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Florie Mar, Mark Crowther, Alex Gold, Genmin Lu, Janet Leeds, Brian Wiens, Vandana Mathur, Janice Castillo, Pamela Conley, Stuart Connolly, John Curnutte
INTRODUCTION: Direct FXa inhibitors have demonstrated convincing anticoagulant efficacy. However, risk of major bleeding is a concern and no specific antidotes are available for reversal. Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors. We report data from the ANNEXA"! Phase 3 registration studies in older healthy subjects anticoagulated with apixaban (apix) or rivaroxaban (riva). METHODS: ANNEXA A&R were 2 phase 3, randomized, double-blind, placebo-controlled studies of AnXa in healthy subjects age 50 to 75 administered either apixaban or rivaroxaban...
August 2016: Neurosurgery
Dianhui Xiu, Lin Liu, Fengli Qiao, Haishan Yang, Lu Cui, Guifeng Liu
The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells...
2016: Gastroenterology Research and Practice
H F Yuan, Y Li, B B Tan, Q Zhao, L Q Fan, W H Ye
OBJECTIVE: To investigate the expression of annexin A7 (ANXA7) in the differentiation and lymphatic metastasis of gastric cancer (GC), and to investigate the relationship between ANXA7 and biological characteristics of GC. METHODS: The clinicopathological data of 124 patients with gastric cancer who underwent surgical treatment in our hospital were retrospectively reviewed and analyzed. Immunohistochemical staining and Western blot were performed to analyze the expression of ANXA 7 in primary GC tissues...
May 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Qifeng Zhao, Ji Wu, Zhiyong Lin, Qingwang Hua, Weixi Zhang, Leping Ye, Guowei Wu, Jie Du, Jie Xia, Maoping Chu, Xingti Hu
Lung ischemia-reperfusion injury (LIRI) is still an unsolved medical issue, which negatively affects the prognosis of many lung diseases. The aim of this study is to determine the effects of RvD1 on LIRI and the potential mechanisms involved. The results revealed that the levels of complement, immunoglobulin, cytokines, sICAM-1, MPO, MDA, CINC-1, MCP-1, ANXA-1, TLR4, NF-κBp65, apoptosis index, and pulmonary permeability index were increased, whereas the levels of SOD, GSH-PX activity, and oxygenation index were decreased in rats with LIRI...
August 2016: Inflammation
Kamrouz Ghadimi, Keith E Dombrowski, Jerrold H Levy, Ian J Welsby
Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding...
2016: Expert Review of Hematology
Sei-Jung Lee, Young Hyun Jung, Eun Ju Song, Kyung Ku Jang, Sang Ho Choi, Ho Jae Han
An inflammatory response is a hallmark of necrosis evoked by bacterial pathogens. Vibrio vulnificus, VvpE, is an elastase that is responsible for tissue necrosis and inflammation; however, the molecular mechanism by which it regulates host cell death has not been characterized. In the present study, we investigate the cellular mechanism of VvpE with regard to host cell death and the inflammatory response of human intestinal epithelial (INT-407) cells. The recombinant protein (r)VvpE (50 pg/ml) caused cytotoxicity mainly via necrosis coupled with IL-1β production...
September 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
De-Hong Yu, Ya-Rong Liu, Xin Luan, Hai-Jun Liu, Yun-Ge Gao, Hao Wu, Chao Fang, Hong-Zhuan Chen
Multidrug resistance is the main cause of clinical chemotherapeutic failure. Antiangiogenic cancer therapy with nanomedicine that allows the targeted delivery of antiangiogenic agents to tumor endothelial cells may contribute to innovative strategies for treating multidrug-resistant cancers. In this study, we developed a new nanodrug delivery system (nano-DDS), with improved antiangiogenic efficacy against multidrug resistant human breast cancer MCF-7/ADR cells. Here, the IF7 ligand was a peptide designed to bind the annexin 1 (Anxa 1), a highly specific marker of the tumor vasculature surface, with high affinity and specificity...
August 19, 2015: Bioconjugate Chemistry
Hu-Fang Yuan, Yong Li, Qun Zhao, Li-Qiao Fan, Bi-Bo Tan, Wei-Hua Ye
OBJECTIVE: To investigate the expression and clinical significance of annexin A7 in the differentiation and lymphatic metastasis of gastric cancer (GC). METHODS: The clinical and pathological data were recorded for analysis. Immunohistochemical staining and Western blot were performed to analyze the expression of ANXA 7 in primary GC tissues. Logistic regression analyses were conducted to evaluate the associations between annexin A7 expression levels and differentiations of GC...
