Comparison of the transcriptome of KP4 controls or resistant to Folfirinox after 96h of treatment with Vehicule or Folfirinox
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE276264 | GEO | 2025/10/31
REPOSITORIES: GEO
Similar Datasets
Project description:Comparison of the transcriptome of KP4 controls or resistant to Folfirinox after 96h of treatment with Vehicule or Folfirinox
| PRJNA1156179 | ENA
Project description:Pancreatic ductal adenocarcinoma is an extreme lethal cancer with a poor treatment response to all the current chemotherapies. We generated a library of PDAC organoid lines from resected tumors, five from treatment-naive patients and five from patients who received neoadjuvant FOLFIRINOX (eight cycles). We assessed weather residual cancer cells in the tumor lesions of the patients treated with neoadjuvant FOLFIRINOX developed resistance to the treatment. Further we perfromed transcriptome analysis to investigate: 1- weather organoids recapitualting their corresponding tumor tissue 2- To investigate any modifications in the expression of the genes inflicted by FOLFIRINOX treatment.
2021-03-23 | GSE169321 | GEO
Project description:The pancreatic cancer tumor microenvironment is dominated primarily by cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs). The interecellular dialogue between CAFs and TAMs and the resulting impact on chemoresistance, specifically to Folfirinox, remains poorly understood. In this study, we sought to understand the impact of primary PDAC CAFs on macrophage reprogramming in a folfirinox-dependent manner and performed various cellular assays (viability, immunophenotyping, phagocytosis, secretory profile analysis) and transcriptomic analysis.
2024-01-10 | GSE226448 | GEO
Project description:Purpose: FOLFIRINOX has become standard therapy for patients with advanced stages pancreatic ductal adenocarcinoma (PDAC). However, only a subset of patients benefits from this therapy and biomarkers to guide clinical decisions are lacking. This study aimed to discover circulating microRNAs (miRNAs) as potential stratifying and monitoring biomarkers in patients with PDAC treated with FOLFIRINOX and to investigate their functional roles. Methods: A microarray was used in plasma samples from a first cohort of 11 patients selected based on their long versus short progression-free survival (PFS) after FOLFIRINOX. Nine miRNAs were validated using RT-qPCR in an independent cohort (n=43). The best discriminative miRNA was evaluated in tumor tissue samples and associated with clinicopathological features by Cox regression analyses. In vitro studies explored its role on cell proliferation, key downstream targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. Results: MiR-181a-5p was validated as significantly down-regulated in non-progressive compared to progressive patients after FOLFIRINOX. In multivariate analysis, this down-regulation correlated with improved PFS and overall survival, especially combined with CA19.9 decline (log-rank p<0.001, HR=0.153, 95% C.I. 0.067–0.347 and log-rank p=0.033, HR=0.201, 95% C.I. 0.070–0.576, respectively). Overexpression of miR-181a-5p increased proliferation of PDAC cells and inversely correlated with expression of ATM. Furthermore, inhibition of miR-181a-5p coupled with oxaliplatin exposure increased DNA damage and decreased cell viability. Conclusion: Our findings endorse miR-181a-5p as a biomarker for monitoring response to FOLFIRINOX and prognostication. MiR-181a-5p inhibition can potentially enhance sensitivity to oxaliplatin by amplifying the DNA damage response and cell death.
2019-01-01 | GSE109647 | GEO
Project description:Folfirinox-dependent reprogramming of macrophages by primary pancreatic cancer CAFs
| PRJNA940346 | ENA
Project description:Aberrant activation of the ERK signaling pathway triggers a protective anticancer response characterized by stable growth arrest and activation of tumor suppressors called cellular senescence. Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that activate the ERK pathway. Pancreatic intraepithelial neoplasia of low degree display high levels of phospho-ERK consistent with senescence acting as a barrier for malignant transformation. However, advanced lesions downregulate phospho-ERK levels circumventing the senescence barrier. Restoring ERK hyperactivation in PDAC using an activated allele of the kinase RAF, leads to ERK-dependent growth arrest with senescence biomarkers. Phosphoproteomics analysis of ERK-dependent senescence in PDAC revealed a decrease in several nucleolar phosphoproteins suggesting that high levels of ERK lead to senescence via nucleolar stress. Consistent with this explanation, ERK-dependent senescent cells displayed intranucleolar foci containing RNA polymerase I. Combining ribosome biogenesis inhibitors with ERK hyperactivation reinforced the senescence response of PDAC cells. The drug cocktail FOLFIRINOX, currently the best treatment for PDAC, also triggered ERK hyperactivation and nucleolar stress characterized by nucleolar foci, solid amyloid aggregates and a decrease in 5.8S and 28S rRNAs. We thus suggest that drugs targeting ribosome biogenesis can improve the senescence anticancer response in pancreatic cancer.
