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https://www.readbyqxmd.com/read/29136529/yap-dependent-axl-overexpression-mediates-resistance-to-egfr-inhibitors-in-nsclc
#1
Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer...
November 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29119801/serum-levels-of-growth-arrest-specific-6-protein-and-soluble-axl-in-patients-with-st-segment-elevation-myocardial-infarction
#2
Guillem Caldentey, Pablo García De Frutos, Helena Cristóbal, Manel Garabito, Antonio Berruezo, Xavier Bosch, Rodolfo San Antonio, Eduardo Flores-Umanzor, Rosario J Perea, Teresa M De Caralt, Jany Rodríguez, José T Ortiz-Pérez
BACKGROUND: Serum soluble AXL (sAXL) and its ligand, Growth Arrest-Specific 6 protein (GAS6), intervene in tissue repair processes. AXL is increased in end-stage heart failure, but the role of GAS6 and sAXL in ST-segment elevation myocardial infarction (STEMI) is unknown. OBJECTIVES: To study the association of sAXL and GAS6 acutely and six months following STEMI with heart failure and left ventricular remodelling. METHODS: GAS6 and sAXL were measured by enzyme-linked immunosorbent assay at one day, seven days and six months in 227 STEMI patients and 20 controls...
November 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#3
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29116257/kidney-cancer-axl-expression-predicts-prognosis
#4
Louise Stone
No abstract text is available yet for this article.
November 8, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29114736/association-of-warfarin-use-with-lower-overall-cancer-incidence-among-patients-older-than-50-years
#5
Gry S Haaland, Ragnhild S Falk, Oddbjørn Straume, James B Lorens
Importance: In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort. Objective: To examine the association between warfarin use and cancer incidence. Design, Setting, and Participants: This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway...
November 6, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/29097911/micropet-ct-imaging-of-axl-downregulation-by-hsp90-inhibition-in-triple-negative-breast-cancer
#6
Wanqin Wang, Jun Zhao, Xiaoxia Wen, Curtis Chun-Jen Lin, Junjie Li, Qian Huang, Yongqiang Yu, Shiaw-Yih Lin, Chun Li
AXL receptor tyrosine kinase is overexpressed in a number of solid tumor types including triple-negative breast cancer (TNBC). AXL is considered an important regulator of epithelial-to-mesenchymal transition (EMT) and a potential therapeutic target for TNBC. In this work, we used microPET/CT with (64)Cu-labeled anti-human AXL antibody ((64)Cu-anti-hAXL) to noninvasively interrogate the degradation of AXL in vivo in response to 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent inhibitor of HSP90. 17-AAG treatment caused significant decline in AXL expression in orthotopic TNBC MDA-MB-231 tumors, inhibited EMT, and delayed tumor growth in vivo, resulting in significant reduction in tumor uptake of (64)Cu-anti-hAXL as clearly visualized by microPET/CT...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29089775/practical-management-of-adverse-events-associated-with-cabozantinib-treatment-in-patients-with-renal-cell-carcinoma
#7
REVIEW
Benjamin S Gerendash, Patricia A Creel
Cabozantinib is an oral tyrosine-kinase inhibitor whose targets include VEGFR, MET, and AXL. Cabozantinib is approved for the treatment of patients with advanced clear-cell renal-cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the pivotal Phase III trial of second-line RCC, cabozantinib was associated with a significant improvement in overall survival, progression-free survival, and antitumor response compared with everolimus. Adverse events (AEs) were common for patients receiving cabozantinib, but were effectively managed with supportive care and dose modifications, as discontinuations of cabozantinib due to an AE were infrequent...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29079834/dynamic-pseudorotaxane-crystals-containing-metallocene-complexes
#8
Kai-Jen Chen, Pei-Lin Chen, Masaki Horie
Molecular machines and switches composed of flexible pseudorotaxanes respond to external stimuli, transducing incident energy into mechanical motions. This study presents thermo- and photoresponsive dynamic pseudorotaxane crystals composed of axle molecules containing ferrocene or ruthenocene groups threaded through dibenzo[24]crown-8 ether rings. The ruthenocene-containing pseudorotaxane exhibits a crystal-to-crystal thermal phase transition at 86 °C, which is much lower than that of the ferrocene-containing pseudorotaxane (128 °C)...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29072795/preparation-of-pillar-5-arene-based-2-rotaxanes-by-a-stopper-exchange-strategy
#9
Jean-Francois Nierengarten, Iwona Nierengarten, Eric Meichsner, Michel Holler, Pauline Pieper, Robert Deschenaux, Béatrice Delavaux-Nicot
A pillar[5]arene-containing rotaxane building block bearing exchangeable stoppers has been prepared in multi-gram scale quantities with high yields from the reaction of 2,4-dinitrophenol (DNP) with the inclusion complex resulting from the association of dodecanedioyl chloride with 1,4-diethoxypillar[5]arene. Stopper exchange reactions have been achieved by treatment of the resulting DNP diester with various amines through an addition-elimination mechanism preventing the unthreading of the axle component during the reaction and thus preserving the [2]rotaxane structures...
