{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T22:50:36Z","timestamp":1763765436754,"version":"3.27.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5783,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,11]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>This study was undertaken to identify potential abnormalities of p27<jats:sup>Kip1<\/jats:sup> and cyclin D1 expression in extrahepatic bile duct carcinomas and to assess the prognostic significance of p27<jats:sup>Kip1<\/jats:sup> and cyclin D1 levels for patients with this disease. Decreased p27<jats:sup>Kip1<\/jats:sup> expression (&lt;50% nuclei staining) and cyclin D1 overexpression (&gt;5% nuclei staining) was observed immunohistochemically in 19 (56%) and 23 (68%) of the 34 tumors examined, respectively. Both decreased p27<jats:sup>Kip1<\/jats:sup> and cyclin D1 overexpression were associated with relapse (<jats:italic toggle=\"yes\">P<\/jats:italic> = .0005 for p27<jats:sup>Kip1<\/jats:sup> and <jats:italic toggle=\"yes\">P<\/jats:italic> = .0004 for cyclin D1). Kaplan-Meier curves showed that both decreased p27<jats:sup>Kip1<\/jats:sup> and cyclin D1 overexpression correlate significantly with shortened survival rates (for p27<jats:sup>Kip1<\/jats:sup>, <jats:italic toggle=\"yes\">P<\/jats:italic> = .0419 and<jats:italic toggle=\"yes\">P<\/jats:italic>= .002 for overall and disease-free survival; for cyclin D1, <jats:italic toggle=\"yes\">P<\/jats:italic> = .0392 and<jats:italic toggle=\"yes\">P<\/jats:italic>= .0021 for overall and disease-free survival). Cox regression model analyses identified decreased p27<jats:sup>Kip1<\/jats:sup> and cyclin D1 overexpression as independent markers predicting death from relapse (<jats:italic toggle=\"yes\">P<\/jats:italic> = .0371, risk ratio: 3.891 for p27<jats:sup>Kip1<\/jats:sup>; <jats:italic toggle=\"yes\">P<\/jats:italic> = .0429, risk ratio: 8.31 for cyclin D1). Decreased p27<jats:sup>Kip1<\/jats:sup> was associated with cyclin D1 overexpression (<jats:italic toggle=\"yes\">P<\/jats:italic> = .0202), and coincident abnormalities of the 2 proteins occurred in 16 of the 34 (47%) tumors, indicating that extrahepatic bile duct carcinoma progression may require synchronous dysfunction of p27<jats:sup>Kip1<\/jats:sup> and cyclin D1 in about half of patients. Patients with tumors showing coincident abnormalities of p27<jats:sup>Kip1<\/jats:sup> and cyclin D1 showed even more frequent recurrence than patients with an alteration in only 1 of the 2 proteins. In conclusion, decreased p27<jats:sup>Kip1<\/jats:sup> expression and cyclin D1 overexpression, alone and in combination, predict poor prognosis in patients with resectable extrahepatic bile duct carcinoma<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510300506","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:40:08Z","timestamp":1091000408000},"page":"1167-1173","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":30,"title":["Decreased p27Kip1 expression and cyclin D1 overexpression, alone and in combination, influence recurrence and survival of patients with resectable extrahepatic bile duct carcinoma"],"prefix":"10.1097","volume":"30","author":[{"given":"Ai-Min","family":"Hui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Makuuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Zhou","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadatoshi","family":"Takayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"year":"1999","author":"Hui","key":"BIB1","unstructured":"Molecular basis of multistep hepatocarcinogenesis: genetic and epigenetic events. 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