Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal-dominant late-onset Parkinson disease. We report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2 is expressed in soluble extracts of human brain, liver, and heart and in cultured human astrocytes, microglia, and oligodendroglia as well as in human neuroblastoma cell lines. We find by Western blotting using a polyclonal antibody of the leucine-rich repeat kinase 2 protein (Lrrk2) specific for C-terminal residues 2,511-2,527 that an apparent full-length protein and several of its fractions are expressed in soluble extracts of normal human brain. By immunocytochemistry, the antibody recognizes neurons, and more weakly astrocytes and microglia, in normal brain tissue. It intensely labels Lewy bodies in Parkinson disease and related neurodegenerative disorders. It also labels a subset of neurofibrillary tangles in Alzheimer disease and the Parkinsonism dementia complex of Guam (PDCG). It labels thorn-shaped astrocytes and oligodendroglial coiled bodies in PDCG; oligodendroglial inclusions in multiple system atrophy; Pick bodies in Pick disease; nuclear and cytoplasmic inclusions in Huntington disease; and intraneuronal and glial inclusions in amyotrophic lateral sclerosis. In summary, LRRK2 is constitutively expressed in neurons and also in glial cells of human brain. It strongly associates with pathological inclusions in several neurodegenerative disorders.
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PMID:LRRK2 expression in normal and pathologic human brain and in human cell lines. 1702

The clinical utility of detecting minimal residual disease (MRD) in children with neuroblastoma (NB) by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) is not clear. This in part reflects the lack of uniform methodology for analysis and reporting. Reference laboratories across Europe have therefore established standard operating procedures (SOPs) for the detection of NB cells by QRT-PCR. Haemopoietic samples are collected into PAXgene blood RNA tubes, which stabilise mRNA for 48 h at room temperature and more than 6 months at -80 degrees C. Tyrosine hydroxylase (TH) was selected as the target for NB cell detection, expression is normalised to beta2-microglobulin and reported using the DeltaDeltaCt method. The sensitivity of QRT-PCR increased from 58% to 90% following the development of SOPs. A robust, transferable, objective method for the detection of NB cells by QRT-PCR has been defined to improve the power and consistency of studies on MRD in children with NB.
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PMID:Standardisation of operating procedures for the detection of minimal disease by QRT-PCR in children with neuroblastoma: quality assurance on behalf of SIOPEN-R-NET. 1702 57

This pilot study was performed to determine whether MYCN expression warrants further investigation as a tumor marker to detect low levels of residual neuroblastoma (NB). Seven NB cell lines and 30 bone marrow (BM) samples from patients with high-risk NB were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) for MYCN expression, and for the established NB marker tyrosine hydroxylase. MYCN was expressed in all 7 NB cell lines, but not in normal peripheral blood, CD34 cells, or BM. In dilution studies using cell lines with or without DNA amplification of MYCN, 1 NB cell in 10 to 10 nucleated blood cells was detectable by RT-PCR. MYCN was identified in all 21 BM samples in which tumor cells were identified by histologic examination, including 4 samples in which tyrosine hydroxylase was not detected. Additionally, expression of both markers was detected in 5 samples that were negative by histology but presumably contained low levels of tumor cells, consistent with the greater sensitivity of RT-PCR compared with morphologic methods. Detection of MYCN RNA was independent of MYCN DNA amplification status. The selective expression of MYCN in tumor cells, and the sensitivity of detection of MYCN by RT-PCR noted in this and other studies, supports further evaluation of MYCN as a NB marker for molecular detection of minimal residual disease.
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PMID:Pilot study to evaluate MYCN expression as a neuroblastoma cell marker to detect minimal residual disease by RT-PCR. 1702 22

Tumor suppressor genes can be inactivated by various mechanisms, including promoter hypermethylation and loss of heterozygosity. We screened the 10q locus for loss of heterozygosity and the promoter methylation status of PTEN, MGMT, MXI1, and FGFR2 in neuroblastic tumors and neuroblastoma cell lines. Expression of these genes in cell lines was analyzed with reverse transcriptase-polymerase chain reaction. Loss of heterozygosity at 10q was detected in 18% of tumors and microsatellite instability in 14%. Promoter hypermethylation of MGMT appeared in 8% of tumors and 25% of cell lines. Correlation between methylation status and lack of expression was evident for PTEN, FGFR2, and MXI1 and was less clear for MGMT. No associations between these alterations and MYCN amplification, 1p deletion, or aggressive tumor histology could be demonstrated, singly or in combination. These data suggest that 10q alterations might be implicated in the development of a small number of neuroblastomas.
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PMID:Loss of heterozygosity and microsatellite instability on chromosome arm 10q in neuroblastoma. 1735 Apr 60

