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https://www.readbyqxmd.com/read/29661238/ep3-prostaglandin-e2-receptor-3-expression-is-a-prognostic-factor-for-progression-free-and-overall-survival-in-sporadic-breast-cancer
#1
Anna Semmlinger, Viktoria von Schoenfeldt, Verena Wolf, Alexandra Meuter, Theresa Maria Kolben, Thomas Kolben, Christine Zeder-Goess, Florian Weis, Julia Gallwas, Rachel Wuerstlein, Kerstin Hermelink, Elisa Schmoeckel, Nadia Harbeck, Doris Mayr, Sven Mahner, Udo Jeschke, Nina Ditsch
BACKGROUND: In various cancers, overexpression of cyclooxygenase (COX)-2 and elevated prostaglandin (PG) E2 synthesis have been associated with tumor development and progression. The potential of COX-2 inhibitors in cancer prevention and treatment has been shown repeatedly; however, their clinical use is limited due to toxicity. PGE2 signals via EP receptors 1-4, whose functions are analyzed in current research in search for targeted anti-PG therapies. EP2 and EP4 rather promote tumorigenesis, while the role of EP3, especially in breast cancer, is not yet clear and both pro- and anti-tumorigenic effects have been described...
April 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29658109/pge-2-ep-4-antagonism-enhances-tumor-chemosensitivity-by-inducing-extracellular-vesicle-mediated-clearance-of-cancer-stem-cells
#2
Meng-Chieh Lin, Shih-Yin Chen, Pei- Lin He, Harvey Herschman, Hua-Jung Li
Cells expressing mesenchymal/basal phenotypes in tumors have been associated with stem cell properties. Cancer stem cells (CSCs) are often resistant to conventional chemotherapy. We explored overcoming mesenchymal CSC resistance to chemotherapeutic agents. Our goal was to reduce CSC numbers in vivo, in conjunction with chemotherapy, to reduce tumor burden. Analysis of clinical samples demonstrated that COX-2/PGE2 /EP4 signaling is elevated in basal-like and chemoresistant breast carcinoma and is correlated with survival and relapse of breast cancer...
April 15, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29629953/utility-of-ber-ep4-and-moc-31-in-basaloid-skin-tumor-detection
#3
Pavandeep Gill, Christopher Naugler, Marie S Abi Daoud
Ber-EP4 has been the traditional immunostain used for the detection of basaloid skin tumors. Recently, MOC-31 has shown be superior to Ber-EP4 in the detection of basosquamous basal cell carcinoma (BCC) and many centers are now using both Ber-EP4 and MOC-31 antibodies together to detect these lesions. The objective of this study was to compare the utility of using both Ber-EP4 and MOC-31 immunostains in the detection of basaloid skin tumors and to better characterize the previously unknown staining properties of MOC-31 in cutaneous lesions...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29626715/targeting-therapeutics-to-bone-by-conjugation-with-bisphosphonates
#4
REVIEW
Robert N Young, Marc D Grynpas
Bisphosphonates target and bind avidly to the mineral (hydroxyapatite) found in bone. This targeting ability has been exploited to design and prepare bisphosphonate conjugate prodrugs to deliver a wide variety of drug molecules selectively to bones. It is important that conjugates be stable in the blood stream and that conjugate that is not taken up by bone is eliminated rapidly. The prodrugs should release active drug at a rate appropriate so as to provide efficacy. Radiolabelling is the best method to quantify and evaluate pharmacokinetics, tissue distribution, bone uptake and release of the active drug(s)...
