{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T05:09:55Z","timestamp":1745039395677},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["15K10165"],"award-info":[{"award-number":["15K10165"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Inflammation plays an important role in hepatocellular carcinoma (HCC) progression. Here, we examined whether antithrombin (AT) plays a role in attenuating HCC progression, via its anti\u2010inflammatory effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HCCs were developed in AT\u2010insufficient (AT<jats:sup>+\/\u2212<\/jats:sup>) mice and wild\u2010type (AT<jats:sup>+\/+<\/jats:sup>) mice treated with diethyl nitrosamine and carbon tetrachloride. AT was administered to AT<jats:sup>+\/\u2212<\/jats:sup> mice. The development of HCC was compared between the three groups. <jats:italic>In vitro<\/jats:italic> study, migration assay was performed. The association of the prognosis of patients with HCC and plasma AT values was clinically examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AT suppressed the release of interleukin (IL)\u20108 from lipopolysaccharide (LPS)\u2010stimulated human neutrophils <jats:italic>in vitro<\/jats:italic>. Huh\u20107 cells that were co\u2010cultured with neutrophils and stimulated with LPS showed significantly enhanced migration; however, Huh\u20107 cells co\u2010cultured with LPS\/AT\u2010stimulated neutrophils showed significantly decreased migration. Moreover, the addition of anti\u2010IL\u20108 antibodies to LPS\u2010stimulated Huh\u20107 cells co\u2010cultured with neutrophils also suppressed migration. AT<jats:sup>+\/\u2212<\/jats:sup> mice (AT plasma activity: 64%) promoted liver cancer, as compared with wild\u2010type mice (AT plasma activity: 135%); AT administration attenuated liver cancer in AT<jats:sup>+\/\u2212<\/jats:sup> mice. Patients with HCC with a preoperative AT level of \u226570% showed better outcomes after liver resection, as compared with those with an AT level of &lt;70%. IL\u20108 expression and neutrophil infiltration in HCC tissues were negatively correlated with the AT level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>AT attenuates HCC progression by regulating neutrophil\/IL\u20108 signaling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13558","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T12:12:10Z","timestamp":1605269530000},"page":"1284-1296","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Antithrombin attenuates the progression of hepatocellular carcinoma by regulating neutrophil\/interleukin\u20108 signaling"],"prefix":"10.1111","volume":"50","author":[{"given":"Sho","family":"Okimoto","sequence":"first","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences Hiroshima University  Kasumi, Hiroshima 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