Advances in neural tissue engineering require a comprehensive understanding of neuronal growth in 3 dimensions. This study compared the gene expression of SH-SY5Y human neuroblastoma cells cultured in 3-dimensional (3D) with those cultured in 2-dimensional (2D) environments. Microarray analysis demonstrated that, in response to varying matrix geometry, SH-SY5Y cells exhibited differential expression of 1,766 genes in collagen I, including those relevant to cytoskeleton, extracellular matrix, and neurite outgrowth. Cells extended longer neurites in 3D collagen I cultures than in 2D. Real-time reverse transcriptase polymerase chain reaction experiments and morphological analysis comparing collagen I and Matrigel tested whether the differential growth and gene expression reflected influences of culture dimension or culture material. SH-SY5Y neuroblastoma cells responded to geometry by differentially regulating cell spreading and genes associated with actin in similar patterns for both materials; however, neurite outgrowth and the expression of the gene encoding for neurofilament varied with the type of material. Electron microscopy and mechanical analysis showed that collagen I was more fibrillar than Matrigel, with larger inter-fiber distance and higher stiffness. Taken together, these results suggest complex cell-material interactions, in which the dimension of the culture material influences gene expression and cell spreading and the structural and mechanical properties of the culture material influence gene expression and neurite outgrowth.
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PMID:Genomic and morphological changes of neuroblastoma cells in response to three-dimensional matrices. 1743 91

Lesch-Nyhan disease is caused by a deficiency of the purine salvage enzyme, hypoxanthine phosphoribosyl transferase (HPRT). The link between HPRT deficiency and the neuropsychiatric symptoms is unknown. In rat B103 neuroblastoma cell membranes and mouse Neuro2a neuroblastoma cell membranes, nucleoside 5'-triphosphatase (NTPase) activity is substantially reduced, whereas in fibroblast membranes from HPRT knock-out mice, NTPase activity is increased. Candidate genes for these NTPase activity changes are ecto-nucleoside 5'-triphosphate diphosphohydrolases (NTPDases). Therefore, we studied expression of NTPDases in B103 cells, Neuro2a cells and skin fibroblasts by reverse transcriptase polymerase chain reaction and restriction enzyme digestion of amplified cDNA fragments. In B103 cells, expression of NTPDases 1, 3 and 6 decreased, whereas expression of NTPDases 4 and 5 increased in HPRT deficiency. In Neuro2a cells, expression of NTPDases 3-6 increased in HPRT deficiency. In fibroblasts, NTPDase 3 expression decreased, and expression of NTPDases 4-6 increased in HPRT deficiency. Collectively, there are complex decreases and increases in NTPDase isoform expression in HPRT deficiency that depend on the specific cell type and species studied. These changes in NTPDase expression may reflect an (insufficient) attempt of cells to compensate for the changes in nucleotide metabolism caused by HPRT deficiency.
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PMID:Complex changes in ecto-nucleoside 5'-triphosphate diphosphohydrolase expression in hypoxanthine phosphoribosyl transferase deficiency. 1745 84

Prion diseases are a group of neurodegenerative disorders characterized by astrocytosis and progressive neuronal degeneration. As a causative agent, prions have been intensely investigated in different experimental models. However, the mechanisms and pathways involved in the prion-induced neurological dysfunction are poorly understood. In this work we have investigated the influence of prion infection on the gene expression profile in a human neuroblastoma cell line. Using a DNA microarray and quantitative reverse transcriptase-polymerase chain reaction methods, we have analysed in SH-SY5Y cells the effects of a synthetic peptide corresponding to the 106-126 neurotoxic region of the cellular human prion protein. Our results show that addition of this peptide to the neuronal culture specifically changes the expression of a relative high number of genes, and causes a progressive neuronal death even in the absence of microglia.
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PMID:Identification of genes differentially expressed in SH-SY5Y neuroblastoma cells exposed to the prion peptide 106-126. 1759 92

