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SRP066956
Homo sapiens
22 Downloadable Samples
IlluminaHiSeq2500
Description
Although mechanisms of acquired resistance of EGFR mutant non-small cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here, we observe that acquired resistance caused by the T790M gatekeeper mutation can occur either by selection of pre-existing T790M clones or via genetic evolution of initially T790M-negative drug tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug tolerant cells had a diminished apoptotic response to third generation EGFR inhibitors that target T790M EGFR; treatment with navitoclax, an inhibitor of BCL-XL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug resistant cancer cells can both pre-exist and evolve from drug tolerant cells, and point to therapeutic opportunities to prevent or overcome resistance in the clinic. Overall design: Examination of mRNA levels of PC9 parental, drug-tolerant, PC9-GR2 and PC9-GR3 cells after treatment with vehicle, gefitinib or WZ4002 for 24 hours.
Publication Title
Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Objective Telmisartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, are antihypertensive agents clinically used as monotherapy or in combination. They exert beneficial cardiovascular effects independently of blood pressure lowering and classic mechanisms of action. In this study, we investigate molecular mechanisms responsible for the off-target effects of telmisartan and telmisartan-amlodipine in endothelial cells (EC), using an unbiased approach.
Publication Title
Telmisartan exerts pleiotropic effects in endothelial cells and promotes endothelial cell quiescence and survival.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The goal of this experiment was to examine the innate immune response to helminth infection in the lung. Hookworms (like many other helminths) use an obligate migration pathway through the lung. Their infection has been characterized in the gut in detail, but early immune responses in the lung have not been fully characterized.
Publication Title
Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Infection with Nippostrongylus brasiliensis results in persistent changes to the lung environment. Cytokine profiling reveals a sustained increase in both Th1 and Th2 transcripts. Cellular populations of macrophages display an alternative phenotype, with upregulation of YM1, Arg1, Mrc1 as well as Class II MHC. These alternatively activated alveolar macrophages (AAAMs) also increase drastically in number. Subsequent challenge with house dust mite (HDM) Dermatophagoides pteronyssinus shows a reduced allergic phenotype, with decreased fold changes in effector cell cytokines of both the Th1 and Th2 variety indicative of the new regulatory environment established in the lung by helminth infection. Histological examination of the lung environment reveals a significant decrease in eosinophila and reduced mucous production by bronchial epithelial cells.
Publication Title
Hookworm-induced persistent changes to the immunological environment of the lung.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 48 Downloadable Samples
- NextSeq 500
Description
To udnderstand the tissue-resident features of antigen-specific memory T cells of the bone marrow and spleen, we performed RNA-Seq and compared expression levels of genes of resting LCMV.GP66-77 specific CD4 T cells isolated from bone marrow (BM) and spleen of LCMV.GP61-80 primed C57BL/6 mice. Overall design: C57BL/6 mice were primed at day 0 with LCMV.GP61-80-NP-MSA + poly(I:C) and immunized again at day 14 with LCMV.GP61-80 + poly(I:C). Sixty days after the last immunization mice were sacrificed and LCMV.GP66–77-specific CD69+ and CD69- memory CD4 T cells were isolated from BM and spleen.
Publication Title
CD69<sup>+</sup> memory T lymphocytes of the bone marrow and spleen express the signature transcripts of tissue-resident memory T lymphocytes.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- NextSeq 500
Description
We performed RNA-Seq and compared expression levels of genes of reactivated LCMV.GP66-77 specific CD4 T cells isolated from bone marrow (BM) and spleen of LCMV.GP61-80 primed C57BL/6 mice. Cells were isolated 3 days after antigenic re-challenge Overall design: C57BL/6 mice were primed at day 0 with LCMV.GP61-80-NP-MSA + poly(I:C) and immunized again at day 14 with LCMV.GP61-80 + poly(I:C). 60 days later, C57BL/6 mice were boosted with LCMV.GP61-80-NP-MSA + poly(I:C) and 3 days after the boost, LCMV specific CD4 T cells were isolated from BM and spleen
Publication Title
Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to identify potential genes that may play an important role in progression of colorectal carcinoma, we screened and validated the global gene expression using cDNA expression array on 36 CRC tissues and compared with 24 non-cancerous colorectal tissue.
Publication Title
Genome-wide expression analysis of Middle Eastern colorectal cancer reveals FOXM1 as a novel target for cancer therapy.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 191 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Normal children, children with SIRS, children with sepsis, and children with septic shock.
Publication Title
Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.
Publication Title
Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rationale: We previously generated genome-wide expression data in children with septic shock, based on whole blood-derive RNA, having the potential to lead the field into novel areas of investigation.
Publication Title
Validating the genomic signature of pediatric septic shock.
Sample Metadata Fields
Sex
View Samples