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)

Three neuroblastoma cell lines established from tumor samples obtained from one patient are described. The three lines were derived from bone marrow aspirates taken at diagnosis, and 13 and 15 months later. The origin of the cell lines PER-106, PER-107, and PER-108 from malignant neuroblasts was confirmed by electron microscopy studies, surface marker analysis, and assessment of MYCN amplification. Cell lines PER-107 and PER-108, which were established from tumor samples obtained at the time of progressive disease, have significantly shorter doubling times than PER-106 and grow mainly substrate-adherent, while cell line PER-106 (established from sample obtained at diagnosis) consists of small round neuroblastic cells which form large aggregates in suspension culture. The electron microscopy studies revealed distinctive neuroblast-like ultrastructure in all cell lines. The MYCN copy number was amplified (greater than 10 copies) in the established cell lines and in the fresh tumor samples and the relative abundance of MYCN RNA in the cell lines correlated roughly with the extent of the MYCN gene amplification. However, distinct phenotypic differences can be demonstrated among these three lines, which provide a model for the further examination of this highly malignant tumor. Detection of MYCN amplification by chromosomal in situ hybridization was performed on this set of cell lines, as reported by McRobert et al. (this issue, pages 128-134).
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PMID:Three neuroblastoma cell lines established from consecutive samples of one patient which show distinct morphologic features, MYCN amplification, and surface marker expression. 158 78

A non-radioactive chromosomal in situ hybridization technique utilizing a biotin-streptavidin-polyalkaline-phosphatase complex was successfully applied to three neuroblastoma cell lines for detection of MYCN amplification. These cell lines, designated PER-106, PER-107, and PER-108, were derived from consecutive bone marrow samples taken from a patient with stage IV neuroblastoma. The cell line derived at diagnosis (PER-106) exhibited MYCN amplification in the form of variable numbers of double-minute chromosomes, small fragments, and rings of varying sizes. This observed variability of MYCN amplification may explain the reported heterogeneity of both MYCN mRNA and protein expression among individual cells of some neuroblastomas. The cell lines derived from subsequent samples (PER-107 and PER-108) contained amplified MYCN as two consistent homogeneously staining regions in every cell. These were located on the short arms of chromosomes 6 and 14. Thus, amplified MYCN was identified in each cell line and demonstrated the concurrent evolution of amplification with cytogenetic abnormalities.
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PMID:Detection of MYCN amplification in three neuroblastoma cell lines by non-radioactive chromosomal in situ hybridization. 158 79

The key elements of circadian clockwork and oxygen homeostasis are the PAS protein family members PER and CLOCK and hypoxia-inducible factor 1alpha (HIF-1alpha). The PAS domain serves as an interface for protein-protein interactions. We asked whether a cross-talk exists between the PAS components of hypoxic and circadian pathways. We found several isoforms of PER1 protein that exhibit tissue-specific size differences. In the mouse brain, a predominantly nuclear 48 kDa isoform that followed a daily rhythm was observed. The 48 kDa form was found in the nuclear fractions derived from mouse liver, Swiss3T3 fibroblasts, and N2A neuroblastoma cells. In mouse kidney and human 293 kidney cells, a 55 kDa PER1 form was detected. CLOCK was observed as a predicted 100 kDa protein in rat-1 cells and in all analyzed mouse tissues including brain, liver, kidney, and spleen. In contrast to PER1, CLOCK protein expression was not rhythmic. Exposure to hypoxia led to increased PER1 and CLOCK protein levels in mice. Based on coimmunoprecipitation experiments that showed protein-protein interaction between PER1 and the alpha subunit of HIF-1, we suggest that these hypoxic effects may be modulated by HIF-1alpha.-Chilov, D., Hofer, T., Bauer, C., Wenger, R. H., Gassmann, M. Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain.
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PMID:Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain. 1172 37

p53 mutations have been reported in cell lines derived from relapsed neuroblastoma tumors. We hypothesize that functional inactivation of p53 by mutation or other mechanisms is common in relapsed neuroblastoma and can contribute to chemoresistance. Our aim was to determine the frequency of p53 mutations, p14(ARF) methylation, or deletion and MDM2 amplification in 23 neuroblastoma cell lines (6 derived at diagnosis and 17 derived at relapse). One cell line was p53 mutant (BE2c) and two cell lines were deleted for p14(ARF) (LAN-6 and SHEP). Two cell lines were methylated for p14(ARF) (GIMEN and PER-108), one of which had low levels of p14(ARF) mRNA expression which increased following demethylation with 5-aza-2/deoxycytidine treatment (GIMEN), and four cell lines were confirmed to be MDM2-amplified. All these cell lines were derived from neuroblastomas at relapse. Inactivation of the p53 pathway was observed in 9 out of 17 neuroblastoma cell lines (53%) established at relapse and in none of the cell lines established from pretreatment tumors. If these data are confirmed in neuroblastoma tumors, this suggests that p53-independent therapy and reactivation of inactive p53 approaches would be useful in the management of relapsed neuroblastoma.
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PMID:Increased frequency of aberrations in the p53/MDM2/p14(ARF) pathway in neuroblastoma cell lines established at relapse. 1648 14