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https://www.readbyqxmd.com/read/29759486/inhibition-of-hdacs-epha2-signaling-axis-with-ww437-demonstrates-promising-preclinical-antitumor-activity-in-breast-cancer
#1
Tao Zhang, Jingjie Li, Xiaojun Ma, Yang Yang, Wei Sun, Wangrui Jin, Lei Wang, Yuan He, Feifei Yang, Zhengfang Yi, Yingqi Hua, Mingyao Liu, Yihua Chen, Zhengdong Cai
Histone deacetylase inhibitors (HDACi) are small molecules targeting epigenetic enzymes approved for hematologic neoplasms, which have also demonstrated clinical activities in solid tumors. In our present study, we screened our internal compound library and discovered a novel HDACi, WW437, with potent anti-breast cancer ability in vitro and in vivo. WW437 significantly inhibited phosphorylated EphA2 and EphA2 expression. Further study demonstrated WW437 blocked HDACs-EphA2 signaling axis in breast cancer. In parallel, we found that EphA2 expression positively correlates with breast cancer progression; and combined use of WW437 and an EphA2 inhibitor (ALW-II-41-27) exerted more remarkable effect on breast cancer growth than either drug alone...
May 11, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29705292/epha2-transmembrane-domain-is-uniquely-required-for-keratinocyte-migration-by-regulating-ephrin-a1-levels
#2
Rosa Ventrella, Nihal Kaplan, Paul Hoover, Bethany E Perez White, Robert M Lavker, Spiro Getsios
EphA2 receptor tyrosine kinase (RTK) is activated by ephrin-A1 ligand, which harbors a GPI-anchor that enhances lipid raft localization. While EphA2 and ephrin-A1 modulate keratinocyte migration and differentiation, the ability of this cell-cell communication complex to localize to different membrane regions in keratinocytes remains unknown. Using a combination of biochemical and imaging approaches, we provide evidence that ephrin-A1 and a ligand-activated form of EphA2 partition outside of lipid raft domains in response to calcium-mediated cell-cell contact stabilization in normal human epidermal keratinocytes (NHEKs)...
April 26, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29679064/author-correction-ephrin-receptor-a2-is-an-epithelial-cell-receptor-for-epstein-barr-virus-entry
#3
Hua Zhang, Yan Li, Hong-Bo Wang, Ao Zhang, Mei-Ling Chen, Zhi-Xin Fang, Xiao-Dong Dong, Shi-Bing Li, Yong Du, Dan Xiong, Jiang-Yi He, Man-Zhi Li, Yan-Min Liu, Ai-Jun Zhou, Qian Zhong, Yi-Xin Zeng, Elliott Kieff, Zhiqiang Zhang, Benjamin E Gewurz, Bo Zhao, Mu-Sheng Zeng
In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl benzoic acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl benzoic acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl benzoic acid derivative...
