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https://www.readbyqxmd.com/read/28213942/pge2-ep4-attenuated-mucosal-injury-via-%C3%AE-arr1-src-egfr-mediated-proliferation-in-portal-hypertensive-gastropathy
#1
Siwei Tan, Xiaoliang Chen, Minyi Xu, Xiaoli Huang, Huiling Liu, Jie Jiang, Yu Lu, Xiaojie Peng, Bin Wu
BACKGROUND AND PURPOSE: Portal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis and a potential cause of bleeding in patients associated with cirrhosis. Suppressed mucosal epithelial proliferation is a crucial pathological characteristic of PHG. Our studies demonstrated an important role of prostaglandin E2 (PGE2 ) and its E-type prostanoid 4 (EP4 ) receptor in the promotion of mucosal proliferation. However, whether β-arrestin1 (β-arr1), a well-established mediator of G-protein-coupled receptors (GPCRs), is involved in the PGE2 /EP4 -mediated mucosal proliferation complex in PHG remains unclear...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#2
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28172421/p040-intestinal-ep4-receptor-is-required-for-homeostasis-of-the-colon-in-mice
#3
Y Matsumoto, A Fukuda, H Seno
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28169162/discovery-of-aat-008-a-novel-potent-and-selective-prostaglandin-ep4-receptor-antagonist
#4
Yoshiyuki Okumura, Tatsuya Yamagishi, Seiji Nukui, Kazunari Nakao
Starting from acylsufonamide HTS hit 2, a novel series of para-N-acylaminomethylbenzoic acids was identified and developed as selective prostaglandin EP4 receptor antagonists. Structural modifications on lead compound 4a were explored with the aim of improving potency, physicochemical properties, and animal PK predictive of QD (once a day) dosing regimen in human. These efforts led to the discovery of the clinical candidate AAT-008 (4j), which exhibited significantly improved pharmacological profiles over grapiprant (1)...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108433/enhanced-ep4-expression-in-a-pulmonary-artery-aneurysm-with-dissection-in-a-patient-with-pulmonary-arterial-hypertension
#5
Satoshi Akagi, Kazufumi Nakamura, Utako Yokoyama, Shingo Kasahara, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Ito
No abstract text is available yet for this article.
February 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28104442/prostaglandin-e2-receptor-4-mediates-renal-cell-carcinoma-intravasation-and-metastasis
#6
Yushan Zhang, Hamsa Thayele Purayil, Joseph B Black, Francis Fetto, Lauren D Lynch, Jude N Masannat, Yehia Daaka
Treatment options for metastatic renal cell carcinoma (RCC) are limited. In this study, we investigated impact of prostaglandin E2 (PGE2) receptor 4 (EP4) on RCC metastasis. We found that knockdown of EP4 in two RCC cell lines, ACHN and SN12C, does not affect xenograft tumor take or growth rate in mice, but reduces metastasis by decreasing tumor intravasation. Using chick chorioallantoic membrane (CAM) assay, we confirmed that blockade of EP4 signaling inhibits tumor intravasation. In vitro studies associated EP4 expression and activity with RCC cell transendothelial migration (TEM)...
January 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28094049/ep4-receptor-promotes-invadopodia-and-invasion-in-human-breast-cancer
#7
Felix Tönisen, Louisiane Perrin, Battuya Bayarmagnai, Koen van den Dries, Alessandra Cambi, Bojana Gligorijevic
The production of Prostaglandin E2 (PGE2) is elevated in human breast cancer cells. The abnormal expression of COX-2, which is involved in the synthesis of PGE2, was recently reported as a critical determinant for invasiveness of human breast cancer cells. Autocrine and paracrine PGE2-mediated stimulation of the PGE2 receptor EP4 transduces multiple signaling pathways leading to diverse patho-physiological effects, including tumor cell invasion and metastasis. It is known that PGE2-induced EP4 activation can transactivate the intracellular signaling pathway of the epidermal growth factor receptor (EGFR)...
