to investigate whether or not HP+ might be toxic towards dopaminergic neurons and perhaps associated with some of the residual moto-function side effects of haloperidol. We therefore investigated the neurotoxicity of HP+ toward cultured human dopamine neuroblastoma cells (SH-SY5Y) and compared it with that of MPP+. HP+ reduced the viability as measured by MTT and [3H]thymidine incorporation methods in SH-SY5Y cells. Cell membrane integrity is reduced by the treatment of HP+ as measured by intracellular LDH levels. The toxicity was concentration and time dependent. Interestingly, HP+ appeared to be more toxic than MPP+ towards the SH-SY5Y cells in early phase in cultures. The toxicity of MPP+ appear to be progressive and subsequently become more than HP+ with prolonged cultivation. In contrary to MPP+, the toxic effect of HP+ towards a dopamine transporter transfected SK-N-MC cell line is not different from its wild type. This indicates that dopamine uptake system is probably not involved in the cytotoxicity caused by HP+.
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PMID:Comparison of cytotoxicity of a quaternary pyridinium metabolite of haloperidol (HP+) with neurotoxin N-methyl-4-phenylpyridinium (MPP+) towards cultured dopaminergic neuroblastoma cells. 858 20

The possibility of imaging monoamine oxidase (MAO) containing neurons through the MAO-mediated conversion of the nonfluorescent tetrahydropyridine compound trans-1-methyl-4-[4-dimethylaminophenylethenyl]-1,2,3,6-tetrahydro pyridine (t-THP) to the corresponding fluorescent trans-1-methyl-4-[4-dimethylaminophenylethenyl]pyridinium species (t-P+) was examined with the aid of human neuroblastoma cells (SH-SY5Y). Fluorescence microscopy and fluorescence measurements established the intracellular formation of a fluorescent species with maximal excitation/emission wavelengths of 485/620 and 530/620 nm corresponding to the fluorescence characteristics of synthetic t-P+. An independent assay confirmed the presence of both MAO-A and MAO-B in these cells. As expected, the development of the fluorescence was inhibited by both clorgyline (an MAO-A inhibitor) and deprenyl (an MAO-B inhibitor). Cytotoxic effects, as determined by trypan blue dye exclusion for viability and by the MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] assay for mitochondrial integrity, were not observed in cells incubated with concentrations of t-THP as high as 10(-3) M for 4 hr. The results from these studies with a neuronal cell line of human origin suggest: (1) that SH-SY5Y cells metabolize and, therefore, can be used for study of tetrahydropyridine compounds in vitro, and (2) that t-THP may be a useful agent to monitor neurodegenerative processes in MAO-rich neurons, including the dopaminergic nigrostriatal neurons that are damaged by the parkinsonian-inducing tetrahydropyrridine MPTP. The potential advantage of using t-THP over related imaging techniques is the possibility of assessing neuronal function by an in vivo processing of the reporter molecule rather than by postmortem immunofluorescent or formaldehyde-based procedures.
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PMID:Biotransformation of the MPTP analog trans-1-methyl-4-[4-dimethylaminophenylethenyl]-1,2,3,6-tetra- hydropyridine to a fluorescent pyridinium metabolite by intact neuroblastoma cells. 866 41

We have studied the hypothesis that 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) is neurotoxic. Salsolinol induced a significant time and dose related inhibition of 3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazoyl blue (MTT) reduction, and increased lactate dehydrogenase release (LDH) release from human SH-SY5Y neuroblastoma cells, at concentrations within the range of 1-methyl-4-phenylpyridinium (MPP+) cytotoxicity, in vitro. Cytotoxicity was not inhibited by the addition of antioxidants, monoamine oxidase inhibitors or imipramine. In confluent monolayers, salsolinol stimulated catecholamine uptake with EC50 values of 17 muM and 11 muM, for noradrenaline and dopamine, respectively. Conversely, at concentrations above 100 muM, salsolinol inhibited the uptake of noradrenaline and dopamine, with IC50 values of 411 muM and 379 muM, respectively. The inhibition of catecholamine uptake corresponded to the increase displacement of [3H]nisoxetine from the uptake 1 site by salsolinol, as the Ki (353 muM) for displacement was similar to the IC50 (411 and 379 muM) for uptake. Salsolinol stimulated catecholamine uptake does not involve the uptake recognition site, or elevation of cAMP, cGMP, or inhibition of protein kinase C. Salsolinol also inhibited both carbachol (1 mM) and K+ (100 mM, Na+ adjusted) evoked released of noradrenaline from SH-SY5Y cells, with IC50 values of 500 muM and 120 muM, respectively. In conclusion, salsolinol appears to be cytotoxic to SH-SY5Y cells, via a mechanism that does not require uptake 1, bioactivation by monoamine oxidase, or membrane based free radical damage. The effects of salsolinol on catecholamine uptake, and the mechanism of toxicity require further investigation.
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PMID:Studies on the neurotoxicity of 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) in SH-SY5Y cells. 874 84


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