Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide transcriptomic profiling of oxaliplatin response

ABSTRACT: Oxaliplatin (OXA) is a member of the family of Pt-containing chemotherapeutic agents that also include cisplatin (CDDP) and carboplatin. OXA is distinguished from these two older drugs by its different spectrum of activity both in preclinical models and in clinical trials. It is the only platinum analogue to have activity in colon cancer, a disease for which this drug has now become a mainstay of therapy. It mainly forms intrastrand adducts between two adjacent guanine residues or guanine and adenine, disrupting DNA replication and transcription. OXA has been reported to be involved in the Nucleotide Excision Repair Pathway (NER), p38 kinase activation, PI3K/AKT pathway and caspase cascade activation through the apoptotic intrinsic pathway. However, not all colon cancer cells show the same sensitivity to OXA. In this study we have compared the changes in RNA expression profiles of colon cancer cell lines with different sensitivity to OXA, determined by IC50.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30011 | GEO | 2011/07/01

SECONDARY ACCESSION(S): PRJNA143685

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Pharmacogenomic Approach for the Identification of Novel Determinants of Resistance to Oxaliplatin in Colon Cancer

2008-02-07 | GSE10405 | GEO

Pharmacogenomic Approach for the Identification of Novel Determinants of Resistance to Oxaliplatin in Colon Cancer

Project description:Oxaliplatin is a member of the family of Pt-containing chemotherapeutic agents that also include cisplatin (CDDP) and carboplatin. OXA is distinguished from these two older drugs by its different spectrum of activity both in preclinical models and in clinical trials. It is the only platinum analogue to have activity in colon cancer, a disease for which this drug has now become a mainstay of therapy. It mainly forms intrastrand adducts between two adjacent guanine residues or guanine and adenine, disrupting DNA replication and transcription. OXA has been reported to be involved in the Nucleotide Excision Repair Pathway (NER), p38 kinase activation, PI3K/AKT pathway and caspases cascade activation through apoptotic intrinsic pathway. However, the downstream molecular events underlying the cytotoxic effects of this chemotherapeutic agent have not been well characterized. This study was developed in order to clarify the multifactoriality of the resistance acquisition process and to identify genes and pathways that could play a role as markers in OXA sensitivity. Keywords: Drug resistance The goal of our experiment was to determine a gene expression profile that discriminates between the OXA-sensitive colorectal cancer cell lines HT29, LoVo, DLD1 and LS513 group and the group of OXA-resistant derived cell lines HTOXAR3, LoVOXAR3, DLDOXAR3 and LSOXAR3 in order to clarify the multifactoriality of the resistance acquisition process and to identify genes and pathways that could play a role as markers in OXA sensitivity. The experimental design used was âRNA-Referenceâ and âDye-Swapâ. Each cell line was analyzed in duplicate, with RNA reference (Stratagene) as reference sample and labeled each biological condition once by Cy3 and once by Cy5. Taking the average of two arrays thus labeled, cancel the dye effect on any particular gene. In total we used 16 slides.

2010-05-26 | E-GEOD-10405 | biostudies-arrayexpress

Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-kB signaling pathway

Project description:Resistance to oxaliplatin (OXA) is a complex process affecting the outcomes of metastatic colorectal cancer (CRC) patients treated with this drug. The NF-kBsignalling pathway deregulation has been proposed as an important mechanism involved in this phenomenon. Here, we show that NF-kBwas hyperactivated in in vitro models of OXA-acquired resistance but was attenuated by the addition of Curcumin, a non-toxic NF-kB inhibitor. The concomitant combination of Curcumin+OXA was more effective and synergistic in cell lines with acquired resistance to OXA, leading to the reversion oftheir resistant phenotype, through the inhibition of the NF-kBsignalling cascade. Transcriptomic profiling revealed the up-regulation of three NF-KB-regulated CXC-chemokines, CXCL8, CXCL1 and CXCL2, in the resistant cells thatwere more efficiently down-regulated after OXA+Curcumin treatment as compared to the sensitive cells. Moreover, CXCL8 and CXCL1 gene silencing made resistant cells more sensitive to OXA through the inhibition of the Akt/NF-kBpathway. High expression of CXCL1 in FFPE samples from explant cultures of CRC patients-derived liver metastaseswas associated with response to OXA+Curcumin.In conclusion, we suggest that combination of OXA+Curcumincould be an effective treatment in CRC patients after progression to OXA-based chemotherapy being CXCL1a good candidate predictive marker to this treatment.

2016-12-07 | GSE76092 | GEO

miR-200b is associated with cisplatin sensitivity in bladder cancer cells

Project description:We aimed to clarify the role of miR-200b in cisplatin (CDDP) sensitivity in bladder cancer (BCa). CDDP resistant T24 cells (T24RC) were transfected with a miR mimic negative control (NC) or a miR-200b mimic, after which cells were treated with or without CDDP. We found that ectopic miR-200b expression re-sensitized the T24RC cells to CDDP. Gene expression microarray analysis revealed that the combination of miR-200b and CDDP affected genes involved in CDDP sensitivity and cytotoxicity.

