{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:14:51Z","timestamp":1788362091404,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K10137"],"award-info":[{"award-number":["21K10137"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K18721"],"award-info":[{"award-number":["20K18721"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Oral squamous cell carcinoma (OSCC) frequently invades the mandibular bone, leading to metastasis and poor prognosis. This study aimed to evaluate the therapeutic effects of locally administered interleukin\u201012 (IL\u201012) using an immunocompetent mouse model mimicking the clinical features of mandibular bone invasion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The effects of IL\u201012 on tumor growth and bone resorption were evaluated using subcutaneous and bone invasion models of OSCC in both immunocompetent and athymic mice. Bone resorption was assessed by micro\u2010computed tomography (CT). In addition, quantitative polymerase chain reaction (qPCR) was performed to quantify the expression of osteoclast markers (\n                      <jats:italic>Acp5<\/jats:italic>\n                      ,\n                      <jats:italic>Ctsk<\/jats:italic>\n                      ) and immune\u2010related genes (\n                      <jats:italic>Ifng<\/jats:italic>\n                      ,\n                      <jats:italic>Fasl<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Intratumoral injection of recombinant murine IL\u201012 (r\u2010mIL\u201012) significantly prolonged mouse survival and suppressed tumor growth in immunocompetent mice. Micro\u2010CT revealed reduced bone resorption in the r\u2010mIL\u201012\u2013treated group. Consistently, qPCR demonstrated downregulation of\n                      <jats:italic>Acp5<\/jats:italic>\n                      and\n                      <jats:italic>Ctsk<\/jats:italic>\n                      , along with upregulation of\n                      <jats:italic>Ifng<\/jats:italic>\n                      and\n                      <jats:italic>Fasl<\/jats:italic>\n                      compared to controls. In contrast, r\u2010mIL\u201012 treatment had no significant effect on tumor growth or bone resorption in athymic mice, underscoring the importance of T cells in controlling bone invasion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that local administration of r\u2010mIL\u201012 may serve as an effective therapeutic approach for OSCC with mandibular bone invasion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70399","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:34:46Z","timestamp":1788359686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intratumoral Administration of Recombinant Murine Interleukin\u201012 Prevents Tumor Progression and Bone Invasion"],"prefix":"10.1111","author":[{"given":"Shun","family":"Kasahara","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Kashiwagi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5303-4763","authenticated-orcid":false,"given":"Toshihiro","family":"Inubushi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics &amp; Dentofacial Orthopedics, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinari","family":"Sugauchi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"},{"name":"Unit of Dentistry The University of Osaka Hospital  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Deyong","sequence":"additional","affiliation":[{"name":"Department of Orthodontics &amp; Dentofacial Orthopedics, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Kurioka","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-1847","authenticated-orcid":false,"given":"Kazuaki","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"},{"name":"Department of Bone and Mineral Research Osaka Women's Children's Hospital  Izumi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-4395","authenticated-orcid":false,"given":"Soju","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-2491","authenticated-orcid":false,"given":"Mikihiko","family":"Kogo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Uchihashi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201019\u20102217"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtumed.2016.04.002"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2018.18.e8"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700001"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201018\u20100381"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab271"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5238.908a"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1359\u20106101(01)00032\u20106"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201005\u20102534"},{"key":"e_1_2_12_11_1","first-page":"645","article-title":"Global Incidence and Risk Factors of Oral Cancer","volume":"156","author":"Ghantous Y.","year":"2017","journal-title":"Harefuah"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2141"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601\u20100825.2010.01781.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.9.4732"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262\u2010014\u20101523\u20101"},{"key":"e_1_2_12_16_1","first-page":"2541","article-title":"Effects of Single\u2010Dose Inter\u2010Leukin\u201012 Exposure on Interleukin\u201012\u2010Associated Toxicity and Interferon\u2010Gamma Production","volume":"90","author":"Leonard J. 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