Evangelisti C.,University of Bologna |
Ricci F.,Servizio di Immunoematologia e Trasfusionale |
Tazzari P.,Servizio di Immunoematologia e Trasfusionale |
Chiarini F.,University of Bologna |
And 8 more authors.
Journal of Cellular Physiology | Year: 2011
Over the past 20 years, survival rates of T-cell acute lymphoblastic leukemia (T-ALL) patients have improved, mainly because of advances in polychemotherapy protocols. Despite these improvements, we still need novel and less toxic treatment strategies targeting aberrantly activated signaling networks which increase proliferation, survival, and drug resistance of T-ALL cells. One such network is represented by the phosphatidylinositol 3-kinase (PI3K)/Akt axis. PI3K inhibitors have displayed some promising effects in preclinical models of T-ALL. Here, we have analyzed the therapeutic potential of the Akt inhibitor, triciribine, in T-ALL cell lines. Triciribine caused cell cycle arrest and caspase-dependent apoptosis. Western blots demonstrated a dose-dependent dephosphorylation of Akt1/Akt2, and of mammalian target of rapamycin complex 1 downstream targets in response to triciribine. Triciribine induced autophagy, which could be interpreted as a defensive mechanism, because an autophagy inhibitor (chloroquine) increased triciribine-induced apoptosis. Triciribine synergized with vincristine, a chemotherapeutic drug employed for treating T-ALL patients, and targeted the side population of T-ALL cell lines, which might correspond to leukemia initiating cells. Our findings indicate that Akt inhibition, either alone or in combination with chemotherapeutic drugs, may serve as an efficient treatment towards T-ALL cells requiring upregulation of this signaling pathway for their proliferation and survival. © 2010 Wiley-Liss, Inc.
Gualandi F.,University of Ferrara |
Curci R.,CNR Institute of Molecular Genetics |
Sabatelli P.,CNR Institute of Molecular Genetics |
Martoni E.,University of Ferrara |
And 4 more authors.
Muscle and Nerve | Year: 2011
Introduction: Collagen VI expression was tested in peripheral blood macrophages from patients with collagen VI-related myopathies and compared with muscle biopsy. Methods: RNA and protein studies were performed in blood macrophages from 5 patients previously diagnosed with either Ullrich congenital muscular dystrophy (UCMD) or Bethlem myopathy (BM). The full spectrum of possible genotypes was considered, including both dominant and recessive UCMD and BM cases. Results: In the dominant BM patient, no collagen VI alterations were detectable in macrophages or muscle biopsy. In the remaining patients, the protein defect caused by the selected mutations, as well as the transcriptional abnormalities, were readily detectable in macrophages, at levels comparable to those observed in muscle biopsy samples and cultured skin fibroblasts. Conclusions: Our data support the suitability of peripheral blood macrophages as a reliable, minimally invasive tool for supplementing or replacing muscle/skin biopsies in the diagnosis and monitoring of collagen VI-related myopathies. © 2011 Wiley Periodicals, Inc.