{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:11:40Z","timestamp":1789189900813,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,12,10]],"date-time":"2007-12-10T00:00:00Z","timestamp":1197244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 518\/A13"],"award-info":[{"award-number":["SFB 518\/A13"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ductal concretions in chronic pancreatitis (CP) are one of the causes of ductal obstruction, resulting in pancreatic ductal hypertension (PDH) and duct ectasia. Ductal epithelium subjected to chronic stress by PDH may undergo molecular alterations, thereby not only initiating and sustaining the inflammatory process but also activating molecules that have transforming potential. Acino\u2010ductal metaplasia and pancreatic intraepithelial neoplasia (PanIN) are frequently seen in CP. Using laser capture microdissection, cDNA microarrays and Ingenuity Pathways Analysis, we found an altered Notch pathway in the ectatic ducts of CP. The microarray data was further validated by real\u2010time PCR. We also found elevated transcripts of Notch receptors, Notch1 and Notch3 in microdissected ectatic ducts of CP. The Notch pathway ligands, Jagged\/Delta\u2010like and a Notch target, HES\u2010related repressor protein (HERP), were up\u2010regulated in ectatic compared to normal pancreatic ducts, while another target of Notch, hairy\/enhancer of split (HES), was down\u2010regulated. The transcripts of Delta\u2010like1 and Jagged1 were increased 3.7\u2010fold and 1.3\u2010fold, respectively, while those of HERP1 were elevated 2.4\u2010fold in the ectatic ducts of CP, compared to normal ducts. Immunohistochemistry showed that Jagged1 was not expressed in normal pancreatic ducts, while it was highly expressed in ectatic ducts. This pattern of Notch component alteration in ectatic ducts was mimicked to some extent\n                    <jats:italic>in vitro<\/jats:italic>\n                    in a human pancreatic duct epithelial (HPDE) cell line, when subjected to a pressure of 200 mmHg for 24 h. Therefore, we conclude that in the ectatic ducts of CP, PDH activates signalling pathways such as Notch, which have transforming potential. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2293","type":"journal-article","created":{"date-parts":[[2007,12,10]],"date-time":"2007-12-10T14:51:05Z","timestamp":1197298265000},"page":"312-319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Evidence of Notch pathway activation in the ectatic ducts of chronic 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