Gemcitabine Drug resistance
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE3344 | GEO | 2007/08/30
SECONDARY ACCESSION(S): PRJNA93257
REPOSITORIES: GEO
Similar Datasets
Project description:KBwt is a KB parental cell; KBHURs is a hydroxyurea resistant KB clone; KBGem is a gemcitabine resistant KB clone Experiment Overall Design: We extracted the RNA from KBwt, KBHURs and KBGem clones, and conducted hybridization with HU95 v2 Chip.
2008-06-12 | E-GEOD-3344 | biostudies-arrayexpress
Project description:To investigate the transcriptional alterations that occur during the development of gemcitabine resistance in pancreatic cancer cells, we established gemcitabine-resistant SW1990 cells, referred to as SW1990R. We then employed RNA-seq to explore the transcriptome changes between the gemcitabine-resistant cells and their parental counterparts.
2024-09-23 | GSE247165 | GEO
Project description:To investigate the transcriptional alterations that occur during the development of gemcitabine resistance in pancreatic cancer cells, we established gemcitabine-resistant AsPC1 cells, referred to as AsPC1R. We then employed RNA-seq to explore the transcriptome changes between the gemcitabine-resistant cells and their parental counterparts.
2024-09-23 | GSE247163 | GEO
Project description:Purpose: Chemotherapy is pivotal in the multimodal treatment of pancreatic cancer patients. In recent years, technical advances have developed experimental methods that unveiled a high degree of inter- and intratumoral heterogeneity in pancreatic cancer. We hypothesized that intratumoral heterogeneity (ITH) impacts response to gemcitabine treatment and demands specific targeting of resistant subclones. Experimental Design: We addressed the effect of ITH on response to gemcitabine treatment using single cell-derived cell lines (SCDCL) from the classical-like cell line BxPC3 and the basal-like cell line Panc-1 which were analyzed by mRNA-seq and mass spectrometry. Results: Individual SCDCLs of the parental tumor cell populations of BxPC3 and Panc-1 showed considerable heterogeneity in response to gemcitabine. Unsupervised principal component analysis (PCA) including the 1,000 most variably expressed genes showed a clustering of the SCDCLs according to their respective sensitivity to gemcitabine treatment for BxPC3, while this clustering was less clear for Panc-1. In BxPC3 SCDCLs, enriched signaling pathways EMT, TNF signaling via NfKB, and IL2STAT5 signaling correlated with more resistant behavior to gemcitabine. In Panc-1 SCDCLs MYC targets V1 and V2 as well as E2F targets were associated with stronger resistance to gemcitabine. Feature extraction of proteomes again identified less proteins whose expression was associated with the response of individual SCDCLs in Panc-1 compared to BxPC3. Based on molecular profiles, we could show that the gemcitabine-resistant SCDCLs of both BxPC3 and Panc-1 are more sensitive to the BET inhibitor JQ1 compared to the respective gemcitabine-sensitive SCDCLs. Conclusions: Our model system of SCDCLs identified gemcitabine-resistant subclones within a parental tumor population and provides evidence for the critical role of ITH for treatment response in pancreatic cancer. Through molecular profiling, we identified specific signaling pathways and protein signatures that might help to explain the differential response to treatment among clones. We exploited these molecular differences for an improved and more targeted therapy of resistant subclones of a heterogeneous tumor.
2023-09-19 | PXD042256 | Pride
Project description:To elucidate the DNA methylation alterations during the development of gemcitabine resistance in pancreatic cancer cells, we utilized both the parental SW1990 cells and their gemcitabine-resistant derivatives, SW1990R cells, to examine DNA methylation patterns. We employed reduced representation bisulfite sequencing (RRBS) assays to uncover the specific CpG methylation profiles.
2024-09-23 | GSE247167 | GEO
Project description:To elucidate the epigenetic events, particularly the dynamic alterations in chromatin accessibility during the development of gemcitabine resistance in pancreatic cancer cells, both the parental SW1990 cells and the gemcitabine-resistant counterparts, SW1990R cells, were employed for mapping of the chromatin accessibility landscape. The ATAC-seq technology was used for precise detection of chromatin accessibility.
