Transcription profiling by array of human NSCLC U1810 residual clones 9 days after a one-hour pulse treatment with cisplatin
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ORGANISM(S): Homo sapiens
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PROVIDER: S-ECPF-GEOD-48244 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Background: The platinum compounds cisplatin and carboplatin are the mainstay of chemotherapy for lung cancer; however, treatment failure remains a critical issue since about 60% of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance. Methods: We analyzed global gene expression profiles in NSCLC clones surviving a pulse treatment with cisplatin by microarray and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA). Results: Cisplatin-surviving NSCLC clones were demonstrated to have heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (DKK1), DNA repair machinery (XRCC2) and cell-cell/ cell-matrix interaction (FMN1 and LGALS9) were among the top deregulated genes by microarray and were subsequently validated by q-RT-PCR. We focused on DKK1, which was previously reported to be overexpressed in NSCLC. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones. Knockdown of DKK1 by siRNA sensitized untreated NSCLC cells to cisplatin, illustrating a putative role of DKK1 in intrinsic platinum resistance. Conclusions: Gene expression analysis identified DKK1 as a putative cisplatin resistance marker and a potential novel therapeutic target to overcome platinum resistance in NSCLC.
2014-04-04 | GSE48244 | GEO
Project description:Background: The platinum compounds cisplatin and carboplatin are the mainstay of chemotherapy for lung cancer; however, treatment failure remains a critical issue since about 60% of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance. Methods: We analyzed global gene expression profiles in NSCLC clones surviving a pulse treatment with cisplatin by microarray and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA). Results: Cisplatin-surviving NSCLC clones were demonstrated to have heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (DKK1), DNA repair machinery (XRCC2) and cell-cell/ cell-matrix interaction (FMN1 and LGALS9) were among the top deregulated genes by microarray and were subsequently validated by q-RT-PCR. We focused on DKK1, which was previously reported to be overexpressed in NSCLC. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones. Knockdown of DKK1 by siRNA sensitized untreated NSCLC cells to cisplatin, illustrating a putative role of DKK1 in intrinsic platinum resistance. Conclusions: Gene expression analysis identified DKK1 as a putative cisplatin resistance marker and a potential novel therapeutic target to overcome platinum resistance in NSCLC. U1810 cells were sparsely seeded for clonogenic survival assay in three separate experiments (replicate 1-3), left untreated or treated with cisplatin for 1 h and then kept for 9 days to assay long-term effects of a single pulse treatment.
2014-04-04 | E-GEOD-48244 | biostudies-arrayexpress
Project description:Affymetrix high-density oligonucleotide microarray analysis was performed to analyse cisplatin-induced gene expression changes in A549 NSCLC cells. Cells were treated with 50 µM of cisplatin for 1 hour and incubated for a further 10 hours in drug-free media before the gene expression changes were investigated. Results show that cisplatin induced changes in the expression of genes involved in apoptosis, cell cycle control, DNA repair and transcription. Experiment Overall Design: Gene expression changes in response to cisplatin were analysed by Microarray technology in A549 NSCLC cells. Cells were treated with 50 µM of cisplatin (or drug-free media) for 1 hour and incubated for a further 10 hours in drug-free media before the cisplatin-induced gene expression changes were investigated. Control and cisplatin-treated samples were collected from three independent experiments.
