Search results for "Imatinib"

Study of the role of “gatekeeper” mutations V654A and T670I of c-kit kinase in the interaction with inhibitors by means mixed molecular dynamics/dock…

2011

The over-expression of c-kit proto-oncogene has been reported in hematopoietic cells, small cell lung cancer, and gastrointestinal stromal tumors. The clinical importance of c-kit expression in tumors focused the research towards inhibitors of this tyrosine kinase. Imatinib (Gleevec®) was the first compound used in therapy, but mutations on c-kit led to reduced effectiveness or ineffectiveness of this treatment. Other compounds are likely to be effective against mutants, such as Sunitinib (Sutent®), but the need for new and most effective inhibitors against mutants is still critical. We report mixed Molecular Dynamics/Docking study with the aim to unveil the molecular mechanism involved in …

Abstract 4372: Chronic myeloid leukemia (CML) exosomes promote angiogenesis in a Src-dependent fashion in vitro and in vivo

2012

Abstract CML is an uncontrolled proliferation of bone marrow myeloid cells driven by the constitutively active fusion product tyrosine kinase BCR/ABL. Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is newly recognized as a factor in CML progression. Exosomes, released by a broad spectrum of cells, are microvesicles that play an important role in cell-to-cell communication both in physiological and pathological conditions. The role of exosomes released by CML cells in angiogenesis is emerging; however, little is known about the mechanisms involved in this process. We first isolated and characterized exosomes released by K562 CML cells and we demonstrated thei…

OCULAR DRUG CARRIERS NANOSTRUTTURATI PER IL TRATTAMENTO DELLE PATOLOGIE DEGENERATIVE DELLA RETINA

Il lavoro di ricerca svolto è stato incentrato sulla preparazione e caratterizzazione di diversi ocular drug carriers nanostrutturati in grado di veicolare molecole bioattive per il trattamento delle retinopatie. Tali sistemi sono stati preparati utilizzando differenti derivati polimerici, ottenuti a partire dall’acido ialuronico (HA) a differente peso molecolare (10-240 kDa). Allo scopo di ottenere micelle polimeriche per la veicolazione di corticosteroidi, sono stati sintetizzati diversi derivati polimerici partendo dall’HA con MW di 10 kDa. Il derivato siglato HAC16b ha mostrato delle caratteristiche vantaggiose, in termini di dimensione, proprietà mucoadesive, valori di drug loading e p…

Imatinib Mesylate and Nilotinib Affect the MHC-Class I Presentation by Modulating the Proteasomal Processing of Antigenic Peptides.

2009

Abstract Abstract 2169 Poster Board II-146 The tyrosine kinase inhibitors (TKIs) Imatinib mesylate (IM, Gleevec, Glivec) and nilotinib (Tasigna, AMN) are currently used in treatment of chronic myeloid leukaemia (CML). IM has been described to influence the function and differentiation of antigen presenting cells, to inhibit the effector function of T lymphocytes and to decrease the immunogenicity of CML cells by downregulation of tumor associated antigens. In the present study, we analyzed the effect of IM and AMN on proteasomal activity in IM-sensitive or IM/AMN- resistant CML cells as well as in patient samples using a biotinylated active site-directed probe, which, covalently binds and l…

Gene Expression Profile of Chronic Myeloid Leukemia Innately Resistant to Imatinib

2007

Background. Most chronic myeloid leukemia patients who receive imatinib as first line-terapy will obtain, after 12 months treatment, complete cytogenetic and molecular response . However several cases will not achieve molecular response, but their innate mechanism(s) of resistance remain poorly understood. We tried to explore the molecular events involved in innate resistance in CML. Study design. Five patients who were molecular “non responder” and seven “major” responder were investigated by using the expression profile of a set of 380 genes. Multiple testing procedure (MTP), Significance Analysis of Microarrays (SAM), Empirical Bayes Analysis of Microarrays (EBAM), False Discovery Rate (…

Targeted Therapy in Gastrointestinal Stromal Tumors

2015

Advances in the understanding of the molecular mechanisms of gastrointestinal stromal tumors (GISTs) pathogenesis have resulted in the development of a treatment approach which has become a model of targeted therapy in oncology. The introduction of imatinib mesylate [inhibiting KIT/PDGFRA (platelet-derived growth factor receptor-α) and their downstream signaling cascade] has dramatically improved the therapy of advanced (inoperable and/or metastatic) GIST. Imatinib has now become the standard of care in the treatment of patients with advanced GIST and its efficacy has been proven also in adjuvant setting after resection of primary high-risk tumors. However, a majority of patients eventually…

Overcoming Imatinib resistance using CAI, a calcium-mediated signal transduction inhibitor: A new therapeutic strategy for chronic myelogenous leucem…

2008

carboxyamidotriazole-orotate inhibits the growth of imatinib resistant chronic myeloid leukaemia cells and modulates exosomes-stimulated angiogenesis

2012

The Bcr/Abl kinase has been targeted for the treatment of chronic myelogenous leukaemia (CML) by imatinib mesylate. Although more common in solid tumors, increased microvessel density was also reported in chronic myelogenous leukaemia and was associated with a significant increase of angiogenic factors, suggesting that vascularity in haematologic malignancies is a controlled process and may play a role in the leukaemogenic process thus representing an alternative therapeutic target. Carboxyamidotriazole-orotate (CTO) is the orotate salt form of carboxyamidotriazole (CAI), an orally bioavailable signal transduction inhibitor that in vitro has been shown to possess antileukaemic activities (1…

V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenou…

2010

Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…

il CAI modula l'espressione di Bcr-Abl tramite l'aumento dei Ros in cellule di leucemia mieloide cronica Imatinib-resistenti

2009

La leucemia mieloide cronica (LMC) è una neoplasia causata da una traslocazione reciproca non bilanciata tra il braccio lungo del cromosoma 9 e quello del cromosoma 22. Tale traslocazione determina la formazione dell’oncogene di fusione bcr-abl codificante per un’oncoproteina con attività tirosin-chinasica costitutiva. Le conoscenze dei meccanismi molecolari alla base della neoplasia, acquisite negli ultimi anni, hanno permesso di sviluppare terapie volte all’inibizione dell’attività chinasica della chimera BCR-ABL. Tra queste, l’imatinib mesilato (IM), inibitore selettivo della protein chinasi, ha rivoluzionato le terapie per la LMC. Sebbene numerosi pazienti in fase cronica, trattati con …