{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T02:17:59Z","timestamp":1723083479877},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T00:00:00Z","timestamp":1143504000000},"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":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Osteosarcoma (OSA) is the most frequent type of primary malignant bone tumor and is apt to occur in children and young adults. Pulmonary metastasis (OSPM) is the major reason for its fatal outcome. Osteocalcin (OC) is a major noncollagenous bone protein whose expression is limited almost exclusively to bone marrow and osteotropic tumors. OC is also known to express in cell lines with bone metastasis feathers. Gene therapy strategies with the OC promoter directing the replication of adenovirus in a tumor\u2010specific manner are a potential modality for OSPM therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We detected OC mRNA expression by RNA <jats:italic>in situ<\/jats:italic> hybridization in OSA and OSPM samples from patients, and tested OC promoter transcriptional activity in OSA and non\u2010OSA cell lines. Then we used a transcriptional replication\u2010competent adenovirus, Ad\u2010OC\u2010E1a, to treat OSPM, and evaluated its tumor\u2010specific replication and killing activities <jats:italic>in vitro<\/jats:italic> as well as anti\u2010OSPM efficacy <jats:italic>in vivo<\/jats:italic> via systemic delivery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OC mRNA was detected in all types of OSA tissues, including OSPM tissues. The transcriptional activity of the OC promoter was much higher in a OSPM cell line SAOS\u20102LM7 and primary OSA cell line MG63 than in non\u2010OSA cell lines, including cell lines from breast cancer, colon cancer, and liver cancer. Ad\u2010OC\u2010E1a expressed E1a protein only in MG63 and SAOS\u20102LM7, which indicated that adenovirus E1a was under strict control by the OC promoter. Ad\u2010OC\u2010E1a demonstrated killing and viral replication activity close to wild\u2010type adenovirus levels in MG63 and SAOS\u20102LM7, but the killing and viral replication activities were attenuated significantly in cells expressing low OC transcriptional activity. To test whether Ad\u2010OC\u2010E1a could be used to target human OSPM <jats:italic>in vivo<\/jats:italic>, SAOS\u20102LM7 pulmonary metastasis models in nude mice were induced and treated by tail\u2010vein injection with Ad\u2010OC\u2010E1a. Compared to tumor nodules in the lung in groups treated with PBS or control virus, the quantity of metastasized tumor nodules decreased significantly. Adenovirus\u2010infected cells were stained immunohistochemically only inside and around the OSPM nodules but spared normal lung tissue and other organs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data demonstrated that OC promoter could direct adenovirus replication by controlling the <jats:italic>E1a<\/jats:italic> gene to target human OSPM in a tumor\u2010specific manner, providing an efficient tool to develop a feasible therapeutic modality for OSPM. Copyright \u00a9 2006 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.904","type":"journal-article","created":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T14:46:29Z","timestamp":1143557189000},"page":"679-689","source":"Crossref","is-referenced-by-count":14,"title":["Anti\u2010tumor efficacy of a transcriptional replication\u2010competent adenovirus, Ad\u2010OC\u2010E1a, for osteosarcoma pulmonary metastasis"],"prefix":"10.1002","volume":"8","author":[{"given":"Xiong","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaeyong","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You\u2010Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung\u2010hee","family":"Bae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong\u2010Ji","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale","family":"VanderPutten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meei\u2010Huey","family":"Jeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinghai","family":"Kao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3,28]]},"reference":[{"key":"e_1_2_5_2_2","first-page":"139","article-title":"American Academy of Pediatrics Section Statement Section on Hematology\/Oncology","volume":"99","author":"Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment","year":"1997","journal-title":"Pediatrics"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9098(199911)72:3<124::AID-JSO3>3.0.CO;2-G"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-3518-8_31"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199901000-00011"},{"key":"e_1_2_5_6_2","first-page":"8","article-title":"Adjuvant chemotherapy of high\u2010grade osteosarcoma of the extremity. 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