Transcription profiling of mouse small intestine following treatment with dexamethosone and DBZ

ABSTRACT: Gamma-secretase inhibitors (GSIs), which block the activation of NOTCH receptors, are being tested in the treatment of T-cell acute lymphoblastic leukemia (T-ALL). Thus far, limited antileukemic cytotoxicity and severe gastrointestinal toxicity have restricted the clinical application of these targeted drugs. Here we show that combination therapy with GSIs plus glucocorticoids can improve the antileukemic effects of GSIs and reduce their gut toxicity in vivo. Inhibition of NOTCH1 signaling in glucocorticoid-resistant T-ALL restored glucocorticoid receptor auto-up-regulation and induced apoptotic cell death through induction of BIM expression. Additionally, cotreatment with glucocorticoids induced Ccnd2 upregulation in the gut which protected mice from the intestinal secretory metaplasia ty

ORGANISM(S): Mus musculus

SUBMITTER: Adolfo Ferrando 

PROVIDER: E-GEOD-11184 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress