@prefix prodottidellaricerca: . @prefix istituto: . @prefix prodotto: . istituto:CDS040 prodottidellaricerca:prodotto prodotto:ID27823 . @prefix pubblicazioni: . @prefix unitaDiPersonaleEsterno: . unitaDiPersonaleEsterno:ID8266 pubblicazioni:autoreCNRDi prodotto:ID27823 . unitaDiPersonaleEsterno:ID8265 pubblicazioni:autoreCNRDi prodotto:ID27823 . @prefix modulo: . modulo:ID5927 prodottidellaricerca:prodotto prodotto:ID27823 . modulo:ID5952 prodottidellaricerca:prodotto prodotto:ID27823 . @prefix rdf: . prodotto:ID27823 rdf:type prodotto:TIPO1101 . @prefix retescientifica: . prodotto:ID27823 rdf:type retescientifica:ProdottoDellaRicerca . @prefix rdfs: . prodotto:ID27823 rdfs:label "Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia. (Articolo in rivista)"@en . @prefix xsd: . prodotto:ID27823 pubblicazioni:anno "2011-01-01T00:00:00+01:00"^^xsd:gYear . @prefix skos: . prodotto:ID27823 skos:altLabel "
Evangelisti C, Ricci F, Tazzari P, Tabellini G, Battistelli M, Falcieri E, Chiarini F, Bortul R, Melchionda F, Pagliaro P, Pession A, McCubrey JA, Martelli AM. (2011)
Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia.
in Leukemia
"^^rdf:HTML ; pubblicazioni:autori "Evangelisti C, Ricci F, Tazzari P, Tabellini G, Battistelli M, Falcieri E, Chiarini F, Bortul R, Melchionda F, Pagliaro P, Pession A, McCubrey JA, Martelli AM."^^xsd:string ; pubblicazioni:paginaInizio "781"^^xsd:string ; pubblicazioni:paginaFine "791"^^xsd:string ; pubblicazioni:numeroVolume "25"^^xsd:string . @prefix ns11: . prodotto:ID27823 pubblicazioni:rivista ns11:ID485716 ; skos:note "ISI Web of Science (WOS)"^^xsd:string ; pubblicazioni:affiliazioni "Department of Human Anatomy, University of Bologna, Bologna, Italy; \nImmunohaematology and Transfusion Center, Policlinico S.Orsola-Malpighi, Bologna, Italy; \nDepartment of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy; \nDepartment of Human, Environmental and Natural Sciences, University of Urbino \u0091Carlo Bo\u0092, Urbino, Italy;\nMolecular Genetics Institute-National Research Council, Sezione di Bologna c/o I.O.R., Bologna, Italy; \nDepartment of Clinical Biomedicine, University of Trieste, Trieste, Italy; \nPaediatric Oncology and Haematology Unit Lalla Seragnoli, University of Bologna, Bologna, Italy ;\nDepartment of Microbiology & Immunology, School of Medicine, East Carolina University, Greenville, NC, USA\n\n"^^xsd:string ; pubblicazioni:titolo "Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia."^^xsd:string ; prodottidellaricerca:abstract "\nThe mammalian Target Of Rapamycin (mTOR) serine/threonine kinase belongs to two multi-protein complexes, referred to as mTORC1 and mTORC2. mTOR-generated signals have critical roles in leukemic cell biology by controlling mRNA translation of genes that promote proliferation and survival. However, allosteric inhibition of mTORC1 by rapamycin has only modest effects in T-cell acute lymphoblastic leukemia (T-ALL). Recently, ATP-competitive inhibitors specific for the mTOR kinase active site have been developed. In this study, we have explored the therapeutic potential of active-site mTOR inhibitors against both T-ALL cell lines and primary samples from T-ALL patients displaying activation of mTORC1 and mTORC2. The inhibitors affected T-ALL cell viability by inducing cell-cycle arrest in G(0)/G(1) phase, apoptosis and autophagy. Western blot analysis demonstrated a Ser 473 Akt dephosphorylation (indicative of mTORC2 inhibition) and a dephosphorylation of mTORC1 downstream targets. Unlike rapamycin, we found a marked inhibition of mRNA translation in T-ALL cell lines treated with active-site mTOR inhibitors. The inhibitors strongly synergized with both vincristine and the Bcl-2 inhibitor, ABT-263. Remarkably, the drugs targeted a putative leukemia-initiating cell sub-population (CD34(+)/CD7(-)/CD4(-)) in patient samples. In conclusion, the inhibitors displayed remarkable anti-leukemic activity, which emphasizes their future development as clinical candidates for therapy in T-ALL.\n" ; prodottidellaricerca:prodottoDi modulo:ID5927 , modulo:ID5952 , istituto:CDS040 ; pubblicazioni:autoreCNR unitaDiPersonaleEsterno:ID8266 , unitaDiPersonaleEsterno:ID8265 . @prefix parolechiave: . prodotto:ID27823 parolechiave:insiemeDiParoleChiave . ns11:ID485716 pubblicazioni:rivistaDi prodotto:ID27823 . parolechiave:insiemeDiParoleChiaveDi prodotto:ID27823 .