Immunotherapy for Third Line Metastatic Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2343551 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:MSI analysis using blood-derived MSI markers
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Project description:Summary To address the issue of retention of somatic cell memory in iPSCs we compared gene expressions of genetically matched human iPSCs derived from fibroblasts and blood. We were using the all-in-one type footprint free SeVdp-iPS system, for generation of uniform iPSC lines Our results show that iPSC lines derived from the same donor are highly similar to each other. Overal design Total RNA was extracted from fibroblasts derived iPSC (N=8) and blood derived iPSC (N=10) as well as parental fibroblasts and peripheral blood mononuclear cells (N=4 different donors: T14; T42; T53; T55). Total RNA was also extracted from spontaneously differentiated Embryonic bodies derived from fibroblasts derived iPSC (N=4) and blood derived iPSC (N=4) from four donors. RNA from control human embryonic stem cell lines (H9, and FES22) was used as control. Samples were run in two different batches (1 and 2).
2016-01-07 | E-MTAB-3825 | biostudies-arrayexpress
Project description:Neuronal activity causes the rapid expression of immediate early genes that are crucial for experience driven changes to synapses, learning, and memory. Here, using both molecular and genome-wide next generation sequencing methods, we report that neuronal activity stimulation triggers the formation of DNA double strand breaks (DSBs) in the promoters of a subset of early-response genes, including Fos, Npas4, and Egr1. Generation of targeted DNA DSBs within Fos and Npas4 promoters is sufficient to induce their expression even in the absence of an external stimulus. Activity-dependent DSB formation is likely mediated by the type II topoisomerase, Topoisomerase IIb (Topo IIb), and knockdown of Topo IIb attenuates both DSB formation and early response gene expression following neuronal stimulation. Our results suggest that DSB formation is a physiological event that rapidly resolves topological constraints to early-response gene expression in neurons. Generation of sequencing data from ChIP-seq with antibodies against γH2AX and Topo IIβ after neuronal activity stimulation, and RNA-seq after etoposide treatment
2015-06-04 | E-GEOD-61887 | biostudies-arrayexpress
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2016-08-18 | E-MTAB-3859 | biostudies-arrayexpress
Project description:The clinical results obtained with organ allografts from marginal or extended donors are less satisfactory over both the short-term and long-term than the outcome of grafting from living donors. Early postoperative graft function depends on several pretransplant factors, with the major donor influences being brain death (BD) and ischemia/reperfusion(I/R) injury. The effects of BD and I/R injury not only reduce the number of functioning nephrons, but also trigger a host immune response to the grafted kidney. It has been hypothesized that allografts from marginal sources may not be biologically inert at the time of surgery, but may already be programmed to initiate or amplify a host response. To exclude the effects of allogenicity, we established a rat renal isograft model using dead donors and compared the results with those obtained after grafting from living donors. In this study, we performed an analysis of the changes of gene expression in rat kidney isografts using samples obtained at 0(pre-transplant) and 1 hour time points since transplantation procedure. The results enhanced our insight into the pathways and cascades that are activated or down-regulated by BD and/or I/R injury. Better knowledge of the key components of BD or I/R injury will provide clues to the factors triggering progression that leads to a decline of organ viability, as well as ideas on how to overcome such graft failures. Such data may also allow us to identify novel biomarkers as predictors of adverse outcomes. Experiment Overall Design: Inbred male Lewis rats were used for these experiments as recipients and donors. The left kidney was transplanted orthotopically by end-to-end anastomosis. The contralateral right kidney was removed at the time of transplantation. The time of operative ischemia for transplantation was 30 min, which did not vary between animals. Donor animals were divided into two groups. The experimental group received kidneys from BD rats, while kidneys from living donors were used in the control group. Brain death was produced by gradually increasing the intracranial pressure that led to brain stem herniation. The rats were mechanically ventilated for a period of 6 hours. We compared the gene expression profiles of renal isografts from BD donors and grafts from living donors using a high-density oligonucleotide microarray that contained approximately 20,500 genes. Experiment Overall Design: For DNA microarray experiments, 200 ng aliquots of total RNA were labeled using the Agilent Low RNA Input Fluorescent Linear Amplification Kit (Agilent Technologies Product) according to the manufacturerâ??s instructions. RNA purified from each kidney graft was used for microarray analysis (Cy3-labeled), with pooled RNA derived from normal kidneys as a template control (Cy5-labeled). After checking the labeling efficiency, 1ï?g aliquots of Cy5-labeled normal control RNA and Cy3-labeled RNA from individual grafts (control 0 hour, 1 hour, BD 0 hour, BD 1 hour, n=3/group) were mixed, and then hybridized to Agilent Rat Oligo Microarrays (Product No. G4130A). After washing, the microarray slides were analyzed with an Agilent Microarray scanner and software (scanner model G2565BA). Data analysis was performed using Agilent Feature Extraction software (Ver. A.7.1.1), and Excel 2003 (Microsoft). The data were imported into GeneSpring 7.0 (Silicon Genetics, Redwood City, CA), with per spot, per chip, and intensity dependent (lowess) normalization being applied for each array. The ratio of the normalized channels (Cy3/Cy5) was used to assess the level of expression.
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Project description:Neuronal activity causes the rapid expression of immediate early genes that are crucial for experience driven changes to synapses, learning, and memory. Here, using both molecular and genome-wide next generation sequencing methods, we report that neuronal activity stimulation triggers the formation of DNA double strand breaks (DSBs) in the promoters of a subset of early-response genes, including Fos, Npas4, and Egr1. Generation of targeted DNA DSBs within Fos and Npas4 promoters is sufficient to induce their expression even in the absence of an external stimulus. Activity-dependent DSB formation is likely mediated by the type II topoisomerase, Topoisomerase IIb (Topo IIb), and knockdown of Topo IIb attenuates both DSB formation and early response gene expression following neuronal stimulation. Our results suggest that DSB formation is a physiological event that rapidly resolves topological constraints to early-response gene expression in neurons.
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