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EPHA2

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https://www.readbyqxmd.com/read/28523741/comparative-membrane-proteomics-analyses-of-breast-cancer-cell-lines-to-understand-the-molecular-mechanism-of-breast-cancer-brain-metastasis
#1
Wenjing Peng, Yu Zhang, Rui Zhu, Yehia Mechref
Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from 5 different breast cancer and a brain cancer cell lines...
May 19, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28507673/aiegen-based-theranostic-system-targeted-imaging-of-cancer-cells-and-adjuvant-amplification-of-antitumor-efficacy-of-paclitaxel
#2
Chao Chen, Zhegang Song, Xiaoyan Zheng, Zikai He, Bin Liu, Xuhui Huang, Deling Kong, Dan Ding, Ben Zhong Tang
Photosensitizers are generally treated as key components for photodynamic therapy. In contrast, we herein report an aggregation-induced emission luminogen (AIEgen)-based photosensitizer (TPE-Py-FFGYSA) that can serve as a non-toxic adjuvant to amplify the antitumor efficacy of paclitaxel, a well-known anticancer drug, with a synergistic effect of "0 + 1 > 1". Besides the adjuvant function, TPE-Py-FFGYSA can selectively light up EphA2 protein clusters overexpressed in cancer cells in a fluorescence turn-on mode, by taking advantage of the specific YSA peptide (YSAYPDSVPMMS)-EphA2 protein interaction...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28507312/design-and-evaluation-of-ephrina1-mutants-with-cerebral-protective-effect
#3
Yuanjun Zhu, Yuanqing Gao, Danping Zheng, Mengyang Shui, Kuai Yu, Xiaoyan Liu, Yuan Lin, Li Su, Wenxing Yang, Yinye Wang
The activation of EphA2 receptor by its natural ligand EphrinA1 causes blood brain barrier dysfunction, and inactivation of EphA2 reduces BBB damage in ischemic stroke. Thus, EphA2 targeted antagonists may serve as neuroprotective agents. We engineered four mutants of EphrinA1, EM1, EM2, EM3 and EM4, respectively. The computational analysis showed that these four mutants were capable of interacting with EphA2. Their potential neuroprotective effects were examined in mouse focal ischemia/reperfusion (I/R) model...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505517/a-modified-adenovirus-vector-mediated-antibody-screening-method-identifies-epha2-as-a-cancer-target
#4
Toshihiro Tanaka, Hiromi Yamada, Masahide Kuroki, Shohta Kodama, Kazuo Tamura, Yasushi Takamatsu
BACKGROUND: We constructed a genetically modified adenovirus vector incorporating an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33). Adv-FZ33 allows an antibody to redirect the vector to a target molecule on the cell surface. We attempted to search for target antigen candidates and antibodies that allowed highly selective gene transduction into malignant tumors. METHODS: Hybridoma libraries producing monoclonal antibodies (mAbs) were screened that increased transduction efficiency in cancer cell lines after cross-linking with Adv-FZ33...
May 12, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28487392/epha2-expression-regulates-inflammation-and-fibroproliferative-remodeling-in-atherosclerosis
#5
Alexandra C Finney, Steven D Funk, Jonette Green, Arif Yurdagul, Mohammad A Rana, Rebecca Pistorius, Miriam Henry, Andrew D Yurochko, Christopher B Pattillo, James G Traylor, Jin Chen, Matthew D Woolard, Christopher G Kevil, A Wayne Orr
Background -Atherosclerotic plaque formation results from chronic inflammation and fibroproliferative remodeling in the vascular wall. We previously demonstrated that both human and mouse atherosclerotic plaques show elevated expression of EphA2, a guidance molecule involved in cell-cell interactions and tumorigenesis. Methods -Here, we assessed EphA2's role in atherosclerosis by deleting EphA2 in a mouse model of atherosclerosis (Apoe(-/-)) and by assessing EphA2 function in multiple vascular cell culture models...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28472014/protection-by-the-eph-ephrin-system-against-mesenteric-ischemia-reperfusion-injury
#6
Valentina Vivo, Irene Zini, Anna Maria Cantoni, Andrea Grandi, Massimiliano Tognolini, Riccardo Castelli, Vigilio Ballabeni, Simona Bertoni, Elisabetta Barocelli
Mesenteric ischemia-reperfusion (I/R)-induced injury targets primarily endothelial and epithelial cells, leading to a cascade of inflammatory events, eventually culminating in life-threatening syndromes. Hitherto, the role of Eph, the largest family of tyrosine kinase receptors, and of their cell-bound ephrin ligands, whose interaction generates a bidirectional signaling, is still debated in I/R injury. The aim of the present work was therefore to investigate the effects produced by unidirectional activation of forward signaling (administration of chimeric protein ephrinA1-Fc), of reverse signaling (EphA2-Fc), or inhibition of both signals (monomeric EphA2 and the protein-protein interaction inhibitor UniPR1331) on the local and systemic inflammatory responses triggered by mesenteric I/R in mice...
