Oxidative stress signaling as the molecular mechanism of chemo-resistance in esophageal cancer

• Project/Area Number: 26461971
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Niigata University
• Principal Investigator: KOSUGI Shin-ichi 新潟大学, 医歯学総合病院, 特任教授 (90401736)
• Co-Investigator(Kenkyū-buntansha): 若井 俊文 新潟大学, 医歯学系, 教授 (50372470) ; 石川 卓 新潟大学, 医歯学総合病院, 准教授 (70586940) ; 羽入 隆晃 新潟大学, 医歯学総合病院, 助教 (50719705) ; 小山 諭 新潟大学, 医歯学系, 教授 (10323966) ; 廣瀬 雄己 新潟大学, 医歯学総合病院, 医員 (10737365) ; 市川 寛 新潟大学, 医歯学系, 助教 (50721875)
• Co-Investigator(Renkei-kenkyūsha): KOMATSU Masaaki 新潟大学, 医歯学系, 教授 (90356254)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 食道外科学 / 食道癌 / 術前補助化学療法 / 酸化ストレス / 術前化学療法 / 治療抵抗性

Outline of Final Research Achievements

We sought to elucidate the molecular mechanism of chemo-resistance in esophageal cancer from the viewpoint of oxidative stress signaling. In esophageal cancer cells, expression of NQO1, a downstream molecule of the pathway, had no significant association with histological response to preoperative chemotherapy but was an independent unfavorable prognostic factor. In addition, NQO1 expression had no significant correlation with expression of Nrf2, although it is a central molecule of the pathway and regulates NQO1 expression under physiological conditions. On the other hand, NQO1 expression in nontumorous squamous epithelium had significant association with clinical response to preoperative chemotherapy and was an independent favorable prognostic factor. NQO1 expression in nontumorous squamous epithelium could be a promising biomarker to predict treatment outcomes after preoperative chemotherapy followed by esophagectomy.

Research Products

• [Journal Article] Prognostic significance of NQO1 expression in esophageal squamous cell carcinoma after preoperative chemotherapy with cisplatin and 5-fluorouracil followed by curative esophagectomy (2016)
  • Author(s): Ichikawa H, Kosugi S, Hirose Y, Matsuda Y, Ishikawa T, Hanyu T, Usui K, Muneoka Y, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Wakai T
  • Journal Title: International Journal of Clinical and Experimental Pathology Volume: 9 Pages: 7393-7401
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Clinical significance of NQO1 expression in nontumorous squamous epithelium of esophageal cancer patients (2016)
  • Author(s): Kosugi S, Ichikawa H, Hanyu T, Ishikawa T, Wakai T
  • Organizer: 15th World Congress of the International Society for Diseases of the Esophagus
  • Place of Presentation: Singapore (Republic of Singapore)
  • Year and Date: 2016-09-19
  • Int'l Joint Research
• [Presentation] Expression of NQO1 in esophageal cancer cells after neoadjuvant chemotherapy (2014)
  • Author(s): Takashi Ishikawa, Shin-ichi Kosugi, Hiroshi Ichikawa, Takaaki Hanyu, Tsutomu Suzuki, Toshifumi Wakai
  • Organizer: 14th World Congress of The International Society for Diseases of the Esophagus
  • Place of Presentation: The Westin Bayshore（バンクーバー、カナダ）
  • Year and Date: 2014-09-24