October 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29072690/the-non-invasive-serum-biomarker-soluble-axl-accurately-detects-advanced-liver-fibrosis-and-cirrhosis
#10
Katharina Staufer, Mirko Dengler, Heidemarie Huber, Rodrig Marculescu, Rudolf Stauber, Carolin Lackner, Hans-Peter Dienes, Danijel Kivaranovic, Christian Schachner, Markus Zeitlinger, Beatrix Wulkersdorfer, Peter Rauch, Gerhard Prager, Michael Trauner, Wolfgang Mikulits
Soluble Axl (sAxl) was recently shown to be strongly released into the blood during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a biomarker of liver diseases. In this study we are the first to evaluate sAxl in human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient elastography (TE; Fibroscan) for its value to detect significant (F≥2), advanced fibrosis (F≥3), and cirrhosis (F4) in different liver disease etiologies and healthy controls. To properly determine the diagnostic accuracy of sAxl, a test cohort as well as a validation cohort was employed using liver biopsy as a reference method...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29060262/quantifying-the-effects-of-on-the-fly-changes-of-seating-configuration-on-the-stability-of-a-manual-wheelchair
#11
Louise Thomas, Jaimie Borisoff, Carolyn J Sparrey
In general, manual wheelchairs are designed with a fixed frame, which is not optimal for every situation. Adjustable on the fly seating allow users to rapidly adapt their wheelchair configuration to suit different tasks. These changes move the center of gravity (CoG) of the system, altering the wheelchair stability and maneuverability. To assess these changes, a computer simulation of a manual wheelchair was created with adjustable seat, backrest, rear axle position and user position, and validated with experimental testing...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29059635/phase-ii-randomised-discontinuation-trial-of-cabozantinib-in-patients-with-advanced-solid-tumours
#12
Patrick Schöffski, Michael Gordon, David C Smith, Razelle Kurzrock, Adil Daud, Nicholas J Vogelzang, Yihua Lee, Christian Scheffold, Geoffrey I Shapiro
BACKGROUND: Cabozantinib is an inhibitor of tyrosine kinases, including MET, vascular endothelial growth factor receptor, AXL and RET. This multi-cohort phase II randomised discontinuation trial explored anticancer activity of cabozantinib in nine tumour types. PATIENTS AND METHODS: Cabozantinib was administered (100 mg, once daily) to patients with advanced, recurrent or metastatic cancers. Those with stable disease at week 12 were randomised 1:1 to cabozantinib or placebo...
October 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29050231/a-phase-i-study-of-foretinib-plus-erlotinib-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer-canadian-cancer-trials-group-ind-196
#13
Natasha B Leighl, Ming-Sound Tsao, Geoffrey Liu, Dongsheng Tu, Cheryl Ho, Frances A Shepherd, Nevin Murray, John R Goffin, Garth Nicholas, Shingo Sakashita, Zhuo Chen, Lucia Kim, Jean Powers, Lesley Seymour, Glenwood Goss, Penelope A Bradbury
PURPOSE: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients. EXPERIMENTAL DESIGN: The primary endpoint was to define the RP2D of foretinib plus erlotinib as continuous oral daily dosing. Secondary objectives included safety, pharmacokinetics, response and potential biomarkers of response including EGFR, KRAS genotype, MET, AXL expression, and circulating HGF levels...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045015/the-small-molecule-mertk-inhibitor-unc2025-decreases-platelet-activation-and-prevents-thrombosis
#14
Brian R Branchford, Timothy J Stalker, Luke Law, Gilbert Acevedo, Susan Sather, Christine Brzezinski, Katina M Wilson, Katherine Minson, Alisa B Lee-Sherick, Pavel Davizon-Castillo, Christopher Ng, Weihe Zhang, Keith B Neeves, Steven R Lentz, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Deborah DeRyckere, Lawrence F Brass, Douglas K Graham, Jorge A Di Paola
BACKGROUND: Gas6 signals through the TAM (TYRO-3, AXL, MERTK) receptor family mediating platelet activation and thrombus formation via activation of the aggregate-stabilizing αIIb β3 integrin. OBJECTIVE: Here we describe anti-thrombotic effects mediated by UNC2025, a small molecule MERTK tyrosine kinase inhibitor. METHODS: MERTK phosphorylation and downstream signaling were assessed by immunoblot. Light transmission aggregometry, flow cytometry, and microfluidic analysis were used to evaluate the impact of MERTK inhibition on platelet activation and stability of aggregate formation in vitro...
