{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T18:04:08Z","timestamp":1773079448535,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T00:00:00Z","timestamp":1515974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T00:00:00Z","timestamp":1515974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP10058"],"award-info":[{"award-number":["GGP10058"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003980","name":"Istituto Toscano Tumori","doi-asserted-by":"publisher","award":["2008"],"award-info":[{"award-number":["2008"]}],"id":[{"id":"10.13039\/501100003980","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Osteosarcoma (OS) is an ultra\u2010rare highly malignant tumor of the skeletal system affecting mainly children and young adults and it is characterized by an extremely aggressive clinical course. OS patients are currently treated with chemotherapy and complete surgical resection of cancer tissue. However, resistance to chemotherapy and the recurrence of disease, as pulmonary metastasis, remain the two greatest challenges in the management, and treatment of this tumor. For these reasons, it is of primary interest to find alternative therapeutic strategies for OS. Dysregulated Hedgehog signalling is involved in the development of various types of cancers including OS. It has also been implicated in tumor\/stromal interaction and cancer stem cell biology, and therefore presents a novel therapeutic strategy for cancer treatment. In our work, we tested the activity of five potent Smoothened (SMO) inhibitors, four acylguanidine and one acylthiourea derivatives, against an OS cell line. We found that almost all our compounds were able to inhibit OS cells proliferation and to reduce Gli1 protein levels. Our results also indicated that SMO inhibition in OS cells by such compounds, induces apoptosis with a nanomolar potency. These findings suggest that inactivation of SMO may be a useful approach to the treatment of patients with OS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26330","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T11:06:41Z","timestamp":1512644801000},"page":"4961-4971","source":"Crossref","is-referenced-by-count":18,"title":["Novel smoothened antagonists as anti\u2010neoplastic agents for the treatment of osteosarcoma"],"prefix":"10.1002","volume":"233","author":[{"given":"Giulia","family":"Bernardini","sequence":"first","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Geminiani","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Gambassi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Orlandini","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Petricci","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Marzocchi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"},{"name":"UOC Patologia Clinica Azienda Ospedaliera Universitaria Senese Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Laschi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Taddei","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Manetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-9086","authenticated-orcid":false,"given":"Annalisa","family":"Santucci","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Chimica e Farmacia Universit\u00e0 degli Studi di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-1918-y"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201100358"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/14789450.2014.900445"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb70328b"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/959248"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063583"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00148581-200810050-00005"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.4420"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2015.1102226"},{"issue":"12","key":"e_1_2_7_11_1","first-page":"547","article-title":"Osteosarcoma: A meta\u2010analysis and review of the literature","volume":"44","author":"Friebele J. 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