May 2, 2017: Shock
https://www.readbyqxmd.com/read/28435450/exome-sequencing-of-oral-squamous-cell-carcinoma-reveals-molecular-subgroups-and-novel-therapeutic-opportunities
#7
Shih-Chi Su, Chiao-Wen Lin, Yu-Fan Liu, Wen-Lang Fan, Mu-Kuan Chen, Chun-Ping Yu, Wei-En Yang, Chun-Wen Su, Chun-Yi Chuang, Wen-Hsiung Li, Wen-Hung Chung, Shun-Fa Yang
Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features...
2017: Theranostics
https://www.readbyqxmd.com/read/28418495/molecular-genetic-analysis-of-pakistani-families-with-autosomal-recessive-congenital-cataracts-by-homozygosity-screening
#8
Jianjun Chen, Qiwei Wang, Patricia E Cabrera, Zilin Zhong, Wenmin Sun, Xiaodong Jiao, Yabin Chen, Gowthaman Govindarajan, Muhammad Asif Naeem, Shaheen N Khan, Muhammad Hassaan Ali, Muhammad Zaman Assir, Fawad Ur Rahman, Zaheeruddin A Qazi, Sheikh Riazuddin, Javed Akram, S Amer Riazuddin, J Fielding Hejtmancik
Purpose: To identify the genetic origins of autosomal recessive congenital cataracts (arCC) in the Pakistani population. Methods: Based on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28414140/shear-stress-inhibits-il-17a-mediated-induction-of-osteoclastogenesis-via-osteocyte-pathways
#9
Chongshan Liao, Tianfan Cheng, Shuai Wang, Chengfei Zhang, Lijian Jin, Yanqi Yang
Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells...
April 14, 2017: Bone
https://www.readbyqxmd.com/read/28378105/effect-of-magnolol-on-cerebral-injury-and-blood-brain-barrier-dysfunction-induced-by-ischemia-reperfusion-in-vivo-and-in-vitro
#10
Xiaoyan Liu, Xiaoling Chen, Yuanjun Zhu, Kewei Wang, Yinye Wang
Magnolol, a neolignan compound isolated from traditional Chinese medicine Magnolia officinalis, has a potentially therapeutic influence on ischemic stroke. Previous studies have demonstrated that cerebral ischemia-reperfusion (I-R) and blood-brain barrier (BBB) are involved in the pathogeneses of stroke. Therefore, in vivo and in vitro studies were designed to investigate the effects of magnolol on I-R-induced neural injury and BBB dysfunction. In cerebral I-R model of mice, cerebral infarct volumes, brain water content, and the exudation of Evans blue were significantly reduced by intravenous injection with magnolol at the doses of 1...
April 4, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28338017/a-role-of-the-sam-domain-in-epha2-receptor-activation
#11
Xiaojun Shi, Vera Hapiak, Ji Zheng, Jeannine Muller-Greven, Deanna Bowman, Ryan Lingerak, Matthias Buck, Bing-Cheng Wang, Adam W Smith
Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#12
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28265009/preclinical-mammalian-safety-studies-of-epharna-dopc-nanoliposomal-epha2-targeted-sirna
#13
Michael J Wagner, Rahul Mitra, Mark J McArthur, Wallace Baze, Kirstin Barnhart, Sherry Wu, Cristian Rodriguez-Aguayo, Xinna Zhang, Robert L Coleman, Gabriel Lopez-Berestein, Anil K Sood
To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice (N=15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model...
March 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28226310/adhesion-of-ligand-conjugated-biosynthesized-magnetite-nanoparticles-to-triple-negative-breast-cancer-cells
#14
John D Obayemi, Jingjie Hu, Vanessa O Uzonwanne, Olushola S Odusanya, Karen Malatesta, Nicolas Anuku, Winston O Soboyejo
This paper presents the results of an experimental study of the adhesion forces between components of model conjugated magnetite nanoparticle systems for improved selectivity in the specific targeting of triple negative breast cancer. Adhesion forces between chemically synthesized magnetite nanoparticles (CMNPs), biosynthesized magnetite nanoparticles (BMNPs), as well as their conjugated systems and triple negative breast cancer cells (MDA-MB-231) or normal breast cells (MCF 10A) are elucidated at a nanoscale...