2018-05-31 | GSE103250 | GEO

Effect of CRISPR/Cas9 activating library on oxaliplatin resistance during oxaliplatin treatment of HepG2 cells [CRISPR cas9]

Project description:To identify key drivers of oxaliplatin, Cas9 protein was overexpressed in HepG2 cells. Next, we treated the cell pool with vehicle or OXA for 3 days to enable positive and negative screening

2023-02-28 | GSE206500 | GEO

High-throughput sequencing analysis of miRNAs expression profiles in the HCT116 colorectal cancer sublines resistant to oxaliplatin (Oxa) or 5-fluorouracil (5-FU).

Project description:In the present study, we investigated miRNA expression changes caused by aquired chemoresistance to 5-FU or Oxa. 40 and 14 miRNAs were detected as differentially expressed in 5-fluouracil- and oxaliplatin-resistant colorectal HCT116 sublines, respectively. Differentially expressed miRNAs determined in the present study could be applied for further development of diagnostic and therapeutic applications for colorectal cancer carcinoma resistant to 5-FU or Oxa.

2019-12-31 | GSE119481 | GEO

Removal of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy.

Project description:The therapeutical efficacy of cisplatin and oxaliplatin depends on the balance between the DNA damage induction and the DNA damage response of tumor cells. Based on clinical evidence, oxaliplatin is administered to cisplatin-unresponsive cancers, but the underlying molecular causes for this tumor specificity are not clear. Hence, stratification of patients based on DNA repair profiling is not sufficiently utilized for treatment selection. Using a combination of genetic, transcriptomic and imaging approaches, we identified factors that promote global genome nucleotide excision repair (GG-NER) of DNA-platinum adducts induced by oxaliplatin, but not by cisplatin. We show that oxaliplatin-DNA lesions are a poor substrate for GG-NER initiating factor XPC and that DDB2 and HMGA2 are required for efficient binding of XPC to oxaliplatin lesions and subsequent GG-NER initiation. Loss of DDB2 and HMGA2 therefore leads to hypersensitivity to oxaliplatin but not to cisplatin. As a result, low DDB2 levels in different colon cancer cells are associated with GG-NER deficiency and oxaliplatin hypersensitivity. Finally, we show that colon cancer patients with low DDB2 levels have a better prognosis after oxaliplatin treatment than patients with high DDB2 expression. We therefore propose that DDB2 is a promising predictive marker of oxaliplatin treatment efficiency in colon cancer.

2023-12-14 | GSE227871 | GEO

Characterization of an Oxaliplatin Sensitivity Predictor in a preclinical Murine Model of Colorectal Cancer

Project description:Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer. Fourty-two human tumors and murine explants of colorectal origin, both primary colon and of various metastatic sites, were processed for total RNA. The samples included RNA from 14 patient samples in addition to RNA from Patient-Derived Colorectal Cancer Explant (PDCCEs) generated from these 14 patient samples. The PDCCEs were processed as fresh frozen whole tumor in addition to formalin-fixed paraffin-embedded (FFPE) tumors.

2012-02-17 | E-GEOD-28691 | biostudies-arrayexpress

Genome-wide single nucleotide resolution of oxaliplatin-DNA adduct repair in drug sensitive and resistant colorectal cancer cell lines

Project description:Platinum-based chemotherapies, including oxaliplatin, are a mainstay in solid tumor treatment and induce cell death by forming intrastrand dinucleotide DNA adducts. Despite their common use, they are highly toxic and approximately half of patients have tumors that are either intrinsically resistant, or that develop resistance. Studies suggest that this resistance is mediated by variations in DNA repair levels or net drug influx. We aimed to better define the roles of nucleotide excision repair and DNA damage formation in platinum resistance by profiling DNA damage levels and repair efficiency in a panel of seven oxaliplatin-sensitive and three oxaliplatin-resistant colorectal cancer cell lines. We assayed repair indirectly as toxicity, and directly measured bulky adduct formation and removal from the genome by slot blot, repair capacity by excision assay, and mapped repair events genome-wide at single nucleotide resolution using XR-Seq. Using this comprehensive approach of combining novel methods and in some cases using proxies for oxaliplatin-DNA damage, we found no significant difference in repair efficiency that could explain the relative sensitivity and resistance of our cell lines. In contrast, the overall levels of oxaliplatin-DNA damage were significantly lower in resistant cells, indicating that decreased formation of damage, rather than increased repair of that damage, is a major determinant of oxaliplatin resistance. Analysis of gene expression using our XR-seq data showed upregulation of membrane transport pathways in resistant cells, and these pathways may contribute to resistance. Additional research is needed to characterize factors mitigating cellular DNA damage formation by platinum compounds.

2020-05-10 | GSE146473 | GEO

Model Establishment of Mice with Oxaliplatin-induced Hepatic Sinusoidal Obstruction Syndrome

Project description:To further explore to mechanisms of oxaliplatin-induced hepatic sinusodial obstruction syndrome, we established a mouse model of OXA-induced HSOS and the difference of mRNA expression level between normal mice and model mice was detected.

2022-09-01 | GSE211859 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data