keyword
MENU ▼
Read by QxMD icon Read
search

AXL

keyword
https://www.readbyqxmd.com/read/28637027/phospho-axl-is-widely-expressed-in-glioblastoma-and-associated-with-significant-shorter-overall-survival
#1
Julia Onken, Peter Vajkoczy, Robert Torka, Claudia Hempt, Victor Patsouris, Frank L Heppner, Josefine Radke
Receptor tyrosine kinase AXL (RTK-AXL) is regarded as a suitable target in glioblastoma (GBM) therapy. Since AXL kinase inhibitors are about to get approval for clinical use, patients with a potential benefit from therapy targeting AXL need to be identified. We therefore assessed the expression pattern of Phospho-AXL (P-AXL), the biologically active form of AXL, in 90 patients with newly diagnosed GBM, which was found to be detectable in 67 patients (corresponding to 74%). We identified three main P-AXL expression patterns: i) exclusively in the tumor vasculature (13%), ii) in areas of hypercellularity (35%), or iii) both, in the tumor vasculature and in hypercellular areas of the tumor tissue (52%)...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635269/the-reduction-potentials-of-fefe-hydrogenase-accessory-iron-sulfur-clusters-provide-insights-into-the-energetics-of-proton-reduction-catalysis
#2
Jacob H Artz, David W Mulder, Michael W Ratzloff, Carolyn E Lubner, Oleg A Zadvornyy, Axl X LeVan, S Garrett Williams, Michael W W Adams, Anne K Jones, Paul W King, John W Peters
An [FeFe]-hydrogenase from Clostridium pasteurianum, CpI, is a model system for biological H2 activation. In addition to the catalytic H-cluster, CpI contains four accessory iron-sulfur [FeS] clusters in a branched series that transfer electrons to and from the active site. In this work, potentiometric titrations have been employed in combination with electron paramagnetic resonance (EPR) spectroscopy at defined electrochemical potentials to gain insights into the role of the accessory clusters in catalysis...
June 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28627676/luteolin-inhibits-angiogenesis-by-blocking-gas6-axl-signaling-pathway
#3
Xiaobo Li, Minfeng Chen, Xueping Lei, Maohua Huang, Wencai Ye, Rijia Zhang, Dongmei Zhang
Growth arrest-specific protein 6 (Gas6) induces the activation of Axl receptor tyrosine kinase (Axl), which plays an important role in angiogenic processes, including proliferation, migration, invasion, tube formation and pericyte recruitment of endothelial cells. The inhibition of Gas6/Axl pathway has been demonstrated to be an effective anti-angiogenic therapy. Luteolin, which is a natural active flavonoid, has been reported to possess anti-angiogenic effects. However, the underlying mechanism of luteolin in anti-angiogenesis is not fully understood...
June 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28626559/reversible-mechanical-protection-building-a-3d-suit-around-a-t-shaped-benzimidazole-axle
#4
Kelong Zhu, Giorgio Baggi, V Nicholas Vukotic, Stephen J Loeb
The T-shaped benzimidazolium/crown ether recognition motif was used to prepare suit[1]anes. These novel mechanically interlocked molecules (MIMs) were fully characterized by (1)H and (13)C NMR spectroscopy, single-crystal X-ray diffraction, UV-vis absorption and fluorescence spectroscopy. By conversion to a suit[1]ane, a simple benzimidazole was shown to be protected from deprotonation by strong base. Moreover, it was demonstrated that this unique three-dimensional encapsulation can be made reversible, thus introducing the concept of "reversible mechanical protection"; a protecting methodology that may have potential applications in synthetic organic chemistry and the design of molecular machinery...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28624695/first-in-human-phase-i-study-of-oral-s49076-a-unique-met-axl-fgfr-inhibitor-in-advanced-solid-tumours
#5
Jordi Rodon, Sophie Postel-Vinay, Antoine Hollebecque, Paolo Nuciforo, Analia Azaro, Valérie Cattan, Lucie Marfai, Isabelle Sudey, Karl Brendel, Audrey Delmas, Stéphanie Malasse, Jean-Charles Soria
BACKGROUND AND OBJECTIVES: S49076 is a novel ATP-competitive tyrosine kinase inhibitor of MET, AXL and FGFR with a unique selectivity profile. A phase I open-label study was undertaken to establish the tolerability profile and determine the recommended dose (RD) and administration schedule. MATERIALS AND METHODS: Patients with advanced solid tumours received S49076 orally once-daily (qd) or twice-daily (bid) in continuous 21-day cycles at escalating doses guided by a 3 + 3 design and followed by an expansion phase at the RD...
June 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28621939/-2-rotaxane-formation-by-transition-state-stabilization
#6
Guillaume De Bo, Guillaume Dolphijn, Charlie T McTernan, David A Leigh
We report on the synthesis of [2]rotaxanes driven by stabilization of the axle-forming transition state. A bifunctional macrocycle, with hydrogen bond donors at one end and acceptors at the other, is used to stabilize the charges that develop during the addition of a primary amine to a cyclic sulfate.
