Investigation of molecular mechanisms involved in carcinogenesis, proliferation and progression of billiary tract carcinoma and its application to clinical treatment

• Project/Area Number: 26460501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: Ojima Hidenori 慶應義塾大学, 医学部(信濃町), 准教授 (80342905)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 胆道領域がん / 細胞株 / 新鮮切除検体 / 遺伝子発現 / データベース / 免疫染色 / 前臨床試験

Outline of Final Research Achievements

We have elucidated the molecular mechanisms of carcinogenesis, proliferation and progression of billiary tract carcinoma (BTC) using numerous BTC-related bio-resources. As a result, four candidate genes associated with different sites of tumor locations were found and immunohistochemical study using surgical specimens confirmed the consistency of their expression with the tumor existing sites. Analysis of 50 candidate genes associated with IDCC (Intraductal Carcinoma Component) as one of the histopathological BTC spreading and malignancy factors revealed that many highly expressed genes in the tumor group without IDCC (high-grade group) were involved in tumor malignancy related with metastasis or invasion. This data supported the clinicopathological features of IDCC. Furthermore, we have established in vitro assay system of BTC that enables preclinical study and appropriates parameters for novel anticancer drugs which targeting the above genes.

Research Products

• [Journal Article] Establishment of various biliary tract carcinoma cell lines and xenograft models for appropriate preclinical studies. (2016)
  • Author(s): Ojima H, Yamagishi S, Shimada K, Shibata T
  • Journal Title: World J Gastroenterol. Volume: 22 Issue: 40 Pages: 9035-9038
  • DOI: 10.3748/wjg.v22.i40.9035
  • Peer Reviewed / Open Access
• [Journal Article] Heat Shock Protein 90 Is a Potential Therapeutic Target in Cholangiocarcinoma. (2015)
  • Author(s): Shirota T, Ojima H, Hiraoka N, Shimada K, Rokutan H, Arai Y, Kanai Y, Miyagawa S, Shibata T.
  • Journal Title: Mol Cancer Ther. Volume: 14 Issue: 9 Pages: 1985-93
  • DOI: 10.1038/ng.3375
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Genomic spectra of biliary tract cancer. (2015)
  • Author(s): Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, Shibata T.
  • Journal Title: Nat Genet. Volume: 47 Issue: 9 Pages: 1003-10
  • DOI: 10.1158/1535-7163.mct-15-0069
  • Peer Reviewed
• [Presentation] Establishment of a preclinical study system for the discovery of ant-cholangiocarcinoma drug (2017)
  • Author(s): Hidenori Ojima, Seri Yamagishi, Yasuhito Arai, Yasunari Sakamoto, Takuji Okusaka. Tatsuhiro Shibata
  • Organizer: The Cholangiocarcinoma Foundation, 4th Annual International Conference
  • Place of Presentation: Salt Lake City, USA
  • Year and Date: 2017-02-01
  • Int'l Joint Research
• [Presentation] 胆管がん細胞株を用いたゲムシタビンとシスプラチン併用による相乗効果の検討 (2015)
  • Author(s): 山岸 せり, 尾島 英知, 坂本 康成, 金井 弥栄
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 胆道癌モデルと臨床検体を用いた大規模前臨床試験システム確立の試み (2015)
  • Author(s): 尾島 英知, 柴田 龍弘, 金井 弥栄
  • Organizer: 第51回日本胆道学会学術集会
  • Place of Presentation: ホテル東日本宇都宮（栃木県宇都宮市）
  • Year and Date: 2015-09-18
• [Presentation] Pathology of the Liver Tumor, an Update (2015)
  • Author(s): 4.尾島英知
  • Organizer: 第74回日本放射線学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-17
  • Invited