April 20, 2018: Nature Microbiology
https://www.readbyqxmd.com/read/29662452/a-novel-epha2-inhibitor-exerts-beneficial-effects-in-pi-ibs-in-vivo-and-in-vitro-models-via-nrf2-and-nf-%C3%AE%C2%BAb-signaling-pathways
#4
Li Zeng, Kaixue Li, Hong Wei, Jingjing Hu, Lu Jiao, Shaoyong Yu, Ying Xiong
Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI-IBS...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29626472/tyrosine-kinase-activity-of-epha2-promotes-its-s897-phosphorylation-and-glioblastoma-cell-proliferation
#5
Yuho Hamaoka, Manabu Negishi, Hironori Katoh
EphA2, a member of the Eph family of receptor tyrosine kinases, has been reported to promote tumor malignancy through phosphorylation of serine 897 (S897). Here, we found that overexpression of wild-type EphA2 induced S897 phosphorylation through ERK activation without growth factors or cytokines and promoted glioblastoma cell proliferation. However, overexpression of a kinase-inactive mutant of EphA2 failed to induce ERK activation, S897 phosphorylation, and promotion of glioblastoma cell proliferation. These data suggest that when overexpressed, EphA2 induces ERK activation through its tyrosine kinase activity, leading to S897 phosphorylation and promotion of glioblastoma cell proliferation...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29582409/epha2-receptor-is-a-key-player-in-the-metastatic-onset-of-ewing-sarcoma
#6
Silvia Garcia-Monclús, Roser López-Alemany, Olga Almacellas-Rabaiget, David Herrero-Martín, Juan Huertas-Martinez, Laura Lagares-Te, Piedad Alba-Pavón, Lourdes Hontecillas-Prieto, Jaume Mora, Enrique de Álava, Santi Rello-Varona, Paloma H Giangrande, Oscar M Tirado
Ewing sarcoma (ES) is the second most common bone malignancy affecting children and young adults with poor prognosis due to high metastasis incidence. Our group previously described that EphA2, a tyrosine kinase receptor, promotes angiogenesis in Ewing sarcoma (ES) cells via ligand-dependent signaling. Now we wanted to explore EphA2 ligand-independent activity, controlled upon phosphorylation at S897 (p-EphA2S897 ), as it has been linked to metastasis in several malignancies. By reverse genetic engineering we explored the phenotypic changes after EphA2 removal or reintroduction...
March 26, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29565486/microrna-338-inhibits-proliferation-migration-and-invasion-of-gastric-cancer-cells-by-the-wnt-%C3%AE-catenin-signaling-pathway
#7
B Song, H-X Lin, L-L Dong, J-J Ma, Z-G Jiang
OBJECTIVE: Emerging evidence suggests aberrant microRNAs (miRNAs) expression is involved in cancer development through multiple. Although miR338 has shown to have tumor suppression ability and anti-migration effects in some cancers, its regulatory role and molecular mechanism in the development of gastric cancer cells yet remains little known. This work aims to investigate miR-338 in regulating Wnt/β-catenin pathway in epithelial-mesenchymal transition (EMT) in gastric cancers. MATERIALS AND METHODS: Human gastric cancer cells were transfected with either miR-338 mimic or erythropoietin-producing hepatocellular (Eph)A2-targeting siRNA...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29554915/g908r-nod2-variant-in-a-family-with-sarcoidosis
#8
Valérie Besnard, Alain Calender, Diane Bouvry, Yves Pacheco, Catherine Chapelon-Abric, Florence Jeny, Hilario Nunes, Carole Planès, Dominique Valeyre
BACKGROUND: Sarcoidosis is a systemic disease characterized by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Exaggerated granulomatous reaction might be triggered in response to unidentified antigens in individuals with genetic susceptibility. The present study aimed to determine the genetic variants implicated in a familial case of sarcoidosis. METHODS: Sarcoidosis presentation and history, NOD2 profile, NF-κB and cytokine production in blood monocytes/macrophages were evaluated in individuals from a family with late appearance of sarcoidosis...
March 20, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29552579/optimizing-epha2-car-t-cells-for-the-adoptive-immunotherapy-of-glioma
#9
Zhongzhen Yi, Brooke L Prinzing, Felicia Cao, Stephen Gottschalk, Giedre Krenciute
Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR) T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29552129/effect-of-galectin-3-on-vasculogenic-mimicry-in-esophageal-cancer-cells
#10
Jingxin Zhang, Guodong Deng, Lili Qiao, Hui Luo, Qiqi Liu, Ning Liang, Jian Xie, Jiandong Zhang
Galectin-3 is a multifunctional β-galactoside binding lectin associated with tumor progression. Previous studies confirmed the roles of galecin-3 overexpression and silencing in the biological behavior of Eca109 human esophageal cancer (EC) cells; galectin-3 may serve a critical role in the vasculogenic mimicry (VM) of tumors. Therefore, the present study examined the effects of galectin-3 knockdown using lentivirus vectors on VM in EC. Eca109 and EC9706 EC cells were transfected with a lentiviral vector to inhibit galectin-3 expression, or a control vector...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29491103/prognostic-significance-of-high-epha1-4-expression-levels-in-locally-advanced-gastric-cancer
#11
Mikito Inokuchi, Masatoshi Nakagawa, Nasri Baogok, Yoko Takagi, Toshiro Tanioka, Kentaro Gokita, Keisuke Okuno, Kazuyuki Kojima
BACKGROUND/AIM: Erythropoietin-producing hepatocellular carcinoma receptor A (EphA) is associated with angiogenesis and invasive tumor progression. In this study, we evaluated the EphA1-4 expression levels in advanced gastric cancer. PATIENTS AND METHODS: Tumor tissues obtained from 114 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. In addition, the impact of EPHA 1-4 mRNA expression on survival was analyzed using the Kaplan-Meier plotter database on the website...
