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SRP059676
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2000
Description
To investigate why dipeptides accumulate in immature CML cells, we examined upstream gene expression patterns. We isolated the most primitive long-term stem cells, short-term stem cells, and KLS- progenitor cells from healthy littermate control and CML-affected mice and performed gene expression profiling using next-generation RNA-sequencing. Overall design: Gene expression profiles of the most primitive long-term (LT) stem cells (CD150+CD48-CD135-KLS+ cells), short-term (ST) stem cells (CD150-CD48-CD135- KLS+ cells), and KLS- progenitor cells from healthy littermate control and CML-affected mice
Publication Title
Dipeptide species regulate p38MAPK-Smad3 signalling to maintain chronic myelogenous leukaemia stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: First- and third-generation retinoids are the main treatment in acne. Even though efficacious, they lack full selectivity for RAR expressed in the epidermis and infundibulum. Objectives: To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. Methods: In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in non-lesional skin of acne patients and compared to ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established. Results: Trifarotene is a selective RAR agonist with >20-fold selectivity over RAR and RAR. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0.01% applied topically is highly comedolytic and has antiinflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, RA metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after four weeks of topical application of trifarotene 0.005% cream. Conclusion: Based on its RAR selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene is expected to provide strong efficacy combined with a favourable safety profile in acne and ichthyotic disorders.
Publication Title
Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene.
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