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Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is a mind aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Gene set enrichment analyses identified several deregulated functions including cell proliferation, migration, DNA damage, regulation of stem cell differentiation and reversion of the epithelial-mesenchymal transition (EMT) phenotype, among others. Combination studies showed a synergistic interaction of EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124 had a good pharmacokinetic profile. In conclusion these experiments demonstrate the antitumor activity of EC-70124 in TNBC paving the way for the future clinical development of this drug alone or in combination with chemotherapy.
Publication Title
Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Old C57BL/6 mice cannot mount an effective innate immune response
Publication Title
Aged mice are unable to mount an effective myeloid response to sepsis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 69 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The polytrauma (PT) murine model has unique transcriptomic responses 2 hrs, 1 day and 3 days after injury. We determined with this clinically relevant model that the increased morbidity in the elderly is secondary to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an 'emergency myelopoietic' response, engendering myeloid cells that fail to clear secondary infection. In addition, the elderly appear unable to effectively resolve their inflammatory response to severe injury.
Publication Title
A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 101 Downloadable Samples
- Affymetrix Clariom S Pico Assay HT (clariomshumanht)
Description
Eight healthy human subjects were enrolled in a 6-day simulated shift work protocol. Blood samples were collected during the two 24-hour measurement periods. Blood samples were collected every 4 hours during both measurement periods. Subjects entered the lab on Day 1. At the start of Day 2, the first 24-hour measurement period was started. Subjects slept according to their habitual sleep/wake schedule, followed by a 16-hour constant posture procedure. On days 3-6, the sleep period was delayed by 10 hours. Following the third night on this schedule, subjects underwent another 24-hour measurement period. During both measurement periods, 7 blood samples were collected and PBMCs were isolated. mRNA was extracted, labelled, and hybridized to microarrays.
Publication Title
Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The very low density lipoprotein receptor (VLDLR) is a multi-ligand receptor that mediates pleiotropic biological processes, such as brain development.
Publication Title
The very low density lipoprotein receptor attenuates house dust mite-induced airway inflammation by suppressing dendritic cell-mediated adaptive immune responses.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We quantified differential gene (mRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control.
Publication Title
HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 856 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global
Publication Title
A genomic storm in critically injured humans.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 587 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Blood was sampled from severe burns patients over time as well as healthy subjects. Genome-wide expression analyses were conducted using the Affymetrix U133 plus 2.0 GeneChip.
Publication Title
Genomic responses in mouse models poorly mimic human inflammatory diseases.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
SRP077708- Homo sapiens
- 38 Downloadable Samples
Illumina HiScanSQ
Description
The aim of this study is to analyze the transcriptome of epithelial (CD326+ enriched) and immune (CD45+ enriched) fraction in Celiac Disease and controls to find differentially expressed genes.
Publication Title
The methylome of the celiac intestinal epithelium harbours genotype-independent alterations in the HLA region.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4+ T helper lymphocytes that express interleukin-17 (Th17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in Th17 cell differentiation and function with susceptibility to Crohns disease, rheumatoid arthritis, and psoriasis1-3. Thus, the pathway towards differentiation of Th17 cells and, perhaps, of related innate lymphoid cells with similar effector functions4, 5, is an attractive target for therapeutic applications. Mouse and human Th17 cells are distinguished by expression of the retinoic acid receptor-related orphan nuclear receptor RORt, which is required for induction of IL-17 transcription and for the manifestation of Th17-dependent autoimmune disease in mice6. By performing a chemical screen with an insect cell-based reporter system, we identified the cardiac glycoside digoxin as a specific inhibitor of RORt transcriptional activity. Digoxin inhibited murine Th17 cell differentiation without affecting differentiation of other T cell lineages and was effective in delaying the onset and reducing the severity of autoimmune disease in mice. At high concentrations, digoxin is toxic for human cells, but non-toxic synthetic derivatives, 20,22-dihydrodigoxin-21,23-diol (Dig(dhd)) and digoxin-21-salicylidene (Dig(sal)), specifically inhibited induction of IL-17 in human CD4+ T cells. Using these small molecule compounds, we demonstrated that RORt is imporant for the maintenance of IL-17 expression in mouse and human effector T cells. These data suggest that derivatives of digoxin can be used as chemical probes for development of RORt-targeted therapeutic agents that attenuate inflammatory lymphocyte function and autoimmune disease.
Publication Title
Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.
Sample Metadata Fields
Treatment
View Samples