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)

Expression of Tyrosine Hydroxylase (TH) is frequently seen in neuroblastomas, the most common extracranial tumor in children, and TH mRNA detection is used for the analysis of microcirculating or micrometastatic disease in this neoplasia. TH is known to have at least seven isoforms produced by alternative splicing of the N-terminal region (exons 1-4), although no other splicing variants have been described downstream. TH expression was analyzed in six samples of neuroblastoma by RT-PCR using highly restrictive conditions and primers between exons 5 and 12, a region of the gene previously considered to be constant. In the analyzed samples we found two novel TH mRNAs, one lacking exon 8, and another lacking exons 8+9. These new splicing variants are described in a region of TH previously reported to be conserved, and that has been used for the design of reverse transcriptase-polymerase chain-reaction assays for the detection of minimal residual disease [Eur. J. Cancer, 27 (1991) 762]. The splicing pattern characteristic of every tumor could allow the monitoring of the minimal residual disease in a tumor-specific manner.
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PMID:New splicing variants for human Tyrosine Hydroxylase gene with possible implications for the detection of minimal residual disease in patients with neuroblastoma. 1249 95

The serial analysis of gene expression (SAGE) technique was used to generate a database of the most abundant transcripts of the MYCN-amplified neuroblastoma cell line IMR-5. A total of 8568 tags were sequenced and shown to represent 4034 unique tags, each of which corresponds to an individual transcript. Expression levels of genes are reflected by the frequency of occurrence of the respective tags. To validate fidelity of SAGE data, relative abundances of seven transcripts were evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Transcripts that were detected nine times or more (>0.1% of the total tag population) accounted for 36% of the total messenger RNA mass but only 3% of the total number of individual transcripts. A strong preponderance of genes involved in protein synthesis, in particular those encoding for ribosomal proteins, were observed among these high-abundance transcripts. Tags corresponding to the amplified gene DDX1 were conspicuously overrepresented in comparison to the other amplified genes MYCN, neuroblastoma amplified gene and MEIS1, which suggests an additional mechanism apart from genomic amplification contributing to the strong upregulation of this gene. This study provides a comprehensive gene expression profile of neuroblastoma cell line IMR-5 and may be used as a reference database for identification of candidate genes that are involved in etiology and pathogenesis of neuroblastoma.
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PMID:Characterization of the gene expression profile of neuroblastoma cell line IMR-5 using serial analysis of gene expression. 1253 80

Neuroblastoma (NB) is characterised by the secretion of catecholamines in approximately 95% of patients. Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine biosynthesis pathway. Expression of the tyrosine hydroxylase gene (TH) is regulated in a tissue-specific manner during neonatal development and differentiation, therefore TH mRNA expression is a specific tumour marker for NB. Here we present a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay using TaqMan technology for detection and quantification of TH mRNA in bone marrow (BM) NB patients. The degree of TH expression was derived from the ratio of the mRNAs of this gene and the reference gene, beta-actin. A ratio greater than 3x10(-2) was considered as positive for TH mRNA presence. Samples were also examined for TH mRNA by first and nested RT-PCR. Seventeen BM samples from 4 patients with disseminated NB (3 stage IV and 1 stage IVs) were evaluated at diagnosis and during treatment. We found a variable degree of TH expression ranging from 0.0344 to 26.3370 in 12/17 positive samples, while no TH mRNA (value lower than 3x10(-2)) was detected in 5/17 samples obtained after consolidation therapy. Our results show a moderate concordance between different qualitative RT-PCR methods and real-time RT-PCR. The real-time RT-PCR results seem to fit better with the natural short-term clinical follow-up of the evaluated patients, with respect to qualitative methods. Real-time TH RT-PCR could therefore be of clinical value for the assessment of a patient's prognosis by monitoring minimal residual disease (MRD).
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PMID:Real-time RT-PCR of tyrosine hydroxylase to detect bone marrow involvement in advanced neuroblastoma. 1257 72

Nicotine exposure can have long lasting effects on nervous system function, some of which must contribute to nicotine dependence. Up-regulation, an increase in numbers of radioligand-binding nicotinic acetylcholine receptors (nAChR), occurs on exposure to nicotine at high concentrations. To determine whether altered gene expression might account for long term changes and up-regulation following nicotine exposure, we assessed effects of 1 h of 1 mm nicotine exposure on alteration of gene expression in the neuron-like SH-SY5Y neuroblastoma clonal line. Repeat and cross-controlled microarray analyses yielded a list of 17 genes from the initially screened approximately 5,000 whose expression was consistently altered following nicotine treatment. Subsequent quantitative, real time reverse transcriptase PCR analyses confirmed altered expression in 14 of 16 genes tested. Further, the general nAChR antagonist, d-tubocurarine, blocked all but two of the observed changes in gene expression, indicating that these changes are dependent on nAChR activation. Use of other antagonists revealed that nAChR subtypes can differentially affect gene expression. The genes affected code for proteins that may be broadly categorized into four groups: transcription factors, protein processing factors, RNA-binding proteins, and plasma membrane-associated proteins. Our results suggest that nicotinic activation of nAChR may have a broad role in affecting cellular physiology through modulating gene expression.
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PMID:Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. 1258 70

