{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:53:20Z","timestamp":1782442400187,"version":"3.54.5"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"DOD","doi-asserted-by":"publisher","award":["PR100654"],"award-info":[{"award-number":["PR100654"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"DOD","doi-asserted-by":"publisher","award":["PR100451"],"award-info":[{"award-number":["PR100451"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"DOD","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammatory bowel disease (IBD) is characterized by chronic inflammation, which can progress to colorectal cancer, with duration of disease being the most important risk factor. Although many factors are involved, the pathogenic link between inflammation and cancer and the role played by the lymphatic system have not been fully investigated. This project uses lymphatic-deficient mice (Angiopoietin-2 [Ang2] knockout) to examine the lymphatic system in the progression of IBD to colorectal cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Angiopoietin-2 wild-type, heterozygote, and knockout mice received a single injection of the procarcinogen azoxymethane and had an IBD-promoting chemical irritant (dextran sodium sulfate) added to their drinking water over a 7-week period. We measured disease activity (weight loss, stool consistency, fecal occult blood) during the study and at sacrifice, collected blood for cytokine\/biomarker (Ang2, interleukin [IL] 1-\u03b2, IL-6, tumor necrosis factor \u03b1 [TNF\u03b1], and VEGF-C) enzyme-linked immunosorbent assay analysis, measured colon length, and assessed tumor burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ang2 knockout (KO) mice exhibited reduced (55%) survival vs wild-type (100%) and heterozygotes (91%; P &amp;lt; 0.01 and P &amp;lt; 0.0001, respectively). Most (&amp;gt;89%) mice developed tumors, and the incidence of colorectal cancer did not differ among the genotypes (P = 0.32). The tumor area was significantly increased in KO mice (P = 0.004). Of the biomarkers measured in the serum, Ang2 and TNF-\u03b1 concentrations were significantly different among the genotypes (P = 3.35e-08 and P = 0.003 respectively). Disease activity was significantly increased in KO mice compared with wild-type and heterozygote mice (P = 0.033).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Lymphatic deficiency, defective lymphangiogenesis, and impaired lymphatic-generated inflammation did not protect against clinical IBD or progression to colorectal cancer in this experimental model.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ibd\/izz112","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T17:49:52Z","timestamp":1559929792000},"page":"1919-1926","source":"Crossref","is-referenced-by-count":8,"title":["Role of Lymphatic Deficiency in the Pathogenesis and Progression of Inflammatory Bowel Disease to Colorectal Cancer in an Experimental Mouse Model"],"prefix":"10.1093","volume":"25","author":[{"given":"Sarah K","family":"Daley","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlys H","family":"Witte","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalicia","family":"Washington","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bernas","sequence":"first","affiliation":[{"name":"Texas Christian University and University of North Texas Health Science Center School of Medicine, Fort Worth, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Kiela","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Thorn","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Tanoue","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Steven","family":"Alexander","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Louisiana Health Sciences Center-Shreveport, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"2020060620042578100_CIT0001","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1136\/gut.48.4.526","article-title":"The risk of colorectal cancer in ulcerative colitis: a 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