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Receptor tyrosine kinase

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https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#1
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441383/the-oral-vegf-receptor-tyrosine-kinase-inhibitor-pazopanib-in-combination-with-the-mek-inhibitor-trametinib-in-advanced-cholangiocarcinoma
#2
Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Vivek Subbiah, Ralph Zinner, Nilofer S Azad
BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28440510/migration-of-oral-squamous-cell-carcinoma-cells-are-induced-by-hgf-c-met-signalling-via-lamellipodia-and-filopodia-formation
#3
Hiroki Yasui, Yuichi Ohnishi, Masahiro Nakajima, Masami Nozaki
The activation of receptor tyrosine kinases (RTKs) results in cellular effects including cell proliferation, survival, migration and invasion; RTKs also play an important role in tumourigenesis. It has been reported that EGFR signalling controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells but not of HSC4 cells, although the proliferation of HSC4 cells is regulated by EGF/EGFR. In the present study, we investigated the roles of EGFR and the c-Met signalling pathway in cell migration via filopodia and lamellipodia formation, which may be prerequisites for migration...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440492/axl-and-gas6-co-expression-in-lung-adenocarcinoma-as-a-prognostic-classifier
#4
Masahiro Seike, Cheol-Hong Kim, Fenfei Zou, Rintaro Noro, Mika Chiba, Arimi Ishikawa, Shinobu Κunugi, Kaoru Kubota, Akihiko Gemma
AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and migration, is also associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated the prognostic significance of the expression of AXL and/or its ligand, growth arrest-specific 6 (GAS6), in completely resected lung AD. We evaluated the relationship between AXL, GAS6, and vimentin expression, as determined by immunohistochemistry (IHC) analysis, with overall survival and disease-free survival in 113 patients with stages I-III lung AD...
April 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440469/clinical-significance-of-akt2-in-advanced-pancreatic-cancer-treated-with-erlotinib
#5
Eri Banno, Yosuke Togashi, Marco A de Velasco, Takuro Mizukami, Yu Nakamura, Masato Terashima, Kazuko Sakai, Yoshihiko Fujita, Ken Kamata, Masayuki Kitano, Masatoshi Kudo, Kazuto Nishio
Akt2 is an isoform of Akt, and an association between Akt2 and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been suggested in pancreatic cancer (PC) in vitro. In this study, we investigated the association between Akt2 expression as evaluated using immunohistochemistry and the outcome of patients with advanced PC who had received treatment with erlotinib (an EGFR-TKI). Although the difference was not significant, patients with high levels of Akt2 expression tended to have a poorer response and a shorter progression-free survival period after treatment with erlotinib plus gemcitabine than those with low expression levels (P=0...
April 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28439883/an-update-for-richter-syndrome-new-directions-and-developments
#6
REVIEW
Toby A Eyre, Anna Schuh
High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally related diffuse large B cell type RS is a chemotherapy-resistant and devastating disease. Patients are typically elderly, immunosuppressed and present with a rapidly deteriorating performance status. Historical outcomes suggest a median overall survival of approximately 8 months. RS remains is an area of high unmet clinical need. The molecular profile and treatment needs of patients are likely to change over time with the advent of novel B cell receptor inhibitors, monoclonal antibodies and BH3 mimetics...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28438610/hyperglycemia-increases-interstitial-cells-of-cajal-via-mapk1-and-mapk3-signaling-to-etv1-and-kit-leading-to-rapid-gastric-emptying
#7
Yujiro Hayashi, Yoshitaka Toyomasu, Siva Arumugam Saravanaperumal, Michael R Bardsley, John A Smestad, Andrea Lorincz, Seth T Eisenman, Gianluca Cipriani, Molly H Nelson Holte, Fatimah J Al Khazal, Sabriya A Syed, Gabriella B Gajdos, Kyoung Moo Choi, Gary J Stoltz, Katie E Miller, Michael L Kendrick, Brian P Rubin, Simon J Gibbons, Adil E Bharucha, David R Linden, Louis James Maher, Gianrico Farrugia, Tamas Ordog
BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in diabetic gastroparesis. However, in approximately 20% of patients with diabetes, gastric emptying (GE) is accelerated. GE is also faster in obese individuals, and is associated with increased blood levels of glucose in patients with type 2 diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic states characterized by rapid GE, we studied mice with mutation of the leptin receptor (Lepr(db/db)), which in our colony had accelerated GE...
