Molecular target therapy induced by hypoxia for scirrhous gastric cancer.

• Project/Area Number: 24591947
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Saga University
• Principal Investigator: KOGA Yasuo 佐賀大学, 医学部, 講師 (30555090)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Jun 佐賀大学, 医学部医学科, 助教 (60404175)
• Co-Investigator(Renkei-kenkyūsha): KITAJIMA Yoshihiko 佐賀大学, 医学部医学科, 助教 (30234256) ; MIYAKE Shusuke 佐賀大学, 医学部医学科, 助教 (70726893)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 胃癌 / 腹膜播種 / 低酸素 / リンパ管新生 / エピゲノム

Outline of Final Research Achievements

The aim of the study was to clarify the role of hypoxia inducible factor (HIF)-1α in the development of peritoneal dissemination of gastric cancer. HIF-1α knockdown (KD) cells were established in the scirrhous gastric cancer cell line 58As9. Using KD and control (SC) cells, the presence of peritoneal dissemination was assessed in orthotopic implantation (o.i.) and intraperitoneal injection (i.p.) models. In the o.i. model, peritoneal dissemination was more frequently observed in the SC mice compared to the KD mice. In the i.p. model, a greater number of disseminated nodules was observed in the KD mice. Angiogenesis and vascular invasion were more aggressive in the SC gastric tumors. We provide a possible mechanism in which peritoneal dissemination of gastric cancer develops via a vascular network whereby HIF-1α activates tumor angiogenesis.

Research Products

• [Presentation] ANGPTL4とLOXL2はスキルス胃癌における腹膜転移の候補遺伝子の可能性がある (2014)
  • Author(s): 馬塲耕一、北島吉彦、三宅修輔、中村淳、柳原吾吉、田中智和、志田雅明、脇山幸大、池田貯、能城浩和
  • Organizer: 第25回日本消化器癌発生学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] ANGPTL4とLOXL2はスキルス胃癌腹膜転移の発生における候補遺伝子の可能性がある (2014)
  • Author(s): 馬塲耕一、北島吉彦、三宅修輔、中村淳、柳原五吉、田中智和、池田貯、能城浩和
  • 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] スキルス胃癌の腹膜播種はHIF-1αにより増強されるリンパ管を介した遠隔転移である (2014)
  • Author(s): 三宅修輔、北島吉彦、中村淳、甲斐敬太、柳原五吉、田中智和、馬塲耕一、宮﨑耕治、能城浩和、井手貴雄、古賀靖大、宮﨑耕治、能城浩和
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-03 – 2014-04-05