Different mechanism of carcinogenesis and development in intrahepatic cholangiocarcinoma according to the level of bile ducts

• Project/Area Number: 23590399
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kyushu University
• Principal Investigator: AISHIMA Shinichi 九州大学, 医学(系)研究科(研究院), 准教授 (70346774)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 胆管癌 / 発がん / 酸化ストレス / 糖代謝 / 浸潤 / 増殖 / 肝内胆管癌 / トランスポーター / BilIN / SiRNA / AFP / ＳＡＬＬ４ / ROBO1 / SLIT / GLUT / transporter / 予後因子 / 浸潤能 / 肝臓 / 胆管がん / iNOS / COX2 / 発癌 / 転移

Research Abstract

Intrahepatic cholangiocarcinomas (ICCs) consist of heterogenous carcinoma arising from different anatomical sites of the liver. This heterogeneity depends on that the origin of ICCs is different level of biliary tree based on the gross and histologic examination. We examined oxidative stress marker related with carcinogenesis, Slit-ROBO1 signal pathway, and glucose metabolism in carcinogenesis and progression of ICCs, exept we did not perform the investigation of bile acid and its receptor in ICC. As a results, 1) cyclooxygenase-2 (COX2) expression is associated with VEGF-C expression and presence of lymph node metastasis, 2) decreased expression of ROBO1 by SiRNA in RBE cells is associated with proliferation and migration, and pomote lymph node metastasis, and 3) Glucose transporter-1 (GLUT1) expression is related with aggressive phenotype of ICCs.

