Mechanism analysis of colorectal ACF and functional analysis of adipocytokines

• Project/Area Number: 24590948
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Cancer Center Japan (2014); Yokohama City University (2012-2013)
• Principal Investigator: TAKAHASHI Hirokazu 独立行政法人国立がん研究センター, 研究所, 研究員 (70438159)
• 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 大腸がん / 化学発がん予防 / メトホルミン / ACF / 大腸発がん / 発がん / 化学予防 / 癌 / トランスレーショナルリサーチ

Outline of Final Research Achievements

Natural history analysis and observation of human rectal ACF were reported (World J Gastrointest Endosc. 2012）. Relationship between colorectal tumor and adipocytokines were also reported (Cancer Sci. 2009). Colorectal tumor suppressive effect of metformin was confirmed using the human ACF as a surrogate marker in a pilot study (Cancer Prev Res. 2010). Based on these findings, multicenter collaborative prospective randomized trial and are under analysis (BMC Cancer. 2012).

Research Products

• [Journal Article] Methylation epigenotypes and genetic features in colorectal laterally spreading tumors (2014)
  • Author(s): Sakai E, Ohata K, Chiba H, Matsuhashi N, Doi N, Fukushima J, Endo H, Takahashi H, Tsuji S, Yagi K, Matsusaka K, Aburatani H, Nakajima A, Kaneda A.
  • Journal Title: Int J Cancer Volume: in press Issue: 7 Pages: 1586-95
  • DOI: 10.1002/ijc.28814
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic factors accelerate colorectal adenoma recurrence. (2014)
  • Author(s): Taniguchi L, Higurashi T, Uchiyama T, Kondo Y, Uchida E, Uchiyama S, Jono F, Hamanaka J, Kuriyama H, Hata Y, Endo H, Takahashi H, Nagase H, Matsuhashi N, Nakajima A.
  • Journal Title: BMC Gastroenterol Volume: 14 Issue: 1 Pages: 187-187
  • DOI: 10.1186/1471-230x-14-187
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Conditional knockout of the leptin receptor in the colonic epithelium revealed the local effects of leptin receptor signaling in the progression of colonic tumors in mice. (2014)
  • Author(s): Higurashi T, Endo H, Uchiyama T, Uchiyama S, Yamada E, Ohkubo H, Sakai E, Takahashi H, Maeda S, Wada K, Natsumeda Y, Hippo Y, Nakajima A, Nakagama H.
  • Journal Title: Carcinogenesis. Volume: 35 Issue: 9 Pages: 2134-41
  • DOI: 10.1093/carcin/bgu135
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Colon epithelial proliferation and carcinogenesis in diet-induced obesity (2013)
  • Author(s): Takahashi H, Hosono K, Endo H, Nakajima A
  • Journal Title: J Gastroenterol Hepatol. Volume: 28 Issue: S4 Pages: 41-47
  • DOI: 10.1111/jgh.12240
  • Peer Reviewed
• [Journal Article] Visceral obesity as a risk factor for left-sided diverticulitis in Japan: a multicenter retrospective study. (2013)
  • Author(s): Yamada E, Ohkubo H, Higurashi T, Sakai E, Endo H, Takahashi H, Uchida E, Tanida E, Izumi N, Kanesaki A, Hata Y, Matsuura T, Fujisawa N, Komatsu K, Maeda S, Nakajima A.
  • Journal Title: Gut Liver. Volume: 7 Issue: 5 Pages: 532-538
  • DOI: 10.5009/gnl.2013.7.5.532
  • Peer Reviewed
• [Journal Article] 肥満・生活習慣病と大腸癌 (2013)
  • Author(s): 遠藤 宏樹, 日暮 琢磨, 高橋 宏和, 中島 淳
  • Journal Title: Gaatroenterological Endoscopy Volume: 55 Pages: 3735-3744
  • NAID: 130003386602
  • Peer Reviewed
• [Journal Article] 肥満症とがん (2013)
  • Author(s): 高橋 宏和, 内山 詩織, 山田 英司, 大久保 秀則, 日暮 琢磨, 酒井 英嗣, 遠藤 宏樹, 中島 淳
  • Journal Title: 臨床消化器内科 Volume: 28 Pages: 1595-1600
  • Peer Reviewed
• [Journal Article] Intermediate methylation epigenotype and its correlation to KRAS mutation in conventional colorectal adenoma (2012)
  • Author(s): Yagi K, Takahashi H, Akagi K, Matsusaka K, Seto Y, Aburatani H, Nakajima A,Kaneda A
  • Journal Title: Am J Pathology Volume: 180(2) Issue: 2 Pages: 616-25
  • DOI: 10.1016/j.ajpath.2011.10.010
  • Peer Reviewed
• [Journal Article] Natural history of human aberrant crypt foci and correlation with risk factors for colorectal cancer. (2012)
