Effect of EGC treatment on genome instability induced by cisplatin treatment
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ABSTRACT:
PROVIDER: PRJNA450996 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cisplatin treatment causes genome instability by single-strand annealing (SSA) activation in some cancer cells. Therefore, we checked whether EGC, a RAD52 inhibitor, can restrain genome instability induced by cisplatin treatment.
2019-09-09 | GSE113384 | GEO
Project description:Here we report that piroxicam/cisplatin combined treatment exerts an apoptotic effect on mesothelioma cells. Genome-wide transcriptome analyses lead us to identify p21 as the possible apoptosis mediator acting as downstream target of the piroxicam/cisplatin treatment.
2011-11-20 | GSE22445 | GEO
Project description:Here we report that piroxicam/cisplatin combined treatment exerts an apoptotic effect on mesothelioma cells. Genome-wide transcriptome analyses lead us to identify p21 as the possible apoptosis mediator acting as downstream target of the piroxicam/cisplatin treatment. To analyze the potential therapeutic effect of the piroxicam/cisplatin treatment at molecular level, and to identify gene expression pattern modifications following the combined treatment, we performed a transcriptional profiling on HGU133A arrays, using cells treated with piroxicam, cisplatin or with piroxicam and cisplatin, choosing the time exposures in which apoptosis induction was absent or evident (8 and 24 hours). Biological duplicates or triplicates were generated for each prototypic situation and data were analyzed using the oneChannelGUI Bioconductor package (Sanges et al., 2007), comparing untreated cells with cells treated in single or combined treatment. After quality controls, the complexity of the data set was reduced removing the non-significant probe sets, resulting in a total of 4,247 out of the 22,283 probe sets present in the microarray. To assess differential expression, linked to piroxicam, cisplatin- and the combined treatment we used an empirical Bayes method together with a false discovery rate (FDR) correction of the P-value. Specifically genes were selected using a corrected p-value M-bM-^IM-$0.05 and |log2(fc)| M-bM-^IM-%1. We detect a total of 536 differentially expressed genes.
2011-11-20 | E-GEOD-22445 | biostudies-arrayexpress
Project description:We compared the gene expression of A549 cells following 24 and 48 hours of treatment with a no-observed-effect level dose of cisplatin. The objective of the study is to identify genes that are differentially expressed in response to sub-lethal doses of cisplatin. This study helps identify not only treatment responses but also changes in gene expression that may confer cytoprotective mechanisms that allow these cells to survive treatment and to develop treatment resistance.
2016-03-03 | GSE73302 | GEO
Project description:OGE sensitizes HCC to cisplatin treatment through inhibition of BRCA1
2024-10-11 | PXD046048 | JPOST Repository
Project description:Profiling of proteolytic events mouse kidneys during cisplatin-induced kidney damage. Kidneys from vehicle-treated mice are compared to cisplatin-treated mice and cisplatin treatment in animals preconditioned by hypoxia or calory restriction regimes.
2018-10-29 | PXD007186 | Pride
Project description:Proteins immunoprecipitated by Neil3 in 4 conditions
- before Cisplatin treatment with inhibition of proteasome
- before Cisplatin treatment without inhibition of proteasome
- after 3h of Cisplatin treatment with inhibition of proteasome
- after 3h of Cisplatin treatment without inhibition of proteasome
2022-06-05 | MSV000089607 | MassIVE
Project description:Clinical use of a major cancer chemotherapeutic agent, cisplatin, is restricted to dose-limiting renal toxicity. A transcriptomic approach enabled us to extract putative molecules including Pleckstrin homology-like domain, family A, member-3 (Phlda3) contributing to the renal injury. This study investigated the expression of Phlda3 and its regulatory role in tubular injury induced by cisplatin in vivo and in vitro. Real-time PCR and immunoblot assays confirmed that Phlda3 was highly up-regulated in the kidney of mice after a single dose of cisplatin treatment, which preceded increases in the blood urea nitrogen or serum creatinine levels. Particularly, the level of Phlda3 transcript was substantially increased at an early time than that of kidney injury molecule-1, and remained elevated. The effect of cisplatin or acetaminophen treatment on Phlda3 expression in the liver was minimal. Consistently, treatment of NRK52E, a renal tubular cell line, with cisplatin caused increases in Phlda3 mRNA and protein. Knockdown of Phlda3 reversed the decrease in cell viability by cisplatin, supporting the role of Phlda3 in cell death. Akt phosphorylation initially increased after cisplatin treatment, but decreased thereafter. Cisplatin treatment elicited p53 accumulation via mdm2 repression, inducing its target genes, p21 and cyclin G1. Phlda3 deficiency attenuated a decrease in Akt phosphorylation by cisplatin, and prevented p53 accumulation, supporting the role of Phlda3 for p53-mediated tubular cell death. Other renal toxicants, cyclosporine A and CdCl2, also enhanced Phlda3-dependent cell death. Overall, nephrotoxicants including cisplatin induce Phlda3, which leads to p53-mediated tubular cell death via mdm2 repression caused by Akt inhibition. Since the datasets reported on the effect of cisplatin on the kidney were obtained from animals treated with multiple and relatively high doses of cisplatin, we did our cDNA array analyses day 3 after a single dose of cisplatin administration to mice (i.p., 15 mg/kg) and compared the profiles of kidney microarray data. The transcriptomic approach enabled us to find the putative genes encoding molecules contributing to renal injury. Among those genes represented on the microarray, 33 genes were found to be differentially expressed by cisplatin treatment when a 2-fold change cutoff was used. The regulation of exemplary mRNAs identified in the array analysis was confirmed by qRT-PCR. C57BL/6 mice (9 weeks old) were intraperitoneally injected with a single dose of cisplatin (15 mg/kg body weight) or vehicle (saline). The cDNA microarray experiments were done for the kidney of mice 3 days after treatment. Each group contained 3 males.