Research Products

• [Journal Article] Histological features of precancerous and early cancerous lesions of biliary tract carcinoma. (2014)
  • Author(s): Aishima S, Kubo Y, Tanaka Y, Oda Y
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: January 21 Issue: 7 Pages: 0-0
  • DOI: 10.1002/jhbp.71
  • Peer Reviewed
• [Journal Article] Follicular pancreatitis, report of a case clinically mimicking pancreatic cancer and literature review. (2014)
  • Author(s): Mizuuchi Y. Aishima S, Hattori M, Ushijima Y, Aso A, Takahata S, Ohtsuka T, Ueda J, Tanaka M, Oda Y.
  • Journal Title: Pathol Res Pract. Volume: 210(2) Issue: 2 Pages: 118-122
  • DOI: 10.1016/j.prp.2013.09.005
  • Peer Reviewed
• [Journal Article] Different roles of inducible nitric oxide synthase and cyclooxygenase-2 in carcinogenesis and metastasis of intrahepatic cholangiocarcinoma (2013)
  • Author(s): Aishima S, Mano Y, Tanaka Y, Kubo Y, Shirabe K, Maehara Y, Oda Y
  • Journal Title: Hum Pathol Volume: 44 Pages: 1031-7
• [Journal Article] Decreased roundabout 1 expression promotes development of intrahepatic cholangiocarcinoma (2013)
  • Author(s): Mano Y, Aishima S, Fukuhara T, Tanaka Y, Kubo Y, Motomura T, Toshima T, Iguchi T, Shirabe K, Maehara Y, Oda Y.
  • Journal Title: Hum Pathol Volume: 44 Pages: 2419-26
• [Journal Article] Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas. (2013)
  • Author(s): Shindo K, Aishima S, Ohuchida K, Fujiwara K, Fujino M, Mizuuchi Y, Hatton M, Mizumoto K. Tanaka M, Oda Y.
  • Journal Title: Mol Cancer Volume: 12(1) Issue: 1 Pages: 168-168
  • DOI: 10.1186/1476-4598-12-168
  • Peer Reviewed
• [Journal Article] Decreased roundabout 1 expression promotes development of intrahepatic cholangiocarcinoma. (2013)
  • Author(s): Mano Y, Aishima S, Fukuhara T, Tanaka Y, Kubo Y, Motomura T, Toshima T, Iguchi T, Shirabe K, Maehara Y, Oda Y
  • Journal Title: Hum Pathol Volume: Nov;44(11) Issue: 11 Pages: 2419-26
  • DOI: 10.1016/j.humpath.2013.03.022
  • Peer Reviewed
• [Journal Article] Tumor-Associated Macrophage Promotes Tumor Progression via STAT3 Signaling in Hepatocellular Carcinoma. (2013)
  • Author(s): 119. Mano Y, Aishima S, Fujita N, Tanaka Y, Kubo Y, Motomura T, Taketomi A, Shirabe K, Maehara Y, Oda Y.
  • Journal Title: Pathobiology. Volume: 80 Issue: 3 Pages: 146-154
  • DOI: 10.1159/000346196
  • Peer Reviewed
• [Journal Article] CD271^+ subpopulation of pancreatic stellate cells correlates with prognosis of pancreatic cancer and is regulated by interaction with cancer cells (2012)
  • Author(s): Kenji Fujiwara
  • Journal Title: PLoS One Volume: 12 Issue: 12 Pages: e52682-e52682
  • DOI: 10.1371/journal.pone.0052682
  • Peer Reviewed
• [Journal Article] An increase in the number of predictive factors augments the likelihood of malignancy in branch duct intraductal papillary mucinous neoplasm of the pancreas (2012)
  • Author(s): Ohtsuka T, Kono H, Nagayoshi Y, Mori Y, Tsutsumi K, Sadakari Y, Takahata S, Morimatsu K, Aishima S, Igarashi H, Ito T, Ishigami K, Nakamura M, Mizumoto K, Tanaka M
  • Journal Title: Surgery Volume: 151 Pages: 76-83
  • NAID: 120005324432
  • Peer Reviewed
• [Journal Article] Different roles of S100P Overexpression in Intrahepatic Cholangiocarcinoma: Carcinogenesis of Perihilar Type and Aggressive Behavior of Peripheral Type. (2011)
  • Author(s): Aishima S, Fujita N, Mano Y, Kubo Y, Tanaka Y, Taketomi A, Shirabe K, Maehara Y, Oda Y
  • Journal Title: Am J Surg Pathol Volume: 35 Pages: 590-598
  • NAID: 120004951589
  • Peer Reviewed
• [Journal Article] Prognostic significance of preoperative imaging in recipients of living donor liver transplantation for hepatocellular carcinoma. (2011)
  • Author(s): Sugimachi K, Shirabe K, Taketomi A, Soejima Y, Iguchi T, Takeishi K, Toshima T, Aishima S, Tajima T, Maehara Y.
  • Journal Title: Transplantation Volume: 91 Pages: 570-574
  • Peer Reviewed
• [Journal Article] Performance of radiological methods in diagnosing hepatocellular carcinoma preoperatively in a recipient of living related liver transplantation: comparison with step section histopathology. (2011)
  • Author(s): Hirakawa M, Yoshimitsu K, Irie H, Tajima T, Nishie A, Asayama Y, Ishigami K, Kakihara D, Taketomi A, Aishima S, Honda H
  • Journal Title: Jpn J Radiol Volume: 29 Pages: 129-137
  • NAID: 50007960200
  • Peer Reviewed
• [Journal Article] Significance of dysadherin and E-cadherin expression in differentiated-type gastric carcinoma with submucosal invasion (2011)
  • Author(s): Maehata Y, Hirahashi M, Aishima S, Kishimoto J, Hirohashi S, Yao T, Takashima H, Tsuneyoshi M, Oda Y