January 10, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28086956/differential-expression-of-e-type-prostanoid-receptors-2-and-4-in-microglia-stimulated-with-lipopolysaccharide
#8
Ester Bonfill-Teixidor, Amaia Otxoa-de-Amezaga, Miriam Font-Nieves, M Glòria Sans-Fons, Anna M Planas
BACKGROUND: Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS. METHODS: Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#9
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28056899/pge2-promotes-breast-cancer-associated-lymphangiogenesis-by-activation-of-ep4-receptor-on-lymphatic-endothelial-cells
#10
Pinki Nandi, Gannareddy V Girish, Mousumi Majumder, Xiping Xin, Elena Tutunea-Fatan, Peeyush K Lala
BACKGROUND: Lymphatic metastasis, facilitated by lymphangiogenesis is a common occurrence in breast cancer, the molecular mechanisms remaining incompletely understood. We had earlier shown that cyclooxygenase (COX)-2 expression by human or murine breast cancer cells promoted lymphangiogenesis and lymphatic metastasis by upregulating VEGF-C/D production by tumor cells or tumor-associated macrophages primarily due to activation of the prostaglandin receptor EP4 by endogenous PGE2. It is not clear whether tumor or host-derived PGE2 has any direct effect on lymphangiogenesis, and if so, whether EP4 receptors on lymphatic endothelial cells (LEC) play any role...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28030966/systemic-drugs-that-influence-titanium-implant-osseointegration
#11
Dragos Apostu, Ondine Lucaciu, Gheorghe Dan Osvald Lucaciu, Bogdan Crisan, Liana Crisan, Mihaela Baciut, Florin Onisor, Grigore Baciut, Radu Septimiu Câmpian, Simion Bran
Titanium implants are widely used on an increasing number of patients in orthopedic and dental medicine. Despite the good survival rates of these implants, failures that lead to important socio-economic consequences still exist. Recently, research aimed at improving implant fixation, a process called osseointegration, has focused on a new, innovative field: systemic delivery of drugs. Following implant fixation, patients receive systemic drugs that could either impair or enhance osseointegration; these drugs include anabolic and anti-catabolic bone-acting agents in addition to new treatments...
January 23, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28029661/multiple-drug-resistance-associated-protein-mrp4-exports-prostaglandin-e2-pge2-and-contributes-to-metastasis-in-basal-triple-negative-breast-cancer
#12
Tyler J Kochel, Jocelyn C Reader, Xinrong Ma, Namita Kundu, Amy M Fulton
Cyclooxygenase-2 (COX-2) and its primary enzymatic product, prostaglandin E2 (PGE2), are associated with a poor prognosis in breast cancer. In order to elucidate the factors contributing to intratumoral PGE2 levels, we evaluated the expression of COX-2/PGE2 pathway members MRP4, the prostaglandin transporter PGT, 15-PGDH (PGE2 metabolism), the prostaglandin E receptor EP4, COX-1, and COX-2 in normal, luminal, and basal breast cancer cell lines. The pattern of protein expression varied by cell line reflecting breast cancer heterogeneity...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27973680/prostaglandin-e2-potentiates-interferon-%C3%AE-induced-nitric-oxide-production-in-cultured-rat-microglia
#13
Takayuki Nagano, Ryo Nishiyama, Ayaka Sanada, Yukiko Mutaguchi, Anna Ioku, Hirohisa Umeki, Satoshi Kishimoto, Daisuke Yamanaka, Shinya H Kimura, Motohiko Takemura
Prostaglandin E2 (PGE2 ) plays crucial roles in managing microglial activation through the prostanoid EP2 receptor, a PGE2 receptor subtype. In this study, we report that PGE2 enhances interferon-γ (IFN-γ)-induced nitric oxide production in microglia. IFN-γ increased the release of nitrite, a metabolite of nitric oxide, which was augmented by PGE2 , although PGE2 by itself slightly affects nitrite release. The potentiating effect of PGE2 was positively associated with increased expression of inducible nitric oxide synthase...
December 14, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27925221/pharmacokinetic-pharmacodynamic-evaluation-of-grapiprant-in-a-carrageenan-induced-inflammatory-pain-model-in-the-rabbit
#14
V De Vito, M Salvadori, A Poapolathep, H Owen, R Rychshanova, M Giorgi
Grapiprant is the novel selective EP4 receptor inhibitor recently issued on the veterinary market for dogs affected by osteoarthritis. The aim of this study was twofold: to evaluate the pharmacokinetics and the pharmacodynamics of grapiprant in the induced inflammatory pain model in the rabbit after a single IV injection of 2 mg/kg; to compare the thermal antinociception effect after 2 mg/kg IV grapiprant, with that generated by 0.5 mg/kg meloxicam SC injected. Rabbits (n = 12) were randomly assigned to two crossover studies (single-dose, two-period crossover)...
December 7, 2016: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27898472/a-case-of-trichogerminoma-with-pilomatrical-differentiation-and-a-unique-immunohistochemical-profile
#15
Jonathan Epperson, Lester Libow
Trichogerminomas are rare adnexal neoplasms first described by Sau et al in 1992. Including the initial report, 20 cases have been reported, all with similar histological features, namely tumor nodules composed of basaloid cells that form densely packed, round nests or "cell balls" and which demonstrate variable degrees of pilosebaceous differentiation. In this study, the authors report a case of a trichogerminoma with pilomatrical differentiation and a unique immunohistochemical profile. The patient is a 71-year-old man with a well-delineated nodule on the top of the scalp...
