نتایج جستجو برای: dasatinib
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Dasatinib, a tyrosine kinase inhibitor, has been shown to produce anti-inflammatory activity and impair vascular integrity in vivo, including during skin wound healing, potentially promoting the repair process. Given that dasatinib is lipophilic small molecule capable of penetrating skin, topical might provide benefits healing. In present study, we investigated impact ointments healing mice. A ...
The most common mechanisms for resistance in patients with chronic myeloid leukemia (CML) receiving imatinib mesylate are BCR-ABL kinase domain (KD) mutations. The mutations are stratifi ed according to in vitro 50% inhibitory concentration (IC 50) values. The F317L KD mutation has been shown to induce a 9-to 13.5-fold increase of dasatinib IC 50 with respect to wild-type BCR-ABL in cellular as...
Earlier use of more potent tyrosine kinase inhibitors such as dasatinib improves response rates for patients with chronic myeloid leukemia (CML). The SRC-ABL Tyrosine Kinase Inhibition Activity Research Trials series displayed dasatinib efficacy in patients with all phases of CML who are resistant or intolerant to imatinib. More recently, dasatinib has been shown to induce rapid and high rates ...
PURPOSE Several oral multikinase inhibitors are known to interact in vitro with the human ATP-binding cassette transporter ABCC4 (MRP4), but the in vivo relevance of this interaction remains poorly understood. We hypothesized that host ABCC4 activity may influence the pharmacokinetic profile of dasatinib and subsequently affect its antitumor properties. EXPERIMENTAL DESIGN Transport of dasati...
The patient succumbed to CNS disease 3 months afterward, despite CNS-directed chemotherapy. Sequencing of the BCR-ABL kinase domain from BM blasts, at the time of BC, and CSF tumor cells, at CNS relapse, did not show any mutation. The lack of BM blastosis, the reduced marrow BCR-ABL levels and the absence of a mutated clone, in BM and CSF, at the onset of meningeal leukemia, indicate that syste...
Neuroblastoma (NB) and Ewing sarcoma (ES) are neuroectodermal tumors typical of pediatric age that, despite aggressive treatment, still present a poor prognosis when in advanced stages. Studies indicate that c-KIT and platelet-derived growth factor receptor (PDGFR) play a substantial role in the proliferation and survival of NB and ES cells. Dasatinib, an oral multi-targeted inhibitor of severa...
PURPOSE Dasatinib is a potent, oral SRC-family kinase inhibitor with preclinical antiproliferative, antimetastatic, and antiosteoclastic activity suggesting dasatinib sensitivity in triple-negative, or basal-like, breast cancer cell lines. This phase 2 trial assessed efficacy and safety of single-agent dasatinib in patients with advanced triple-negative breast cancer (TNBC). EXPERIMENTAL DESI...
Purpose: Several oral multikinase inhibitors are known to interact in vitro with the human ATP-binding cassette transporter ABCC4 (MRP4), but the in vivo relevance of this interaction remains poorly understood. We hypothesized that host ABCC4 activity may influence the pharmacokinetic profile of dasatinib and subsequently affect its antitumor properties. Experimental Design: Transport of dasati...
Purpose: To analyze the effect of the combination of Dasatinib, a multikinase inhibitor, plus Nutlin-3, a nongenotoxic activator of the p53 pathway, in primary B chronic lymphocytic leukemia (B-CLL) patient samples and B leukemic cell line models. Experimental Design: The induction of cytotoxicity was evaluated in both primary B-CLL cell samples (n 1⁄4 20) and in p53 (EHEB, JVM-2) and p53 (MEC-...
PURPOSE Dasatinib is a prototypic short half-life BCR-ABL1 tyrosine kinase inhibitor. The recommended dose of dasatinib for chronic myeloid leukemia in chronic phase was changed from 70 mg twice daily to 100 mg once daily following a Phase III dose-optimization study. To better understand the superior benefit-risk profile of dasatinib 100 mg once daily, exposure-response was characterized for e...
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