February 6, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28165374/evaluation-of-epha2-and-ephb4-as-targets-for-image-guided-colorectal-cancer-surgery
#15
Marieke A Stammes, Hendrica A J M Prevoo, Meyke C Ter Horst, Stéphanie A Groot, Cornelis J H Van de Velde, Alan B Chan, Lioe-Fee de Geus-Oei, Peter J K Kuppen, Alexander L Vahrmeijer, Elena B Pasquale, Cornelis F M Sier
Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH...
February 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28154322/non-canonical-activation-of-receptor-tyrosine-kinases-in-cancer-progression
#16
REVIEW
Hiroaki Sakurai
 Receptor tyrosine kinases (RTKs) are known to be key regulators of cancer cell proliferation, migration, invasion and metastatic spread. Ligand-binding to the extracellular domain triggers canonical activation of the intracellular tyrosine kinase domain. In contrast, it has become evident that RTKs are also regulated by non-canonical tyrosine kinase-independent mechanisms via phosphorylation of their serine/threonine residues. In this review, I mainly introduce our recent findings on the non-canonical regulation of epidermal growth factor receptor (EGFR), ErbB2 and erythropoietin-producing hepatocellular receptor A2 (EphA2), and discuss the roles of non-canonical activation of RTKs in cancer progression and resistance to targeted cancer agents...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28005388/metadynamics-for-perspective-drug-design-computationally-driven-synthesis-of-new-protein-protein-interaction-inhibitors-targeting-the-epha2-receptor
#17
Matteo Incerti, Simonetta Russo, Donatella Callegari, Daniele Pala, Carmine Giorgio, Ilaria Zanotti, Elisabetta Barocelli, Paola Vicini, Federica Vacondio, Silvia Rivara, Riccardo Castelli, Massimiliano Tognolini, Alessio Lodola
Metadynamics (META-D) is emerging as a powerful method for the computation of the multidimensional free-energy surface (FES) describing the protein-ligand binding process. Herein, the FES of unbinding of the antagonist N-(3α-hydroxy-5β-cholan-24-oyl)-l-β-homotryptophan (UniPR129) from its EphA2 receptor was reconstructed by META-D simulations. The characterization of the free-energy minima identified on this FES proposes a binding mode fully consistent with previously reported and new structure-activity relationship data...
January 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27994652/to-excavate-biomarkers-predictive-of-the-response-for-capecitabine-plus-rad001-through-nanostring-based-multigene-assay-in-advanced-gastric-cancer-patients
#18
Hansang Lee, Jeeyun Lee, Insuk Sohn, Se Hoon Park, Joon Oh Park, Young Suk Park, Kyoung-Mee Kim, Won Ki Kang, Seung Tae Kim
Comprehensive characterization of individual patients' tumour is important to realize personalized medicine. Here, we investigate to identify subsets that benefit from capecitabine plus RAD001 in advanced gastric cancer (GC) patients by comprehensive high-throughput genomic analysis (nCounter assay). Archival tumour tissue blocks, if possible, were collected at phase II trial of capecitabine plus RAD001 in 47 refractory GC patients (at clinicaltrials.gov NCT#01099527). A total of 42 formalin-fixed, paraffin-embedded (FFPE) tumour samples were available for nanostring based-multigene Assay...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27978884/-expressions-of-angiogenesis-related-factors-cd105-epha2-and-ephrina1-in-laryngeal-squamous-cell-carcinoma-and-clinical-implication
#19
J Su, X B Ji, J H Xie, W Li
Objective: To investigate the expressions of endoglin (CD105), erythropoietin-producing hepatocyte receptor A2 (EphA2) and its ligand ephrinA1 proteins in laryngeal squamous cell carcinoma (LSCC) and the relationship between their expressions and the clinicopathological factors of LSCC. Methods: The expressions of CD105, EphA2 and EphrinA1 proteins were detected with immunohistochemical staining in LSCC in 76 cases and adjacent normal laryngeal tissues (ANLT) (S-P) in 25 cases.SPSS 17.0 software was used to analyze the data...
December 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/27903608/progranulin-and-the-receptor-tyrosine-kinase-epha2-partners-in-crime
#20
Babykumari Chitramuthu, Andrew Bateman
Progranulin is a secreted protein with roles in tumorigenesis, inflammation, and neurobiology, but its signaling receptors have remained unclear. In this issue, Neill et al. (2016. J. Cell Biol https://doi.org/10.1083/jcb.201603079) identify the tyrosine kinase EphA2 as a strong candidate for such a receptor, providing insight into progranulin and EphA2 signaling.
December 5, 2016: Journal of Cell Biology
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