Search results for " TYR"

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

2020

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI an…

3D Architecture and Plio-Quaternary evolution of the Paola Basin: New insights to the Forearc of the Tyrrhenian-Ionian Subduction System

2018

The 3D stratigraphic architecture and the Pliocene to Quaternary evolution of the Paola Basin (offshore western Calabria), a segment in the fore-arc of the Tyrrhenian-Ionian subduction system, are reconstructed by using a grid of unpublished of multi-channels, high-penetration, seismic-reflection profiles acquired in the frame of the project SINBUS, integrated by bathymetric data from EMODnet-Bathymetry portal. The Paola Basin is a NNW-SSE elongated, ~ 60 km long and ~20 km wide, slightly asymmetric syncline, which hosted Plio-Quaternary deposits up to 5.5 km thick in its depocenter. The Plio-Quaternary sequence shows an eastward progradational internal geometry that becomes sub-horizontal …

Young woman with Branchio-Oto-Renal Syndrome and a novel mutation in the EYA-1 gene

2011

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disease clinically characterized by the coexistence of some or all of the following major disorders: deafness, cervical branchial fistulae, preauricular pits, and renal abnormalities. Most families with BOR syndrome have mutations on the EYA-1 gene on chromosome 8q. We present the case of a 23-year-old Italian woman without a familial history of BOR syndrome. The patient, who had hearing loss and a history of surgeries for correction of bilateral cervical branchial fistulae and bilateral preauricular pits, presented with renal impairment, hypertension and overt proteinuria. DNA sequencing showed a novel heterozygous mutation 1420-14…

Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?

2007

AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3, PDGFRα/β and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%), VEGFR2 (80%), VEGFR3 (67%), PDGFRα (82%) and PDGFRβ (82%) expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additiona…

Does expression of receptor tyrosine kinases in gastric adenocarcinoma correlate with clinicopathological parameters?

2009

Introduction: The prognosis for patients with gastric cancer depends on the stage of the disease. Radical surgery and lymph node dissection represent the only curative intent and are the standard therapeutic option for patients with limited disease. As new multi-targeted receptor tyrosine kinase inhibitors (RTK) are ermerging in the therapy of diverse malignomas, our aim was to analyze the relevance of the targeted receptor tyrosine kinases on local growth, lymphatic dissemination and overall survival in gastric adenocarcinoma. Methods: The (co-)expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ and EGFR1 was analyzed by RT-PCR in 56 consecutive samples of human gastric adenocarci…

First estimates of density and distribution of the alien crab Percnon gibbesi (Decapoda, Percnidae) in the "Capo Gallo-Isola delle Femmine" MPA

2013

Cytotoxic and protein kinase inhibiting nakijiquinones and nakijiquinols from the sponge Dactylospongia metachromia.

2014

Chemical investigation of the sponge Dactylospongia metachromia afforded five new sesquiterpene aminoquinones (1-5), two new sesquiterpene benzoxazoles (6 and 7), the known analogue 18-hydroxy-5-epi-hyrtiophenol (8), and a known glycerolipid. The structures of all compounds were unambiguously elucidated by one- and two-dimensional NMR and by MS analyses, as well as by comparison with the literature. Compounds 1-5 showed potent cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 1.1 to 3.7 μM. When tested in vitro for their inhibitory potential against 16 different protein kinases, compounds 5, 6, and 8 exhibited the strongest inhibitory activity against AL…

Synthesis of 2H-Imidazo[2',1':2,3] [1,3]thiazolo[4,5-e]isoindol-8-yl-phenylureas with promising therapeutic features for the treatment of acute myelo…

2022

Despite progressive advances in understanding the molecular biology of acute myeloid leukemia (AML), the conventional therapeutic approach has not changed substantially, and the outcome for most patients is poor. Thus, continuous efforts on the discovery of new compounds with improved features are required. Following a multistep sequence, we have identified a new tetracyclic ring system with strong antiproliferative activity towards several haematological cell lines. The new compounds possess structural properties typical of inactive-state-binding kinase inhibitors and are structurally related to quizartinib which is known as type-II tyrosine kinase inhibitor. In particular, the high activi…

γ-Glutamyl cysteine modulates the inflammatory response via protein phosphatases

2015

Acute pancreatitis (AP) is an acute inflammatory process of the pancreatic gland that may lead to severe systemic complications. Cytokines and oxidative stress play a role in the early pathophysiological events of the disease. Previous studies have shown the antioxidant properties of γ-glutamyl cysteine (γ–GC), a metabolic precursor for the synthesis of glutathione. C57BL/6 mice were treated with cerulein (7 injections each with 50 μg/kg bw). To evaluate the effects of γ-GC, a group of mice with AP was treated with γ-GC (75 mg/kg bw) administered in two doses at 4 and 7 hours after the first cerulein injection. Plasma lipase activity was measured and histological studies were performed to c…

Integrin cytoplasmic domain and pITAM compete for spleen tyrosine kinase binding

2019

ABSTRACTIn hematopoietic tissues cell-cell communication involves immunoreceptors and specialized cell adhesion receptors that both mediate intracellular signals. Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase involved in the downstream signaling of both immunoreceptors tyrosine activation motif (ITAM) receptors and integrin family cell adhesion receptors. Both phosphorylated ITAM (pITAM) and integrins bind to the regulatory domain of Syk composed of two Src homology 2 (SH2) domains. The interaction with pITAM is mediated by binding of a specific phosphotyrosine to each of the SH2 domains, leading to conformational changes and Syk kinase activation. Integrins bind to the int…