April 21, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28438385/small-molecules-inhibit-stat3-activation-autophagy-and-cancer-cell-anchorage-independent-growth
#8
Donghui Zhou, Maya Z Springer, David Xu, Degang Liu, Andy Hudmon, Kay F Macleod, Samy O Meroueh
Triple-negative breast cancers (TNBCs) lack the signature targets of other breast tumors, such as HER2, estrogen receptor, and progesterone receptor. These aggressive basal-like tumors are driven by a complex array of signaling pathways that are activated by multiple driver mutations. Here we report the discovery of 6 (KIN-281), a small molecule that inhibits multiple kinases including maternal leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X-linked (BMX) with single-digit micromolar IC50s...
March 23, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28437395/global-survey-of-the-immunomodulatory-potential-of-common-drugs
#9
Gregory I Vladimer, Berend Snijder, Nikolaus Krall, Johannes W Bigenzahn, Kilian V M Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger, Giulio Superti-Furga
Small-molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules, as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Unexpectedly, ∼10% of the agents tested affected these cell-cell interactions differentially...
April 24, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28437026/analyzing-epidermal-growth-factor-receptor-mutation-status-changes-in-advanced-non-small-cell-lung-cancer-at-different-sampling-time-points-of-blood-within-one%C3%A2-day
#10
Jin Wang, Hua Bai, Chaoyu Hong, Jie Wang, Tong-Hua Mei
BACKGROUND: We investigated whether different sampling time-points within one day would influence epidermal growth factor receptor mutation (EGFRm) status in plasma and evaluated the clinical outcomes according to the quantity analysis of EGFRm in circulating tumor DNA (ctDNA) in non-small-cell lung cancer (NSCLC). METHODS: EGFR-tyrosine kinase inhibitor naïve advanced NSCLC patients who carried EGFRm in both tissues and ctDNA were enrolled in this study. Plasma samples were collected at three time-points within one day (at 8 am, 11 am and 2 pm) for EGFRm analysis by droplet digital PCR...
April 24, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28436622/congenital-intestinal-fibrosarcoma-with-rapid-recurrence-requiring-adjuvant-chemotherapy
#11
Wing Shan Queenie See, Daniel Ka Leung Cheuk, Ka Fai To, Philip Pun Ching Ip, Alan Kwok Shing Chiang, Shau Yin Ha, Godfrey Chi Fung Chan
A total of 16 cases of congenital fibrosarcoma have been reported from 1975 to March 2015. Five of the 16 had abnormal fusion between erythroblast transformation specific translocation variant 6 and neurotrophin recptor gene neurotrophic tyrosine kinase, receptor, type 3 (ETV6-NTRK3); in another five out of 16 this was absent, and six were not tested. All were managed by surgical resection but none involved metastasis. Herein we report the case of a newborn baby girl with congenital fibrosarcoma negative for ETV6-NTRK3 gene fusion, who presented with ileal perforation and positive resection margin...
April 24, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28436498/integrative-meta-modeling-identifies-endocytic-vesicles-late-endosome-and-the-nucleus-as-the-cellular-compartments-primarily-directing-rtk-signaling
#12
Jared C Weddell, Princess I Imoukhuede
Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms. Therefore, towards understanding the differential endocytic compartment signaling roles, and identifying how to achieve signal transduction control for RTKs, we delineate how endocytosis regulates RTK signaling...
April 24, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28436250/effect-of-treatment-dose-reductions-in-the-setting-of-hand-foot-syndrome-on-survival-outcomes-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-vascular-endothelial-growth-factor-receptor-inhibitors
#13
Erin B Bailey, Joseph Merriman, Benjamin Maughan, Austin Poole, Srinivas K Tantravahi, Archana M Agarwal, Julia A Batten, Shiven B Patel, Sumanta K Pal, David D Stenehjem, Neeraj Agarwal
Purpose Hand-foot syndrome is a common dose limiting toxicity of vascular endothelial growth factor receptor tyrosine kinase inhibitors used for treatment of patients with metastatic renal cell carcinoma. The effect of treatment dose reductions, in the context of hand-foot syndrome, on survival outcomes is reported. Methods This was a retrospective case series of patients receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors from 1 January 2004 to 31 October 2013. The main outcomes were progression-free and overall survival in these patients experiencing hand-foot syndrome and undergoing treatment dose reductions...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28435529/-18-f-labeled-pyrido-3-4-d-pyrimidine-as-an-effective-probe-for-imaging-of-l858r-mutant-epidermal-growth-factor-receptor
#14
Hiroyuki Kimura, Haruka Okuda, Masumi Ishiguro, Kenji Arimitsu, Akira Makino, Ryuichi Nishii, Anna Miyazaki, Yusuke Yagi, Hiroyuki Watanabe, Ikuo Kawasaki, Masahiro Ono, Hideo Saji
In nonsmall-cell lung carcinoma patients, L858R mutation of epidermal growth factor receptor (EGFR) is often found, and molecular target therapy using EGFR tyrosine kinase inhibitors is effective for the patients. However, the treatment frequently develops drug resistance by secondary mutation, of which approximately 50% is T790M mutation. Therefore, the ability to predict whether EGFR will undergo secondary mutation is extremely important. We synthesized a novel radiofluorinated 4-(anilino)pyrido[3,4-d]pyrimidine derivative ([(18)F]APP-1) and evaluated its potential as a positron emission tomography (PET) imaging probe to discriminate the difference in mutations of tumors...