Tumor growth and metastasis require that tumor cells must have either the potential to shift genetically or epigenetically between proliferative and invasive phenotypes or both phenotypes simultaneously. In the present study, we demonstrated that neuroblastoma growth and invasion were distinct processes that were carried out by proliferative and invasive phenotypes of tumor cells, respectively. Two subpopulations from human neuroblastoma cell line were isolated: highly invasive (HI) cells and low-invasive (LI) cells. HI and LI cells had different proliferative rate and metastatic ability in vitro and in vivo. In addition, they had distinct activated signal pathways and sensitivities to chemotherapy drugs. Affymetrix microarray and quantitative reverse transcriptase-polymerase chain reaction revealed that visinin-like protein-1 (VSNL-1) mRNA in HI cells was significantly higher than that in LI cells. We also observed that VSNL-1 was over-expressed in tumor specimens from patients with distant organ metastases compared with those without metastases. Furthermore, the invasive and proliferative phenotypes of neuroblastoma cells could be exchanged by regulation of VSNL-1 expression in vitro and in vivo. Up-regulation of VSNL-1 potentiated the anoikis-resistant ability of neuroblastoma cell. The expression of anoikis inhibitor TrkB, intracellular adhesion molecule 1, major histocompatibility complex class I, CD44 and CD44v6 was associated with VSNL-1 level. These results suggested that distinct roles of proliferative and invasive phenotypes contributed to neuroblastoma progression and strongly demonstrated that VSNL-1 played a very important role in neuroblastoma metastasis.
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PMID:Involvement of visinin-like protein-1 (VSNL-1) in regulating proliferative and invasive properties of neuroblastoma. 1761 61

The aim of this study was to explore the effect of 0NO-54918-07, a stable prostacyclin analogue, on the current-voltage (IV) curve and the intracellular Ca2+ concentration [Ca2+]i of NG108-15 neuroblastoma x glioma hybrid cells. The IV curve was measured with ramp pulses from -70 to 0 mV, and [Ca2+]i was determined with Fura 2. Bath application of 0.2 muM ONO-54918-07 reversibly increased the holding current at -70 mV by -81.1 +/- 14.8 pA (mean +/- SEM, n = 35) and the slope of the IV curve between -70 and -50 mV by the factor 2.24 +/- 0.24. The effect of 0.2 microM prostaglandin PGE1 was similar (DeltaI (hold) = -96.1 +/- 29.9 pA, g/g (control) = 2.72 +/- 0.44, n = 9). ONO-54918-07 concentrations of 0.04, 2 and 6 microM were also effective. From the dose-response curve, the concentration for the half maximal effect was obtained as 0.054 microM. When cells did not respond to ONO-54918-07, an effect could sometimes be elicited by a ramp pulse or by a second ONO-54918-07 application 30-50 min after the first. The effect of ONO-54918-07 was not affected by pre-treatment with the EP1 antagonists ONO-8713 or SC-51089. However, a 14-40 min pre-treatment with 1 microM RO3244794, a selective prostacyclin receptor (IP) antagonist, abolished the effect of 0.2 microM PGE1. The effect of 0.2 microM ONO-54918-07 vanished completely in the presence of 5 microM RO32446794. ONO-54918-07 and PGE1 produced a slow increase in [Ca2+]i that lasted at least 6 min. Delta[Ca2+]i induced by both substances reached approximately 12% of the peak Delta[Ca2+]i induced by application of bradykinin. In only a few cells, PGE1 produced a brief, transient rise of [Ca2+]i. Using reverse transcriptase polymerase chain reaction, a prominent expression of the IP was detected in NG108-15 cells. It is concluded that ONO-54918-07 mimics the effect of PGE1, supporting the notion that the PGE1 effect on NG108-15 cells is mediated by IP receptors.
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PMID:ONO-54918-07, a stable prostacyclin analogue, mimics the effect of prostaglandin PGE1 on NG108-15 cells. 1795 10

Down syndrome candidate region 1 (DSCR1; also known as RCAN1 or Adapt78) has been shown to be induced by calcium overload and oxidative stress which are included in the pathogenic hallmarks of the ischemic diseases. After ischemic stroke, inflammatory responses play an important role in the exacerbation of neuronal loss. In this study, we investigated the expression pattern of DSCR1 in the mouse cortex after transient middle cerebral artery occlusion (MCAO). Then, in vitro studies were taken to address whether inflammatory mediators could induce DSCR1. Male C57BL/6 mice were subjected to transient MCAO for 35 min and sacrificed at 6, 24, and 72 h after the reperfusion. The expression of DSCR1 began to increase in layer VI of the peri-infarct cortex at 24 h and was prominently enhanced at 72h after transient MCAO. Moreover, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that the induction of the DSCR1 isoform 4 (DSCR1-4) mRNA preceded the expression of the DSCR1 protein. In in vitro studies, tumor necrosis factor alpha and interleukin-1beta (IL-1beta) were found to induce strong upregulation of DSCR1-4 mRNA. Furthermore, western blot analysis revealed that overexpression of DSCR1-4 in SK-N-SH neuroblastoma cells attenuated IL-1beta-induced cyclooxygenase 2 and intercellular adhesion molecule 1 expression. These results demonstrate upregulation of DSCR1 in the mouse peri-infarct cortex following transient MCAO. In addition, our results suggest that inflammatory mediators such as TNFalpha and IL-1beta can induce DSCR1-4 transcription, which may be associated with the alleviation of inflammatory processes.
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PMID:Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke. 1848 47


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