{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:51:30Z","timestamp":1790898690452,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:00:00Z","timestamp":1504742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PIC\/IC\/83023\/2007"],"award-info":[{"award-number":["PIC\/IC\/83023\/2007"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Despite remarkable progress in polychemotherapy protocols, pediatric B\u2010cell acute lymphoblastic leukemia (B\u2010ALL) remains fatal in around 20% of cases. Hence, novel targeted therapies are needed for patients with poor prognosis. Glucocorticoids (GCs) are drugs commonly administrated for B\u2010ALL treatment. Activation of the phosphatidylinositol 3\u2010kinase (PI3K)\/Akt\/mammalian target of rapamycin signaling pathway is frequently observed in B\u2010ALL and contributes to GC\u2010resistance. Here, we analyzed for the first time to our knowledge, the therapeutic potential of pan and isoform\u2010selective PI3K p110 inhibitors, alone or combined with dexamethasone (DEX), in B\u2010ALL leukemia cell lines and patient samples. We found that a pan PI3K p110 inhibitor displayed the most powerful cytotoxic effects in B\u2010ALL cells, by inducing cell cycle arrest and apoptosis. Both a pan PI3K p110 inhibitor and a dual \u03b3\/\u03b4 PI3K p110 inhibitor sensitized B\u2010ALL cells to DEX by restoring nuclear translocation of the GC receptor and counteracted stroma\u2010induced DEX\u2010resistance. Finally, gene expression analysis documented that, on one hand the combination consisting of a pan PI3K p110 inhibitor and DEX strengthened the DEX\u2010induced up\u2010 or down\u2010regulation of several genes involved in apoptosis, while on the other, it rescued the effects of genes that might be involved in GC\u2010resistance. Overall, our findings strongly suggest that PI3K p110 inhibition could be a promising strategy for treating B\u2010ALL patients by improving GC therapeutic effects and\/or overcoming GC\u2010resistance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26135","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T12:57:01Z","timestamp":1501851421000},"page":"1796-1811","source":"Crossref","is-referenced-by-count":35,"title":["Phosphatidylinositol 3\u2010kinase inhibition potentiates glucocorticoid response in B\u2010cell acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"233","author":[{"given":"Cecilia","family":"Evangelisti","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cappellini","sequence":"additional","affiliation":[{"name":"Department of Human Social and Health Sciences University 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