March 2018: Anticancer Research
https://www.readbyqxmd.com/read/29482609/microrna-302b-negatively-regulates-il-1%C3%AE-production-in-response-to-msu-crystals-by-targeting-irak4-and-epha2
#12
Teng Ma, Xiao Liu, Zhifu Cen, Chuan Xin, Mingfeng Guo, Chaoyu Zou, Wenpeng Song, Rou Xie, Kailun Wang, Hong Zhou, Jun Zhang, Zhen Wang, Ce Bian, Kaijun Cui, Jiong Li, Yu-Quan Wei, Jing Li, Xikun Zhou
BACKGROUND: Interleukin-1β (IL-1β) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1β is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism...
February 26, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29476773/a-potential-role-for-eph-receptor-signalling-during-migration-of-corneal-endothelial-cells
#13
Jennifer Walshe, Neil A Richardson, Najla Khaled Al Abdulsalam, Sally-Anne Stephenson, Damien G Harkin
The corneal endothelium is a monolayer of epithelial cells that lines the posterior surface of the cornea and is essential for maintenance of corneal transparency. Wound healing within the corneal endothelium typically occurs through cell spreading and migration rather than through proliferation. The mechanisms that control corneal endothelial cell migration are unclear. In this study we demonstrate that cultures of corneal endothelial cells display reduced migration in scratch wound assays, and reduced levels of E-cadherin mRNA, following suppression of ligand-activated Eph receptor signalling by treatment with lithocholic acid...
May 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29470068/reduction-of-circulating-cancer-cells-and-metastases-in-breast-cancer-models-by-a-potent-epha2-agonistic-peptide-drug-conjugate
#14
Ahmed F Salem, Si Wang, Sandrine Billet, Jie-Fu Chen, Parima Udompholkul, Luca Gambini, Carlo Baggio, Hsian-Rong Tseng, Edwin M Posadas, Neil A Bhowmick, Maurizio Pellecchia
EphA2 overexpression has been associated with metastasis in multiple cancer types, including melanomas and ovarian, prostate, lung, and breast cancers. We have recently proposed the development of peptide-drug conjugates (PDCs) using agonistic EphA2-targeting agents, such as the YSA peptide or its optimized version, 123B9. Although our studies indicated that YSA- and 123B9-drug conjugates can selectively deliver cytotoxic drugs to cancer cells in vivo, the relatively low cellular agonistic activities (i.e., the high micromolar concentrations required) of the agents toward the EphA2 receptor remained a limiting factor to the further development of these PDCs in the clinic...
March 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29449527/tr-4-nuclear-receptor-suppresses-hcc-cell-invasion-via-downregulating-the-epha2-expression
#15
Ren'an Jin, Hui Lin, Gonghui Li, Junjie Xu, Liang Shi, Chawnshang Chang, Xiujun Cai
Early studies indicated that testicular nuclear receptor 4 (TR4 ) could function as a suppressor in the transcriptional regulation of the HBV core gene expression, which might then influence the development of hepatocellular carcinoma (HCC). The direct linkage between TR4 and HCC progression, however, remained unclear. Here, via a human clinical sample survey, we found that 13 of the 18 HCC patients studied had lower TR4 expression in metastatic lesions than in matched primary HCC lesions, suggesting that TR4 may play a negative role in HCC metastasis...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29440749/publisher-correction-epha2-is-an-epithelial-cell-pattern-recognition-receptor-for-fungal-%C3%AE-glucans
#16
Marc Swidergall, Norma V Solis, Michail S Lionakis, Scott G Filler
In the version of this Article originally published, technical problems led to errors in Figs. 2d and 5b. In the western blot panel in Fig. 2d, actin bands were misaligned at the bottom of the image and did not line up with the other bands in the panel; the corrected figure is shown below. In Fig. 5b, the upper right panel had an incorrect title of 'CXCL3/KC'; it should have instead been 'CXCL1/KC'. These errors have now been corrected in all versions of the Article.