2014: International Journal of Clinical and Experimental Pathology
Z Boudhraa, C Merle, D Mazzocut, J M Chezal, C Chambon, E Miot-Noirault, M Theisen, B Bouchon, F Degoul
Annexin A1 deregulation is often associated with cancer. Indeed we have shown that annexin A1 is overexpressed in melanoma and promotes metastases by formyl peptide receptor stimulation and MMP2 expression. Here, we demonstrated in different melanoma cell lines that annexin A1-MMP2 induction is mediated by MAPK and STAT3 pathways. To decipher endogenous annexin A1 action mode, we showed that annexin A1 is externalized in A375 cells and cleaved by a membrane-associated serine protease, allowing the release of a pro-invasive annexin A1 peptide in the extra cellular environment...
December 2014: Archives of Dermatological Research
Zhizhen Dong, Min Yao, Haijian Zhang, Li Wang, Hua Huang, Meijuan Yan, Wei Wu, Dengfu Yao
Hepatocyte Annexin A2 (ANXA2) expression is associated with the progression and metastasis of hepatocellular carcinoma (HCC). Circulating ANXA2 levels in HCC patients are significantly higher compared with that of patients with benign liver disease. ANXA2 levels have been found to correlate with hepatitis B virus infection, extrahepatic metastasis and portal vein thrombus. By contrast, ANXA2 levels do not correlate with tumour size and AFP levels. However, the underlying mechanisms of ANXA2 remain obscure. The results of the current study identified that abnormalities in hepatic ANXA2 expression were localised to the cell membrane and cytoplasm of HCC tissues and mainly in the cytoplasm of para-cancerous tissues...
January 2014: Oncology Letters
Xian Wang, Shengjie Zhang, Jianbin Zhang, Emily Lam, Xin Liu, Jie Sun, Lifeng Feng, Haiqi Lu, Jun Yu, Hongchuan Jin
BACKGROUND: The aberrant activation of oncogenic signaling such as Ras/MAPK signaling is a frequent event in human cancers. In addition to genetic changes, epigenetic silencing of inhibitors in Ras/MAPK signaling contributes to the activation of Ras/MAPK signaling. Recently, ANXA6 has been shown to interact with Ras-GAP1 and inhibit Ras activation in human breast cancer. However, whether and how it is involved in human cancers remain unknown. METHODS: Real-time PCR was used to determine ANXA6 expression in gastric cancer cells and primary gastric carcinomas...
2013: American Journal of Translational Research
Yoshie Takizawa, Yukiko Kosuge, Hiroyo Awaji, Emi Tamura, Ayako Takai, Takaaki Yanai, Reiko Yamamoto, Koichi Kokame, Toshiyuki Miyata, Rieko Nakata, Hiroyasu Inoue
Resveratrol, a polyphenolic phytoalexin found in red wine and various plants, has been reported to up-regulate the expression of endothelial NO synthase (eNOS) in human umbilical vein endothelial cells (HUVEC). However, this effect was neither long term in nature nor physiologically relevant at the concentration of resveratrol studied. In the present study, we investigated the effects of repeated treatments with a lower concentration of resveratrol on the expression of genes in HUVEC. The expression levels of eNOS and silent mating type information regulation 2 homologue 1 (SIRT1) were up-regulated in HUVEC by repeated treatments with 1 μm-resveratrol for 6 d, but not with fenofibrate...
December 2013: British Journal of Nutrition
S Seidel, H Neymeyer, T Kahl, T Röschel, K Mutig, R Flower, J Schnermann, S Bachmann, A Paliege
Annexin A1 (ANXA1) exerts anti-inflammatory effects through multiple mechanisms including inhibition of prostaglandin synthesis. Once secreted, ANXA1 can bind to G protein-coupled formyl peptide receptors (Fpr) and activate diverse cellular signaling pathways. ANXA1 is known to be expressed in cells of the juxtaglomerular apparatus, but its relation to the expression of cyclooxygenase 2 (COX-2) in thick ascending limb and macula densa cells has not been elucidated. We hypothesized that ANXA1 regulates the biosynthesis of COX-2...
September 15, 2012: American Journal of Physiology. Renal Physiology
Iu V Vakhitova, E I Antipina, R S Yamidanov, R Iu Khisamutdinova, F S Zarudiĭ, N Zh Baschenko, V A Dokichev, Iu V Tomilov, O M Nefedov
The goal of the current work is to study the molecular mechanisms underlay the action of 5- amino-exo-3-azatricyclo[,6)]decan-4-one (P-11) with combined antiarrhythmic, nootropic, anti-inflammatory and anaesthetic activities. The aconitine-induced experimental rat model of cardiac arrhythmia has been used in our study. Aconitine was administered once intravenously in a dose 50 microg/kg whereas experimental animal group received P-11 in a dose 0.3 mg/kg (the compound was injected intravenously 2 min before acute aconitine treatment)...
