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https://www.readbyqxmd.com/read/27904686/fisetin-a-dietary-phytochemical-overcomes-erlotinib-resistance-of-lung-adenocarcinoma-cells-through-inhibition-of-mapk-and-akt-pathways
#1
Liang Zhang, Yi Huang, Wenlei Zhuo, Yi Zhu, Bo Zhu, Zhengtang Chen
Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904650/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#2
REVIEW
Jose Manuel Ruiz-Morales, Daniel Y C Heng
The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI)...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27899998/expression-level-of-crkl-and-axl-combined-with-exon-19-deletion-in-egfr-and-alk-status-confer-differential-prognosis-of-lung-adenocarcinoma-subtypes
#3
Yi-Ran Cai, Yu-Jie Dong, Hong-Bo Wu, Da-Ping Yu, Li-Juan Zhou, Dan Su, Li Zhang, Xue-Jing Chen
Non-small cell lung cancer (NSCLC) is a lethal cancer-related disease in population. Adenocarcinoma (AC) is subclassified into several subtypes based on the new classification by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society in 2011. Correlation between original expression of Crk-like (CRKL) and anaplastic lymphoma receptor tyrosine kinase in diverse histological components of AC and epidermal growth factor receptor (EGFR) or ALK status was evaluated by immunohistochemistry and sequencing in present study...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27897389/new-insights-into-the-difference-between-rotaxane-and-pseudorotaxane
#4
He-Lue Sun, Heng-Yi Zhang, Zhen Dai, Xu Han, Yu Liu
Rotaxane and pseudorotaxane are two sorts of different mechanically interlocked molecular architectures, and there is obvious topological difference and boundary between them. In this work, a "suggested [2]rotaxane 1α-CD" was constructed based on an axle molecule 1 bearing two terminal ferrocene groups and a wheel component α-cyclodextrin (α-CD), but the result obtained indicated that the ferrocene group cannot prevent α-CD dethreading under UV irradiation. That is, 1α-CD is just a pseudo[2]rotaxane...
November 29, 2016: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#5
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27893463/inhibition-of-the-gas6-axl-pathway-augments-the-efficacy-of-chemotherapies
#6
Mihalis S Kariolis, Yu Rebecca Miao, Anh Diep, Shannon E Nash, Monica M Olcina, Dadi Jiang, Douglas S Jones, Shiven Kapur, Irimpan I Mathews, Albert C Koong, Erinn B Rankin, Jennifer R Cochran, Amato J Giaccia
The AXL receptor and its activating ligand, growth arrest-specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. However, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. Here, we have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27882820/phase-ii-randomized-study-of-the-igf-1r-pathway-modulator-axl1717-compared-to-docetaxel-in-patients-with-previously-treated-locally-advanced-or-metastatic-non-small-cell-lung-cancer
#7
Michael Bergqvist, Georg Holgersson, Igor Bondarenko, Elena Grechanaya, Alexey Maximovich, György Andor, Maria Klockare, Marcus Thureson, Markus Jerling, Johan Harmenberg
BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT). MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype...
November 24, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27882345/institutional-implementation-of-clinical-tumor-profiling-on-an-unselected-cancer-population
#8
Lynette M Sholl, Khanh Do, Priyanka Shivdasani, Ethan Cerami, Adrian M Dubuc, Frank C Kuo, Elizabeth P Garcia, Yonghui Jia, Phani Davineni, Ryan P Abo, Trevor J Pugh, Paul van Hummelen, Aaron R Thorner, Matthew Ducar, Alice H Berger, Mizuki Nishino, Katherine A Janeway, Alanna Church, Marian Harris, Lauren L Ritterhouse, Joshua D Campbell, Vanesa Rojas-Rudilla, Azra H Ligon, Shakti Ramkissoon, James M Cleary, Ursula Matulonis, Geoffrey R Oxnard, Richard Chao, Vanessa Tassell, James Christensen, William C Hahn, Philip W Kantoff, David J Kwiatkowski, Bruce E Johnson, Matthew Meyerson, Levi A Garraway, Geoffrey I Shapiro, Barrett J Rollins, Neal I Lindeman, Laura E MacConaill
BACKGROUND. Comprehensive genomic profiling of a patient's cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population has yet to be reported. METHODS. We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27876698/axl-in-ovarian-cancer-a-step-forward-for-clinical-breakthrough
#9
EDITORIAL
Marialuisa Sensi, Silvana Canevari, Antonella Tomassetti
No abstract text is available yet for this article.
