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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2015; 21(29): 8776-8786
Published online Aug 7, 2015. doi: 10.3748/wjg.v21.i29.8776
Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan
Author contributions: Tanida S study concept, data acquisition, data analysis, drafting of the manuscript; Kataoka H, Kamiya T and Joh T study concept, supervision; Mizoshita T, Ozeki K and Katano T technical support and data analysis.
Supported by Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science, No. 25460957.
Conflict-of-interest statement: All authors declare that there are no conflicts of interest regarding this work.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Satoshi Tanida, MD, PhD, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan. stanida@med.nagoya-cu.ac.jp
Telephone: +81-52-8538211 Fax: +81-52-8520952
Received: April 2, 2015
Peer-review started: April 4, 2015
First decision: April 23, 2015
Revised: May 8, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: August 7, 2015
Processing time: 127 Days and 19.1 Hours
Abstract

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.

Keywords: Tumor necrosis factor-α; Shedding; Integrin α4β7; Epidermal growth factors

Core tip: The main goal of ulcerative colitis (UC) therapy is to induce and maintain long-term corticosteroid-free remission. Therapies such as anti-tumor necrosis factor (TNF)-α and integrin α4β7 neutralizing antibodies have emerged in recent times, but are not universally efficacious; additional treatments are needed. We have recently demonstrated that annexin (ANX) A2 inhibition may be a new therapeutic strategy to prevent TNF-α shedding during inflammatory bowel disease (IBD) inflammation. Here we focus on effective therapies for UC patients that are currently available, or will be in the near future, and the potential of ANX A2 as a new molecular target for IBD treatment.