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Ehrnrooth Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008723","name":"Finnish Medical Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003125","name":"Finnish Cultural Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Mucoepidermoid carcinoma (<jats:styled-content style=\"fixed-case\">MEC<\/jats:styled-content>) is the most common salivary gland malignancy. Although several biomarkers have been evaluated, histological grade remains the most valuable prognostic marker. Toll\u2010like receptor 9 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9) is an immune receptor recognizing microbial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>. Its expression associates with prognosis or cancer properties in several cancers. This study examined the role of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 in <jats:styled-content style=\"fixed-case\">MEC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty patients with salivary gland <jats:styled-content style=\"fixed-case\">MEC<\/jats:styled-content> were collected from two <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>innish university hospitals, and tumor samples were stained for <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9. Salivary gland high\u2010grade <jats:styled-content style=\"fixed-case\">MEC<\/jats:styled-content> cell line (<jats:styled-content style=\"fixed-case\">UT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MUC<\/jats:styled-content>\u20101) was cultured to assess <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 and <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013 expression. The function of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 was studied <jats:italic>in vitro<\/jats:italic> using traditional <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>atrigel<jats:sup>\u00ae<\/jats:sup> invasion assay and novel human myoma organotypic model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cancer\u2010specific survival was related with tumor grade (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01), and there were no deaths in patients with low\u2010grade <jats:styled-content style=\"fixed-case\">MEC<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 was expressed in 56 of 60 (93%) tumors. High <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 expression indicated better survival in the patient series (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002) and showed a trend for association with lower disease stage (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.06) and higher differentiation grade (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.068). In multivariate analysis, <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 expression was prognostically insignificant due to heavy correlation to disease stage and higher gradus. Treating <jats:styled-content style=\"fixed-case\">UT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MUC<\/jats:styled-content>\u20101 cells with <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 ligand CpG <jats:italic>in vitro<\/jats:italic> induced <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013 expression and invasion in <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>atrigel<jats:sup>\u00ae<\/jats:sup> invasion assay, whereas decreased invasion was seen in myoma organotypic model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Functional <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 is present in salivary <jats:styled-content style=\"fixed-case\">MEC<\/jats:styled-content>, and high level of expression may indicate good prognosis. However, more studies are needed to evaluate biological consequences of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 interaction in tumor cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12160","type":"journal-article","created":{"date-parts":[[2014,2,3]],"date-time":"2014-02-03T11:07:25Z","timestamp":1391425645000},"page":"530-537","source":"Crossref","is-referenced-by-count":14,"title":["Toll\u2010like receptor 9 expression in mucoepidermoid salivary gland carcinoma may associate with good prognosis"],"prefix":"10.1111","volume":"43","author":[{"given":"Johanna","family":"Korvala","sequence":"first","affiliation":[{"name":"Department of Dentistry University of Oulu Oulu Finland"},{"name":"Medical Research Center Oulu Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Harjula","sequence":"additional","affiliation":[{"name":"Department of Dentistry University of Oulu Oulu 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