Telomerase activity (TA) is the most recently recognized prognostic factor in neuroblastoma, and its outstanding predictive power was documented by several studies. However, TA measurements require fresh tumor tissue that is not always available in daily clinical practice. We previously described a reverse transcriptase-polymerase chain reaction assay that we used to investigate the possible prognostic relevance of the telomerase catalytic subunit, hTERT, at the mRNA level. Because hTERT mRNA undergoes alternative splicing as a regulatory mechanism of TA, we discriminated between truncated and full-length hTERT transcripts. In a retrospective study on 124 neuroblastomas, 56 (45.2%) tumors showed spliced hTERT transcripts, whereas 30 (24.2%) contained full-length hTERT transcripts. The presence of both spliced and full-length hTERT transcripts was significantly associated with MYCN amplification. hTERT in general showed no correlation to other prognostic factors, ie, International Neuroblastoma Staging System stage, International Neuroblastoma Pathology classification grade, or age at diagnosis, whereas the presence of full-length transcripts was significantly associated with higher stages. The presence of any hTERT transcripts carried no significant prognostic information, yet full-length hTERT transcripts were highly predictive of poor outcome (P < 0.0001). In a multivariate analysis, full-length hTERT transcripts and International Neuroblastoma Pathology classification grade emerged as the sole independent predictors of event-free survival, with relative risks of 10.0 and 3.9, respectively. The strong statistical correlation of full-length hTERT transcripts with clinical outcome in neuroblastoma suggests that the reverse transcriptase-polymerase chain reaction analysis of hTERT transcripts may be equatable to TA measurements. Because this assay is well suited for archival material, it could become a useful adjunct in evaluating the prognosis of individual neuroblastoma cases.
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PMID:Full-length telomerase reverse transcriptase messenger RNA is an independent prognostic factor in neuroblastoma. 1259 34

Antioxidants have concentration-dependent neuroprotective and proapoptotic activities in models of Parkinson's disease. The aim of our study was to determine gene-protein pathways of the antioxidants, dopamine (DA), R-apomorphine (R-APO), melatonin, and green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), in neuroblastoma cells, using a customized cDNA microarray and quantitative reverse transcriptase-polymerase chain reaction gene expression techniques. We demonstrate a concentration-dependent correlation between these compounds and modulation of cell survival/cell death-related gene pathways. High toxic concentration of DA (500 microM), R-APO (50 microM), melatonin (50 microM), and EGCG (50 microM) exhibited a similar profile of proapoptotic gene expression, increasing the level of bax, caspase-6, fas ligand, and the cell-cycle inhibitor gadd45 genes, while decreasing antiapoptotic bcl-2 and bcl-xL. Conversely, the low neuroprotective concentrations (1-10 microM) of these compounds induced an antiapoptotic response. Melatonin displayed an extremely low index of mortality, which may be partially explained by the observation that a high concentration did not significantly affect the expression of mitochondrial Bcl-2 family members, bcl-2 and bax. Protein analysis of Bcl-2, Bax, and activated caspase-3 correlated with the gene expression pattern. Our results provide for the first time new insights into the molecular events involved in the dose-dependent neuroprotective and neurotoxic activities of catechols and indole amine compounds.
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PMID:cDNA gene expression profile homology of antioxidants and their antiapoptotic and proapoptotic activities in human neuroblastoma cells. 1262 34

The clinicobiological feature of neuroblastoma is enigmatic because spontaneous regression often occurs in early stages of tumors of the patients under 1 year of age, while rapid growth usually occurs in the tumors of the patients over 1 year of age. Such difference in the clinical behavior may be caused by the difference in the pattern of gene expression among the subsets of neuroblastoma. To understand the molecular basis of neuroblastoma biology, we decided to identify the novel genes expressed differentially between favorable and unfavorable neuroblastomas. The oligo-capping cDNA libraries were constructed from different subsets of neuroblastomas. After random selection and DNA sequencing, the differentially expressed genes between favorable and unfavorable neuroblastomas were screened by reverse transcriptase-PCR. The clinical significance of gene expression was evaluated based on the results of Northern blot analysis. We have identified a novel gene Nbla03145 (alpha), also cloned and termed by another group as ECEL1, which encodes a new member of putative zinc-binding metalloendopeptidase (endothelin-converting enzyme) with unknown substrate. We also cloned a COOH-terminally truncated Nbla03145/ECEL1beta which is expressed only in thymus. In primary NBLs, the alpha isoform is more preferentially expressed than the beta isoform. High levels of Nbla03145/ECEL1 expression were significantly correlated with a younger age (p=0.0005), lower stages (p=0.0019), high level of TrkA expression (p</=0.00005), a single copy of MYCN (p<0.00005) and the tumors found by mass screening (p<0.00005). Decreased expression of Nbla03145/ECEL1 mRNA was significantly associated with poor prognosis (log-rank test: p=0.012). The present results have shown that expression of Nbla03145/ECEL1 is a novel prognostic marker of neuroblastoma. Further analysis of the gene may also give a cue to the understanding of the role of endothelin-like signaling in neuroblastoma and to the development of diagnostic and therapeutic strategies against aggressive tumors.
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PMID:High expression of the novel endothelin-converting enzyme genes, Nbla03145/ECEL1alpha and beta, is associated with favorable prognosis in human neuroblastomas. 1263 73