2024-09-23 | GSE251994 | GEO
Project description:We examined the microarray-based expression profiles of the cells to identify genes associated with gemcitabine resistance Using a set of parental and gemcitabine resistant cell line, MKN28 and RMKN28, we studied mRNA transcription levels by microarray analysis to see if there are any of the key molecules for development of acquisition of the GEM resistance.
2015-05-01 | E-GEOD-58118 | biostudies-arrayexpress
Project description:Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but unfortunately the effectiveness of any regimen is limited, and recurrence rates are high. Here, we established and characterized two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR) to investigate the molecular mechanisms associated with acquired resistance in vitro. The transcriptome profiling of parental and gemcitabine resistant cells revealed differential expression of multiple protein-coding genes and enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, quantitative phosphotyrosine proteomic analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as Abl, PDGFRA, EphB2 and members of the Src-family that could be novel therapeutic targets against drug resistance in GBC. In line with this, NOZ GemR cells showed increased sensitivity toward the multikinase inhibitor dasatinib compared with parental cells. In conclusion, our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant gallbladder cancer cells, which greatly expands our understanding of the underlying mechanisms of acquired drug-resistance in GBC. Moreover, this new gemcitabine resistant GBC models could be exploited either to study alternative mechanisms of resistance or to explore new therapies for chemotherapy-refractory GBC.
2023-05-03 | PXD036348 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a poor prognosis, and resistance to gemcitabine, a frontline chemotherapeutic agent, poses a significant challenge to effective treatment. Unraveling the molecular underpinnings of gemcitabine resistance is essential for devising novel therapeutic strategies. Here we derived gemcitabine-resistant and parental pancreatic cancer cell lines from KPC mouse models of PDAC. Employing a multi-omics approach, we integrated RNA-seq, ATAC-seq, and ChIP-seq analyses to characterize the genome-wide alterations in gene transcription, chromatin accessibility, histone modifications, and transcription factor (TF) binding in resistant cells. High-throughput chromatin conformation capture (Hi-C) was used to explore 3D chromatin remodeling. Our analyses identified differentially expressed genes (DEGs) critical for gemcitabine metabolism and resistance, notably Rrm1 and Cdadc1. We observed the upregulation of NF-kB, p53, and MAPK pathways, and the downregulation of mTORC1, MYC targets, and reactive oxygen species pathways. Differentially accessible regions (DARs) showed a significant positive correlation with the expression patterns of DEGs and histone mark H3K27 acetylation. Motif enrichment analyses revealed that TFs from the AP-1, Fox, and Hox families were significantly enriched at DARs, underscoring Foxa1 as a pivotal regulator of resistance-associated genes. We discovered that 3D chromatin reorganization, particularly the enhancement of enhancer-promoter interactions involving super-enhancer (SE) reprogramming mediated by Foxa1 and Ctcf/Smc3, drives the expression of critical resistance genes. Targeting Foxa1 or disrupting SE-associated transcription using JQ1, a bromodomain inhibitor, effectively inhibited resistant cell proliferation and enhanced gemcitabine sensitivity. In summary, this study elucidates the role of TF-mediated chromatin remodeling in gemcitabine resistance and suggests that targeting super-enhancers could be a promising therapeutic strategy to overcome resistance in PDAC, potentially revolutionizing drug therapy for this disease.
2024-11-30 | GSE278100 | GEO
Project description:Resistance of Calu3 NSCLC cells to the cytotoxic nucleoside analog gemcitabine (2',2'-difluorodeoxycytidine) can be prevented as well as reversed by the rexinoid X receptor selective agonist bexarotene. This study was designed to investigate the changes in gene expression associated with gemcitabine resistance and its reversal by bexarotene. In addition to the parental Calu3 cells and the 10 cycles of treatment of the gemcitabine resistant Calu3 cells with vehicle or bexarotene, analogous treatment paradigms with gemcitabine alone as well as the combination of both compounds have been included as controls. (However, it has to be noted that in the combination treatment, cells that were re-sensitized by bexarotene have largely been removed from the culture before harvest due to the cytotoxic activity of gemcitabine.) Keywords: cell type comparison, compound effects
2007-01-31 | GSE6914 | GEO