November 2011: Bioorganicheskaia Khimiia
Ronan S Rogers, Moyez Dharsee, Suzanne Ackloo, Jeremy M Sivak, John G Flanagan
We investigate the role of glial cell activation in the human optic nerve caused by raised intraocular pressure, and their potential role in the development of glaucomatous optic neuropathy. To do this we present a proteomics study of the response of cultured, optic nerve head astrocytes to biomechanical strain, the magnitude and mode of strain based on previously published quantitative models. In this case, astrocytes were subjected to 3 and 12% stretches for either 2 h or 24 h. Proteomic methods included nano-liquid chromatography, tandem mass spectrometry, and iTRAQ labeling...
February 2012: Molecular & Cellular Proteomics: MCP
Jinn-Shiun Chen, Yeh-Pin Chou, Kuei-Tien Chen, Ray-Ping Hung, Jau-Song Yu, Yu-Sun Chang, Err-Cheng Chan
BACKGROUND: Annexins (ANXAs) belong to a superfamily of closely related calcium and membrane-binding proteins and are overexpressed in some carcinomas. The overexpression of ANXAs presumably induces an autoantibody response, but this has not been demonstrated for sera from colorectal cancer (CRC) patients. STUDY: We examined serum samples from 220 CRC patients and 216 healthy volunteers to evaluate the ANXA autoantibody response in patients by using an enzyme-linked immunosorbent assay with recombinant ANXA A4 as the antigen...
February 2011: Journal of Clinical Gastroenterology
Tae-Ho Kim, Jung Min Hong, Eun-Soon Shin, Hyun-Ju Kim, Yoon Shin Cho, Jong-Young Lee, Sang-Han Lee, Eui Kyun Park, Shin-Yoon Kim
OBJECTIVE: The pathogenesis of osteonecrosis of the femoral head (ONFH) probably reflects multiple etiologies. Recent studies have explored associations between genetic mutations and/or polymorphisms and ONFH. Annexins (ANXs) have been implicated in many physiological functions, including blood coagulation, inflammation, apoptosis, as well as Ca(2+) homeostasis in bone cells, all of which may be associated with ONFH. The aim of this study was to evaluate the possible association of AnnexinA (ANXA) family gene polymorphisms with ONFH...
July 2009: Bone
Isabel Olivares, Alicia Ballester, Luis Lombardia, Orlando Dominguez, Cecilio López-Galíndez
To investigate cellular factors involved in HIV-1 chronic infection, three cell lines chronically infected with the same HIV-1 viral isolate (s61) were studied by cDNA microarray analysis. Two T cell lines, H61 and M61, showed the characteristics of a persistent infection whereas U61 cell line displayed a latent infection pattern. Analysis of genes with altered expression in the three cell lines revealed evidence of apoptosis control by up-regulation of anti-apoptotic genes and down-regulation of pro-apoptotic genes...
January 2009: Virus Research
Zhiyong Yang, Harry A Quigley, Mary E Pease, Yanqin Yang, Jiang Qian, Danielle Valenta, Donald J Zack
PURPOSE: The authors studied retinal gene expression changes in rats after experimental intraocular pressure elevation and optic nerve transection to elucidate molecular mechanisms of retinal ganglion cell (RGC) death. METHODS: Translimbal laser photocoagulation was used to induce unilateral IOP elevation in 41 albino Wistar rats. In 38 additional animals, unilateral transection of the optic nerve was performed. Retinas were harvested 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 8 weeks after each treatment, and total RNA was isolated...
December 2007: Investigative Ophthalmology & Visual Science
George G Ignotz, Margaret Y Cho, Susan S Suarez
The sperm of eutherian mammals are held in a storage reservoir in the caudal segment of the oviduct by binding to the mucosal epithelium. The reservoir serves to maintain the fertility of sperm during storage and to reduce the incidence of polyspermic fertilization. Bovine sperm bind to the epithelium via seminal vesicle secretory proteins in the bovine seminal plasma protein (BSP) family, namely, PDC109 (BSPA1/A2), BSPA3, and BSP30K, which coat the sperm head. Our objective was to identify the receptors for bull sperm on the oviductal epithelium...
December 2007: Biology of Reproduction
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