Development of a novel high sensitivity molecular imaging for ACF

• Project/Area Number: 26293176
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokushima
• Principal Investigator: TAKAYAMA Tetsuji 徳島大学, 大学院医歯薬学研究部, 教授 (10284994)
• Co-Investigator(Kenkyū-buntansha): 佐野 茂樹 徳島大学, 大学院医歯薬学研究部, 教授 (20226038) ; 中川 忠彦 徳島大学, 大学院医歯薬学研究部, 特任助教 (40634275) ; 六車 直樹 徳島大学, 大学院医歯薬学研究部, 准教授 (90325283)
• Co-Investigator(Renkei-kenkyūsha): NAKANO Michiyasu 徳島大学, 大学院医歯薬学研究部, 助教 (60550001)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: molecular imaging / ACF / 蛍光標識プローブ / 分子イメージング / 蛍光プローブ

Outline of Final Research Achievements

We analyzed aberrant crypt foci (ACF) tissues using microarray to find a specific molecule for molecular imaging of ACF. Then, we found Glutathione S-transferase(GST)-pi、EGFR, glut-1 are overexpressed in ACF as a specific molecule for ACF molecular imaging. Synthesizing fluorescent probe targeting GST-pi, EGFR and glut-1, we clearly identified ACF on the colorectal mucosa in azxymethane-injected mouse model under fluorescence microscope. We also clearly visualized human ACF on colorectal mucosa resected from patients with colorectal cancers under fluorescence microscope. Thus, we were able to detect human and rodent precancerous ACF lesions using molecular imaging technique.

Research Products

• [Journal Article] Narrow Band Imaging as an Efficient and Economical Tool in Diagnosing Colorectal Polyps (2015)
  • Author(s): Muguruma N, Takayama T.
  • Journal Title: Clinical Endoscopy Volume: 48 Pages: 461-3
  • DOI: 10.5946/ce.2015.48.6.461
  • Peer Reviewed / Open Access
• [Journal Article] B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P. (2015)
  • Author(s): Inoue A, Okamoto K, Fujino Y, Nakagawa T, Muguruma N, Sannomiya K, Mitsui Y, Takaoka T, Kitamura S, Miyamoto H, Okahisa T, Fujimori T, Imoto I, Takayama T
  • Journal Title: Br J Cancer Volume: 112 Pages: 403-412
  • DOI: 10.1038/bjc.2014.545
  • Peer Reviewed
• [Journal Article] Biomarkers for predicting the efficacy of anti-epidermal growth factor receptor antibody in the treatment of colorectal cancer. (2014)
  • Author(s): Okada Y, Miyamoto H, Goji T, Takayama T.
  • Journal Title: Digestion Volume: 89 Pages: 18-23
  • DOI: 10.1159/000356202
  • Peer Reviewed
• [Presentation] Optical Molecular imaging of Aberrant Crypt Foci in the Human Colon by Glutathione S-Transferase-Activated Fluorogenic Probe (2017)
  • Author(s): Muguruma N, Okamoto K, Takayama T
  • Organizer: Digestive Disease Week
  • Place of Presentation: Chicago (USA)
  • Int'l Joint Research
• [Presentation] A New Theranostic Combination of Fluorescent Molecular Imaging and Laser Therapy Targeting c-KIT in Gastrointestinal Stromal Tumors (2017)
  • Author(s): Fujimoto S, Muguruma N, Okamoto K, Takayama T
  • Organizer: Digestive Disease Week
  • Place of Presentation: Chicago (USA)
  • Int'l Joint Research
• [Presentation] Molecular imaging targeting epidermal growth factor receptor in detection and evaluation of therapeutic efficacy for colorectal cancer (2016)
  • Author(s): Miyamoto Y, Muguruma N, Fujimoto S, Nakagawa T, Kitamura S, Kimura T, Okamoto K, Sogabe M, Okahisa T, Takayama T
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] Chemoprevention for colorectal cancer targeting aberrant crypt foci (2016)
  • Author(s): Takayama T, Okamoto K, Muguruma N
  • Organizer: The 5th International Forum of the 102nd General Meeting of the Japanese Society of Gastroenterology
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] 分子解析に基づいたAberrant crypt fociの新規イメージング技術開発 (2016)
  • Author(s): 六車直樹, 岡本耕一, 高山哲治
  • Organizer: 日本がん予防学術大会2016
  • Place of Presentation: 名古屋大学 (愛知県名古屋市)
• [Presentation] Endoscopic molecular imaging of colorectal cancer targeting epidermal growth factor receptor (2015)
  • Author(s): Muguruma N, Miyamoto Y, Fujimoto S, Nakagawa T, Takayama T
  • Organizer: Asia Pacific Digestive Week 2015
  • Place of Presentation: Taipei,Taiwan
  • Year and Date: 2015-12-03
  • Int'l Joint Research
• [Presentation] SSA/P-cancer sequenceにおけるACFの前癌病変としての意義 ― 右側大腸癌のバイオマーカーとしてのACF ― (2015)
  • Author(s): 岡本耕一、藤野泰輝、中川忠彦、井上篤、松本早代、田中久美子、三宮勝隆、北村晋志、六車直樹、岡久稔也、高山哲治
  • Organizer: がん予防学術大会さいたま
  • Place of Presentation: ラフレさいたま（埼玉県さいたま市）
  • Year and Date: 2015-06-05 – 2015-06-06
• [Presentation] 大腸癌におけるEpidermal Growth Factor Receptor（EFGR）をターゲットとした分子イメージングと薬効評価 (2014)
  • Author(s): 宮本佳彦，六車直樹，北村晋志，影本開三，岡田泰行，岡崎 潤，松本早代， 末内辰尚，三井康裕，田中久美子，藤野泰輝，木村哲夫，宮本弘志，高山哲治.
  • Organizer: 第88回日本消化器内視鏡学会総会
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2014-10-23 – 2014-10-26
• [Presentation] Optical Molecular Imaging and Assessment of Therapeutic Response of Colorectal Cancer Targeting Epidermal Growth Factor Receptor. (2014)
  • Author(s): Muguruma N，Miyamoto Y，Fujimoto S，Fujino Y，Okada Y，Kitamura S，Kimura T，Okamoto K，Miyamoto H，Takayama T.
  • Organizer: The world Molecular Imaging Congress.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2014-09-17 – 2014-09-20