Human telomeres are several kilobases of repeated (TTAGGG)(n) sequences at the ends of chromosomes, a short fragment of which is lost with each cell division. This shortening serves as a "mitotic clock" which limits the number of divisions that a normal somatic cell can undergo. Cells undergoing continuous division need some method of bypassing this clock. One such method is the expression of telomerase. This ribonucleoprotein is an enzyme that rebuilds the lost portion of the telomeres. Between 80-95% of tumors are telomerase-positive, including ovarian carcinoma, hepatocellular carcinoma, neuroblastoma, leukemia/lymphoma, and cancers of the breast, prostate, lung, kidneys and bladder, as well as many immortalized cell lines. While absent in most normal tissues, this enzyme is expressed at higher levels in germline tissues, bone marrow, and lymphocytes. Due to the expression of telomerase in most tumor cells and its absence in most normal tissues, telomerase inhibitors are being investigated as possible anticancer agents. This review focuses on non-reverse transcriptase inhibitor, non-oligonucleotide and non-G-quartet interactive agent telomerase inhibitors. These agents include: differentiating agents, kinases and phosphatases, cell cycle and apoptosis regulating agents, immunotherapeutic agents, antibiotics, steroids, bisindole derivatives, and a variety of other compounds. These agents hold much promise for the future treatment of malignancies.
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PMID:The 'other' telomerase inhibitors: non-G-quadruplex interactive agent, non-antisense, non-reverse transcriptase telomerase inhibitors. 1267 26

The alpha-ketoisocaproic acid (KIC) is a short branched-chain monocarboxylate, which accumulates in neural cells. It plays an important role in maintaining nitrogen balance in the brain, a process of a great importance for shuttling of glutamine and glutamate between astrocytes and neurons. Higher accumulation of KIC in isolated cerebral cortex neurons at lower external pH, as well as sensitivity of this process to alpha-cyano-4-hydroxycinnamate indicate an involvement of a transporter, belonging to the family of monocarboxylate transporters (MCT).The expression of MCT1 and MCT2 isoforms in the brain cells was studied using reverse transcriptase-polymerase chain reaction (RT-PCR) method. The mRNA coding MCT1 was detected in astrocytes, brain endothelial cells, tumour cells (neuroblastoma and glioma) and in cortex neurons of newborn rats, but not in adult ones. MCT2, which is less abundant isoform than MCT1, was expressed in astrocytes, in brain endothelial cells and at low level in newborn rats' neurons, being absent in neurons from adult brain.The observed sensitivity of KIC accumulation towards SH-groups reagents did not fit to the known characteristics of MCT1 and MCT2. Therefore, the change of MCT expression during brain development, as well as lack of MCT1 and MCT2 in neurons of adults, point to another MCT isoform being involved in alpha-ketoisocaproic acid accumulation. This could be either one of other known MCT isoforms or a new member of family MCT, specific towards branched chain alpha-ketoacids.
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PMID:Expression of monocarboxylic acid transporters (MCT) in brain cells. Implication for branched chain alpha-ketoacids transport in neurons. 1274 73

A sensitive quantitative-competitive reverse transcriptase-polymerase chain reaction method was developed to measure micro-opioid receptor (MOR) mRNA expression in SHSY-5Y neuroblastoma cells. Differentiation of SHSY-5Y cells with either retinoic acid (RA) or 12-o-tetradecanoyl-phorbol-13-acetate (TPA) significantly increased MOR mRNA levels. Morphine treatment (10 microM) for 24 h decreased MOR mRNA levels in control, as well as RA- and TPA-differentiated cells. In contrast, chronic exposure to the opioid peptides endomorphin-1 or endomorphin-2 significantly increased MOR mRNA levels in undifferentiated and RA-differentiated cells. An opioid antagonist, naloxone, reversed the morphine and endomorphin-1 and -2 effects on MOR mRNA levels in undifferentiated SHSY-5Y cells, but naloxone had differential reversing effects on the agonists' regulation of MOR mRNA in RA- or TPA-differentiated cells. To investigate whether the changes in MOR mRNA expression paralleled changes in MOR receptor function, intracellular cAMP accumulation in SHSY-5Y cells was measured. After chronic treatment with morphine, forskolin-induced cAMP levels in SHSY-5Y cells were significantly higher than those of untreated control cells. In contrast, forskolin-induced cAMP accumulation levels were lower in cells treated with endomorphin-1 or -2 than in untreated control cells. Together, our studies indicate that the opioid alkaloid morphine and the opioid peptides endomorphin-1 and -2 differentially regulate MOR mRNA expression and MOR function in SHSY-5Y cells.
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PMID:Morphine and endomorphins differentially regulate micro-opioid receptor mRNA in SHSY-5Y human neuroblastoma cells. 1275 18


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