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https://www.readbyqxmd.com/read/28804547/epha2-targeted-intratumoral-therapy-for-non-small-cell-lung-cancer-using-albumin-mesospheres
#1
Hung-Yen Lee, Kamal A Mohammed, Fredric Kaye, Brij M Moudgil, Najmunnisa Nasreen
Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer mortality and the prognosis of patients with advanced or metastatic NSCLC is poor. Despite significant advances in diagnosis and treatment, little improvement has been seen in NSCLC mortality. Recently, Intratumoral Chemotherapy, a direct local delivery of chemotherapeutic drugs, has shown promise in clinical studies. However, toxicity and high dosage of chemotherapeutic agents used for treatment are a limitation. Moreover, these drugs damage indiscriminately, cancerous as well as normal tissues...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28791195/nanoplasmonic-quantification-of-tumor-derived-extracellular-vesicles-in-plasma-microsamples-for-diagnosis-and-treatment-monitoring
#2
Kai Liang, Fei Liu, Jia Fan, Dali Sun, Chang Liu, Christopher J Lyon, David W Bernard, Yan Li, Kenji Yokoi, Matthew H Katz, Eugene J Koay, Zhen Zhao, Ye Hu
Tumour-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays require large samples, are time-consuming, low-throughput and costly, and thus impractical for clinical use. Here, we describe a rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumor-derived EVs from as little as 1 μL of plasma. The assay uses the binding of antibody-conjugated gold nanospheres and nanorods to EVs captured by EV-specific antibodies on a sensor chip to produce a local plasmon effect that enhances tumour-derived EV detection sensitivity and specificity...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28775148/the-tumor-suppressor-protein-opcml-potentiates-anti-egfr-and-anti-her2-targeted-therapy-in-her2-positive-ovarian-and-breast-cancer
#3
Elisa Zanini, Louay S Louis, Jane Antony, Evdoxia Karali, Imoh S Okon, Arthur B McKie, Sebastian Vaughan, Mona El-Bahrawy, Justin Stebbing, Chiara Recchi, Hani Gabra
OPCML is a tumor suppressor gene that is frequently inactivated in ovarian cancer and many other cancers by somatic methylation. We have previously shown that OPCML exerts its suppressor function by negatively regulating a spectrum of receptor tyrosine kinases (RTKs), such as ErbB2/HER2, FGFR1 and EphA2, thus attenuating their related downstream signaling. The physical interaction of OPCML with this defined group of RTKs is a prerequisite for their downregulation. Overexpression/gene amplification of EGFR and HER2 is a frequent event in multiple cancers including ovarian and breast cancers...
August 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28746857/enhancing-irreversible-electroporation-by-manipulating-cellular-biophysics-with-a-molecular-adjuvant
#4
Jill W Ivey, Eduardo L Latouche, Megan L Richards, Glenn J Lesser, Waldemar Debinski, Rafael V Davalos, Scott S Verbridge
Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration...
July 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28743499/all-trans-retinoic-acid-attenuates-bleomycin-induced-pulmonary-fibrosis-via-downregulating-epha2-ephrina1-signaling
#5
Ah Young Leem, Mi Hwa Shin, Ivor S Douglas, Joo Han Song, Kyung Soo Chung, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Joon Chang, Young Sam Kim, Moo Suk Park
The role of all-trans retinoic acid (ATRA) in pulmonary fibrosis is relatively unknown, although this metabolite modulates cell differentiation, proliferation, and development. We aimed to evaluate the role of ATRA in bleomycin-induced pulmonary fibrosis, and whether the mechanism involves EphA2-EphrinA1 and PI3K-Akt signaling. We evaluated three groups of mice: a control group (intraperitoneal DMSO injection 3 times weekly after PBS instillation), bleomycin group (intraperitoneal DMSO injection 3 times weekly after bleomycin instillation), and bleomycin + ATRA group (intraperitoneal ATRA injection 3 times weekly after bleomycin instillation)...
July 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28740575/identification-of-novel-diagnostic-and-prognostic-mirna-signatures-in-endometrial-cancer
#6
Muralidharan Jayaraman, Rangasudhagar Radhakrishnan, Cara A Mathews, Mingda Yan, Sanam Husain, Katherine M Moxley, Yong Sang Song, Danny N Dhanasekaran
With the goal of identifying diagnostic and prognostic biomarkers in endometrial cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84-cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96-5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR-374a and let-7 family of miRNAs in endometrial cancer. We validated the dysregulated expression of the identified miRNAs in a panel of endometrial cancer cell-lines...
May 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28705041/ionizing-radiation-induces-epha2-s897-phosphorylation-in-a-mek-erk-rsk-dependent-manner
#7
Paul R Graves, Shaun U Din, Mark Ashamalla, Hani Ashamalla, Thomas S K Gilbert, Lee M Graves
PURPOSE: The EphA2 tyrosine kinase is frequently overexpressed in human tumors that are also treated with radiation. However, few studies have examined the effect of radiation on the EphA2 receptor itself. The purpose of this project was to investigate the impact of radiation on EphA2 to better understand mechanisms of radioresistance. MATERIALS AND METHODS: Cell lines were exposed to X-rays and assayed for changes in EphA2 protein levels and phosphorylation over time by Western blotting...
