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別タイトル
原発性硬化性胆管炎ではcyclooxygenase-2とmicrosomal prostaglandin E synathase-1の発現が亢進し、胆管発がんへの関与が示唆される
著者
キーワード
primary sclerosing cholangitis
cyclooxygenase-2
microsomal prostaglandin E synthase-1
cholangiocarcinoma
NDC
医学
抄録(英)
Cholangiocarcinoma (CCA) occurs frequently in primary sclerosing cholangitis (PSC). Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) induced by inflammation are believed to mediate prostaglandin E2 (PGE2) production thereby promoting carcinogenesis. Their expression in PSC-associated CCA tissues and non-neoplastic bile duct epithelial cells (BDECs) in PSC was investigated. COX-2 and mPGES-1 levels in 15 PSC patients (7 with CCA) were scored using immunohistochemical staining. The results were compared with those obtained in CCA tissues and non-neoplastic BDECs (controls) of 15 sporadic CCA patients. Non-neoplastic BDECs from large and small bile ducts were investigated separately. The mRNA expression levels of COX-2 and mPGES-1 in CCA tissues were analyzed by quantitative polymerase chain reaction. Ki-67 immunostaining was performed to evaluate cell proliferation. COX-2 was strongly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC. This expression was significantly upregulated in both compared with sporadic CCA tissues and non-neoplastic BDECs in sporadic CCA (both P<0.01). mPGES-1 was expressed at moderate to strong levels in PSC. Compared with controls, the expression was significantly higher in non-neoplastic small BDECs (P<0.01). COX-2 mRNA levels were significantly higher in PSC-associated tissues than in sporadic CCA tissues (P<0.01). Conversely, no differences were observed in mPGES-1 mRNA levels. Ki-67 labeling indices were higher in PSC-associated CCA tissues and non-neoplastic BDECs in PSC than in controls. In conclusion, COX-2 and mPGES-1 were highly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC, suggesting the involvement of COX-2 and mPGES-1 in cholangiocarcinogenesis.
作成年月日
2014-11-21
言語
英語
NII資源タイプ
学位論文
広大資料タイプ
学位論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
ETD
権利情報
Copyright(c) by Author
関連情報(references)
Yasutaka Ishii, Tamito Sasaki, Masahiro Serikawa, Tomoyuki Minami, Akihito Okazaki, Masanobu Yukutake, Takashi Ishigaki, Keiichi Kosaka, Teruo Mouri, Satoshi Yoshimi, Akinori Shimizu, Tomofumi Tsuboi and Kazuaki Chayama; Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Implications for cholangiocarcinogenesis; INTERNATIONAL JOURNAL OF ONCOLOGY 43: 1073-1079, 2013 (DOI: 10.3892/ijo.2013.2038)
関連情報URL(references)
http://dx.doi.org/10.3892/ijo.2013.2038
学位記番号
甲第6375号
授与大学
広島大学(Hiroshima University)
学位名
博士(医学)
学位名の英名
Philosophy in Medical Science
学位の種類の英名
doctoral
学位授与年月日
2014-03-23
部局名
医歯薬学総合研究科