{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:28:36Z","timestamp":1791289716236,"version":"4.3.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Acta Radiol"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Novel anti-angiogenic treatments are increasingly complementing established cancer therapy strategies in head and neck tumors. Contrast-enhanced magnetic resonance imaging (MRI) can be applied for early and non-invasive therapy monitoring by non-invasive quantitative assessment of tumor microcirculation as in\u00a0vivo imaging biomarkers of therapy response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To monitor the anti-angiogenic effects of a novel combination therapy on experimental head and neck squamous cell carcinomas (HNSCC) with dynamic contrast-enhanced (DCE)-MRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>Athymic rats ( n\u2009=\u200918) with subcutaneous HNSCC xenografts were investigated by DCE-MRI before and after 7 days of a daily triple therapy regimen combining the COX-II-inhibitor celecoxib, the matrix-metalloproteinase-inhibitor GM6001, and the uPA-inhibitor upamostat. Quantitative measurements of tumor blood flow (tBF), tumor blood volume (tBV), and permeability-surface area product (PS) were calculated and validated by immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mean tBF and tBV in triple-therapy animals decreased significantly from day 0 to day 7 (tBF, 41.0\u2009\u00b1\u200914.2 to 20.4\u2009\u00b1\u20095.7\u2009mL\/100\u2009mL\/min; P\u2009&lt;\u20090.01; tBV, 17.7\u2009\u00b1\u20093.9 to 7.5\u2009\u00b1\u20093.3%; P\u2009&lt;\u20090.01). No significant effects on PS were observed in either group ( P\u2009&gt;\u20090.05). Immunohistochemical analysis showed a significantly lower tumor vascularity in the therapy group than in the control group (CD31), significantly fewer Ki-67+ proliferating tumor cells and significantly more Capase-3+ apoptotic tumor cells ( P\u2009&lt;\u20090.05). Significant ( P\u2009&lt;\u20090.05) correlations were observed between tBF\/tBV and CD31 (tBF, r\u2009=\u20090.84; tBV, r\u2009=\u20090.70), tBV and Ki-67 (r\u2009=\u20090.62), as well as tBF and caspase-3 (r\u2009=\u2009\u22120.64).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DCE-MRI may be a suitable tool for the non-invasive monitoring of the anti-vascular effects of this innovative triple therapy regimen with potential for clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0284185114527444","type":"journal-article","created":{"date-parts":[[2014,3,7]],"date-time":"2014-03-07T23:10:39Z","timestamp":1394233839000},"page":"294-303","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["DCE-MRI biomarkers for monitoring an anti-angiogenic triple combination therapy in experimental hypopharynx carcinoma xenografts with immunohistochemical validation"],"prefix":"10.1177","volume":"56","author":[{"given":"Alexander","family":"Sterzik","sequence":"first","affiliation":[{"name":"Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp M","family":"Paprottka","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Zengel","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun","family":"Hirner","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Ro\u00dfpunt","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Eschbach","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Havla","sequence":"additional","affiliation":[{"name":"Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ingrisch","sequence":"additional","affiliation":[{"name":"Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian F","family":"Reiser","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Nikolaou","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens 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