Akt-mTOR and Autophagy in Colitic Cancer

• Project/Area Number: 25670570
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: NOZAWA HIROAKI 東京大学, 医学部附属病院, 講師 (80529173)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Hironori 東京大学, 医学部附属病院, 登録研究員 (20376445) ; SUNAMI Eiji 東京大学, 医学部附属病院, 登録研究員 (70345205) ; WATANABE Toshiaki 東京大学, 医学部附属病院, 教授 (80210920)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: colitic cancer / 炎症性腸疾患 / 発癌 / ｍＴＯＲ / mTOR

Outline of Final Research Achievements

In mouse models for colitic cancer using azoxymethan (AOM) and dextran sodium sulfate (DSS), tumors developed mainly in the proximal colon. The expression level of 4E-BP1 was higher in tumors than normal mucosa by immunohistochemical study, which was confirmed by western blotting. However, the level of urine 8-OH-dG as a marker of oxidative stress was unchanged by AOM and/or DSS treatment. The association between colitic cancer and Akt-mTOR signaling axis should be elucidated by more extensive experiments.

Research Products

• [Journal Article] Clinical patterns and progression of ulcerative proctitis in the Japanese population: A retrospective study of incidence and risk factors influencing progression. (2016)
  • Author(s): Anzai H, Hata K, Kishikawa J, Ishii H, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Colorectal Dis. Volume: 18 Issue: 3
  • DOI: 10.1111/codi.13237
  • Peer Reviewed
• [Journal Article] Laparoscopy-assisted versus open surgery for multiple colorectal cancers with two anastomoses: a cohort study. (2016)
  • Author(s): Nozawa H, Ishihara S, Murono K. Yasuda K, Otani K, Nishikawa T, Tanaka T, Kiyomatsu T, Hata K, Kawai K, Yamaguchi H, Watanabe T.
  • Journal Title: SpringerPlus Volume: 5 Issue: 1 Pages: 287-287
  • DOI: 10.1186/s40064-016-1948-4
  • Peer Reviewed
• [Journal Article] Surveillance colonoscopy for colitis-associated dysplasia and cancer in ulcerative colitis patients. (2015)
  • Author(s): Hata K, Kishikawa J, Anzai H, Shinagawa T, Kazama S, Ishii H, Nozawa H, Kawai K, Kiyomatsu T, Tanaka J, Tanaka T, Nishikawa T, Otani K, Yasuda K, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Dig Endosc Volume: 28 Issue: 3 Pages: 260-5
  • DOI: 10.1111/den.12505
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Successful treatment of rectovaginal fistula complicating ulcerative colitis with infliximab: a case report and review of the literature. (2015)
  • Author(s): Nirei T, Kazama S, Hiyoshi M, Tsuno NH, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kanazawa T, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: J Clin Med Res Volume: 7 Issue: 1 Pages: 59-61
  • DOI: 10.14740/jocmr1987w
  • Peer Reviewed
• [Journal Article] Comparison of Functional Outcomes of Patients Who Underwent Hand-Sewn or Stapled Ileal Pouch-Anal Anastomosis for Ulcerative Colitis. (2015)
  • Author(s): Ishii H, Kawai K, Hata K, Shuno Y, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Nozawa H, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Int Surg. Volume: 100 Issue: 7-8 Pages: 1169-1176
  • DOI: 10.9738/intsurg-d-15-00012.1
  • Peer Reviewed
• [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: 713-20
  • DOI: 10.1016/j.surg.2015.09.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Metachronous tubulovillous and tubular adenomas of the anal canal. (2015)
  • Author(s): Nozawa H, Ishihara S, Morikawa T, Tanaka J, Yasuda K, Ohtani K, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Hata K, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Fukayama M, Watanabe T.
  • Journal Title: Diagn Pathol. Volume: 10 Issue: 1 Pages: 139-139
  • DOI: 10.1186/s13000-015-0379-9
  • Peer Reviewed
• [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 Res. Volume: 35 Pages: 5073-5078
  • Peer Reviewed
• [Journal Article] Predictors and outcome of complete removal of colorectal cancer with synchronous lung metastases. (2015)
  • Author(s): Nozawa H, Tanaka J, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Hata K, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Nakamura J, Kokudo N, Watanabe T.
  • Journal Title: Mol Clin Oncol. Volume: 3 Pages: 1041-1047
  • Peer Reviewed
• [Journal Article] Small bowel adenocarcinoma arising in a patient with hereditary hemorrhagic telangiectasia: A case report. (2015)
