Clinicopathological significance of hypoxia-related molecules in gastrointestinal stromal tumor

• Project/Area Number: 24590413
• 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: YAMAMOTO Hidetaka 九州大学, 大学病院, 准教授 (30404073)
• Research Collaborator: ZAITSU Yoko
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 胃腸管間質腫瘍 / 低酸素 / HIF / コハク酸脱水素酵素 / マイクロRNA

Outline of Final Research Achievements

We examined the significance of accumulation of HIF (hypoxia-induced factor) and SDH (succinate dehydrogenase) in gastrointestinal stromal tumor (GIST). HIF-1α overexpression was correlated with worse prognosis. The expression level of miR-210, a target of HIF-1α was higher in high-grade GISTs. Therefore, HIF-1α accumulation and miR-210 overexpression may play an important role in the progression of GIST. In addition, in a subset of GIST, SDH deficiency may induce the accumulation of HIF-1α.

Research Products

• [Journal Article] Gastrointestinal stromal tumor: Recent advances in pathology and genetics (2015)
  • Author(s): Yamamoto H, Oda Y
  • Journal Title: Pathology International Volume: 65 Issue: 1 Pages: 9-18
  • DOI: 10.1111/pin.12230
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression in gastrointestinal mesenchymal tumors. (2014)
  • Author(s): Yamamoto H, Arakaki K, Morimatsu K, Zaitsu Y, Fujita A, Kohashi K, Hirahashi M, Motoshita J, Oshiro Y, Oda Y.
  • Journal Title: Human Pathology Volume: 45 Issue: 3 Pages: 481-487
  • DOI: 10.1016/j.humpath.2013.10.010
  • Peer Reviewed
• [Journal Article] Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumours. (2013)
  • Author(s): Yamamoto H, Handa M, Tobo T, Setsu N, Fujita K, Oshiro Y, Mihara Y, Yoshikawa Y, Oda Y.
  • Journal Title: Histopathology Volume: 63 Issue: 2 Pages: 194-207
  • DOI: 10.1111/his.12159
  • Peer Reviewed
• [Journal Article] 悪性軟部腫瘍におけるシグナル伝達因子異常の病理学的研究 (2013)
  • Author(s): 山元英崇、小田義直
  • Journal Title: 癌と化学療法 Volume: 40 Pages: 314-317
• [Journal Article] Fascin-1 overexpression and miR-133b down-regulation in the progression of gastrointestinal stromal tumor. (2013)
  • Author(s): Yamamoto H
  • Journal Title: Modern Pathology Volume: 26 Issue: 4 Pages: 563-571
  • DOI: 10.1038/modpathol.2012.198
  • Peer Reviewed
• [Journal Article] Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumours. (2013)
  • Author(s): Yamamoto H, Handa M, Tobo T, Setsu N, Fujita K, Oshiro Y, Mihara Y, Yoshikawa Y, Oda Y.
  • Journal Title: Histopatholgy Volume: 印刷中
  • Peer Reviewed
• [Presentation] HIF-1αとmiR-210は胃腸管間質腫瘍(GIST)の悪性化進展に関与する (2015)
  • Author(s): 山元英崇、財津瑛子、小田義直
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08 – 2015-10-10
• [Presentation] 紡錘型細胞軟部肉腫におけるAkt-mTORシグナル経路の活性化とその治療応用の可能性 (2014)
  • Author(s): 小田義直、山田裕一、孝橋賢一、山元英崇、岩本幸英
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 炎症性筋線維芽細胞腫瘍におけるALK, ROS1発現 (2014)
  • Author(s): 山元英崇、田口健一、吉田朗彦、中野貴史、孝橋賢一、小田義直
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 消化管間葉系腫瘍の鑑別 (2013)
  • Author(s): 山元英崇
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Invited
• [Presentation] 分子病理学的予後因子とFNCLCC grading systemの比較 (2013)
  • Author(s): 山元英崇、遠藤誠、薛宇孝、高橋祐介、山田裕一、孝橋賢一、小田義直
  • Organizer: 第46回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京
• [Presentation] 分子病態に基づいた胃腸管間質腫瘍の亜型の確立と腫瘍進展メカニズムの解明 (2013)
  • Author(s): 山元英崇
  • Organizer: 第59回日本病理学会秋期特別総会
  • Place of Presentation: 甲府
  • Invited
• [Presentation] Fascin-1 overexpression and miR-133b down-regulation in the progression of gastrointestinal stromal tumor. (2013)
  • Author(s): Yamamoto H, Kohashi K, Fujita A, Oda Y.
  • Organizer: The 102nd Annual Meeting of the United States and Canadian Academy of Pathology
  • Place of Presentation: Baltimore, USA
• [Book] 癌診療指針のための病理診断プラクティス 骨軟部腫瘍 (2013)
  • Author(s): 山元英崇
  • Total Pages: 411
  • Publisher: 中山書店