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28435290/altered-status-of-programmed-death-ligand-1-after-recurrence-in-resected-lung-adenocarcinoma-patients
#15
Jun Chen, Hui Li, Ronglin Pang, Jia Huang
PURPOSE: Programmed death-ligand 1 (PD-L1) is found to be overexpressed in non-small cell lung cancer. The present study intended to evaluate the status of PD-L1 expression in patients with resection and recurrent lung adenocarcinoma. PATIENTS AND METHODS: Matched resection and recurrent tumor samples were harvested from 65 lung adenocarcinoma patients. Immunohistochemistry was used to evaluate the status of PD-L1 expression. Kaplan-Meier method was used for survival analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28435285/exploratory-cohort-study-and-meta-analysis-of-bim-deletion-polymorphism-in-patients-with-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer-treated-with-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#16
Si Sun, Hui Yu, Huijie Wang, Xinmin Zhao, Xintai Zhao, Xianghua Wu, Jie Qiao, Jianhua Chang, Jialei Wang
BACKGROUND: Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations might develop primary and secondary resistance to tyrosine kinase inhibitors (TKIs). The proapoptotic protein Bcl-2-like 11 (BIM) is a key modulator of apoptosis triggered by EGFR-TKIs. The recent studies have indicated that some patients with positive EGFR mutations were refractory to EGFR-TKIs if they harbored a BIM deletion polymorphism. The purpose of this study was to investigate whether BIM polymorphism predicts treatment efficacy of EGFR-TKIs in Chinese NSCLC patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28433077/development-and-clinical-utility-of-a-blood-based-test-service-for-the-rapid-identification-of-actionable-mutations-in-non-small-cell-lung-carcinoma
#17
Hestia Mellert, Trudi Foreman, Leisa Jackson, Dianna Maar, Scott Thurston, Kristina Koch, Amanda Weaver, Samantha Cooper, Nicholas Dupuis, Ubaradka G Sathyanarayana, Jakkie Greer, Westen Hahn, Dawne Shelton, Paula Stonemetz, Gary A Pestano
Nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746-A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK) transcripts 1/2/3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28432840/detection-of-egfr-mutations-in-patients-with-non-small-cell-lung-cancer-by-high-resolution-melting-comparison-with-other-methods
#18
Carlos Martínez-Carretero, Fernando Iguaz Pascual, Antonio Rus, Ivan Bernardo
BACKGROUND: The discovery of mutations in the epidermal growth factor receptor gene (EGFR) related to the clinical response to tyrosine kinase inhibitors, has transformed the management of non-small cell lung cancer (NSCLC). Several methods have been developed for determination of mutations in EGFR, with different sensitivity and potential ability to detect a different number of mutations. METHODS: We developed a screening method by high resolution melting (HRM) to detect EGFR mutations, and compared the results of 123 fixed in formalin and paraffin embedded (FFPE) tumor tissue samples with the detection of mutations by allele-specific PCR...
April 22, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28432761/protein-s-sulfhydration-by-hydrogen-sulfide-in-cardiovascular-system
#19
REVIEW
Guoliang Meng, Shuang Zhao, Liping Xie, Yi Han, Yong Ji
Hydrogen sulfide (H2 S), independent on any specific transporters, plays a number of biological effects on cardiovascular systems. However, the detailed mechanism of H2 S is not yet clear until now. Recently, a novel post-translational modification induced by H2 S, named S-sulfhydration, has been proposed. S-sulfhydration is a chemical modification on specific cysteine residues of target proteins by H2 S. There are several methods for S-sulfhydration detection, such as modified biotin switch assay, maleimide assay with fluorescent thiol modifying regents, tag-switch method and mass spectrometry...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432529/ginseng-derived-panaxadiol-saponins-promote-hematopoiesis-recovery-in-cyclophosphamide-induced-myelosuppressive-mice-potential-novel-treatment-of-chemotherapy-induced-cytopenias
#20
Xin Sun, Yan-Na Zhao, Song Qian, Rui-Lan Gao, Li-Ming Yin, Li-Pei Wang, Beng-Hock Chong, Su-Zhan Zhang
OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). METHODS: Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot...
April 22, 2017: Chinese Journal of Integrative Medicine
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