  • Author(s): Ohkubo H, Takahashi H, Yamada E, Sakai E, Higurashi T, Uchiyama T, Hosono K, Endo H, Taguri M, Nakajima A.
  • Journal Title: Oncol Rep. Volume: 27 Pages: 1475-1480
  • DOI: 10.3892/or.2012.1631
  • Peer Reviewed
• [Journal Article] Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial. (2012)
  • Author(s): Higurashi T, Takahashi H, Endo H, Hosono K, Uchiyama T, Hata Y,Ezuka A, Yamanaka S, Inayama Y,et.al.
  • Journal Title: BMC Cancer. Volume: 12(1) Issue: 1 Pages: 118-118
  • DOI: 10.1186/1471-2407-12-118
  • Peer Reviewed
• [Journal Article] Number of aberrant crypt foci in the rectum is a useful surrogate marker of colorectal adenoma recurrence. (2012)
  • Author(s): Takashi Uchiyama
  • Journal Title: Dig Endosc Volume: 24 Issue: 5 Pages: 353-7
  • DOI: 10.1111/j.1443-1661.2012.01289.x
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a double-blind randomized controlled trial. (2012)
  • Author(s): Takuma Higurashi
  • Journal Title: BMC Cancer Volume: 12 Issue: 1 Pages: 413-413
  • DOI: 10.1186/1471-2407-12-413
  • Peer Reviewed
• [Journal Article] Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas. (2012)
  • Author(s): Kunihiro Hosono
  • Journal Title: World J Gastroenterol. Volume: 18 Issue: 38 Pages: 5360-8
  • DOI: 10.3748/wjg.v18.i38.5360
  • Peer Reviewed
• [Journal Article] Relationship of human rectal aberrant crypt foci and formation of colorectal polyp: One-year following up after polypectomy. (2012)
  • Author(s): Hirokazu Takahashi
  • Journal Title: World J Gastrointest Endosc Volume: 4 Issue: 12 Pages: 561-4
  • DOI: 10.4253/wjge.v4.i12.561
  • Peer Reviewed
• [Presentation] Eicosapentenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a double-blind randomized controlled trial
  • Author(s): Higurashi T, Uchiyama S, Yamada E, Sakai E, Ohkubo H, Endo H, Takahashi H, Nakajima A
  • Organizer: 2013 21th UEGW
  • Place of Presentation: Berlin, Germany
• [Presentation] Low dose metformin suppess colorectal ACF and normal mucosal proliferation by activate AMPK, but little effect for the adenoma and CIS
  • Author(s): Higurashi T, Hosono K, Yamada E, Ohkubo H, Sakai E, Iida H, Endo H, Takahashi H, Nakajima A
  • Organizer: Digestive Disease Week 2013
  • Place of Presentation: Orlando, USA
• [Presentation] The genetic alterations and unique epigenetype of laterally spreading colorectal tumors
  • Author(s): Sakai E, Ohata K, Uchiyama S, Yamada E, Higurashi T, Ohkubo H, Endo H, Takahashi H, Nakajima A, Matsuhashi N, Fukushima J, Aburatani H, Kaneda A
  • Organizer: 2013 JCA
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] The histopathological characteristics of mucin-depleted foci in patients with sporadic colorectal cancer
  • Author(s): Sakai E, Takahashi H, Yamada E, Higurashi T, Ohkubo H, Hosono K, Endo H, Kato S, Nakajima A, Cui C, Takamatsu R, Yoshimi N.
  • Organizer: AACR Annual Meeting 2012
  • Place of Presentation: Chicago, USA
• [Presentation] Aberrant crypt foci (ACF) の測定範囲と大腸ポリープの検討
  • Author(s): 藤井徹朗, 高橋宏和, 中島 淳
  • Organizer: 第84回日本消化器内視鏡病学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] Low dose resveratrol do not inhibit colorectal tumor initiation but progression via suppression of STAT 3 signal
  • Author(s): Sakai E, Endo H, ,Nakajima A, Yamada E, Higurashi T, Ohkubo H, Takahashi H
  • Organizer: 2012 JCA
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] Colorectal tumor growth induced by leptin signals analysis of cre/flox mouse model
  • Author(s): Higurashi T, Endo H, Sakai E, Ohkubo H, Yamada E, Takahashi H, Nakajima A
  • Organizer: 2012 JCA
  • Place of Presentation: ロイトン札幌（北海道）
• [Book] Lifestyle and Cancer Prevention (2014)
  • Author(s): Takahashi H
  • Total Pages: 16
  • Publisher: Nova Science Publishers