{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:10:45Z","timestamp":1790748645751,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,6]],"date-time":"2006-12-06T00:00:00Z","timestamp":1165363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adenoviruses can cause severe toxicity in immunocompromised individuals. Although clinical trials have confirmed the potency and safety of selectively oncolytic adenoviruses for treatment of advanced cancers, increasingly effective agents could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the effect of chlorpromazine, an inhibitor of clathrin\u2010dependent endocytosis and apigenin, a cell cycle regulator, on adenovirus replication and toxicity. First, we evaluated the <jats:italic>in vitro<\/jats:italic> replication of a tumor targeted Rb\u2010p16 pathway selective oncolytic adenovirus (Ad5\/3\u2010\u039424) and a wild\u2010type adenovirus in normal cells, fresh liver samples and in ovarian cancer cell lines. Further, we analyzed the <jats:italic>in vitro<\/jats:italic> cell killing efficacy of adenoviruses in the presence and absence of the substances. Moreover, the effect on <jats:italic>in vivo<\/jats:italic> efficacy, replication and liver toxicity of the adenoviruses was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> reduction of adenovirus replication and associated toxicity with chlorpromazine and apigenin. Effective doses were well within what would be predicted safe in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Chlorpromazine and apigenin might reduce the replication of adenovirus, which could provide a safety switch in case replication\u2010associated side effects are encountered in patients. In addition, these substances could be useful for the treatment of systemic adenoviral infections in immunosuppressed patients. Copyright \u00a9 2006 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.984","type":"journal-article","created":{"date-parts":[[2006,12,6]],"date-time":"2006-12-06T10:49:25Z","timestamp":1165402165000},"page":"3-9","source":"Crossref","is-referenced-by-count":24,"title":["Chlorpromazine and apigenin reduce adenovirus replication and decrease replication associated toxicity"],"prefix":"10.1002","volume":"9","author":[{"given":"Anna","family":"Kanerva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Raki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuuli","family":"Ranki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merja","family":"S\u00e4rkioja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarmo","family":"Koponen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee A.","family":"Desmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aija","family":"Helin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf\u2010H\u00e5kan","family":"Stenman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Isoniemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krister","family":"H\u00f6ckerstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Ristim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akseli","family":"Hemminki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12,6]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.08.002"},{"key":"e_1_2_5_3_2","first-page":"1666","article-title":"Phase III randomized clinical trial of intratumoral injection of E1B gene\u2010deleted adenovirus (H101) combined with cisplatin\u2010based chemotherapy in treating squamous cell cancer of head and neck or esophagus","volume":"23","author":"Xia ZJ","year":"2004","journal-title":"Ai Zheng"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0104-3"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/78638"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/89901"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302517"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.386"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.08.016"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro817"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.123.5.1107"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2498"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00200-4"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.754"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(89)90026-9"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a007071"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1017\/S000711459900080X"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.984","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.984","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T22:41:02Z","timestamp":1696891262000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.984"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12,6]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,1]]}},"alternative-id":["10.1002\/jgm.984"],"URL":"https:\/\/doi.org\/10.1002\/jgm.984","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"value":"1099-498X","type":"print"},{"value":"1521-2254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,12,6]]}}}