April 4, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29604964/selective-inhibition-of-histamine-evoked-ca-2-signals-by-compartmentalized-camp-in-human-bronchial-airway-smooth-muscle-cells
#5
Philippa Dale, Victoria Head, Mark R Dowling, Colin W Taylor
Intracellular Ca2+ and cAMP typically cause opposing effects on airway smooth muscle contraction. Receptors that stimulate these pathways are therapeutic targets in asthma and chronic obstructive pulmonary disease. However, the interactions between different G protein-coupled receptors (GPCRs) that evoke cAMP and Ca2+ signals in human bronchial airway smooth muscle cells (hBASMCs) are poorly understood. We measured Ca2+ signals in cultures of fluo-4-loaded hBASMCs alongside measurements of intracellular cAMP using mass spectrometry or [3 H]-adenine labeling...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29599139/protective-role-of-mpges-1-microsomal-prostaglandin-e-synthase-1-derived-pge-2-prostaglandin-e2-and-the-endothelial-ep4-prostaglandin-e-receptor-in-vascular-responses-to-injury
#6
Huifeng Hao, Sheng Hu, Qing Wan, Chuansheng Xu, Hong Chen, Liyuan Zhu, Zhenyu Xu, Jian Meng, Richard M Breyer, Nailin Li, De-Pei Liu, Garret A FitzGerald, Miao Wang
OBJECTIVE: Deletion of mPGES-1 (microsomal prostaglandin E synthase-1)-an anti-inflammatory target alternative to COX (cyclooxygenase)-2-attenuates injury-induced neointima formation in mice. This is attributable to the augmented levels of PGI2 (prostacyclin)-a known restraint of the vascular response to injury, acting via IP (I prostanoid receptor). To examine the role of mPGES-1-derived PGE2 (prostaglandin E2) in vascular remodeling without the IP. APPROACH AND RESULTS: Mice deficient in both IP and mPGES-1 (DKO [double knockout] and littermate controls [IP KO (knockout)]) were subjected to angioplasty wire injury...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29596308/ep4-as-a-therapeutic-target-for-aggressive-human-breast-cancer
#7
REVIEW
Mousumi Majumder, Pinki Nandi, Ahmed Omar, Kingsley Chukwunonso Ugwuagbo, Peeyush K Lala
G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis...
March 29, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29593738/prostaglandin-e-2-inhibits-group-2-innate-lymphoid-cell-activation-and-allergic-airway-inflammation-through-e-prostanoid-4-cyclic-adenosine-monophosphate-signaling
#8
Yu Zhou, Wei Wang, Conghui Zhao, Yan Wang, Haoming Wu, Xiuyuan Sun, Youfei Guan, Yu Zhang
Evidence is accumulating that group 2 innate lymphoid cells (ILC2) play an important role in allergic airway inflammation by producing a large amount of type 2 cytokines. But it remains poorly understood how its activities are properly controlled in vivo . Here, we demonstrated that prostaglandin E2 (PGE2 ) had a profound inhibitory effect on IL-33-induced ILC2 expansion and IL-5 and IL-13 production in vitro . This effect was mimicked by PGE1 -alcohol but attenuated by ONO-AE3-208, indicating a selective action through the E-prostanoid 4 (EP4) receptor...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29574419/facilitation-of-il-22-production-from-innate-lymphoid-cells-by-prostaglandin-e-2-prevents-experimental-lung-neutrophilic-inflammation
#9
Jennifer M Felton, Rodger Duffin, Calum T Robb, Siobhan Crittenden, Stephen M Anderton, Sarah E M Howie, Moira K B Whyte, Adriano G Rossi, Chengcan Yao
Acute lung injury is a neutrophil-dominant, life-threatening disease without effective therapies and better understanding of the pathophysiological mechanisms involved is an urgent need. Here we show that interleukin (IL)-22 is produced from innate lymphoid cells (ILC) and is responsible for suppression of experimental lung neutrophilic inflammation. Blocking prostaglandin E2 (PGE2 ) synthesis reduces lung ILCs and IL-22 production, resulting in exacerbation of lung neutrophilic inflammation. In contrast, activation of the PGE2 receptor EP4 prevents acute lung inflammation...
March 24, 2018: Thorax
https://www.readbyqxmd.com/read/29533280/polymorphous-sweat-gland-carcinoma-an-immunohistochemical-and-molecular-study
#10
Shira Ronen, Irene Aguilera-Barrantes, Tamara Giorgadze, Petr Šteiner, Petr Grossmann, Saul Suster
Polymorphous sweat gland carcinoma is an uncommon low-grade malignant adnexal tumor with a marked predilection for the distal extremities. Histologically, the lesions are characterized by a cellular proliferation showing a combination of growth patterns, including trabecular, solid, tubular, cribriform, or adenoid cystic and pseudopapillary. The immunohistochemical and molecular profile of these tumors has not yet been properly addressed. We have studied 3 cases of polymorphous sweat gland carcinoma using a broad panel of immunohistochemical markers including cytokeratin AE1/AE3, CK5/6, MOC31, p40, p63, p16, chromogranin, synaptophysin, CD56, MIB-1, estrogen receptor, progesterone receptor, androgen receptor, BER-EP4, smooth muscle actin, epithelial membrane antigen, carcinoembryonic antigen, CD117, S100 protein, HBME-1, DOG1, vimentin, and mammaglobin...
