Search results for "TYROSINE KINASE"
showing 10 items of 362 documents
Alterations in Tight- and Adherens-Junction Proteins Related to Glaucoma Mimicked in the Organotypically Cultivated Mouse Retina Under Elevated Press…
2020
Purpose To scrutinize alterations in cellular interactions and cell signaling in the glaucomatous retina, mouse retinal explants were exposed to elevated pressure. Methods Retinal explants were prepared from C57bl6 mice and cultivated in a pressure chamber under normotensive (atmospheric pressure + 0 mm Hg), moderately elevated (30 mm Hg), and highly elevated (60 mm Hg) pressure conditions. The expression levels of proteins involved in the formation of tight junctions (zonula occludens 1 [ZO-1], occludin, and claudin-5) and adherens junctions (VE-cadherin and β-catenin) and in cell-signaling cascades (Cdc42 and activated Cdc42 kinase 1 [ACK1]), as well as the expression levels of the growth…
Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina
2020
Retinal ganglion cells (RGCs) are the only output neurons of the vertebrate retina, integrating signals from other retinal neurons and transmitting information to the visual centers of the brain. The death of RGCs is a common outcome in many optic neuropathies, such as glaucoma, demyelinating optic neuritis and ischemic optic neuropathy, resulting in visual defects and blindness. There are currently no therapies in clinical use which can prevent RGC death in optic neuropathies; therefore, the identification of new targets for supporting RGC survival is crucial in the development of novel treatments for eye diseases. In this study we identify that the receptor tyrosine kinase, Tyro3, is crit…
Phosphorylated immunoreceptor tyrosine-based activation motifs and integrin cytoplasmic domains activate spleen tyrosine kinase via distinct mechanis…
2018
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated immunoreceptor tyrosine-based activation motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues. In addition to its immunoreceptor function, Syk is activated downstream of integrin pathways, and integrins bind to the same region in Syk a…
New 3-Aryl-2-(2-Thienyl)acrylonitriles with High Activity against Hepatoma Cells
2021
New 2-(thien-2-yl)-acrylonitriles with putative kinase inhibitory activity were prepared and tested for their antineoplastic efficacy in hepatoma models. Four out of the 14 derivatives were shown to inhibit hepatoma cell proliferation at (sub-)micromolar concentrations with IC50 values below that of the clinically relevant multikinase inhibitor sorafenib, which served as a reference. Colony formation assays as well as primary in vivo examinations of hepatoma tumors grown on the chorioallantoic membrane of fertilized chicken eggs (CAM assay) confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic capsase-3 activity, whil…
Liquid Biopsy in Gastrointestinal Stromal Tumor
2017
Over the past 15 years, gastrointestinal stromal tumors (GISTs) have emerged from a poorly understood neoplasm to a well-defined tumor entity. Starting from 2000, the discovery of gain-of-function mutations involving KIT or PDGFRα (platelet-derived growth factor-α) genes and the development of tyrosine kinase inhibitors (TKIs), such as imatinib, revolutionized dramatically the management of GISTs. Due to the almost continual emergence of new data about biological complexity of GISTs and more sophisticated whole-genome technologies, to date, the role of molecular biology is clinically important to drive therapeutic decision making.
NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients
2016
International audience; Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST. Phenotypes based on disbalanced NKp30B/NKp30C ratio (Del…
NUOVI AGENTI TERAPEUTICI PER IL TRATTAMENTO DI PATOLOGIE EMATOLOGICHE
2019
La presente invenzione si riferisce al campo di nuove molecole tetracicliche, aventi un sistema tetraciclico, e loro impiego come medicamenti di patologie ematologiche in particolare per il trattamento della leucemia mieloide acuta (AML) in pazienti emizigoti FLT3/ITD resistenti alle terapie convenzionali.
NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF HAEMATOLOGICAL PATHOLOGIES
2021
An in-depth evaluation of acalabrutinib for the treatment of mantle-cell lymphoma
2020
Introduction: Regimens involving intensive immuno-chemotherapy, followed by high-dose therapy and autologous stem cell transplant represent the standard treatment for younger fit patients with mantle cell lymphoma (MCL). Targeted approaches (i.e. ibrutinib, bortezomib, and lenalidomide) represent the backbone of therapy for relapsed cases. Areas covered: Acalabrutinib is a novel small molecule with a butynamide moiety specifically designed to irreversibly inhibit Bruton tyrosine kinase (BTK), which is more potent and selective than ibrutinib. Relevant publications have been identified through literature searches using the terms 'mantle cell lymphoma' and 'acalabrutinib'. Expert opinion: Aca…
Novel mutations of the MET proto-oncogene in papillary renal carcinomas.
1999
Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET proto-oncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of t…