{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:11:59Z","timestamp":1761217919447},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:00:00Z","timestamp":1506384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K09001"],"award-info":[{"award-number":["15K09001"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Reduced expression in immortalized cells (REIC)\/dickkopf\u20103 (Dkk\u20103) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC\/Dkk\u20103\u2010expressing adenoviral vector (Ad\u2010REIC) was found to induce cancer\u2010selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re\u2010construct an Ad\u2010REIC vector, termed the Ad\u2010SGE\u2010REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad\u2010SGE\u2010REIC on hepatocellular carcinoma (HCC) was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK\u2010Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1\u20106) were used in this study. REIC\/Dkk\u20103 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined <jats:italic>in vitro<\/jats:italic>, and the anti\u2010tumor effects of Ad\u2010SGE\u2010REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti\u2010tumor immunological effects on the immunocompetent mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>REIC\/Dkk\u20103 expression was decreased in HCC cell lines and HCC tissues. Ad\u2010SGE\u2010REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated <jats:italic>in vivo<\/jats:italic> anti\u2010cancer immunostimulatory effects on the HCC cell line (Hepa1\u20106).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ad\u2010SGE\u2010REIC treatment not only enhanced cell killing effects <jats:italic>in vitro<\/jats:italic> but also elicited significant therapeutic effects, with tumor growth suppression, <jats:italic>in vivo<\/jats:italic>. REIC\/Dkk\u20103 gene therapy using Ad\u2010SGE\u2010REIC potentially represents an innovative new therapeutic tool for HCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.13757","type":"journal-article","created":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T01:03:01Z","timestamp":1486429381000},"page":"1769-1777","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Promising therapeutic efficacy of a novel reduced expression in immortalized cells\/dickkopf\u20103 expressing adenoviral vector for hepatocellular carcinoma"],"prefix":"10.1111","volume":"32","author":[{"given":"Hiroaki","family":"Sawahara","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences  Okayama 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