March 6, 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29527151/protective-effects-of-l-902-688-a-prostanoid-ep4-receptor-agonist-against-acute-blood-brain-barrier-damage-in-experimental-ischemic-stroke
#11
Kelly M DeMars, Austin O McCrea, David M Siwarski, Brian D Sanz, Changjun Yang, Eduardo Candelario-Jalil
Ischemic stroke occurs when a clot forms in the brain vasculature that starves downstream tissue of oxygen and nutrients resulting in cell death. The tissue immediately downstream of the blockage, the core, dies within minutes, but the surrounding tissue, the penumbra is potentially salvageable. Prostaglandin E2 binds to four different G-protein coupled membrane receptors EP1-EP4 mediating different and sometimes opposing responses. Pharmacological activation of the EP4 receptor has already been established as neuroprotective in stroke, but the mechanism(s) of protection are not well-characterized...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29522761/overexpression-of-prostaglandin-e2-ep4-receptor-improves-cardiac-function-after-myocardial-infarction
#12
Timothy D Bryson, Xiaosong Gu, Remonda M Khalil, Safa Khan, Liping Zhu, Jiang Xu, Edward Peterson, Xiao-Ping Yang, Pamela Harding
BACKGROUND: Prostaglandin E2 (PGE2 ) signals through 4 separate G-protein coupled receptor sub-types to elicit a variety of physiologic and pathophysiological effects. We recently reported that PGE2 via its EP3 receptor could reduce cardiac contractility of isolated myocytes and the working heart preparation. We thus hypothesized that there is an imbalance in the EP3/EP4 ratio towards EP3 in the failing heart and that overexpression of EP4 in a mouse model of heart failure would improve cardiac function...
March 6, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29510514/ep4-agonist-l-902-688-suppresses-endmt-and-attenuates-right-ventricular-cardiac-fibrosis-in-experimental-pulmonary-arterial-hypertension
#13
Ying-Ju Lai, I-Chen Chen, Hsin-Hsien Li, Chung-Chi Huang
Right ventricular (RV) hypertrophy is characterized by cardiac fibrosis due to endothelial-mesenchymal transition (EndMT) and increased collagen production in pulmonary arterial hypertension (PAH) patients, but the mechanisms for restoring RV function are unclear. Prostanoid agonists are effective vasodilators for PAH treatment that bind selective prostanoid receptors to modulate vascular dilation. The importance of prostanoid signaling in the RV is not clear. We investigated the effects of the EP4-specific agonist L-902,688 on cardiac fibrosis and TGF-β-induced EndMT...
March 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29497417/the-possible-effect-of-b-cell-epitopes-of-epstein-barr-virus-early-antigen-membrane-antigen-latent-membrane-protein-1-and-2a-on-systemic-lupus-erythematosus
#14
Jianxin Tu, Xiaobing Wang, Guannan Geng, Xiangyang Xue, Xiangyang Lin, Xiaochun Zhu, Li Sun
This study was aimed to evaluate the role of B-cell epitopes of Epstein-Barr virus (EBV) Early antigen protein D (EA), envelope glycoprotein GP340/membrane antigen (MA), latent membrane protein (LMP)-1, and LMP-2A in systemic lupus erythematosus (SLE). B-cell epitopes were predicted by analyzing secondary structure, transmembrane domains, surface properties, and homological comparison. 60 female mice were randomized equally into 12 groups: 1-10 groups were immunized by epitope peptides (EPs) 1-10, respectively, while 11 and 12 groups were PBS and Keyhole limpet hemocyanin (KLH) control groups...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29490676/pharmacological-characterisation-of-cr6086-a-potent-prostaglandin-e-2-receptor-4-antagonist-as-a-new-potential-disease-modifying-anti-rheumatic-drug
#15
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29488342/pge2-ep3-signaling-exacerbates-hippocampus-dependent-cognitive-impairment-after-laparotomy-by-reducing-expression-levels-of-hippocampal-synaptic-plasticity-related-proteins-in-aged-mice
#16
Jing-Yu Xiao, Bing-Rui Xiong, Wen Zhang, Wen-Chang Zhou, Hui Yang, Feng Gao, Hong-Bing Xiang, Anne Manyande, Xue-Bi Tian, Yu-Ke Tian
AIM: Multifactors contribute to the development of postoperative cognitive dysfunction (POCD), of which the most important mechanism is neuroinflammation. Prostaglandin E2 (PGE2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE2 and its receptors signaling pathway were involved in the pathophysiology of POCD. METHODS: Sixteen-month old male C57BL/6J mice were exposed to laparotomy...
