{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:39:05Z","timestamp":1790437145166,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science, and Culture, Japan","award":["15K10446"],"award-info":[{"award-number":["15K10446"]}]},{"name":"Ministry of Education, Science, and Culture, Japan","award":["25293283"],"award-info":[{"award-number":["25293283"]}]},{"name":"Ministry of Education, Science, and Culture, Japan","award":["25293323"],"award-info":[{"award-number":["25293323"]}]},{"name":"Ministry of Education, Science, and Culture, Japan","award":["25462057"],"award-info":[{"award-number":["25462057"]}]},{"name":"Ministry of Education, Science, and Culture, Japan","award":["25462333"],"award-info":[{"award-number":["25462333"]}]},{"name":"National Cancer Center Research and Development Fund","award":["23-A-10"],"award-info":[{"award-number":["23-A-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor\u2010specific replicating oncolytic adenovirus <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (<jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content>) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 and <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> against osteosarcomas with bone destruction. The antitumor activity of <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 and <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, <jats:styled-content style=\"fixed-case\">MNNG<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">HOS<\/jats:styled-content>, Sa<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>\u20102). The cytotoxic effect of <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 and\/or <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> was measured by assay of cell apoptosis. The effect of <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 and <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 and <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> decreased the viability of human osteosarcoma cells. Combination therapy with <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 and <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> displayed a synergistic antitumor effect, in which <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 promoted apoptosis through suppression of anti\u2010apoptotic myeloid cell leukemia 1 (<jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content>1). Combination therapy significantly inhibited tumor\u2010mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of <jats:styled-content style=\"fixed-case\">OBP<\/jats:styled-content>\u2010301 and <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> suppresses osteosarcoma progression via suppression of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content>1 and osteoclast activation.<\/jats:p>","DOI":"10.1111\/cas.13316","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T12:26:12Z","timestamp":1499430372000},"page":"1870-1880","source":"Crossref","is-referenced-by-count":18,"title":["Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction"],"prefix":"10.1111","volume":"108","author":[{"given":"Yasuaki","family":"Yamakawa","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-1050","authenticated-orcid":false,"given":"Hiroshi","family":"Tazawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"},{"name":"Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Hasei","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Osaki","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Omori","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Sugiu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Komatsubara","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Uotani","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Kunisada","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"},{"name":"Medical Materials for Musculoskeletal Reconstruction Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Urata","sequence":"additional","affiliation":[{"name":"Oncolys BioPharma, Inc. 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