2012-06-29 | E-GEOD-35257 | biostudies-arrayexpress
Project description:Clinical use of a major cancer chemotherapeutic agent, cisplatin, is restricted to dose-limiting renal toxicity. A transcriptomic approach enabled us to extract putative molecules including Pleckstrin homology-like domain, family A, member-3 (Phlda3) contributing to the renal injury. This study investigated the expression of Phlda3 and its regulatory role in tubular injury induced by cisplatin in vivo and in vitro. Real-time PCR and immunoblot assays confirmed that Phlda3 was highly up-regulated in the kidney of mice after a single dose of cisplatin treatment, which preceded increases in the blood urea nitrogen or serum creatinine levels. Particularly, the level of Phlda3 transcript was substantially increased at an early time than that of kidney injury molecule-1, and remained elevated. The effect of cisplatin or acetaminophen treatment on Phlda3 expression in the liver was minimal. Consistently, treatment of NRK52E, a renal tubular cell line, with cisplatin caused increases in Phlda3 mRNA and protein. Knockdown of Phlda3 reversed the decrease in cell viability by cisplatin, supporting the role of Phlda3 in cell death. Akt phosphorylation initially increased after cisplatin treatment, but decreased thereafter. Cisplatin treatment elicited p53 accumulation via mdm2 repression, inducing its target genes, p21 and cyclin G1. Phlda3 deficiency attenuated a decrease in Akt phosphorylation by cisplatin, and prevented p53 accumulation, supporting the role of Phlda3 for p53-mediated tubular cell death. Other renal toxicants, cyclosporine A and CdCl2, also enhanced Phlda3-dependent cell death. Overall, nephrotoxicants including cisplatin induce Phlda3, which leads to p53-mediated tubular cell death via mdm2 repression caused by Akt inhibition. Since the datasets reported on the effect of cisplatin on the kidney were obtained from animals treated with multiple and relatively high doses of cisplatin, we did our cDNA array analyses day 3 after a single dose of cisplatin administration to mice (i.p., 15 mg/kg) and compared the profiles of kidney microarray data. The transcriptomic approach enabled us to find the putative genes encoding molecules contributing to renal injury. Among those genes represented on the microarray, 33 genes were found to be differentially expressed by cisplatin treatment when a 2-fold change cutoff was used. The regulation of exemplary mRNAs identified in the array analysis was confirmed by qRT-PCR.
2012-06-30 | GSE35257 | GEO
Project description:Genome instability is a hallmark of most human cancers and is exacerbated following cellular exposure to exogenous/endogenous chemicals that can promote replication stress, activation of low-fidelity DNA repair pathways and DNA damage. However, the effects drugs/chemicals have in promoting nuclear genome instability and mutagenesis in normal cells as early biomarkers of cancer risk remains unexplored. Here, we present the Drug-induced Genome Instability Test (DiGIT), a systems level approach that identifies the genome instability risk of drugs/chemicals by measuring activated mutagenic DNA repair and resulting structural rearrangements at the gene level in mammalian genomes. We found drugs previously classified as being non-genotoxic by classic genotoxicity assays, induced genome instability in proliferative mammalian cells, including normal human mammary epithelial fibroblasts (HMECs), bone marrow, duodenum and CD19+ B cells. 53BP1 (a key mediator of mutagenic DNA repair) foci were increased in a dose-dependent manner in HMECs following treatment with compounds known to induce genomic instability (low-dose aphidicolin, duvelisib, idelalisib and hydralazine) and compounds suspected of causing genomic instability based on carcinogenicity outcomes (amiodarone). Non-genotoxic compounds (mannitol, alosteron, diclofenac and zonisamide) not associated with cancer risk did not induce effects on the recruitment of 53BP1. To evaluate genomic instability in vivo, Sprague Dawley rats were treated with cyclophosphamide, a known anti-cancer therapeutic. Short-term treatment resulted in drug-induced somatic translocations and deletions at genes associated with cancer risk in proliferating normal cells from the bone marrow and duodenum. Collectively, DiGIT comprising cell- and whole-genome sequencing-based approaches can aid in de-risking genotoxicity and/or cancer liabilities of therapeutic and complement the current genetic toxicology battery.
2019-09-18 | PRJEB34208 | EVA