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Receptor tyrosine kinase

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https://www.readbyqxmd.com/read/28811962/an-ror1-bi-specific-t-cell-engager-provides-effective-targeting-and-cytotoxicity-against-a-range-of-solid-tumors
#1
Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M Davidoff, Claudio Sorio, Amit Chunilal Nathwani, Marco Della Peruta
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811476/lyn-and-fyn-function-as-molecular-switches-that-control-immunoreceptors-to-direct-homeostasis-or-inflammation
#2
Sanae Ben Mkaddem, Amaya Murua, Héloise Flament, Dimitri Titeca-Beauport, Carine Bounaix, Luca Danelli, Pierre Launay, Marc Benhamou, Ulrich Blank, Eric Daugas, Nicolas Charles, Renato C Monteiro
Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28811127/attenuation-of-sunitinib-induced-cardiotoxicity-through-the-a3-adenosine-receptor-activation
#3
Hardip Sandhu, Samantha Cooper, Afthab Hussain, Christopher Mee, Helen Maddock
Sunitinib is an anti-cancer tyrosine kinase inhibitor associated with severe cardiotoxic adverse effects. Using rat Langendorff heart model and human acute myeloid leukemia 60 (HL60) cell line we detected the involvement of protein kinase C (PKC) α during Sunitinib-induced cardiotoxicity and the effect of Sunitinib on cancer progression. The cardioprotective and anti-cancer properties of the A3 adenosine receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) were investigated...
August 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#4
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28808993/multiplexed-liquid-chromatography-multiple-reaction-monitoring-mass-spectrometry-quantification-of-cancer-signaling-proteins
#5
Yi Chen, Kate J Fisher, Mark Lloyd, Elizabeth R Wood, Domenico Coppola, Erin Siegel, David Shibata, Yian A Chen, John M Koomen
Quantitative evaluation of protein expression across multiple cancer-related signaling pathways (e.g., Wnt/β-catenin, TGF-β, receptor tyrosine kinases (RTK), MAP kinases, NF-κB, and apoptosis) in tumor tissues may enable the development of a molecular profile for each individual tumor that can aid in the selection of appropriate targeted cancer therapies. Here, we describe the development of a broadly applicable protocol to develop and implement quantitative mass spectrometry assays using cell line models and frozen tissue specimens from colon cancer patients...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808573/osimertinib-induced-interstitial-lung-disease-in-a-patient-with-non-small-cell-lung-cancer-pretreated-with-nivolumab-a-case-report
#6
Osamu Takakuwa, Tetsuya Oguri, Takehiro Uemura, Kazuki Sone, Satoshi Fukuda, Minami Okayama, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Ken Maeno, Akio Niimi
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#7
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28808303/nlrp3-inflammasome-activation-results-in-liver-inflammation-and-fibrosis-in-mice-infected-with-schistosoma-japonicum-in-a-syk-dependent-manner
#8
Ya-Qi Lu, Shan Zhong, Nan Meng, Yin-Ping Fan, Wang-Xian Tang
Granulomatous and fibrosing inflammation in response to soluble egg antigen (SEA) from Schistosoma japonicum (S. japonicum) is the main pathological process of S. japonicum infection. Inflammasome activation has recently been implicated in the pathogenesis of liver disease. However, the role of inflammasome activation in schistosomiasis-associated liver fibrosis (SSLF) has not been extensively studied. In this study, it is demonstrated that the NLRP3 inflammasome is markedly activated in mouse HSCs both in vivo and in vitro during S...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#9
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808012/bdnf-trkb-controls-cocaine-induced-dendritic-spines-in-rodent-nucleus-accumbens-dissociated-from-increases-in-addictive-behaviors
#10
Ethan M Anderson, Anne Marie Wissman, Joyce Chemplanikal, Nicole Buzin, Daniel Guzman, Erin B Larson, Rachael L Neve, Eric J Nestler, Christopher W Cowan, David W Self
Chronic cocaine use is associated with prominent morphological changes in nucleus accumbens shell (NACsh) neurons, including increases in dendritic spine density along with enhanced motivation for cocaine, but a functional relationship between these morphological and behavioral phenomena has not been shown. Here we show that brain-derived neurotrophic factor (BDNF) signaling through tyrosine kinase B (TrkB) receptors in NACsh neurons is necessary for cocaine-induced dendritic spine formation by using either localized TrkB knockout or viral-mediated expression of a dominant negative, kinase-dead TrkB mutant...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807678/metformin-lowers-%C3%AE-synuclein-phosphorylation-and-upregulates-neurotrophic-factor-in-the-mptp-mouse-model-of-parkinson-s-disease
#11
Nikita Katila, Sunil Bhurtel, Sina Shadfar, Sunil Srivastav, Sabita Neupane, Uttam Ojha, Gil-Saeng Jeong, Dong-Young Choi
In spite of the massive research for the identification of neurorestorative or neuroprotective intervention for curing Parkinson's disease (PD), there is still lack of clinically proven neuroprotective agents. Metformin, a common anti-hyperglycemic drug has been known to possess neuroprotective properties. However, specific mechanisms by which metformin protects neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity remain to be elucidated. In this study, we assessed the neuroprotective effects of metformin in the subchronic MPTP model of PD, and explored its feasible mechanisms for neuroprotection...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807234/third-generation-egfr-tkis-in-egfr-mutated-nsclc-where-are-we-now-and-where-are-we-going
