{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:10:59Z","timestamp":1777385459146,"version":"3.51.4"},"reference-count":23,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Rhinol\ufffdAllergy"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Methotrexate (MTX) is a very effective treatment for chronic inflammatory diseases, which are often associated with increased angiogenesis. Angiogenesis is dependent on a perfectly coordinated balance between endogenous-positive and -negative regulatory factors, including vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). The aim of this study was to investigate the effects of MTX on levels of VEGF, Ang-1, and Ang-2 in organ-cultured nasal polyps (NPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To determine the effects of MTX, NP tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of MTX (10 or 100 micromoles) for 24 hours. Hematoxylin and eosin, and TUNEL (terminal deoxynucleotidyl transferase [Tdt]-mediated dUTP-biotin nick-end labeling) staining were performed to observe apoptosis. Enzyme-linked immunosorbent assay was used to quantify tissue concentrations of VEGF, Ang-1, and Ang-2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MTX treatment resulted in marked alterations in inflammatory cells, especially eosinophils. In contrast, the mucosal epithelium, microvessels including arterioles, veins and capillaries, and fibroblasts maintained their structure. TUNEL\n                      <jats:sup>+<\/jats:sup>\n                      cells (apoptotic cells) were seen in the MTX-treated specimens. The more induction of TUNEL\n                      <jats:sup>+<\/jats:sup>\n                      cells was observed 100-micromolar MTX-treated specimens. VEGF and Ang-1 levels were significantly lower, and Ang-2 levels were significantly higher in NPs treated with 100-micromolar MTX than in nontreated NPs (p &lt; 0.01.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MTX may inhibit the growth of NPs via local regulation of VEGF, Ang-1, and Ang-2 protein levels. We suggest that MTX can be used to treat NPs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2500\/ajra.2011.25.3618","type":"journal-article","created":{"date-parts":[[2011,7,11]],"date-time":"2011-07-11T07:17:22Z","timestamp":1310368642000},"page":"e129-e132","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Effects of Methotrexate on Vascular Endothelial Growth Factor, Angiopoietin 1, and Angiopoietin 2 in Nasal Polyps"],"prefix":"10.1177","volume":"25","author":[{"given":"Seong Kook","family":"Park","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Busan Paik Hospital, Busan, Korea"},{"name":"Paik Institute for Clinical Research, Busan Paik Hospital, Busan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeong In","family":"Kim","sequence":"additional","affiliation":[{"name":"Paik Institute for Clinical Research, Busan Paik Hospital, Busan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Il","family":"Yang","sequence":"additional","affiliation":[{"name":"Paik Institute for Clinical Research, Busan Paik Hospital, Busan, Korea"},{"name":"Departments of Pathology, Busan Paik Hospital, Busan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae Young","family":"Hur","sequence":"additional","affiliation":[{"name":"Anatomy and Research Center for Tumor Immunology, Inje University School of Medicine, Busan Paik Hospital, Busan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,7,1]]},"reference":[{"key":"bibr1-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.12.6.7539273"},{"key":"bibr2-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.11.6.9194526"},{"key":"bibr3-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2003.01297.x"},{"key":"bibr4-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114322"},{"key":"bibr5-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2008.22.3190"},{"key":"bibr6-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.55"},{"key":"bibr7-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2045"},{"key":"bibr8-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00231-5"},{"key":"bibr9-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2008.01745.x"},{"key":"bibr10-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1185\/03007990802643466"},{"key":"bibr11-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.2000.15b24.x"},{"key":"bibr12-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20085"},{"key":"bibr13-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2010.24.3480"},{"key":"bibr14-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2006.09.014"},{"key":"bibr15-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.supplement_2.2106065"},{"key":"bibr16-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210731"},{"key":"bibr17-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200001010-00003"},{"key":"bibr18-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.3"},{"key":"bibr19-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2005.07.003"},{"key":"bibr20-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2676"},{"key":"bibr21-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1554"},{"key":"bibr22-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00876.x"},{"key":"bibr23-ajra.2011.25.3618","doi-asserted-by":"publisher","DOI":"10.3109\/02770900903242704"}],"container-title":["American Journal of Rhinology &amp; 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