  • Author(s): Yoshioka Y, Nozawa H, Tanaka J, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Hata K, kazama S, Yamaguchi H, Ishihara S, Sunami S, Kitayama J, Watanabe T.
  • Journal Title: Oncol Lett. Volume: 11 Pages: 2137-2139
  • Peer Reviewed
• [Journal Article] Modelling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. (2015)
  • Author(s): Matano M,Date S, Shimokawa M, Takano A, Fujii M, Ohta Y, Watanabe T, Kanai T, Sato T.
  • Journal Title: Nature Medicine Volume: 21(3) Issue: 3 Pages: 256-262
  • DOI: 10.1038/nm.3802
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic Significance of the Lymph Node Ratio in Stage IV Colorectal Cancer Patients who have Undergone Curative Resection. (2015)
  • Author(s): Ozawa T, Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kanazawa T, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Ann Surg Oncol Volume: 22 Issue: 5 Pages: 1513-9
  • DOI: 10.1245/s10434-014-4184-6
  • Peer Reviewed
• [Journal Article] Characteristics and prognosis of colorectal cancer associated with rheumatic disease. (2015)
  • Author(s): Kishikawa J, Kawai K, Tsuno N, Yamaguchi H, Ishihara S, Sunami E, Watanabe T.
  • Journal Title: Int Surg Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Incidence and prognostic significance of positive peritoneal lavage in colorectal cancer. (2015)
  • Author(s): Nishikawa T, Sunami E, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Kazama S, Nozawa H, Ishihara S, Watanabe T.
  • Journal Title: Surg Today Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Prognostic impact of primary tumor resection and lymph node dissection in stage IV colorectal cancer with unresectable metastasis: a propensity score analysis in a multicenter retrospective study. (2014)
  • Author(s): Ishihara S, Hayama T, Yamada H, Nozawa K, Matsuda K, Miyata H, Yoneyama S, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Kanazawa T, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Hashiguchi Y, Sugihara K, Watanabe T.
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: 9 Pages: 2949-55
  • DOI: 10.1245/s10434-014-3719-1
  • Peer Reviewed / Open Access
• [Journal Article] Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells. (2014)
  • Author(s): Kaneko M
  • Journal Title: J Cancer Res Clin Oncol. Volume: 140(5) Issue: 5 Pages: 769-81
  • DOI: 10.1007/s00432-014-1628-0
  • Peer Reviewed
• [Journal Article] Surgery for luminal Crohn's disease. (2014)
  • Author(s): Yamamoto T, Watanabe T.
  • Journal Title: World J Gastroenterol Volume: 20(1) Issue: 1 Pages: 78-90
  • DOI: 10.3748/wjg.v20.i1.78
  • Peer Reviewed
• [Presentation] Surveillance colonoscopy for detecting ulcerative colitis-associated neoplasia in a single institution: results of a 35-year surveillance program in the Japanese population (2016)
  • Author(s): Anzai H, Hata K, Kishikawa J, Yasuda K, Otani K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Yamaguchi H, Ishihara S, Kitayama J, Watanabe T.
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Presentation] 潰瘍性大腸炎術後慢性回腸嚢炎のリスクファクターに対するメタアナリシス (2016)
  • Author(s): 畑啓介、石原聡一郎、野澤宏彰、山口博紀、川合一茂、清松知充、田中敏明、田中潤一郎、安田幸嗣、西川武司、大谷研介、北山丈二、石井博章、安西紘幸、渡邉聡明
  • Organizer: 第116 回日本外科学会定期学術集集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-04-14
• [Presentation] 潰瘍性大腸炎に対する腹腔鏡手術 (2015)
  • Author(s): 畑啓介、石原聡一郎、須並英二、山口博紀、野澤宏彰、川合一茂、清松知充、田中潤一郎、田中敏明、西川武司、渡邉聡明
  • Organizer: 第77 回日本臨床外科学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-26
• [Presentation] 潰瘍性大腸炎に対する大腸全摘，回腸嚢肛門管吻合術後合併症の検討 (2015)
  • Author(s): 安西紘幸、畑啓介、石井博章、岸川純子、安田幸嗣、西川武司、田中敏明、田中潤一郎、清松知充、川合一茂、野澤宏彰、風間伸介、山口博紀、石原聡一郎、須並英二、渡邉聡明
  • Organizer: 第70回日本大腸肛門病学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-11-13
• [Presentation] 潰瘍性大腸炎術後の回腸嚢炎のリスクファクター (2015)
  • Author(s): 畑啓介、石井博章、風間伸介、川合一茂、野澤宏彰、山口博紀、石原聡一郎、須並英二、北山丈二、渡邉聡明
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15
• [Presentation] 潰瘍性大腸炎術後回腸嚢炎の検討 (2015)
  • Author(s): 安西紘幸、風間伸介、岸川純子、西川武司、田中敏明、田中潤一郎、畑啓介、清松知充、川合一茂、野澤宏彰、金沢孝満、山口博紀、石原聡一郎、須並英二、北山丈二、渡邉聡明
  • Organizer: 第11回日本消化管学会総会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-13 – 2015-02-15
• [Presentation] テムシロリムスとクロロキン併用に よる大腸癌増殖抑制効果の増強．
  • Author(s): 野澤宏彰、金子学、須並英二、北山丈二、渡邉聡明．
  • Organizer: 第72回日本癌学会総会学術総会
  • Place of Presentation: 横浜