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RDC and cisplatin transcriptomes

ABSTRACT: Ruthenium based compound have developed for anticancer therapy Identification of the transcriptomes induced by either cisplatin or a ruthenium-based compound (RDC) that are both cytotoxic. Cells were treated with either cisplatin or RDC at their IC50 and for 6h or 24h.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66493 | GEO | 2015/03/05

SECONDARY ACCESSION(S): PRJNA277134

REPOSITORIES: GEO

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RDC and cisplatin transcriptomes

Project description:Ruthenium based compound have developed for anticancer therapy Identification of the transcriptomes induced by either cisplatin or a ruthenium-based compound (RDC) that are both cytotoxic. Cells were treated with either cisplatin or RDC at their IC50 and for 6h or 24h. 15 samples are in the experiment. Each condition has been done in triplicates. Ct is control; R6 is RDC applied for 6h, R24 is RDC applied for 24h, C6 is ciplatin applied 6h and C24 is cisplatin applied for 24h. U87 cells were used.

2015-03-05 | E-GEOD-66493 | biostudies-arrayexpress

Transcription profiling by array of human A2780 ovarianc cancer cells and cisplatin resistant derivate cells treated with cisplatin or liposomal cisplatin

Project description:A2780 ovarian cancer cells and a cisplatin resistant derivate of A2780 cells, obtained from ECACC, UK, No. 93112519 [A2780] and No. 93112517 [A2780 cis] were seeded out in T-75 flasks at a density of 2x106 for A2780sens and 3x106 for A2780cis cells in 15 ml of medium and preincubated overnight. Medium was removed and 15 ml fresh medium (37M-0C) with different concentrations of cisplatin, liposomal cisplatin or empty liposomes were added and incubated for 72 h at 37M-0C in a 5% CO2 incubator. In case of A2780sens cells, 1.72 M-5M cisplatin (IC50 concentration) and in case of A2780cis cells 8.94 M-5M cisplatin (IC50 concentration) were added. Liposomal formulations contained equal cisplatin concentrations. Empty liposomes were added in the same concentration as the liposomal cisplatin, to analyze the impact of liposomal lipids (A2780sens: 0.80M-5mol lipid, A2780cis: 4.15 M-5mol lipid). After incubation, medium was removed and cells were washed thrice with 10 ml PBS. 1 ml RLT-buffer was added and cells lysates were stored at -80M-0C until RNA extraction.

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The anticancer Ruthenium drug BOLD-100 regulates apoptosis of BRAFMT colorectal cancer cells through modulation of the AhR/ROS/ATR signalling axis.

Project description:The understanding of how oncogenes modulate the mechansim of action of compounds relies on interrogating acute and longer transcriptional changes following treatment. We report here the transcriptional profiles of an isogenic cell line model VACO432 (BRAFMT V600E/WT) and VT1 (BRAFWT/-) following 3H and 24H treatment with a novel ruthenium compound BOLD-100. We compare the two cell line models based on their BRAF status to identify transcriptional changes modulted by oncogenic BRAF.

2024-01-10 | GSE252858 | GEO

Homo sapiens

Project description:RDC and cisplatin transcriptomes

| PRJNA277134 | ENA

Microarray analysis of HK-2 cells treated with cisplatin

Project description:Chemotherapeutic use of cisplatin is limited by its severe side effects. In this study, we demonstrated that cisplatin induces cell death in a proximal tubular cell line by suppressing glycolysis- and tricarboxylic acid (TCA)/mitochondria-related genes. HK-2 cells were cultured to confluence in 100mm dishes. Total RNA was extracted (QIAGEN, Valencia, CA, USA), and the concentration in the samples was measured using a Micro UV-Vis fluorescence spectrophotometer (Malcom, Tokyo, JAPAN). Sample of 10ɥg of Total RNA from HK-2 cells were labeled with biotin (3'IVT Labeling Kit, Affymetrix, USA) and hybridized (GeneAtlas Hybridization, Wash, and Stain Kit for 3' IVT Arrays, Affymetrix). The Microarray platform used was Affymetrix HG U219 Array Strip. The arrays were scanned in a GeneAtlas scanner controlled by GeneAtlas Software (Affymetrix, Sta. Clara, USA). Genes were later filtered according to expression fold change (Affymetrix Expression Console software, Affymetrix) Using Affymetrix GeneAtlas System, we determined the gene expression profiles of HK-2 cells treated with cisplatin. Two replicates were made for each timepoints (control, 6h and 24h).

