Search results for "STAT5"
showing 7 items of 37 documents
Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML).
2004
Fms-like tyrosine kinase 3 (FLT3) receptor mutations as internal tandem duplication (ITD) or within the kinase domain are detected in up to 35% of patients with acute myeloid leukemia (AML). N-benzoyl staurosporine (PKC412), a highly effective inhibitor of mutated FLT3 receptors, has significant antileukemic efficacy in patients with FLT3-mutated AML. Mutation screening of FLT3 exon 20 in AML patients (n = 110) revealed 2 patients with a novel mutation (Y842C) within the highly conserved activation loop of FLT3. FLT3-Y842C-transfected 32D cells showed constitutive FLT3 tyrosine phosphorylation and interleukin 3 (IL-3)-independent growth. Treatment with PKC412 led to inhibition of proliferat…
Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor
2009
Abstract In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of the juxtamembrane (JM) of FLT3 have been shown to play a crucial role in driving proliferation and survival of the leukemic clone. Here, we report the identification of FLT3_ITD mutations located in non-JM domains of the FLT3-receptor. This novel type of FLT3_ITD mutation was found in 216 of 753 (28.7%) of unselected FLT3_ITD-positive AML cases. An FLT3 receptor harbouring a prototypic non-JM ITD (FLT3_ITD627E) mediated constitutive phosphorylation of FLT3 and of STAT5, suggesting that non-JM ITDs confer constitutive activation of the receptor. FLT3_ITD627E induced transformation of hematopoietic 32D cells and …
Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma.
2010
Signal transducer and activator of transcription (STAT)-3 inhibitors play an important role in regulating immune responses. Galiellalactone (GL) is a fungal secondary metabolite known to interfere with the binding of phosphorylated signal transducer and activator of transcription (pSTAT)-3 as well of pSTAT-6 dimers to their target DNA in vitro. Intra nasal delivery of 50 μg GL into the lung of naive Balb/c mice induced FoxP3 expression locally and IL-10 production and IL-12p40 in RNA expression in the airways in vivo. In a murine model of allergic asthma, GL significantly suppressed the cardinal features of asthma, such as airway hyperresponsiveness, eosinophilia and mucus production, after…
STAT proteins: From normal control of cellular events to tumorigenesis
2003
Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is …
THE ANTINEOPLASTIC ROLE OF STAT5 INHIBITION IN BCRABL1-POSITIVE CELLS EXPOSED TO PIMOZIDE ALONE AND IN COMBINATION WITH DASATINIB AND PONATINIB
2021
EVEN though the last decades have seen the success of the targeted treatments for BCRABL1-positive Chronic Myeloid Leukemia (CML), with the outstanding achievement of placing selected patients into the so called treatment-free remission, a minor part of these subjects face TKI resistance and/or intolerance. Resistance is a challenging point in the clinical management of CML, occurring in approximately 10–20% of CML cases, due to several mechanisms, among which point mutations of the BCR‐ABL kinase domain, BCRABL overexpression or alternative splicing, sub-efficient plasma concentration of the inhibitor and abnormal drug efflux/influx. The Signal Transducer and Activators of Transcription (S…
Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice
2015
Duchenne Muscular Dystrophy is characterized by muscle wasting and decreased aerobic metabolism. Exercise and blocking of myostatin/activin signaling may independently or combined counteract muscle wasting and dystrophies. The effects of myostatin/activin blocking using soluble activin receptor-Fc (sActRIIB-Fc) administration and wheel running were tested alone or in combination for seven weeks in dystrophic mdx mice. Expression microarray analysis revealed decreased aerobic metabolism in the gastrocnemius muscle of mdx mice compared to healthy mice. This was not due to reduced home-cage physical activity, and was further downregulated upon sActRIIB-Fc treatment in enlarged muscles. However…
Mapping the actions of prolactin in the brain: sexual dimorphism, steroid regulation and the neuroendocrinology of maternal behaviour
2017
El comportamiento maternal cumple la función de proteger a la descendencia en su periodo de mayor vulnerabilidad y asegurar su supervivencia y bienestar. Esta colección de conductas sociales será expresada por la madre exclusivamente durante el periodo postparto, como resultado de la modulación del sustrato neural responsable de la expresión de la conducta social y reproductiva. Los agentes que llevan a cabo dicha modulación para inducir la expresión del comportamiento maternal incluyen, entre otros, señales endocrinas específicas de la gestación y lactancia. Entre éstas destaca la prolactina, hormona adenohipofisaria estrechamente vinculada con la adaptación del organismo a la maternidad. …