January 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27869171/epigenetic-activation-of-the-prostaglandin-receptor-ep4-promotes-resistance-to-endocrine-therapy-for-breast-cancer
#16
J F Hiken, J I McDonald, K F Decker, C Sanchez, J Hoog, N D VanderKraats, K L Jung, M Akinhanmi, L E Rois, M J Ellis, J R Edwards
Approximately 75% of breast cancers express estrogen receptor α (ERα) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit ER signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the upregulation of alternative growth signals. The mechanisms that drive this resistance-especially epigenetic events that alter gene expression-are, however, not well understood...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27864128/prostaglandin-e2-activates-yap-and-a-positive-signaling-loop-to-promote-colon-regeneration-after-colitis-but-also-carcinogenesis-in-mice
#17
Han-Byul Kim, Minchul Kim, Young-Soo Park, Intae Park, Tackhoon Kim, Sung-Yeun Yang, Charles J Cho, DaeHee Hwang, Jin-Hak Jung, Sanford D Markowitz, Sung Wook Hwang, Suk-Kyun Yang, Dae-Sik Lim, Seung-Jae Myung
BACKGROUND & AIMS: Prostaglandin E2 (PGE2) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE2 signaling pathway that contribute to tumor formation. We investigated whether yes-associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE2 function. METHODS: DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE2, with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse-transcription polymerase chain reaction, transcriptional reporter, and proliferation assays...
February 2017: Gastroenterology
https://www.readbyqxmd.com/read/27835919/pka-and-apicomplexan-parasite-diseases
#18
M Haidar, G Ramdani, E J Kennedy, G Langsley
The cAMP-dependent protein kinase PKA is a well-characterized member of the serine-threonine protein AGC kinase family and is the effector kinase of cAMP signaling. As such, PKA is involved in the control of a wide variety of cellular processes including metabolism, cell growth, gene expression and apoptosis. cAMP-dependent PKA signaling pathways play important roles during infection and virulence of various pathogens. Since fluxes in cAMP are involved in multiple intracellular functions, a variety of different pathological infectious processes can be affected by PKA signaling pathways...
November 11, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27829645/an-ep4-receptor-agonist-inhibits-cardiac-fibrosis-through-activation-of-pka-signaling-in-hypertrophied-heart
#19
Qi Wang, Toru Oka, Kiyoshi Yamagami, Jong-Kook Lee, Hiroshi Akazawa, Atsuhiko T Naito, Taku Yasui, Takamaru Ishizu, Yoshikazu Nakaoka, Yasushi Sakata, Issei Komuro
Cardiac fibrosis is a pathological feature of myocardium of failing heart and plays causative roles in arrhythmia and cardiac dysfunction, but its regulatory mechanisms remain largely elusive. In this study, we investigated the effects of the novel EP4 receptor agonist ONO-0260164 on cardiac fibrosis in hypertrophied heart and explored the regulatory mechanisms in cardiac fibroblasts.In a mouse model of cardiac hypertrophy generated by transverse aortic constriction (TAC), ONO-0260164 treatment significantly prevented systolic dysfunction and progression of myocardial fibrosis at 5 weeks after TAC...
February 7, 2017: International Heart Journal
https://www.readbyqxmd.com/read/27827823/g-csf-induced-sympathetic-tone-provokes-fever-and-primes-anti-mobilizing-functions-of-neutrophils-via-pge2
#20
Yuko Kawano, Chie Fukui, Masakazu Shinohara, Kanako Wakahashi, Shinichi Ishii, Tomohide Suzuki, Mari Sato, Noboru Asada, Hiroki Kawano, Kentaro Minagawa, Akiko Sada, Tomoyuki Furuyashiki, Satoshi Uematsu, Shizuo Akira, Toshimitsu Uede, Shuh Narumiya, Toshimitsu Matsui, Yoshio Katayama
Granulocyte colony-stimulating factor (G-CSF) is widely used for peripheral blood stem/progenitor mobilization. G-CSF causes low-grade fever that is ameliorated by non-steroidal anti-inflammatory drugs (NSAIDs), suggesting the activation of arachidonic acid (AA) cascade. How G-CSF regulated this reaction was assessed. G-CSF treatment in mice resulted in fever, which was canceled in prostaglandin E synthase (mPGES-1)-deficient mice. Mobilization efficiency was twice higher in chimeric mice lacking mPGES-1, specifically in hematopoietic cells, suggesting that PGE2 from hematopoietic cells modulated bone marrow (BM) microenvironment...
November 8, 2016: Blood
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