November 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27874141/halogen-bonding-rotaxanes-for-nitrate-recognition-in-aqueous-media
#10
Sean W Robinson, Paul D Beer
Targeting the biologically and environmentally important nitrate anion, halogen bonding (XB) has been incorporated into three novel [2]rotaxane structural frameworks via an axle component containing covalently linked 3,5-bis-iodotriazole pyridine-pyridinium motifs. This has enabled the recognition of nitrate in aqueous media containing up to 90% water with equivalent binding affinity to chloride, illustrating the potency of XB for anion recognition in highly competitive aqueous solvent mixtures.
November 22, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27872884/data-on-clinical-characteristics-of-a-heart-failure-patients-cohort-with-reduced-ejection-fraction-and-analysis-of-the-circulating-values-of-five-different-heart-failure-biomarkers-high-sensitivity-troponin-t-galectin-3-c-terminal-propeptide-of-type-i-procollagen
#11
M Batlle, B Campos, M Farrero, M Cardona, B González, M A Castel, J Ortiz, E Roig, M J Pulgarín, J Ramírez, J L Bedini, M Sabaté, P García de Frutos, F Pérez-Villa
In this article, the full description of a heart failure with reduced ejection fraction (HF_REF) cohort of 192 patients is provided. Tables with the baseline demographic, prior history, ECG parameters, echocardiographic parameters, laboratory values and pharmacological treatment of these patients are included. Also, the quartile values of the analyzed circulating biomarkers: high sensitivity Troponin T (hs-TnT), galectin-3 (Gal-3), C-terminal propeptide of type I procollagen (CICP), soluble AXL (sAXL) and Brain Natriuretic Peptide (BNP) are given...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27871779/intraocular-pressure-measurement-after-dsaek-by-icare-goldmann-applanation-and-dynamic-contour-tonometry-a-comparative-study
#12
A Achiron, O Blumenfeld, H Avizemer, L Karmona, G Leybowich, V Man, E Bartov, Z Burgansky-Eliash
PURPOSE: Corneal thickness inevitably increases following Descemet's stripping automated endothelial keratoplasty (DSAEK), owing to the addition of a donor graft. The current study compares different devices in assessing post-DSAEK intraocular pressure (IOP). METHODS: We compared IOP values measured by the Goldmann tonometry (GAT), iCare rebound tonometry (iCare) and Pascal dynamic contour tonometry (PDCT) in eyes following DSAEK. Agreement between measurements was calculated with correlation analysis and Bland-Altman plots...
November 18, 2016: Journal Français D'ophtalmologie
https://www.readbyqxmd.com/read/27869170/androgen-receptor-promotes-melanoma-metastasis-via-altering-the-mirna-539-3p-usp13-mitf-axl-signals
#13
Y Wang, Z Ou, Y Sun, S Yeh, X Wang, J Long, C Chang
Early studies demonstrated that male melanoma patients have worse survival than female patients, yet the detailed mechanisms for this gender difference remain unclear. We analyzed around 100 cases of human melanoma and found that androgen receptor (AR) positive melanoma patients have worse survival outcomes compared with AR-negative melanoma patients. Here we report that AR can have positive roles to increase melanoma cell invasion in multiple cell lines in vitro and a mouse model in vivo. Mechanism dissection suggest that AR increases melanoma cell invasion via modulating the MITF-AXL signals via altering the miRNA-539-3p/USP13 signaling to increase MITF protein degradation through a reduction of de-ubiquitination...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27856601/axl-blockade-by-bgb324-inhibits-bcr-abl-tyrosine-kinase-inhibitor-sensitive-and-resistant-chronic-myeloid-leukemia
#14
Isabel Ben Batalla, Robert Erdmann, Heather Jørgensen, Rebecca Mitchell, Thomas Ernst, Gunhild von Amsberg, Philippe Schafhausen, Janna L Velthaus, Stephen Rankin, Richard E Clark, Steffen Koschmieder, Alexander Schultze, Subir Mitra, Peter Vandenberghe, Tim H Brümmendorf, Peter Carmeliet, Andreas Hochhaus, Klaus Pantel, Carsten Bokemeyer, G Vignir Helgason, Tessa L Holyoake, Sonja Loges
PURPOSE: BCR-ABL kinase inhibitors are employed successfully for chronic myeloid leukemia (CML) treatment. However, resistant disease and persistence of BCR-ABL1-independent leukemia stem and progenitor cells (LSPC) remain clinical challenges. The receptor tyrosine kinase Axl can mediate survival and therapy resistance of different cancer cells. We investigated the therapeutic potential of Axl inhibition in CML. EXPERIMENTAL DESIGN: We used primary cells from CML patients and TKI-sensitive and -resistant BCR-ABL1+ CML cell lines and a novel Ponatinib-resistant cell line KCL-22 PonR...
