Does inhibition of p38 MAPK improve intestinal disturbances and oxidative stress induced in a rabbit endotoxemia model?
Lipopolysaccharide decreases the duodenal contractility in rabbits and increases the production of free radicals. p38 MAPK is a mediator of these effects.
CML patients treated with tyrosine kinase inhibitors (TKIs) have showed a 5-year estimated overall survival of 89%, with cumulative complete cytogenetic response of 87%. However, development of drug resistance is a common feature of the disease progression. This study aimed at showing the effect of 7KC as a cytotoxic and sensitizing agent of multidrug resistance CML cell lines. The cellular and molecular basis of this compound were elucidated using a comprehensive strategy based on quantitative proteomic and cell biology assays. We showed that 7KC induced cell death and overcomes drug resistance in CML through mechanisms that go beyond the classical MDR1 pathways.