Transcriptional profiling of FOLFIRI treated VAKPS Tumoroids
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE237837 | GEO | 2024/10/17
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptional profiling of FOLFIRI treated VAKPS Tumoroids
| PRJNA996913 | ENA
Project description:The aim of the experiment is to elucidate changes in tumor heterogeneity upon chemotherapy treatment. The experiment includes non-treated samples, samples right after chemotherapy treatment (FOLFIRI) and organoids recovered from FOLFIRI. It was conducted in two different genetic backgrounds, AKP (Apc KO, KrasG12D and P53 KO) and APS (Apc KO, P53 and Smad4KO). In addition to that, the organoids carry an inducible Cre-ERT2 knock-in allele in the mex3a locus. Upon 4-OH-Tamoxifen induction, Mex3a cells will recombine the tracing allele stop-TdTomato, enabling the tracing of this subpopulation. To understand the fate of the traced cells, samples right after chemotherapy and in the recovery setting were sorted based on their tomato expression. This enables a single cell tracing experiment.
2022-05-13 | E-MTAB-11145 | biostudies-arrayexpress
Project description:In this study, we sought to understand the effects of a rare PAX3-WWTR1 fusion in a tumoroid line derived from an embryonal rhabdomyosarcoma sample through fusion knockdown.
2025-02-28 | E-MTAB-13715 | biostudies-arrayexpress
Project description:3D tumoroids have revolutionized in vitro/ex vivo cancer biology by recapitulating the complex diversity of tumors. While tumoroid provide new insights into cancer development and treatment response, several limitations remain. The tumor microenvironment, especially the immune system, strongly influences tumor development. Absence of immune cells in tumoroids may yield flawed conclusions. Macrophages, key players in tumor progression, pose integration challenges into tumoroid. In this study, we established three optimized and standardized methods for co-culturing human macrophages with breast cancer tumoroids: a semi-liquid model and two matrix-embedded models tailored for specific applications. Optimizing culture conditions, we tracked interactions and macrophage infiltration using flow cytometry and light sheet microscopy. Macrophages not only influenced tumoroid molecular profiles but also chemotherapy response. This underscores the importance of increasing the complexity of current 3D models to more accurately reflect in vivo conditions. The three models have different application and can be used in various ways.
2024-05-31 | PXD052016 | Pride
Project description:Sadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: “A colorectal cancer classification system that associates cellular phenotype and responses to therapy”. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response.
2014-09-10 | GSE54483 | GEO
Project description:Purpose of the study: the goal of this study was to use Next-generation sequencing to investigate the gene expression profile of skeletal muscle from mice exposed to chemotherapy (Folfiri) for up to 5 weeks. Methods: Standard methods were used for polyA mRNA-seq library construction, EZBead preparation and Next-Gen sequencing, based on Life Technologies SOLiD5000xl system. Briefly, one microgram total RNA per sample was applied for library preparation. PolyA mRNA was first captured using the standard protocol of Dynabeads® mRNA DIRECT™ Micro Kit (Life Technologies, #61021). Following the enrichment of polyA mRNA, the cDNA library was prepared and barcoded per sample using the standard protocol of SOLiD Total RNA-seq Kit (Life Technologies, #4445374). Each barcoded library was quantified by Bioanalyzer High Sensitivity DNA chip (Agilent, #5067-4626) and pooled in equal molarity. EZBead preparation, bead library amplification, and bead enrichment were then conducted using Life Technologies EZ Bead™ E80 System (Life technologies, #4453095). Approximately four hundred forty million library-enriched beads per lane were deposited onto a SOLiD5500xl FlowChip (6 lanes/chip). Finally sequencing by ligation was carried out using standard single-read, 5’-3’ strand-specific sequencing procedure (75b-read) on SOLiD5500xl Sequencer. The resulting 75 bp solid reads were mapped to Mus musculus mm9 reference genome using in-house mapping pipelines that utilizes bfast-0.7.0a [67]. In brief, using our RNA-seq pipeline, low quality reads and reads mapped to rRNA/tRNAs were first discarded. The remaining reads were mapped to reference genome mm9 and a splice-junction library, respectively; the genomic and splice-junction library mapping were merged at the end. The gene based expression levels were calculated using bamutils from NGSUtils based on the RefSeq gene annotation of mm9. Differential expression of genes across different treatments was determined with edgeR Results: Gene expression profiling, performed by means of RNA-Sequencing analysis, identified a limited number of genes that were significantly modulated (False Discovery Rate < 0.05) following Folfiri administration. Interestingly, the pathway analysis showed marked down-regulation of the regulators of mitochondrial metabolism Ucp1, Cidea1 and Acot2, as well as the marker of muscle cell proliferation/pluripotency Fhl3 . Further, we found increased expression of regulators of lipid metabolism and transport (such as Fabp1, Apoa1, Apob, Apoa2, Alb, Prkcz and Scd2) as well as acute phase response proteins (such as Alb, Fga and Fgb), and members of the PPAR signaling and markers of the Energy metabolism (such as Dnah5) were reported . Conclusions: Our study represents the first gene expression profiling of muscle from mice exposed to chemotherapy. The findings from our study identified several signaling pathways that were modulated following chemotherapy administration. These results will contribute to identify new modulators of muscle wasting associated with Folfiri administration, that might also represent putative new targets of interventions.
2016-05-18 | GSE80473 | GEO
Project description:Purpose of the study: the goal of this study was to use Next-generation sequencing to investigate the gene expression profile of skeletal muscle from mice exposed to chemotherapy (Folfiri) for up to 5 weeks. Methods: Standard methods were used for polyA mRNA-seq library construction, EZBead preparation and Next-Gen sequencing, based on Life Technologies SOLiD5000xl system. Briefly, one microgram total RNA per sample was applied for library preparation. PolyA mRNA was first captured using the standard protocol of Dynabeads® mRNA DIRECT⢠Micro Kit (Life Technologies, #61021). Following the enrichment of polyA mRNA, the cDNA library was prepared and barcoded per sample using the standard protocol of SOLiD Total RNA-seq Kit (Life Technologies, #4445374). Each barcoded library was quantified by Bioanalyzer High Sensitivity DNA chip (Agilent, #5067-4626) and pooled in equal molarity. EZBead preparation, bead library amplification, and bead enrichment were then conducted using Life Technologies EZ Bead⢠E80 System (Life technologies, #4453095). Approximately four hundred forty million library-enriched beads per lane were deposited onto a SOLiD5500xl FlowChip (6 lanes/chip). Finally sequencing by ligation was carried out using standard single-read, 5â-3â strand-specific sequencing procedure (75b-read) on SOLiD5500xl Sequencer. The resulting 75 bp solid reads were mapped to Mus musculus mm9 reference genome using in-house mapping pipelines that utilizes bfast-0.7.0a [67]. In brief, using our RNA-seq pipeline, low quality reads and reads mapped to rRNA/tRNAs were first discarded. The remaining reads were mapped to reference genome mm9 and a splice-junction library, respectively; the genomic and splice-junction library mapping were merged at the end. The gene based expression levels were calculated using bamutils from NGSUtils based on the RefSeq gene annotation of mm9. Differential expression of genes across different treatments was determined with edgeR Results: Gene expression profiling, performed by means of RNA-Sequencing analysis, identified a limited number of genes that were significantly modulated (False Discovery Rate < 0.05) following Folfiri administration. Interestingly, the pathway analysis showed marked down-regulation of the regulators of mitochondrial metabolism Ucp1, Cidea1 and Acot2, as well as the marker of muscle cell proliferation/pluripotency Fhl3 . Further, we found increased expression of regulators of lipid metabolism and transport (such as Fabp1, Apoa1, Apob, Apoa2, Alb, Prkcz and Scd2) as well as acute phase response proteins (such as Alb, Fga and Fgb), and members of the PPAR signaling and markers of the Energy metabolism (such as Dnah5) were reported . Conclusions: Our study represents the first gene expression profiling of muscle from mice exposed to chemotherapy. The findings from our study identified several signaling pathways that were modulated following chemotherapy administration. These results will contribute to identify new modulators of muscle wasting associated with Folfiri administration, that might also represent putative new targets of interventions. Next-generation sequencing of RNA extracted from quadriceps muscle of CD2F1 male mice exposed to either Folfiri (a combination of 5-FU, Leucovorin and CPT-11) or vehicle alone (n=4) for up to 5 weeks.
2016-05-18 | E-GEOD-80473 | biostudies-arrayexpress
Project description:This experiment is aimed at studying the effect of two different chemotherapies (FOLFOX and FOLFIRI) on colorectal cancer cell lines (HCT116 and HT29) at different time points. Two early time points (8h and 16h) are used to evaluate the acute response, while a late time point (two weeks, LT) is used to evaluate the long-term effect. After two week exposure, cells are grown without treatments for additional two weeks, to evaluate the transcriptomic of cells which survived the chemotherapy. A pool of the same cells has been independently profiled by scGET-seq.
2023-09-01 | E-MTAB-12949 | biostudies-arrayexpress
Project description:This experiment is aimed at studying the effect of two different chemotherapies (FOLFOX and FOLFIRI) on gene expression of HCT116 colorectal cancer cell line at different time points. Two early time points (8h and 16h) are used to evaluate the acute response, while a late time point (two weeks, LT) is used to evaluate the long-term effect. After two week exposure, cells are grown without treatments for additional two weeks, to evaluate the transcriptomic of cells which survived the chemotherapy. For all time points, untreated cells (CTRL) are also collected.
2023-09-01 | E-MTAB-12950 | biostudies-arrayexpress
Project description:This experiment is aimed at studying the effect of two different chemotherapies (FOLFOX and FOLFIRI) on chromatin accessibility of HCT116 colorectal cancer cell line at different time points. Two early time points (8h and 16h) are used to evaluate the acute response, while a late time point (two weeks, LT) is used to evaluate the long-term effect. After two week exposure, cells are grown without treatments for additional two weeks, to evaluate the chromatin landscapes of cells which survived the chemotherapy. A pool of the same cells has been independently profiled by scRNA-seq.
2023-09-01 | E-MTAB-12952 | biostudies-arrayexpress