November 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27852702/gas6-axl-signaling-regulates-self-renewal-of-chronic-myelogenous-leukemia-stem-cells-by-stabilizing-%C3%AE-catenin
#15
Yanli Jin, Danian Nie, Juan Li, Xin Du, Yuhong Lu, Yangqiu Li, Chang Liu, Jingfeng Zhou, Jingxuan Pan
PURPOSE: Quiescent leukemia stem cells (LSCs) are important resources of resistance and relapse in chronic myelogenous leukemia (CML). Thus, strategies eradicating CML LSCs are required for cure. In this study, we discovered that AXL tyrosine kinase was selectively overexpressed in primary CML CD34+ cells. However, the role of AXL and its ligand Gas6 secreted by stromal cells in the regulation of self-renewal capacity of LSCs has not been well investigated. EXPERIMENTAL DESIGN: The function of CML CD34+ cells was evaluated by flow cytometer, CFC/replating, long-term culture-initiating cells (LTC-IC), CML mouse model driven by human BCR-ABL gene and NOD-scid-IL2Rg-/- (NSI) mice...
November 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27843613/mechanisms-of-resistance-to-egfr-targeted-drugs-lung-cancer
#16
REVIEW
Floriana Morgillo, Carminia Maria Della Corte, Morena Fasano, Fortunato Ciardiello
Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains unfavourable because of the occurrence of either intrinsic or acquired resistance. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing EGFR-TKIs resistance mechanisms discovered in preclinical models and in patients with NSCLC...
2016: ESMO Open
https://www.readbyqxmd.com/read/27842445/cabozantinib-in-genitourinary-malignancies
#17
Tian Zhang, Se Eun Park, Cierra Hong, Daniel J George
Cabozantinib inhibits a variety of cellular receptors including VEGFR1-3, MET, AXL, RET, FLT3 and KIT. These signaling pathways have been shown to be important in genitourinary malignancies. Along its clinical development, it has shown most activity in advanced renal cell carcinoma; the METEOR study compared cabozantinib to everolimus and showed clinically and statistically significant improvements in both progression-free survival and overall survival. Herein, we review the development of cabozantinib in the genitourinary malignancies of renal cell carcinoma, prostate adenocarcinoma and urothelial carcinoma...
November 15, 2016: Future Oncology
https://www.readbyqxmd.com/read/27835047/cabozantinib-for-the-treatment-of-renal-cell-carcinoma
#18
Bernard Escudier, Julie C Lougheed, Laurence Albiges
Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy...
November 22, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27834845/the-receptor-tyrosine-kinase-axl-in-cancer-progression
#19
REVIEW
Erinn B Rankin, Amato J Giaccia
The AXL receptor tyrosine kinase (AXL) has emerged as a promising therapeutic target for cancer therapy. Recent studies have revealed a central role of AXL signaling in tumor proliferation, survival, stem cell phenotype, metastasis, and resistance to cancer therapy. Moreover, AXL is expressed within cellular components of the tumor microenvironment where AXL signaling contributes to the immunosuppressive and protumorigenic phenotypes. A variety of AXL inhibitors have been developed and are efficacious in preclinical studies...
November 9, 2016: Cancers
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#20
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
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