July 14, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28686661/engineering-of-monobody-conjugates-for-human-epha2-specific-optical-imaging
#8
Min-A Kim, Hee Seung Yoon, Seung-Hwan Park, Dong-Yeon Kim, Ayoung Pyo, Hyeon Sik Kim, Jung-Joon Min, Yeongjin Hong
In a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E. coli. E1-Rluc8 and E1-EGFP specifically bound to hEphA2 in human prostate cancer PC3 cells but not in human cervical cancer HeLa cells, which express hEphA2 at high and low levels, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28674216/microrna-200c-increases-radiosensitivity-of-human-cancer-cells-with-activated-egfr-associated-signaling
#9
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H Kim, David J Lee, In Ah Kim
MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c...
July 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28648759/epha2-and-ephrin-a5-are-not-a-receptor-ligand-pair-in-the-ocular-lens
#10
Catherine Cheng, Velia M Fowler, Xiaohua Gong
Eph-ephrin bidirectional signaling is essential for eye lens transparency in humans and mice. Our previous studies in mouse lenses demonstrate that ephrin-A5 is mainly expressed in the anterior epithelium, where it is required for maintaining the anterior epithelial monolayer. In contrast, EphA2 is localized in equatorial epithelial and fiber cells where it is essential for equatorial epithelial and fiber cell organization and hexagonal cell shape. Immunostaining of lens epithelial and fiber cells reveals that EphA2 and ephrin-A5 are also co-expressed in anterior fiber cell tips, equatorial epithelial cells and newly formed lens fibers, although they are not precisely colocalized...
September 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28637002/associations-of-high-altitude-polycythemia-with-polymorphisms-in-epha2-and-agt-in-chinese-han-and-tibetan-populations
#11
Lijun Liu, Yao Zhang, Zhiying Zhang, Yiduo Zhao, Xiaowei Fan, Lifeng Ma, Yuan Zhang, Haijin He, Longli Kang
High altitude polycythemia (HAPC) refers to the long-term living in the plateau of the hypoxia environment is not accustomed to cause red blood cell hyperplasia. The pathological changes are mainly the various organs and tissue congestion, blood stasis and hypoxia damage. Although chronic hypoxia is the main cause of HAPC, the related molecular mechanisms remain largely unclear. This study aims to explore the genetic basis of HAPC in the Chinese Han and Tibetan populations. We enrolled 100 patients (70 Han, 30 Tibetan) with HAPC and 100 healthy control subjects (30 Han, 70 Tibetan)...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636467/normal-epithelial-cells-trigger-epha2-dependent-rasv12-cell-repulsion-at-the-single-cell-level
#12
William Hill, Catherine Hogan
Epithelial cells expressing oncogenic Ras (RasV12) are detected by normal neighbors and are often extruded from tissues. We recently demonstrated that differential EphA2 signaling drives the segregation of mutant cells from normal monolayers via cell repulsion and increased RasV12 cell contractility. EphA2 signaling on RasV12 cells is triggered by ephrin-A ligands presented by normal cells. Here, we show that normal epithelial cells trigger the repulsion and enhanced contractility of Ras-transformed epithelial cells at the single cell level...
June 21, 2017: Small GTPases
https://www.readbyqxmd.com/read/28631589/comparison-of-protein-expression-during-wild-type-and-e1b-55k-deletion-adenovirus-infection-using-quantitative-time-course-proteomics
#13
Yen Rong Fu, Andrew S Turnell, Simon Davis, Kate J Heesom, Vanessa C Evans, David A Matthews
Adenovirus has evolved strategies to usurp host-cell factors and machinery to facilitate its life cycle, including cell entry, replication, assembly and egress. Adenovirus continues, therefore, to be an important model system for investigating fundamental cellular processes. The role of adenovirus E1B-55k in targeting host-cell proteins that possess antiviral activity for proteasomal degradation is now well established. To expand our understanding of E1B-55k in regulating the levels of host-cell proteins, we performed comparative proteome analysis of wild-type, and E1B-55k-deletion, adenovirus-infected cancer cells...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28624791/epha2-affects-the-sensitivity-of-oxaliplatin-by-inducing-emt-in-oxaliplatin-resistant-gastric-cancer-cells
#14
Qiaocheng Wen, Zihua Chen, Zhikang Chen, Jinxiang Chen, Ran Wang, Changhao Huang, Weijie Yuan
Erythropoietin-producing hepatocellular receptor A2 (EphA2) is upregulated in gastric cancer tissues and cells, which is accompanied by epithelial-mesenchymal transition (EMT). The current study was designed to establish the oxaliplatin-resistant human gastric cancer cell line SGC-7901/L-OHP, to determine if EMT in these cells could be reversed, and to determine if the susceptibility of these cells to oxaliplatin was affected by silencing EphA2 expression. We found that EphA2 expression levels were upregulated in gastric cancer and associated with chemotherapy sensitivity...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28602916/structural-investigation-of-a-c-terminal-epha2-receptor-mutant-does-mutation-affect-the-structure-and-interaction-properties-of-the-sam-domain
#15
Flavia A Mercurio, Susan Costantini, Concetta Di Natale, Luciano Pirone, Stefano Guariniello, Pasqualina L Scognamiglio, Daniela Marasco, Emilia M Pedone, Marilisa Leone
Ephrin A2 receptor (EphA2) plays a key role in cancer, it is up-regulated in several types of tumors and the process of ligand-induced receptor endocytosis, followed by degradation, is considered as a potential path to diminish tumor malignancy. Protein modulators of this mechanism are recruited at the cytosolic Sterile alpha motif (Sam) domain of EphA2 (EphA2-Sam) through heterotypic Sam-Sam associations. These interactions engage the C-terminal helix of EphA2 and close loop regions (the so called End Helix side)...
