{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:11:51Z","timestamp":1790673111695,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T00:00:00Z","timestamp":1458259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>Cyclooxygenase\u20102 (COX\u20102) and its downstream product prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) play a key role in generation of the inflammatory microenvironment in tumor tissues. Gastric cancer is closely associated with <jats:italic>Helicobacter pylori<\/jats:italic> infection, which stimulates innate immune responses through Toll\u2010like receptors (TLRs), inducing COX\u20102\/PGE<jats:sub>2<\/jats:sub> pathway through nuclear factor\u2010\u03baB activation. A pathway analysis of human gastric cancer shows that both the COX\u20102 pathway and Wnt\/\u03b2\u2010catenin signaling are significantly activated in tubular\u2010type gastric cancer, and basal levels of these pathways are also increased in other types of gastric cancer. Expression of interleukin\u201011, chemokine (C\u2010X\u2010C motif) ligand 1 (CXCL1), CXCL2, and CXCL5, which play tumor\u2010promoting roles through a variety of mechanisms, is induced in a COX\u20102\/PGE<jats:sub>2<\/jats:sub> pathway\u2010dependent manner in both human and mouse gastric tumors. Moreover, the COX\u20102\/PGE<jats:sub>2<\/jats:sub> pathway plays an important role in the maintenance of stemness with expression of stem cell markers, including CD44, Prom1, and Sox9, which are induced in both gastritis and gastric tumors through a COX\u20102\/PGE<jats:sub>2<\/jats:sub>\u2010dependent mechanism. In contrast, disruption of <jats:italic>Myd88<\/jats:italic> results in suppression of the inflammatory microenvironment in gastric tumors even when the COX\u20102\/PGE<jats:sub>2<\/jats:sub> pathway is activated, indicating that the interplay of the COX\u20102\/PGE<jats:sub>2<\/jats:sub> and TLR\/MyD88 pathways is needed for inflammatory response in tumor tissues. Furthermore, TLR2\/MyD88 signaling plays a role in maintenance of stemness in normal stem cells as well as gastric tumor cells. Accordingly, these results suggest that targeting the COX\u20102\/PGE<jats:sub>2<\/jats:sub> pathway together with TLR\/MyD88 signaling, which would suppress the inflammatory microenvironment and maintenance of stemness, could be an effective preventive or therapeutic strategy for gastric cancer.<\/jats:p>","DOI":"10.1111\/cas.12901","type":"journal-article","created":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T07:48:45Z","timestamp":1454312925000},"page":"391-397","source":"Crossref","is-referenced-by-count":216,"title":["Inflammation in gastric cancer: Interplay of the COX\u20102\/prostaglandin E<sub>2<\/sub> and Toll\u2010like receptor\/MyD88 pathways"],"prefix":"10.1111","volume":"107","author":[{"given":"Kanae","family":"Echizen","sequence":"first","affiliation":[{"name":"Division of Genetics Cancer Research Institute Kanazawa University Kanazawa Japan"},{"name":"AMED\u2010CREST AMED, Japan Agency for Medical Research and Development Tokyo 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