Search results for "Tyro"

2017

Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thoroug…

The soluble form of pan-RTK inhibitor and tumor suppressor LRIG1 mediates downregulation of AXL through direct protein–protein interaction in gliobla…

2019

Abstract Background Targeted approaches for inhibiting epidermal growth factor receptor (EGFR) and other receptor tyrosine kinases (RTKs) in glioblastoma (GBM) have led to therapeutic resistance and little clinical benefit, raising the need for the development of alternative strategies. Endogenous LRIG1 (Leucine-rich Repeats and ImmunoGlobulin-like domains protein 1) is an RTK inhibitory protein required for stem cell maintenance, and we previously demonstrated the soluble ectodomain of LRIG1 (sLRIG1) to potently inhibit GBM growth in vitro and in vivo. Methods Here, we generated a recombinant protein of the ectodomain of LRIG1 (sLRIG1) and determined its activity in various cellular GBM mo…

2018

AbstractThe cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between E-cadherin deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib. ROS1 inhibitor…

Epithelial-to-mesenchymal transition in the context of epidermal growth factor receptor inhibition in non-small-cell lung cancer

2018

The identification of oncogenic driver mutations in non-small-cell lung cancer (NSCLC) has led to the development of targeted drugs. Tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) target lung tumours bearing EGFR-activating mutations. This new therapeutic strategy has greatly improved tumour response rates. However, drug resistance invariably occurs during TKI-based treatment. Epithelial-to-mesenchymal transition (EMT) is one of the resistance mechanisms identified in EGFR-mutated NSCLC treated with TKIs. In this review we gather together the most important findings on this phenomenon in relation to cancer stem cells and cancer epigenetics. We…

FRI0014 Antioxidant role of microvesicles from adipose tissue-derived mesenchymal stem cells in human osteoarthritic chondrocytes

2017

Background Oxidative stress results in the disruption of normal physiologic signaling leading to inflammatory changes, cartilage degradation and osteoarthritis (OA) progression (1). Recent advances have revealed the role of cell-derived microvesicles (MV) as a new mechanism of cell-to-cell communication with potential therapeutic applications. We have shown previously the antiinflammatory effects of human adipose tissue-derived mesenchymal stem cells (AD-MSC) conditioned medium in OA chondrocytes (2). Objectives We have isolated the MV fraction from the secretome of AD-MSC to investigate its activity on oxidative stress and inflammation in OA chondrocytes stimulated with interleukin (IL)-1β…

2018

Chardonnay wines from Burgundy, obtained from musts with three levels of clarification (Low, Medium and High) during two consecutive vintages (2009 and 2010) and for two kinds of closures (screw caps and synthetic coextruded closures) were analyzed chemically and sensorially. Three bottles per turbidity level were opened in 2015 in order to assess the intensity of the reductive and/or oxidative aromas (REDOX sensory scores) by a trained sensory panel. The chemical analyses consisted in polyphenols and colloids quantification, followed by a proteomic characterization. For the two vintages, the REDOX sensory scores appeared to be driven both by the type of closure and to a lesser extent by th…

Modern diversification of the amino acid repertoire driven by oxygen

2017

All extant life employs the same 20 amino acids for protein biosynthesis. Studies on the number of amino acids necessary to produce a foldable and catalytically active polypeptide have shown that a basis set of 7-13 amino acids is sufficient to build major structural elements of modern proteins. Hence, the reasons for the evolutionary selection of the current 20 amino acids out of a much larger available pool have remained elusive. Here, we have analyzed the quantum chemistry of all proteinogenic and various prebiotic amino acids. We find that the energetic HOMO-LUMO gap, a correlate of chemical reactivity, becomes incrementally closer in modern amino acids, reaching the level of specialize…

Are glutamate and asparagine necessary for tyrosinase activity of type-3 copper proteins?

2018

Abstract Type-3 copper proteins (T3CPs) are complex proteins which share similar active sites. Two copper atoms (CuA and CuB) bind dioxygen as a peroxide in a side on coordination. This protein family comprises the enzymes tyrosinase and catechol oxidase as well as the oxygen transporter hemocyanin. T3CPs occur in almost all organisms and exhibit a number of essential functions. In particular, they are involved in all kinds of enzymatic browning reactions and immune defense. The chemical basis of the two catalytic processes, i.e., the o-hydroxylation of monophenols and the two-electron oxidation to o-quinones, is still discussed. Investigations on natural enzymes with known crystal structur…

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…

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

2020

Intestinal epithelial cells (IECs) play a pivotal role in maintaining intestinal homeostasis. Different noxious agents, among them also anticancer therapies, can impair intestinal epithelial integrity triggering inflammation and oxidative stress. A frequent complication of chemotherapy is gastrointestinal mucositis, strongly influencing the effectiveness of therapy, increasing healthcare costs, and impairing patients&rsquo