| S-ECPF-GEOD-6410 | biostudies-other
Project description:BackgroundCisplatin-based chemotherapy is a therapeutic strategy against non-small cell lung cancer (NSCLC). However, cancers relapse after chemotherapy due to a dormant state of residual cancer cells. Extracellular vesicles and particles (EVPs) are active carriers of proteins and nucleic acid. Here, we aimed to study the molecular alterations and proteomic characteristics of EPV in dormant and reactivated cancer cells induced by cisplatin.MethodsWe used a short-term single dose of cisplatin to induce the dormant and reactivated cell status. We examined the gene expressional profiling and proteomic profiling of EVPs from dormant and reactivated cancer cells by RNA-sequencing and LC-MS/MS.ResultsWe found substantial changes in gene expression and protein level in EVP. The genes with higher expression in dormant cancer cells were lipid transporter- and lipid metabolic-related genes. A total of 111 EVP proteins were upregulated in dormant cancer cells compared to those in control cells. Fifty differential expressed proteins (DEPs) were identified in EVPs from reactivated cancer cells compared to those in dormant cancer cells. Among the DEPs, we found that apolipoproteins such as APOA1 and APOE were significantly increased in dormant cancer cell-derived EVPs. Integration of EVP proteomes with transcriptional profiles of cancer cells revealed that the proteomic profiling of EVP derived from cancer cells can reflect the cellular status of cancer cells, which showed an activated lipid metabolism in dormant state.ConclusionLipoproteins enriched in EVPs reflect the activated lipid metabolism in dormant cancer cells and may provide potential biomarkers or therapeutic targets for cisplatin-based therapy.
| S-EPMC8487815 | biostudies-literature
Project description:We describe the comprehensive analysis of the yeast proteome in just over one hour of optimized analysis. We achieve this expedited proteome characterization with improved sample preparation, chromatographic separations, and by using a new Orbitrap hybrid mass spectrometer equipped with a mass filter, a collision cell, a high-field Orbitrap analyzer, and, finally, a dual cell linear ion trap analyzer (Q-OT-qIT, Orbitrap Fusion). This system offers high MS(2) acquisition speed of 20 Hz and detects up to 19 peptide sequences within a single second of operation. Over a 1.3 h chromatographic method, the Q-OT-qIT hybrid collected an average of 13,447 MS(1) and 80,460 MS(2) scans (per run) to produce 43,400 (x) peptide spectral matches and 34,255 (x) peptides with unique amino acid sequences (1% false discovery rate (FDR)). On average, each one hour analysis achieved detection of 3,977 proteins (1% FDR). We conclude that further improvements in mass spectrometer scan rate could render comprehensive analysis of the human proteome within a few hours.
| S-EPMC3879625 | biostudies-literature
Project description:Recent advances in chromatography and mass spectrometry (MS) have made rapid and deep proteomic profiling possible. To maximize the performance of the recently produced Orbitrap hybrid mass spectrometer, we have developed a protocol that combines improved sample preparation (including optimized cellular lysis by extensive bead beating) and chromatographic conditions (specifically, 30-cm capillary columns packed with 1.7-μm bridged ethylene hybrid material) and the manufacture of a column heater (to accommodate flow rates of 350-375 nl/min) that increases the number of proteins identified across a single liquid chromatography-tandem MS (LC-MS/MS) separation, thereby reducing the need for extensive sample fractionation. This strategy allowed the identification of up to 4,002 proteins (at a 1% false discovery rate (FDR)) in yeast (Saccharomyces cerevisiae strain BY4741) over 70 min of LC-MS/MS analysis. Quintuplicate analysis of technical replicates reveals 83% overlap at the protein level, thus demonstrating the reproducibility of this procedure. This protocol, which includes cell lysis, overnight tryptic digestion, sample analysis and database searching, takes ∼24 h to complete. Aspects of this protocol, including chromatographic separation and instrument parameters, can be adapted for the optimal analysis of other organisms.