June 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28621419/tam-receptor-signaling-in-development
#7
Tal Burstyn-Cohen
TYRO3, AXL and MERTK comprise the TAM family of receptor protein tyrosine kinases. Activated by their ligands, protein S (PROS1) and growth-arrest-specific 6 (GAS6), they mediate numerous cellular functions throughout development and adulthood. Expressed by a myriad of cell types and tissues, they have been implicated in homeostatic regulation of the immune, nervous, vascular, bone and reproductive systems. The loss-of-function of TAM signaling in adult tissues culminates in the destruction of tissue homeostasis and diseased states, while TAM gain-of-function in various tumors promotes cancer phenotypes...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619752/the-met-axl-fgfr-inhibitor-s49076-impairs-aurora-b-activity-and-improves-the-antitumor-efficacy-of-radiotherapy
#8
Céline Clémenson, Cyrus Chargari, Winchygn Liu, Michele Mondini, Charles Ferté, Mike F Burbridge, Valérie Cattan, Anne Jacquet-Bescond, Eric Deutsch
Several therapeutic agents targeting HGF/MET signaling are under clinical development as single agents or in combination, notably with anti-EGFR therapies in non-small cell lung cancer (NSCLC). However, despite increasing data supporting a link between MET, irradiation and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic. S49076 is an oral ATP-competitive inhibitor of MET, AXL and FGFR1-3 receptors that is currently in phase I/II clinical trials in combination with gefinitib in NSCLC patients whose tumors show resistance to EGFR inhibitors...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28606996/targeting-endothelin-receptor-signalling-overcomes-heterogeneity-driven-therapy-failure
#9
Michael P Smith, Emily J Rowling, Zsofia Miskolczi, Jennifer Ferguson, Loredana Spoerri, Nikolas K Haass, Olivia Sloss, Sophie McEntegart, Imanol Arozarena, Alex von Kriegsheim, Javier Rodriguez, Holly Brunton, Jivko Kmarashev, Mitchell P Levesque, Reinhard Dummer, Dennie T Frederick, Miles C Andrews, Zachary A Cooper, Keith T Flaherty, Jennifer A Wargo, Claudia Wellbrock
Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a "MITF-high" phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance "AXL-high" phenotype. > 50% of melanomas progress with enriched "AXL-high" populations, and because AXL is linked to de-differentiation and invasiveness avoiding an "AXL-high relapse" is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF-induced expression of endothelin 1 (EDN1)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28604685/a-tnf-jnk-axl-erk-signaling-axis-mediates-primary-resistance-to-egfr-inhibition-in-glioblastoma
#10
Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib
Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in turn of c-Jun N-terminal kinase (JNK), the Axl receptor tyrosine kinase and extracellular signal-regulated kinases (ERK)...
June 12, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28599309/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#11
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596680/role-of-axl-in-invasion-and-drug-resistance-of-colon-and-breast-cancer-cells-and-its-association-with-p53-alterations
#12
Wael M Abdel-Rahman, Noura A Al-Khayyal, Vidhya A Nair, S R Aravind, Maha Saber-Ayad
AIM: To characterize AXL receptor tyrosine kinase (AXL) expression in relationship to tumor protein P53 (TP53 gene, p53 protein) and its role in tumor invasion and response to therapy. METHODS: We used 14 cell lines, including 3 isogenic pairs carrying mutant/knockout p53, to gain insight into the relationship between AXL and TP53. These included HCT116, HCT116.p53 mutant, RKO, and RKO.p53(-/-) lines (all from colon cancers) as well as breast cancer cell lines MCF7 and 1001 (MCF7-p53 mutant clone)...
May 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28596300/clear-cell-renal-cell-carcinoma-is-linked-to-epithelial-to-mesenchymal-transition-and-to-fibrosis
#13
Lea Landolt, Øystein Eikrem, Philipp Strauss, Andreas Scherer, David H Lovett, Christian Beisland, Kenneth Finne, Tarig Osman, Mohammad M Ibrahim, Gro Gausdal, Lavina Ahmed, James B Lorens, Jean Paul Thiery, Tuan Zea Tan, Miroslav Sekulic, Hans-Peter Marti
Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq(®) Access library preparation protocol and TruSeq Small RNA library preparation kit...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28594431/distinguishing-two-ammonium-and-a-triazolium-sites-of-interactions-in-a-three-station-2-rotaxane-molecular-shuttle
#14
Frédéric Coutrot, Philip Waelès, Karine Fournel-Marotte
In this paper, we report on the synthesis of a tri-stable [2]rotaxane molecular shuttle, in which the motion of the macrocycle is triggered by either specific protonation/deprotonation or specific carbamoylation/decarbamoylation of an alkylbenzylamine. The threaded axle is surrounded by a dibenzo[24]crown[8](DB24C8) and contains three sites of different affinities for the macrocycle. An Nmethyltriazolium acts as a molecular station of weak affinity for the DB24C8 and is located in the core of the encircled molecular axle...