  • Journal Title: Hum Pathol Volume: 42 Pages: 558-567
  • Peer Reviewed
• [Journal Article] Outcomes of hepatic resection for huge hepatocellular carcinoma (≧10 cm in diameter) (2011)
  • Author(s): Yamashita Y., et al
  • Journal Title: J SurgOncol Volume: 104 Issue: 3 Pages: 292-8
  • DOI: 10.1002/jso.21931
  • Peer Reviewed
• [Journal Article] Histologic classification of microscopic portal venous invasion to predict prognosis in hepatocellular carcinoma (2011)
  • Author(s): Fujita N, Aishima S, Iguchi T, Mano Y, Taketomi A, Shirabe K, Honda H, Tsuneyoshi M, Oda Y
  • Journal Title: Human Pathol Volume: 42 Pages: 1531-1538
  • Peer Reviewed
• [Journal Article] Invasive carcinoma derived from intestinal-type intraductal papillary mucinous neoplasm is associated with minimal invasion, colloid carcinoma, and less invasive behavior, leading to a better prognosis (2011)
  • Author(s): Nakata K, Ohuchida K, Aishima S, Sadakari Y, Kayashima T, Miyasaka Y, Nagai E, Mizumoto K, Tanaka M, Tsuneyoshi M, Oda Y
  • Journal Title: Pancreas Volume: 40 Pages: 581-587
  • Peer Reviewed
• [Journal Article] Cystic tumors of the liver : On the problems of diagnostic criteria (2011)
  • Author(s): Mano Y,, et al
  • Journal Title: Pathol Res Pract Volume: 207 Issue: 10 Pages: 659-63
  • DOI: 10.1016/j.prp.2011.07.006
  • Peer Reviewed
• [Journal Article] MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis (2011)
  • Author(s): Nakata K, Ohuchida K, Mizumoto K, Kayashima T, Ikenaga N, Sakai H, Lin C, Fujita H, Otsuka T, Aishima S, Nagai E, Oda Y
  • Journal Title: Surgery Volume: 150 Pages: 916-922
• [Journal Article] Nuclear atypia grading score is a useful prognostic factor in papillary gastric adenocarcinoma (2011)
  • Author(s): Nakashima Y, Yao T, Hirahashi M, Aishima S, Kakeji Y, Maehara Y, Tsuneyoshi M.
  • Journal Title: Histopathology Volume: 59 Issue: 5 Pages: 841-849
  • DOI: 10.1111/j.1365-2559.2011.04035.x
  • Peer Reviewed
• [Journal Article] Histological and immunohistological findings in biliary intraepithelial neoplasia arising from a background of chronic biliary disease compared with liver cirrhosis of non-biliary aetiology (2011)
  • Author(s): Aishima S., et al
  • Journal Title: Histopathology Volume: 59 Issue: 5 Pages: 867-75
  • DOI: 10.1111/j.1365-2559.2011.04011.x
  • Peer Reviewed
• [Journal Article] Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma
  • Author(s): Kubo Y, Aishima S, Tanaka Y, Shindo K, Mizuuchi Y, Abe K, Shirabe K, Maehara Y, Honda H, Oda Y
  • Journal Title: Hum Pathol Volume: 2014
• [Presentation] 肝内胆管癌の発癌・転移におけるiNOS, COX2発現の役割 (2012)
  • Author(s): 相島慎一, 久保雄一郎, 田中ゆき, 間野洋平, 小田義直
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] 肝内胆管癌におけるGlucose transporter(GLUT)の役割 (2012)
  • Author(s): 久保雄一郎, 相島慎一, 半田瑞樹, 田中ゆき, 間野洋平, 小田義直
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] 肝内胆管癌の発癌・転移におけるiNOS、COX2発現の役割 (2012)
  • Author(s): 相島慎一、久保雄一郎、田中ゆき、間野洋平、小田義直:
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] 肝内胆管癌におけるGlucose transporter (GULT)の役割 (2012)
  • Author(s): 久保雄一郎、相島慎一、半田瑞樹、田中ゆき、間野洋平、小田義直
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] 末梢型肝内胆管癌の病理学的特徴: 傍肝門型との比較 (2012)
  • Author(s): 相島慎一、間野洋平、久保雄一郎、田中ゆき、調憲、前原喜彦、小田義直
  • Organizer: 第48回日本肝臓学会
  • Place of Presentation: 金沢
• [Presentation] 腫瘍関連マクロファージによる肝細胞癌におけるSTAT3シグナル活性化に関する研究 (2011)
  • Author(s): 間野洋平, 相島慎一, 田中ゆき, 久保雄一郎, 藤田展宏, 武冨紹信, 前原喜彦, 小田義直
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 硬化性胆管炎、慢性胆管炎からの発癌：BilINを中心に (2011)
  • Author(s): 相島慎一、小田義直
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
• [Presentation] 混合型肝癌の組織診断―問題点と診断手順― (2011)
  • Author(s): 相島慎一、間野洋平、田中ゆき、久保雄一郎、武冨紹信、調憲、前原喜彦、小田義直
  • Organizer: 第47回日本肝癌研究会
  • Place of Presentation: 静岡
• [Presentation] 膵神経内分泌腫瘍におけるGLUT1/2発現について
  • Author(s): 藤野稔 相島慎一 小田義直
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
• [Presentation] 慢性肝炎・肝硬変におけるBile duct adenomaの意義
  • Author(s): 相島慎一 久保雄一郎 田中ゆき 小田義直
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
• [Presentation] 膵・胆道細胞診の基礎
  • Author(s): 相島慎一
  • Organizer: 第54回日本臨床細胞学会
  • Place of Presentation: 大阪
• [Presentation] 胆管癌におけるARG発現の生物学的意義
  • Author(s): 花木由香 相島慎一 服部正見 水内祐介 久保雄一郎 田中ゆき 小田義直
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
• [Book] 病理と臨床 (2013)
  • Author(s): 相島慎一、小田義直
  • Total Pages: 7
  • Publisher: 文光堂
• [Book] 病理と臨床 特集胆膵病理I (2013)
  • Author(s): 相島慎一、小田義直
  • Total Pages: 7
  • Publisher: 文光堂
• [Book] 肝胆膵2011 特集混合型肝癌および胆管形質を示す肝細胞癌：肝ステム細胞のインパクト (2011)
  • Author(s): 相島慎一
  • Publisher: 株式会社アークメディア
• [Remarks]
  • URL: http://www.surgpath.med.kyushu-u.ac.jp/ap/