| S-EPMC6434932 | biostudies-literature
Project description:Hamsters will spontaneously 'split' and exhibit two rest-activity cycles each day when housed in constant light (LL). The suprachiasmatic nucleus (SCN) is the locus of a brain clock organizing circadian rhythmicity. In split hamsters, the right and left SCN oscillate 12 h out of phase with each other, and the twice-daily locomotor bouts alternately correspond to one or the other. This unique configuration of the circadian system is useful for investigation of SCN communication to efferent targets. To track phase and period in the SCN and its targets, we measured wheel-running and FOS expression in the brains of split and unsplit hamsters housed in LL or light-dark cycles. The amount and duration of activity before splitting were correlated with latency to split, suggesting behavioral feedback to circadian organization. LL induced a robust rhythm in the SCN core, regardless of splitting. The split hamsters' SCN exhibited 24-h rhythms of FOS that cycled in antiphase between left and right sides and between core and shell subregions. In contrast, the medial preoptic area, paraventricular nucleus of the hypothalamus, dorsomedial hypothalamus and orexin-A neurons all exhibited 12-h rhythms of FOS expression, in-phase between hemispheres, with some detectable right-left differences in amplitude. Importantly, in all conditions studied, the onset of FOS expression in targets occurred at a common phase reference point of the SCN oscillation, suggesting that each SCN may signal these targets once daily. Finally, the transduction of 24-h SCN rhythms to 12-h extra-SCN rhythms indicates that each SCN signals both ipsilateral and contralateral targets.
| S-EPMC4014115 | biostudies-literature
Project description:AimsThe timing of increase in 1-hour PG and its utility as an earlier predictor of both prediabetes (PreDM) and type 2 diabetes (T2D) compared to 2-hour PG (2 h-PG) are unknown. To evaluate the timing of crossing of the 1 h-PG ≥ 155 mg/dl (8.6 mmol/L) for PreDM and 209 mg/dl (11.6 mmol/L) for T2D and respective current 2 h-PG thresholds of 140 mg/dl (7.8 mmol/L) and 200 mg/dl (11.1 mmol/L).MethodsSecondary analysis of 201 Southwest Native Americans who were followed longitudinally for 6-10 years and had at least 3 OGTTs.ResultsWe identified a subset of 43 individuals who first developed PreDM by both 1 h-PG and 2 h-PG criteria during the study. For most (32/43,74%), 1 h-PG ≥ 155 mg/dl was observed before 2 h-PG reached 140 mg/dl (median [IQR]: 1.7 [-0.25, 4.59] y; mean ± SEM: 5.3 ± 1.9 y). We also identified a subset of 33 individuals who first developed T2D during the study. For most (25/33, 75%), 1 h-PG reached 209 mg/dl earlier (median 1.0 [-0.56, 2.02] y; mean ± SEM: 1.6 ± 0.8 y) than 2 h-PG reached 200 mg/dl, diagnostic of T2D.Conclusions1 h-PG ≥ 155 mg/dl is an earlier marker of elevated risk for PreDM and T2D than 2 h-PG ≥ 140 mg/dl.
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Project description:Nanoscale coherent light sources offer potentially ultrafast modulation speeds, which could be utilized for novel sensors and optical switches. Plasmonic periodic structures combined with organic gain materials have emerged as promising candidates for such nanolasers. Their plasmonic component provides high intensity and ultrafast nanoscale-confined electric fields, while organic gain materials offer fabrication flexibility and a low acquisition cost. Despite reports on lasing in plasmonic arrays, lasing dynamics in these structures have not been experimentally studied yet. Here we demonstrate, for the first time, an organic dye nanoparticle-array laser with more than a 100 GHz modulation bandwidth. We show that the lasing modulation speed can be tuned by the array parameters. Accelerated dynamics is observed for plasmonic lasing modes at the blue side of the dye emission.
| S-EPMC6117104 | biostudies-literature
Project description:Affymetrix high-density oligonucleotide microarray analysis was performed to analyse cisplatin-induced gene expression changes in A549 NSCLC cells. Cells were treated with 50 µM of cisplatin for 1 hour and incubated for a further 10 hours in drug-free media before the gene expression changes were investigated. Results show that cisplatin induced changes in the expression of genes involved in apoptosis, cell cycle control, DNA repair and transcription. Experiment Overall Design: Gene expression changes in response to cisplatin were analysed by Microarray technology in A549 NSCLC cells. Cells were treated with 50 µM of cisplatin (or drug-free media) for 1 hour and incubated for a further 10 hours in drug-free media before the cisplatin-induced gene expression changes were investigated. Control and cisplatin-treated samples were collected from three independent experiments.
2008-06-14 | E-GEOD-6410 | biostudies-arrayexpress