June 8, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28590526/gas-phase-fragmentation-of-1-adamantylbisimidazolium-salts-and-their-complexes-with-cucurbit-7-uril-studied-using-selectively-2-h-labeled-guest-molecules
#15
Andrea Čablová, Michal Rouchal, Barbora Hanulíková, Jan Vícha, Lenka Dastychová, Zdeňka Prucková, Robert Vícha
RATIONALE: Bisimidazolium salts (BIMs) represent an interesting family of ditopic ligands that are used in the construction of supramolecular systems with hosts based on cyclodextrins or cucurbit[n]urils. Understanding the fragmentation mechanism of individual BIMs and how this mechanism changes after complexation with cucurbit[n]urils can bring new insight into the intrinsic host-guest relationship, thereby allowing utilization of mass spectrometry to describe binding behavior. METHODS: Selectively (2) H-labeled bisimidazolium salts were prepared and fully characterized by spectroscopic methods...
June 7, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28589904/decitabine-vorinostat-combination-treatment-in-acute-myeloid-leukemia-activates-pathways-with-potential-for-novel-triple-therapy
#16
Christine S Young, Kathryn M Clarke, Laura M Kettyle, Alexander Thompson, Ken I Mills
Despite advancements in cancer therapeutics, acute myeloid leukemia patients over 60 years old have a 5-year survival rate of less than 8%. In an attempt to improve this, epigenetic modifying agents have been combined as therapies in clinical studies. In particular combinations with Decitabine and Vorinostat have had varying degrees of efficacy. This study therefore aimed to understand the underlying molecular mechanisms of these agents to identify potential rational epi-sensitized combinations.Combined Decitabine-Vorinostat treatment synergistically decreased cell proliferation, induced apoptosis, enhanced acetylation of histones and further decreased DNMT1 protein with HL-60 cells showing a greater sensitivity to the combined treatment than OCI-AML3...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588707/identification-of-potential-target-genes-associated-with-the-effect-of-propranolol-on-angiosarcoma-via-microarray-analysis
#17
Shiyong Zhou, Pengfei Liu, Wenhua Jiang, Huilai Zhang
The purpose of the present study was to explore the effect of propranolol on angiosarcoma, and the potential target genes involved in the processes of proliferation and differentiation of angiosarcoma tumor cells. The mRNA expression profile (GSE42534) was downloaded from the Gene Expressed Omnibus database, including three samples without propranolol treatment (control), three samples with propranolol treatment for 4 h and three samples with propranolol treatment for 24 h. The differentially expressed genes (DEGs) in angiosarcoma tumor cells with or without propranolol treatment were obtained via the limma package of R and designated DEGs-4 h and DEGs-24 h...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28577322/programed-synthesis-of-molecular-wires-with-fixed-insulation-and-defined-length-based-on-oligo-phenylene-ethynylene-and-permethylated-%C3%AE-cyclodextrins
#18
Hiroshi Masai, Tetsuaki Fujihara, Yasushi Tsuji, Jun Terao
The development of new tuning methods for π-conjugated insulated molecular wires with strictly defined axle lengths and macrocyclic covering positions/degrees, would provide unprecedented insight into insulation effects in functionalized materials. Herein, iterative reactions of oligo(phenylene ethynylene) (OPE) linked with permethylated α-cyclodextrins were carried out to fabricate insulated molecular wires with a defined length and insulation on the desired area. Insulated OPEs were elongated in a stepwise manner using sequential coupling/deprotection reactions...
June 3, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28576947/the-slow-cycling-phenotype-a-growing-problem-for-treatment-resistance-in-melanoma
#19
REVIEW
Antonio Ahn, Aniruddha Chatterjee, Michael R Eccles
Treatment resistance in metastatic melanoma is a longstanding issue. Current targeted therapy regimes in melanoma largely target the proliferating cancer population, leaving slow-cycling cancer cells undamaged. Consequently, slow-cycling cells are enriched upon drug therapy and can remain in the body for years until acquiring proliferative potential that triggers cancer relapse. Here we overview the molecular mechanisms of slow-cycling cells that underlie treatment resistance in melanoma. Three main areas of molecular reprogramming are discussed that mediate slow cycling and treatment resistance...
June 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28564701/the-impact-of-lens-opacity-on-sd-oct-retinal-nerve-fiber-layer-and-bruch-s-membrane-opening-measurements-using-the-anatomical-positioning-system-aps
#20
Matthias M Mauschitz, Felix Roth, Frank G Holz, Monique M B Breteler, Robert P Finger
Purpose: To evaluate the impact of lens opacity on retinal nerve fiber layer thickness (RNFLT) and Bruch's membrane opening (BMO) measurements. Methods: Fifty-nine randomly selected patients without any other relevant ocular pathology undergoing elective routine cataract surgery in two specialized eye clinics were enrolled. RNFLT, BMO area, and BMO minimum rim width (BMO-MRW) were assessed with the Heidelberg Engineering Spectralis OCT using the anatomical positioning system (APS) prior to and 1 day after cataract surgery using a ring scan at different eccentricities of the disc (3...
May 1, 2017: Investigative Ophthalmology & Visual Science
keyword
keyword
74916
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"