October 17, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29030012/mafb-enhances-efferocytosis-in-raw264-7-macrophages-by-regulating-axl-expression
#15
Masamichi Sato, Yoko Shibata, Sumito Inoue, Akira Igarashi, Yoshikane Tokairin, Keiko Yamauchi, Tomomi Kimura, Takako Nemoto, Kento Sato, Hiroshi Nakano, Shuichi Abe, Michiko Nishiwaki, Maki Kobayashi, Sujeong Yang, Yukihiro Minegishi, Kodai Furuyama, Isao Kubota
The transcription factor MafB is involved in cellular differentiation and phagocytosis in macrophages. Macrophages phagocytose apoptotic cells in vivo; this process, which is known as efferocytosis, requires Axl receptor tyrosine kinase (Axl) activity. However, the association between MafB and efferocytosis, as well as that between MafB and Axl, in macrophages is unknown. We hypothesized that MafB modulates macrophage efferocytosis by regulating Axl expression. Fluorescent-labeled apoptotic thymocytes were added to RAW264...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29028616/simultaneous-determination-of-a-novel-c-met-axl-dual-target-small-molecule-inhibitor-bpi-9016m-and-its-metabolites-in-human-plasma-by-liquid-chromatography-tandem-mass-spectrometry-application-in-a-pharmacokinetic-study-in-chinese-advanced-solid-tumor-patients
#16
Xinge Cui, Xin Zheng, Ji Jiang, Fenlai Tan, Lieming Ding, Pei Hu
BPI-9016M is a novel dual-target small-molecule inhibitor targeting c-Met and AXL, which was developed by Betta Pharmaceuticals Co., Ltd (Hangzhou, China). It has great potential in the treatment of advanced cancer. A high throughput quantitation method, based on liquid chromatography-tandem mass spectrometry, was developed and validated for the simultaneous determination of BPI-9016M and its main metabolite, M1 and M2-2, in human plasma with a sample preparation method of precipitation of protein. Liquid chromatographic separation was performed with a gradient elution of formic acid-10mM ammonium acetate aqueous solution (1:1000, v/v) and acetonitrile at a flow rate of 0...
October 8, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29024938/expression-and-role-of-tyro3-and-axl-as-potential-therapeutical-targets-in-leiomyosarcoma
#17
Carmela Dantas-Barbosa, Tom Lesluyes, François Le Loarer, Fréderic Chibon, Isabelle Treilleux, Jean-Michel Coindre, Pierre Meeus, Mehdi Brahmi, Olivia Bally, Isabelle Ray-Coquard, Marie-Pierre Sunyach, Axel Le Cesne, Olivier Mir, Sylvie Bonvalot, Maud Toulmonde, Antoine Italiano, Pierre Saintigny, Myriam Jean-Denis, Francoise Ducimetiere, Dominique Ranchere, Hiba El Sayadi, Laurent Alberti, Jean-Yves Blay
BACKGROUND: Leiomyosarcoma (LMS) are 15% of adult sarcomas and remain seldom curable in metastatic phase. The TAM receptors and their ligands are overexpressed or activated in multiple malignancies, including LMS. METHODS: The TAM receptor and ligand expression was evaluated in LMS cell lines and 358 sarcoma samples by either gene expression or immunohistochemistry. TYRO3 and AXL were knocked down. Crizotinib and foretinib were investigated in vitro. RESULTS: High expression of TYRO3 and AXL was detected in LMS cell lines...
October 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28989663/impact-of-mechanical-bonding-on-the-redox-switching-of-tetrathiafulvalene-in-crown-ether-ammonium-2-rotaxanes
#18
Hendrik V Schröder, Sebastian Sobottka, Maite Nößler, Henrik Hupatz, Marius Gaedke, Biprajit Sarkar, Christoph A Schalley
Switchable crown ether-ammonium [2]rotaxanes with a redox-active tetrathiafulvalene (TTF) unit implemented in their wheels were synthesised and fully characterised. Reversible operation in two modes is possible, in which the [2]rotaxane's axle is either charged or neutral. Cyclic voltammetry experiments reveal the effects of mechanical bonding on the electrochemical properties of TTF and show the [2]rotaxanes to perform a distinct function in both modes. In the charged mode, redox-switching is dominated by strong electrostatic repulsion in the [2]rotaxane which subsequently leads to a macrocycle translation along the axle...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28989644/unravelling-the-electronic-structure-and-dynamics-of-an-isolated-molecular-rotary-motor-in-the-gas-phase
#19
Reece Beekmeyer, Michael A Parkes, Luke Ridgwell, Jamie W Riley, Jiawen Chen, Ben L Feringa, Andrew Kerridge, Helen H Fielding
Light-driven molecular motors derived from chiral overcrowded alkenes are an important class of compounds in which sequential photochemical and thermal rearrangements result in unidirectional rotation of one part of the molecule with respect to another. Here, we employ anion photoelectron spectroscopy to probe the electronic structure and dynamics of a unidirectional molecular rotary motor anion in the gas-phase and quantum chemistry calculations to guide the interpretation of our results. We find that following photoexcitation of the first electronically excited state, the molecule rotates around its axle and some population remains on the excited potential energy surface and some population undergoes internal conversion back to the electronic ground state...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28986088/expression-of-tyrosine-kinase-receptor-axl-is-associated-with-worse-outcome-of-metastatic-renal-cell-carcinomas-treated-with-sunitinib
#20
Luís Eduardo Zucca, Mariana Andozia Morini Matushita, Renato José da Silva Oliveira, Cristovam Scapulatempo-Neto, Marcos Alves de Lima, Guilherme Gomes Ribeiro, Cristiano Ribeiro Viana, Flavio Mavignier Cárcano, Rui Manuel Reis
BACKGROUND: Renal cell carcinoma (RCC) represents 2%-3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib...
October 3, 2017: Urologic Oncology
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