{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:49:13Z","timestamp":1792669753961,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Store-operated Ca2+ release\u2013activated Ca2+ (CRAC) channels are involved in the pathogenesis of rheumatoid arthritis (RA) and have been studied as therapeutic targets in the management of RA. We investigated the efficacy and safety of CRAC inhibitors, including a neutralizing Ab (hCRACM1-IgG) and YM-58483, in the treatment of RA. Patient-derived T cell and B cell activity was suppressed by hCRACM1-IgG as well as YM-58483. Systemically constant, s.c. infused CRAC inhibitors showed anti-inflammatory activity in a human-NOD\/SCID xenograft RA model as well as protective effects against the destruction of cartilage and bone. hCRACM1-IgG appeared to be safe for systemic application, whereas YM-58483 showed hepatic and renal toxicity in xenograft mice. Treatment with both CRAC inhibitors also caused hyperglycemia in xenograft mice. These results indicate the potential of hCRACM1-IgG and YM-58483 as anti-immunological agents for the treatment of RA. However, some safety issues should be addressed and application methods should be optimized prior to their clinical use.<\/jats:p>","DOI":"10.4049\/jimmunol.1700192","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T00:30:19Z","timestamp":1500337819000},"page":"1584-1595","source":"Crossref","is-referenced-by-count":39,"title":["Efficiency and Safety of CRAC Inhibitors in Human Rheumatoid Arthritis Xenograft Models"],"prefix":"10.1093","volume":"199","author":[{"given":"Shuang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ehime University Graduate School of Medicine , Shitsugawa, Toon-shi, Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine , Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Takemasa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ehime University Graduate School of Medicine , Shitsugawa, Toon-shi, Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4871-9685","authenticated-orcid":false,"given":"Yasuyuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ehime University Graduate School of Medicine , Shitsugawa, Toon-shi, Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizou","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Integrated Center for Sciences, Ehime University , Shitsugawa, Toon-shi, Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kiyoi","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Integrated Center for Sciences, Ehime University , Shitsugawa, Toon-shi, Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-8127","authenticated-orcid":false,"given":"Hiroyuki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Proteo-Science Center, Ehime University , Matsuyama, Ehime 791-8577,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomio","family":"Ogasawara","sequence":"additional","affiliation":[{"name":"Proteo-Science Center, Ehime University , Matsuyama, Ehime 791-8577,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Sawasaki","sequence":"additional","affiliation":[{"name":"Proteo-Science Center, Ehime University , Matsuyama, Ehime 791-8577,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Yasukawa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine , Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Maeyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ehime University Graduate School of Medicine , Shitsugawa, Toon-shi, Ehime 791-0295,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"2025030614285632700_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.39480","article-title":"2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis","volume":"68","author":"Singh","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"2025030614285632700_r2","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/clpt.2011.256","article-title":"A dose-response meta-analysis for quantifying relative efficacy of biologics in rheumatoid arthritis","volume":"90","author":"Mandema","year":"2011","journal-title":"Clin. 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