June 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28590061/porphyromonas-gingivalis-lipopolysaccharide-regulates-ephrin-eph-signalling-in-human-periodontal-ligament-fibroblasts
#16
M Li, C Zhang, L Jin, K Matsuo, Y Yang
OBJECTIVE: EphrinA2-EphA2 and ephrinB2-EphB4 critically engage in bidirectional signalling to modulate alveolar bone remodelling. The present study aimed to investigate the effects of lipopolysaccharides (LPS) derived from Porphyromonas gingivalis on ephrin/Eph signalling in periodontal ligament fibroblasts (PDLFs). MATERIAL AND METHODS: The primary cultured PDLFs were incubated in the absence (as a control) or presence of P. gingivalisLPS at 0.001-10 μg/mL for 24 hours...
June 7, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28587437/overexpression-and-correlation-of-hif-2%C3%AE-vegfa-and-epha2-in-residual-hepatocellular-carcinoma-following-high-intensity-focused-ultrasound-treatment-implications-for-tumor-recurrence-and-progression
#17
Lun Wu, You-Shun Zhang, Meng-Liang Ye, Feng Shen, Wei Liu, Hong-Sheng Hu, Sheng-Wei Li, Hong-Wei Wu, Qin-Hua Chen, Wen-Bo Zhou
Rapid growth of residual tumors can occur as a result of their recurrence and progression. The present study aimed to investigate the expression of hypoxia inducible factor-2 subunit α (HIF-2α), vascular endothelial growth factor A (VEGFA), erythropoietin-producing hepatocellular A2 (EphA2) and angiogenesis in residual hepatocellular carcinoma (HCC), following treatment with high-intensity focused ultrasound (HIFU) ablation, in order to investigate the association between protein expression and tumor recurrence and growth...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28585531/small-extracellular-vesicles-secreted-from-senescent-cells-promote-cancer-cell-proliferation-through-epha2
#18
Masaki Takasugi, Ryo Okada, Akiko Takahashi, David Virya Chen, Sugiko Watanabe, Eiji Hara
Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation. However, the altered secretome of senescent cells can promote the growth of the surrounding cancer cells. Although extracellular vesicles (EVs) have emerged as new players in intercellular communication, their role in the function of senescent cell secretome has been largely unexplored. Here, we show that exosome-like small EVs (sEVs) are important mediators of the pro-tumorigenic function of senescent cells. sEV-associated EphA2 secreted from senescent cells binds to ephrin-A1, that is, highly expressed in several types of cancer cells and promotes cell proliferation through EphA2/ephrin-A1 reverse signalling...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28581527/targeting-epha2-impairs-cell-cycle-progression-and-growth-of-basal-like-triple-negative-breast-cancers
#19
W Song, Y Hwang, V M Youngblood, R S Cook, J M Balko, J Chen, D M Brantley-Sieders
Basal-like/triple-negative breast cancers (TNBCs) are among the most aggressive forms of breast cancer, and disproportionally affects young premenopausal women and women of African descent. Patients with TNBC suffer a poor prognosis due in part to a lack of molecularly targeted therapies, which represents a critical barrier for effective treatment. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for TNBC. EphA2 expression is enriched in the basal-like molecular subtype in human breast cancers...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28560458/epha2-receptor-activation-with-ephrin-a1-ligand-restores-cetuximab-efficacy-in-nras-mutant-colorectal-cancer-cells
#20
Elisabet Cuyàs, Bernardo Queralt, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Javier A Menendez
Patients with wild-type KRAS metastatic colorectal cancer (mCRC) that harbors NRAS activating mutations do not benefit from anti-EGFR therapies. Very little is known about oncogenic NRAS signaling driving mCRC unresponsiveness to the EGFR-directed antibody cetuximab. Using a system of paired NRAS-mutant and wild-type isogenic mCRC cell lines to explore signaling pathways engaged by the common oncogenic NRAS Q61K variant upon challenge with cetuximab, we uncovered an unexpected mechanism of resistance to cetuximab involving dysregulation of the ephrin-A1/EphA2 signaling axis...
May 30, 2017: Oncology Reports
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