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Differential gene expression for A2780 human ovarian cancer cells when exposed to a new osmium-based anticancer agent

Project description:Platinum-based metallodrugs are the most widely used anticancer agents. Their reduced effectiveness after repeat dosing (resistance) constitutes a major clinical problem. In this experiment we study a potent organo-osmium compound with improved activity over cisplatin and no cross-resistance in platinum-resistant cancers. A2780 cells were exposed to an osmium anticancer compound and to a negative control solution, in triplicate. At 0, 4, 12, 24 and 48 h, cells were collected for each condition, and whole cell RNA was extracted. Samples were purified and QC checked before Truseq library preparation and Illumina sequencing. Each sample had approximately 30 million paired-end reads. Samples were mapped to the human genome using Tophat2 and differential expression analysed using edgeR.

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Project description:Cisplatin, one of the most widely used anticancer drugs, crosslinks DNA and ultimately induces cell death. However, the genomic pattern of cisplatin-DNA adducts remains unknown, due to the lack of a reliable and sensitive genome-wide method. Here we present “cisplatin-seq” to identify genome-wide cisplatin crosslinking sites at base-resolution. Cisplatin-seq reveals that mitochondrial DNA is a preferred target of cisplatin. For nuclear genome, cisplatin-DNA adducts are enriched within promoters and regions harboring transcription termination sites. While the density of GG dinucleotide determines the initial crosslinking of cisplatin, binding of proteins to the genome largely contributes to the accumulative pattern of cisplatin-DNA adducts.

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Proteome Analysis of Non-Small Cell Lung Cancer Cell Line Secretomes and Patient Sputum Reveals Biofluid Biomarker Candidates for Cisplatin Response Prediction

Project description:We profiled the secretomes of six NSCLC cell lines with varying IC50-values for cisplatin, using label-free GeLC-MS/MS-based proteomics. Out of a total dataset of 2618 proteins, 304 proteins showed significant differences in expression levels between cisplatin sensitive and insensitive cell lines. Functional data mining revealed that the secretion of typically extracellular factors was associated with a higher sensitivity towards cisplatin, while cisplatin insensitivity correlated with increased secretion of theoretically intra-cellular proteins, in line with enhanced levels of non-conventional secretion in cisplatin insensitive cell lines. Stringent statistical analysis and quantitative filtering yielded 41 top biomarker candidates, many of which could also be detected in NSCLC patient sputum using label-free GeLC-MS/MS-based proteomics. A published gene expression dataset was used to determine which of our top secretome cisplatin response prediction candidates might have predictive value in terms of overall survival in patients that received platinum-based treatment. This analysis yielded two cisplatin sensitivity (UGGT1 and MATN2) and one cisplatin resistance (MAP4) candidates that may serve as potential biomarkers for cisplatin response prediction in NSCLC patients in the future.

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E-GEOD-66493

Project description:Transcription profiling by array of human U87 cells treated with cytotoxic anticancer drug cisplatin or a ruthenium-based compound for 6 or 24 hours compared to untreated controls

2015-03-16 | E-GEOD-66493 | ExpressionAtlas

Proteome Analysis of Non-Small Cell Lung Cancer Cell Line Secretomes and Patient Sputum Reveals Biofluid Biomarker Candidates for Cisplatin Response Prediction

Project description:We profiled the secretomes of 6 NSCLC cell lines with varying IC50-values for cisplatin, using label-free GeLC-MS/MS-based proteomics. Out of a total dataset of 2618 proteins, 304 proteins showed significant differences in expression levels between cisplatin sensitive and insensitive cell lines. Functional data mining revealed that the secretion of typically extracellular factors was associated with a higher sensitivity towards cisplatin, while cisplatin insensitivity correlated with increased secretion of theoretically intra-cellular proteins. Stringent statistical analysis and quantitative filtering yielded 58 biomarker candidates, 34 of which could be detected in clinical biofluids of lung cancer patients such as sputum using label-free LC-MS/MS-based proteomics. To assess performance of these biofluid biomarker candidates, we correlated protein expression with patient survival using a publically available clinical gene expression data set (GSE14814). We thus identified 3 top candidates with potential predictive value in determining cisplatin response (UGGT1, COL6A1 and MAP4) for future development as non-invasive biomarkers to guide treatment decisions.

2019-02-15 | PXD011315 | Pride

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