{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:15:08Z","timestamp":1789604108640,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,9,23]],"date-time":"2013-09-23T00:00:00Z","timestamp":1379894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>Oncolytic virotherapy using adenoviruses has potential for therapeutic benefits in malignant mesothelioma. However, the downregulation of coxsackie virus\/adenovirus receptor (<jats:styled-content style=\"fixed-case\">CAR<\/jats:styled-content>) expression is frequently a critical rate\u2010limiting factor that impedes the effectiveness of adenovirus serotype 5 (Ad5)\u2010based vectors in many cancer types. We evaluated<jats:styled-content style=\"fixed-case\">CAR<\/jats:styled-content>(Ad5 receptor) and<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 (adenovirus serotype 35 [Ad35] receptor) expression in six human malignant mesothelioma cell lines. Very low<jats:styled-content style=\"fixed-case\">CAR<\/jats:styled-content>expression was observed in<jats:styled-content style=\"fixed-case\">MSTO<\/jats:styled-content>\u2010211H and<jats:styled-content style=\"fixed-case\">NCI<\/jats:styled-content>\u2010H2052 cells, whereas the other cell lines showed strong expression. In contrast,<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 was highly expressed in all mesothelioma cell lines. On this basis, we replaced the<jats:styled-content style=\"fixed-case\">CAR<\/jats:styled-content>binding sequence of Ad5 with the<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 binding sequence of Ad35 in the replication\u2010defective adenoviruses and the tumor\u2010specific midkine promoter\u2010regulated oncolytic adenoviruses. By this fiber modification, the infectivity, virus progeny production, and<jats:italic>in vitro<\/jats:italic>cytocidal effects of the adenoviruses were significantly enhanced in low<jats:styled-content style=\"fixed-case\">CAR<\/jats:styled-content>\u2010expressing<jats:styled-content style=\"fixed-case\">MSTO<\/jats:styled-content>\u2010211H and<jats:styled-content style=\"fixed-case\">NCI<\/jats:styled-content>\u2010H2052 cells, also resulting in similar or even higher levels in high<jats:styled-content style=\"fixed-case\">CAR<\/jats:styled-content>\u2010expressing mesothelioma cell lines. In<jats:styled-content style=\"fixed-case\">MSTO<\/jats:styled-content>\u2010211H xenograft models, the fiber\u2010modified oncolytic adenovirus significantly enhanced antitumor effect compared to its equivalent Ad5\u2010based vector. Our data demonstrate that Ad35 fiber modification of binding tropism in a midkine promoter\u2010regulated oncolytic Ad5 vector confers transductional targeting to oncolytic adenoviruses, thereby facilitating more effective treatment of malignant mesothelioma.<\/jats:p>","DOI":"10.1111\/cas.12267","type":"journal-article","created":{"date-parts":[[2013,8,21]],"date-time":"2013-08-21T09:08:37Z","timestamp":1377076117000},"page":"1433-1439","source":"Crossref","is-referenced-by-count":22,"title":["Enhanced antitumor efficacy of fiber\u2010modified, midkine promoter\u2010regulated oncolytic adenovirus in human malignant mesothelioma"],"prefix":"10.1111","volume":"104","author":[{"given":"Misato","family":"Takagi\u2010Kimura","sequence":"first","affiliation":[{"name":"Department of Genetics Hyogo College of Medicine Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Yamano","sequence":"additional","affiliation":[{"name":"Department of 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