SN-38 as a radio-sensitizer for colorectal cancer by suppressing radiation-induced HIF-1a overexpression

• Project/Area Number: 26462005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Kawai Kazushige 東京大学, 医学部附属病院, 講師 (80571942)
• Co-Investigator(Kenkyū-buntansha): 石原 聡一郎 東京大学, 医学部附属病院, 講師 (00376443) ; 山口 博紀 東京大学, 医学部附属病院, 登録研究員 (20376445) ; 津野 寛和 東京大学, 医学部附属病院, 客員研究員 (50282637) ; 須並 英二 東京大学, 医学部附属病院, 登録研究員 (70345205) ; 渡邉 聡明 東京大学, 医学部附属病院, 教授 (80210920)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 放射線療法 / SN-38 / HIF-1α / 化学放射線療法 / 直腸癌 / CPT-11 / 大腸癌

Outline of Final Research Achievements

HIF-1a is the key molecule induced by hypoxia. It activates various pathways protecting cell and tissue from hypoxic stress. Radiotherapy is one of the standard therapy for colorectal cancer, and we found that radiation induced HIF-1a in colorectal cancer cells. We also found that SN-38, which is widely used as an anti-cancer drug for colorectal cancer, effectively suppressed HIF-1a induced by radiation. SN-38 was demonstrated to be a promising radio-sensitizer for colorectal cancer.

Research Products

• [Journal Article] Intraoperative colonoscopy in patients with colorectal cancer: A review of recent developments. (2016)
  • Author(s): Kawai K, Iida Y, Ishihara S, Yamaguchi H, Nozawa H, Hata K, Kiyomatsu T, Tanaka T, Nishikawa T, Yasuda K, Otani K, Murono K, Watanabe T.
  • Journal Title: Digestive Endoscopy Volume: 未定 Issue: 6 Pages: 633-640
  • DOI: 10.1111/den.12663
  • Peer Reviewed
• [Journal Article] Level of arterial ligation in sigmoid colon and rectal cancer surgery. (2016)
  • Author(s): Yasuda K, Kawai K, Ishihara S, Murono K, Otani K, Nishikawa T, Tanaka T, Kiyomatsu T, Hata K, Nozawa H, Yamaguchi H, Aoki S, Mishima H, Maruyama T, Sako A, Watanabe T.
  • Journal Title: World Journal of Surgical Oncology Volume: 14 Issue: 1
  • DOI: 10.1186/s12957-016-0819-3
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic impact of lymph node dissection is different for male and female colon cancer patients: a propensity score analysis in a multicenter retrospective study (2016)
  • Author(s): Ishihara S, Otani K, Yasuda K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Nozawa H, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Sugihara K, Watanabe T.
  • Journal Title: International Journal of colorectal disease Volume: 未定 Issue: 6 Pages: 1149-1155
  • DOI: 10.1007/s00384-016-2558-x
  • Peer Reviewed
• [Journal Article] CD133 Expression at the Metastatic Site Predicts Patients' Outcome in Colorectal Cancer with Synchronous Liver Metastasis. (2016)
  • Author(s): Kishikawa J, Kazama S, Oba K, Hasegawa K, Anzai H, Harada Y, Abe H, Matsusaka K, Hongo K, Oba M, Yasuda K, Otani K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Yamaguchi H, Ishihara S, Sunami E, Ushiku T, Kitayama J, Fukayama M, Kokudo N, Watanabe T.
  • Journal Title: Annals of Surgical Oncology Volume: 未定
  • Peer Reviewed
• [Journal Article] CD133 Expression in Lymph Node Metastases Is Associated with Tumor Aggressiveness During Lymph Node Metastasis in Colorectal Cancer. (2015)
  • Author(s): Kazama S, Kishikawa J, Yasuda K, Otani K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Nozawa H, Yamaguchi H, Ishihara S, Sunami E, Watanabe T. Anticancer Res. 2015 Dec;35(12):6599-605.
  • Journal Title: Anticancer Research Volume: 35 Pages: 6599-605
  • Peer Reviewed
• [Journal Article] Nomograms for colorectal cancer: A systematic review. (2015)
  • Author(s): Kawai K, Sunami E, Yamaguchi H, Ishihara S, Kazama S, Nozawa H, Hata K, Kiyomatsu T, Tanaka J, Tanaka T, Nishikawa T, Kitayama J, Watanabe T.
  • Journal Title: World Journal of Gastroenterology Volume: 21 Issue: 41 Pages: 11877-86
  • DOI: 10.3748/wjg.v21.i41.11877
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Outcome of salvage surgery for colorectal cancer initially treated by upfront endoscopic therapy (2015)
  • Author(s): Nozawa H, Ishihara S, Fujishiro M, Kodashima S, Ohtani K, Yasuda K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Kazama S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Surgery Volume: 159 Issue: 3 Pages: 713
  • DOI: 10.1016/j.surg.2015.09.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic Impact of Histologic Type in Curatively Resected Stage IV Colorectal Cancer: A Japanese Multicenter Retrospective Study. (2015)
  • Author(s): Shibata J, Kawai K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Nozawa H, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Sugihara K, Watanabe T.
  • Journal Title: Annals of Surgical Oncology Volume: Suppl 3 Issue: S3 Pages: 621-629
  • DOI: 10.1245/s10434-015-4846-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (SHOGUN trial). (2015)
  • Author(s): Matsusaka S, Ishihara S, Kondo K, Horie H, Uehara K, Oguchi M, Murofushi K, Ueno M, Mizunuma N, Shimbo T, Kato D, Okuda J, Hashiguchi Y, Nakazawa M, Sunami E, Kawai K, Yamashita H, Okada T, Ishikawa Y, Nakajima T, Watanabe T.
  • Journal Title: Radiotherapy and Oncology Volume: 116 Issue: 2 Pages: 209-13
  • DOI: 10.1016/j.radonc.2015.08.002
  • Peer Reviewed / Open Access
• [Journal Article] Large Colorectal Carcinoma Is Predictive of Recurrence After Adjuvant Chemotherapy Using Oxaliplatin. (2015)
  • Author(s): Nozawa H, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Anticancer Research Volume: 35 Pages: 5073-8
  • Peer Reviewed
• [Presentation] 大腸癌細胞におけるSN-38のHIF-1α抑制による放射線増感剤としての作用 (2017)
  • Author(s): 奥野 貴之、川合 一茂、石原 聡一郎、 大谷 研介、 西川 武司、田中 敏明、清松 知充、畑 啓介、野澤 宏彰、渡邉 聡明
  • Organizer: 第72回日本消化器外科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2017-07-20