February 27, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29482767/pge-2-downregulates-lps-induced-inflammatory-responses-via-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway-in-bovine-endometrial-epithelial-cells
#17
Yuan Shen, Bo Liu, Wei Mao, Ruifeng Gao, Shuang Feng, Yinghong Qian, Jindi Wu, Shuangyi Zhang, Long Gao, Changqi Fu, Qianru Li, Yang Deng, Jinshan Cao
Postpartum bacterial infections of the uterus cause endometritis in dairy cows. Inflammatory responses to bacterial infections in the bovine uterus were generated through pattern recognition receptors (PRRs) that bind to pathogen-associated molecules such as lipopolysaccharide (LPS) from Escherichia coli. Among these PRRs, Toll-like receptor 4 (TLR4) is primarily responsible for LPS recognition, which triggers inflammatory responses via mitogen-activated protein kinases (MAPKs) and NF-κB signaling activation, resulting in the expression of inflammatory mediators in mammals such as IL-8 and IL-6...
February 2018: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/29473135/immunomodulatory-effects-of-cp-25-on-splenic-t-cells-of-rats-with-adjuvant-arthritis
#18
Yang Wang, Chen-Chen Han, Dongqian Cui, Ting-Ting Luo, Yifan Li, Yuwen Zhang, Yang Ma, Wei Wei
Rheumatoid arthritis (RA) is an autoimmune disease in which T cells play an important role. Paeoniflorin-6-oxy-benzenesulfonate (CP-25) shows a strong anti-inflammatory and immunomodulatory effect in the joint of adjuvant arthritis (AA) rats, but the role of the spleen function is still unclear. The aim of this study was to research how CP-25 regulated spleen function of AA rats. Male Sprague-Dawley rats were administered with CP-25 (50 mg/kg) orally from day 17 to 29 after immunization. The spleen histopathological changes were analyzed by hematoxylin-eosin staining...
February 23, 2018: Inflammation
https://www.readbyqxmd.com/read/29458169/inhibition-of-microsomal-prostaglandin-e-synthase-1-facilitates-liver-repair-after-hepatic-injury-in-mice
#19
Nobuyuki Nishizawa, Yoshiya Ito, Koji Eshima, Hirotoki Ohkubo, Ken Kojo, Tomoyoshi Inoue, Joan Raouf, Per-Johan Jakobsson, Satoshi Uematsu, Shizuo Akira, Shuh Narumiya, Masahiko Watanabe, Masataka Majima
BACKGROUND & AIMS: Liver repair following hepatic ischemia/reperfusion (I/R) injury is crucial to survival. This study aims to examine the role of endogenous prostaglandin E2 (PGE2 ) produced by inducible microsomal PGE synthase-1 (mPGES-1), a terminal enzyme of PGE2 generation, in liver injury and repair following hepatic I/R. METHODS: mPGES-1 deficient (mPGES-1-/- ) mice or their wild counterparts (WT) were subjected to partial hepatic ischemia followed by reperfusion...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29455241/cox-2-derived-pge-2-triggers-hyperplastic-renin-expression-and-hyperreninemia-in-aldosterone-synthase-deficient-mice
#20
Christian Karger, Katharina Machura, André Schneider, Christian Hugo, Vladimir T Todorov, Armin Kurtz
Pharmacological inhibition or genetic loss of function defects of the renin angiotensin aldosterone system (RAAS) causes compensatory renin cell hyperplasia and hyperreninemia. The triggers for the compensatory stimulation of renin synthesis and secretion in this situation may be multimodal. Since cyclooxygenase-2 (COX-2) expression in the macula densa is frequently increased in states of a defective RAAS, we have investigated a potential role of COX-2 and its derived prostaglandins for renin expression and secretion in aldosterone synthase-deficient mice (AS-/- ) as a model for a genetic defect of the RAAS...
February 17, 2018: Pflügers Archiv: European Journal of Physiology
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