2024-06-10 | PXD032257 | Pride
Project description:The purpose of this study was to determine whether leukemia cells can escape from drug-induced senescence; determine the phenotype of the senescent, and escaped cells, and whether senescent leukemia cells can be specifically eliminated prior to their escape. Methods: DA3/EPOR cells were treated with 200ng/ml doxorubicin for 24 hr. Cells were confirmed to enter and exit senescence based on, proliferating and SA-gal staining. mRNA transcriptional profiles of naïve proliferating, senescent, and escaped DA3/EPOR murine leukemia cells were generated by deep sequencing, in biological triplicate, using Illumina NovaSeq 6000 at a depth of 25 million pair-ended reads that were 100 bp in length. The sequence reads that passed quality filters, the first 13 nucleotides were removed from each read. Alignment to the MM10 indexed genome was done using HiSAT2. Read counts were genereated using HTSEQ, which were then used for differential expression. Differential expression was performed on Rstudio using EdgeR. qRT–PCR was performed for validation. Results: We report that DA3/EPOR leukemia cells enter and escape a doxorubicin (Dox)-induced senescence, dependent on erythropoietin (EPO). EPO is necessary for DA3/EPOR cells to survive the senescent state. Senescent DA3/EPOR cells undergo a transcriptional reprogramming, which is largely reversible upon escape. Escaped DA3/EPOR cells mirror naïve, never senescent DA3/EPOR cell, and respond similarly to Dox. Senescent DA3/EPOR cells mimic a diapause-like state, and undergo metabolic changes. Senescent DA3/EPOR cells and some drug-induced senescent human acute myeloid leukemia (AML) cells can be eliminated with chloroquine, a lysosome inhibitor. Lastly, we show with The Cancer Genome Atlas publicly available data that the senescent signature is associated with decreased survival in AML and multiple other cancers. Conclusion: Leukemia cells persist through drug treatment by entering a reversible senescent state that mimics diapause. Senescent leukemia cells depend on lysosome activity to persist, and treatment with chloroquine, a lysosome inhibitor, can eliminate senescent leukemia cells.
2023-08-09 | GSE186200 | GEO
Project description:The engulfment of live cells by other live cells, also known as cannibalism, can result in the death of engulfed cells. Recently, we show that autophagy favors the accumulation of E-cadherins on the surface of cannibal cells, thereby enhancing their capacity to engulf and eliminate live cells. Importantly, cannibal cells exhibited genomic instability and activated a senescence program that we termed “entescence”. In breast cancer patients, neoadjuvant chemotherapy response was associated with the induction of entescence. Conversely, the suppression of entescence by dominant negative mutants of p53 favored the proliferation of aneuploid cannibal cells and predicts cancer progression. Our data indicate that entescence is a non-cell-autonomous program of senescence that compromises cancer development. In this context, we analyzed using CGH array the genomic features of cells that escape from entescence. The first goal of this experiment is to confirm the aneuploidy of cannibal cells and the second aim is to identify genomic alterations associated to cellular cannibalism. To isolate and purify cellular clones obtained from cannibal cells that escaped entescence, homotypic cultures of HCT116 p53R248W/- cells that have been half labeled with 5-chloromethylfluorescein diacetate (CMFDA) and half labeled with 5-(and-6)-(((4-chloromethyl)benzoyl)amino) tetramethylrhodamine (CMTMR) were irradiated (or not) with 4 Gy, cultured for 24 hours and purified using the BD Influx™cell sorter (Becton Dickinson). Single cells and cannibal cells were seeded in microtiter 96-well plates (with one single structure per well). Sorted populations (single cell and cannibal cell) were then validated by fluorescence microscopy. Thus, 3 control clones (samples 1-3), 16 clones that ‘escaped’ to spontaneous entescence (samples 4-19), 5 irradiated clones (samples 20-24) and 16 clones that ‘escaped’ to IR-mediated entescence (samples 25-40) were generated and analyzed using CGH array. Entescence is a novel senescence program initiated by cellular cannibalism that prevents genomic instability and tumor progression.
2019-01-01 | E-MTAB-6802 | biostudies-arrayexpress
Project description:Patient-derived organoids after neoadjuvant FOLFIRINOX predict therapy resistance in pancreatic ductal adenocarcinoma
| PRJNA716264 | ENA
Project description:Immune checkpoint bloackade (ICB)-based or natural cancer immune responses largely eliminate tumours. Yet, they require additional mechanisms to arrest those cancer cells that are not rejected. Cytokine-induced senescence (CIS) can stably arrest cancer cells, suggesting that interferon-dependent induction of senescence-inducing cell cycle regulators is needed to control those cancer cells that escape from killing. Here we report in two different cancers sensitive to T cell-mediated rejection, we show that deletion of the senescence-inducing cell cycle regulators p16Ink4a/p19Arf (Cdkn2a) or p21Cip1 (Cdkn1a) in the tumour cells abrogated both, the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB have losses of senescence-inducing genes and amplifications of senescence inhibitors. Metastatic cells also resist CIS. Such genetic and functional alterations are infrequent in metastatic melanomas regressing during ICB. Thus, activation of tumour-intrinsic, senescence-inducing cell cycle regulators is required to stably arrest those cancer cells that escape from eradication.
| EGAS00001004151 | EGA