{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T14:05:40Z","timestamp":1775916340222,"version":"3.50.1"},"reference-count":75,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral squamous cell carcinoma (OSCC) represents a significant global oral health concern. Non\u2010anticoagulant heparin (NH) emerges as a promising solution considering the enhanced survival observed with anticoagulants in cancer treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used the MTS assay (0\/24\/48\/72\u2009h), scratch assay (MuviCyte, 0\u201318\u2009h), invasion Matrigel (24\u2009h), and cytotoxic assay (0\u201324\u2009h) to assess the in\u00a0vitro effects of NH and heparin (10, 20, 40, 80\u2009U\/mL) on three oral human cell lines (H400\/H357\/OKF6) as well as their ability to interfere with the chemotherapeutic agents 5FU and cisplatin (1\u20135\u2009\u03bcg\/mL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Remarkably, NH not only significantly induced a significant cytotoxic effect on both cancer cell lines at 80\u2009U\/mL but also inhibited proliferation at 48\/72\u2009h to a comparable extent as heparin. Notably, neither drug exhibited cytotoxic effects on the normal cells. Furthermore, in H400\/H357 cells, both heparin and NH significantly inhibit the cell migration and invasion rate. Importantly, the combination of these drugs with commonly used chemotherapeutic agents for OSCC treatment did not compromise their efficacy against the tested cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NH demonstrates promising potential without compromising the efficacy of commonly used chemotherapeutic agents. These results underscore the need for the translation of this research to preclinical animal models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.15288","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:39:07Z","timestamp":1741714747000},"page":"1672-1683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non\u2010Anticoagulant Heparin: An In\u00a0Vitro Investigation of a Novel Therapeutic Approach for Oral Cancer"],"prefix":"10.1111","volume":"31","author":[{"given":"S. A.","family":"Hamza","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health Sciences Melbourne Dental School  Carlton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Paolini","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health Sciences Melbourne Dental School  Carlton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. M.","family":"O'Brien\u2010Simpson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health Sciences Melbourne Dental School  Carlton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Singleton","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health Sciences Melbourne Dental School  Carlton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Patini","sequence":"additional","affiliation":[{"name":"Head and Neck Department, \u201cFondazione Policlinico Universitario A. Gemelli \u2013 IRCCS\u201d School of Dentistry Catholic University of Sacred Heart \u2013 Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health Sciences Melbourne Dental School  Carlton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-2511","authenticated-orcid":false,"given":"A.","family":"Celentano","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health Sciences Melbourne Dental School  Carlton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906\u2010016\u20101046\u20108"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14546"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2803"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010013\u20102877\u2010x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.3.1503"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910524"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16723"},{"key":"e_1_2_10_9_1","volume-title":"Oral Diseases","author":"Biagio R.","year":"2020"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000073298"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061615598"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.549412"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.12.009"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167\u20105273(16)12004\u20102"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010030\u201034521\u20101_20"},{"issue":"4","key":"e_1_2_10_16_1","first-page":"637","article-title":"Retention of Antilipemic Activity by Periodate\u2010Oxidized Non\u2010Anticoagulant Heparins","volume":"36","author":"Casu B.","year":"1986","journal-title":"Arzneimittel\u2010Forschung"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000175157"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.05.026"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010018\u20100795\u2010z"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.2.181"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4409"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097\u20100142(197507)36:1<129::aid\u2010cncr2820360109>3.0.co;2\u2010s"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2011.211"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2004.00868.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.12.014"},{"key":"e_1_2_10_26_1","volume-title":"Chemistry and Biology of Heparin and Heparan Sulfate","author":"Garg H. 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