March 2018: Nature Microbiology
https://www.readbyqxmd.com/read/29429298/-the-influence-of-epha2-overexpression-on-proliferation-and-apoptosis-of-human-lens-epithelial-cells-exposed-to-high-concentration-dexamethasone-in-vitro
#17
C X Ma, G Y Zheng
Objective: To construct lentiviral-mediated EphA2 overexpression vectors, transfect them into human lens epithelial cells (HLE-B3) in vitro , and investigate the effect of EphA2 gene overexpression on the proliferation and apoptosis of HLE-B3 exposed to high-concentration dexamethasone. Methods: Experimental Study. The pCDH-CMV- MCS-EF1-RFP plasmid was set up by the digestion of NOTⅠand XbaⅠ double restriction enzyme and ligation of CE ligase, and then the plasmid was transformed into DH10B cells. Seven clons were picked for enzymatic digestion and the clons with correct results were chosen for sequencing...
February 11, 2018: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29392820/emerging-roles-of-extracellular-vesicles-in-cellular-senescence-and-aging
#18
REVIEW
Masaki Takasugi
Cellular senescence is a cellular program that prevents the proliferation of cells at risk of neoplastic transformation. On the other hand, age-related accumulation of senescent cells promotes aging at least partially due to the senescence-associated secretory phenotype, whereby cells secrete high levels of inflammatory cytokines, chemokines, and matrix metalloproteinases. Emerging evidence, however, indicates that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29392452/ysa-conjugated-mesoporous-silica-nanoparticles-effectively-target-epha2-overexpressing-breast-cancer-cells
#19
Zhi Liu, Zijian Tao, Qing Zhang, Song Wan, Fenglin Zhang, Yan Zhang, Guanyu Wu, Jiandong Wang
PURPOSE: Neoadjuvant chemotherapy is commonly used to treat patients with locally advanced breast cancer and a common option for primary operable disease. However, systemic toxicity including cardiotoxicity and inefficient delivery are significant challenges form any chemotherapeutics. The development of targeted treatments that lower the risk of toxicity has, therefore, become an active area of research in the field of novel cancer therapeutics. Mesoporous silica nanoparticles (MSNs) have attracted significant attention as efficient drug delivery carriers, due to their high surface area and tailorable mesoporous structures...
April 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29370800/a-novel-immortalized-hepatocyte-like-cell-line-imhc-supports-in-vitro-liver-stage-development-of-the-human-malarial-parasite-plasmodium-vivax
#20
Yongyut Pewkliang, Siriwan Rungin, Kaewta Lerdpanyangam, Apisak Duangmanee, Phongthon Kanjanasirirat, Phichaya Suthivanich, Khanit Sa-Ngiamsuntorn, Suparerk Borwornpinyo, Jetsumon Sattabongkot, Rapatbhorn Patrapuvich, Suradej Hongeng
BACKGROUND: Eradication of malaria is difficult because of the ability of hypnozoite, the dormant liver-stage form of Plasmodium vivax, to cause relapse in patients. Research efforts to better understand the biology of P. vivax hypnozoite and design relapse prevention strategies have been hampered by the lack of a robust and reliable model for in vitro culture of liver-stage parasites. Although the HC-04 hepatoma cell line is used for culturing liver-stage forms of Plasmodium, these cells proliferate unrestrictedly and detach from the culture dish after several days, which limits their usefulness in a long-term hypnozoite assay...
January 25, 2018: Malaria Journal
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