8 research outputs found
Small bowel cancer diagnosis: role of nuclear magnetic resonance
The diagnosis of small intestine tumors is challenging. Even in the era of modern medicine, standard approaches including echography, computed tomography-scan and conventional endoscopy are unable to reveal small bowel lesions. Video-capsule has substantially improved the evaluation of small bowel; however this procedure cannot be proposed to all patients and in particular to those experiencing intestine sub-occlusion. Nuclear magnetic resonance (NMR) of the abdomen is an additional diagnostic approach that offers high sensitivity in the identification of small bowel lesions. Here, we describe a case of small bowel neoplasia identified with NMR of the abdomen
Non genomic loss of function of tumor suppressors in CML: BCR-ABL promotes IκBα mediated p53 nuclear exclusion
Reversible Pancytopenia Caused by Oral Letrozole Assumption in a Patient With Recurrent Breast Cancer
Therapeutic inhibition of USP7-PTEN network in chronic lymphocytic leukemia: a strategy to overcome TP53 mutated/deleted clones
Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder with either indolent or aggressive clinical course. Current treatment regiments have significantly improved the overall outcomes even if higher risk subgroups - those harboring TP53 mutations or deletions of the short arm of chromosome 17 (del17p) - remain highly challenging. In the present work, we identified USP7, a known de-ubiquitinase with multiple roles in cellular homeostasis, as a potential therapeutic target in CLL. We demonstrated that in primary CLL samples and in CLL cell lines USP7 is: i) over-expressed through a mechanism involving miR-338-3p and miR-181b deregulation; ii) functionally activated by Casein Kinase 2 (CK2), an upstream interactor known to be deregulated in CLL; iii) effectively targeted by the USP7 inhibitor P5091. Treatment of primary CLL samples and cell lines with P5091 induces cell growth arrest and apoptosis, through the restoration of PTEN nuclear pool, both in TP53-wild type and -null environment. Importantly, PTEN acts as the main tumor suppressive mediator along the USP7-PTEN axis in a p53 dispensable manner. In conclusion, we propose USP7 as a new druggable target in CLL
Morgana acts as an oncosuppressor in chronic myeloid leukemia
We recently described morgana as an essential protein able to regulate centrosome du- plication and genomic stability, by inhibiting ROCK. Here we show that morgana 1/2 mice spontaneously develop a lethal myeloproliferative disease resembling human atypical chronic myeloid leukemia (aCML), preceded by ROCK hyperactivation, centrosome am- plification, and cytogenetic abnormalities in the bone marrow (BM). Moreover, we found that morgana is underexpressed in the BM of patients affected by atypical CML, a disorder of poorly understood molecular basis, characterized by nonrecurrent cytogenetic abnormalities. Morgana is also underexpressed in the BM of a portion of patients affected by Philadelphia-positive CML (Ph1 CML) caused by the BCR-ABL oncogene, and in this condition, morgana underexpression predicts a worse response to imatinib, the standard treatment for Ph1 CML. Thus, morgana acts as an oncosuppressor with different modalities: (1) Morgana underexpression induces centrosome amplifi- cation and cytogenetic abnormalities, and (2) in Ph1 CML, it synergizes with BCR-ABL signaling, reducing the efficacy of imatinib treatment. Importantly, ROCK inhibitionin the BM of patients underexpressing morgana restored the efficacy of imatinib to induce apoptosis, suggesting that ROCK inhibitors, combined with imatinib treatment, can overcome suboptimal responses in patients in which morgana is underex- pressed.Fil: Di Savino, Augusta. Universitã â Di Torino; ItaliaFil: Panuzzo, Cristina. Universitã â Di Torino; ItaliaFil: Rocca, Stefania. Universitã â Di Torino; ItaliaFil: Familiari, Ubaldo. Universitã â Di Torino; ItaliaFil: Piazza, Rocco. Universita Degli Studi Di Milano; ItaliaFil: Crivellaro, Sabrina. Universitã â Di Torino; ItaliaFil: Carrà, Giovanna. Universitã â Di Torino; ItaliaFil: Ferretti, Roberta. Universitã â Di Torino; ItaliaFil: Fusella, Federica. Universitã â Di Torino; ItaliaFil: Giugliano, Emilia. Universitã â Di Torino; ItaliaFil: Camporeale, Annalisa. Universitã â Di Torino; ItaliaFil: Franco, Irene. Universitã â Di Torino; ItaliaFil: Miniscalco, Barbara. Harvard Medical School; Estados UnidosFil: Cutrin, Juan Carlos. Universitã â Di Torino; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Turco, Emilia. Universita di Torino; ItaliaFil: Silengo, Lorenzo. Universita di Torino; ItaliaFil: Hirsch, Emilio. Universita di Torino; ItaliaFil: Rege Cambrin, Giovanna. Universita di Torino; ItaliaFil: Gambacorti Passerin, Carlo. Universita Degli Studi Di Milano; ItaliaFil: Pandolfi, Pier Paolo. Universita di Torino; Italia. Harvard Medical School; Estados UnidosFil: Papotti, Mauro. Universita di Torino; ItaliaFil: Saglio, Giuseppe. Universita di Torino; ItaliaFil: Tarone, Guido. Universita di Torino; ItaliaFil: Morotti, Alessandro. Universita di Torino; ItaliaFil: Brancaccio, Mara. Universita di Torino; Itali