#12
REVIEW
A Russo, T Franchina, G R R Ricciardi, V Smiroldo, M Picciotto, M Zanghì, C Rolfo, V Adamo
The therapeutic landscape of Non Small Lung Cancer (NSCLC) has been profoundly changed over the last decade with the clinical introduction of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) and the discovery of EGFR activating mutations as the major predictive factor to these agents. Despite impressive clinical activity against EGFR-mutated NSCLCs, the benefit seen with 1st and 2nd generation EGFR TKIs is usually transient and virtually all patients become resistant. Several different mechanisms of acquired resistance have been reported to date, but the vast majority of patients develop a secondary exon 20 mutation in the ATP-binding site of EGFR, namely T790M...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28806950/precision-medicine-approaches-to-lung-adenocarcinoma-with-concomitant-met-and-her2-amplification
#13
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
BACKGROUND: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models. METHODS: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28806774/fibroblast-growth-factor-receptor-1-mediates-internalization-of-pathogenic-spotted-fever-rickettsiae-into-host-endothelium
#14
Abha Sahni, Jignesh Patel, Hema P Narra, Casey L C Schroeder, David H Walker, Sanjeev K Sahni
Rickettsial infections continue to cause serious morbidity and mortality in severe human cases around the world. Host cell adhesion and invasion is an essential requisite for intracellular growth, replication, and subsequent dissemination of pathogenic rickettsiae. Heparan sulfate proteoglycans [HSPGs] facilitate the interactions between fibroblast growth factor(s) and their tyrosine kinase receptors resulting in receptor dimerization/activation and have been implicated in bacterial adhesion to target host cells...
2017: PloS One
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#15
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#16
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28805349/crispr-assisted-receptor-deletion-reveals-distinct-roles-for-erbb2-and-erbb3-in-skin-keratinocytes
#17
Maik Dahlhoff, Nadege Gaborit, Sebastian Bultmann, Heinrich Leonhardt, Yosef Yarden, Marlon R Schneider
While the epidermal growth factor receptor (EGFR) is an established regulator of skin development and homeostasis, the functions of the related tyrosine kinase receptors ERBB2 and ERBB3 in this tissue have only recently been examined. Previously reported, skin-specific deletion of each of these receptors in mice resulted in similar defects in keratinocyte proliferation and migration, resulting in impaired wound healing and tumorigenesis. Because both ERBB2 and ERBB3 are targets for treating an array of cancer types, it is important to examine the consequences of receptor inhibition in human keratinocytes...
August 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28805145/pdgf-vegf-related-receptor-affects-transglutaminase-activity-to-control-cell-migration-during-crustacean-hematopoiesis
#18
Kingkamon Junkunlo, Chadanat Noonin, Kenneth Söderhäll, Irene Söderhäll
The platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor whose ligand is PDGF, is crucial in the transduction of extracellular signals into cells and mediates numerous processes, such as cell proliferation, differentiation, survival and migration. We demonstrate the important roles of a receptor tyrosine kinase related to the PDGF/VEGF family protein (PVR) in controlling hematopoietic progenitor cell migration by affecting extracellular transglutaminase (TGase) activity. Pl_PVR1, GenBank accession number KY444650, is highly expressed in hemocytes and the hematopoietic tissue (HPT)...
August 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28801183/paired-phase-ii-studies-of-erlotinib-bevacizumab-for-advanced-bronchioloalveolar-carcinoma-or-never-smokers-with-advanced-non-small-cell-lung-cancer-swog-s0635-and-s0636-trials
#19
Howard L West, James Moon, Antoinette J Wozniak, Philip Mack, Fred R Hirsch, Martin J Bury, Myron Kwong, Dorothy D Nguyen, Dennis F Moore, Jieling Miao, Mary Redman, Karen Kelly, David R Gandara
BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636)...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28800750/angiopoietin-1-deficiency-increases-tumor-metastasis-in-mice
#20
Iacovos P Michael, Martina Orebrand, Marta Lima, Beatriz Pereira, Olga Volpert, Susan E Quaggin, Marie Jeansson
BACKGROUND: Angipoietin-1 activation of the tyrosine kinase receptor Tek expressed mainly on endothelial cells leads to survival and stabilization of endothelial cells. Studies have shown that Angiopoietin-1 counteracts permeability induced by a number of stimuli. Here, we test the hypothesis that loss of Angiopoietin-1/Tek signaling in the vasculature would increase metastasis. METHODS: Angiopoietin-1 was deleted in mice just before birth using floxed Angiopoietin-1 and Tek mice crossed to doxycycline-inducible bitransgenic ROSA-rtTA/tetO-Cre mice...
August 11, 2017: BMC Cancer
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