潰瘍性大腸炎関連大腸癌の新規分子マーカーの同定と治療法の開発

2015 Fiscal Year Research-status Report

• Project/Area Number: 15K08974
• Research Institution: Keio University
• Principal Investigator: 岩男 泰 慶應義塾大学, 医学部, 教授 (40168547)
• Co-Investigator(Kenkyū-buntansha): 金井 隆典 慶應義塾大学, 医学部, 教授 (40245478) ; 佐藤 俊朗 慶應義塾大学, 医学部, 准教授 (70365245)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 内視鏡 / 潰瘍性大腸炎 / 大腸癌 / 幹細胞

Outline of Annual Research Achievements

潰瘍性大腸炎患者関連大腸癌（CAC）は潰瘍性大腸炎患者の急増とともに，発症数の増加が懸念されている．CACは通常の大腸癌と異なり，大腸全摘術が標準的な治療法であるため，その鑑別診断技術の向上が急務である．本研究ではオルガノイド技術を用い，CACと通常型大腸癌の遺伝子変異・遺伝子発現変化の統合的な解析を行い，CAC分子マーカーの探索を行う．オルガノイド技術による疾患上皮細胞のクローン増幅は極小サンプルからのオミックス解析を可能とし，CACのようなサンプル量に制限のある疾患研究に極めて有用な手段である．得られた分子マーカーの病理組織学的発現解析はCACの診断技術向上と患者の治療法最適化に応用されることが期待できる．

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

H27年度は5例の潰瘍性大腸炎患者関連大腸癌（CAC）由来オルガノイドの作製を行った．潰瘍性大腸炎由来組織は正常粘膜上皮に比し，樹立効率が悪かったが，培養技術の最適化により安定的に樹立できるようになった．樹立したオルガノイドに対し，エキソーム解析およびマイクロアレイ解析による網羅的な遺伝子変異・遺伝子発現解析を行った．本研究は研究計画通り順調に進んでいる．

Strategy for Future Research Activity

潰瘍性大腸炎患者関連大腸癌（CAC）は比較的希少な疾患であるが，研究施設における豊富な症例から順次臨床検体の収集とオルガノイド樹立・解析を行っていく．

Research Products

• [Journal Article] Coping strategies for possible flare-ups and their perceived effectiveness in patients with inflammatory bowel disease (2016)
  • Author(s): Tanaka M, Kawakami A, Iwao Y, Fukushima T, Yamamoto-Mitani N
  • Journal Title: Gastroenterol Nurs Volume: 39 Pages: 42-7
  • DOI: 10.1097/SGA.0000000000000201
  • Peer Reviewed / Open Access
• [Journal Article] Endoscopic Severity Predicts Long-Term Prognosis in Crohn's Disease Patients with Clinical Remission. (2016)
  • Author(s): Naganuma M, Hisamatsu T, Matsuoka K, Kiyohara H, Arai M, Sugimoto S, Mori K, Nanki K, Ohno K, Mutaguchi M, Mizuno S, Bessho R, Nakazato Y, Hosoe N, Inoue N, Iwao Y, Ogata H, Kanai T
  • Journal Title: Digestion Volume: 93 Pages: 66-71
  • DOI: 10.1159/000441767
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study. (2016)
  • Author(s): Sugimoto S, Naganuma M, Kiyohara H, Arai M, Ono K, Mori K, Saigusa K, Nanki K, Takeshita K, Takeshita T, Mutaguchi M, Mizuno S, Ogata H, Iwao Y, Kanai T
  • Journal Title: Digestion Volume: 93 Pages: 193-201
  • DOI: 10.1159/000444217
  • Peer Reviewed / Open Access
• [Journal Article] Evidence-based clinical practice guidelines for management of colorectal polyps (2015)
  • Author(s): Tanaka S, Saitoh Y, Matsuda T, Igarashi M, Matsumoto T, Iwao Y, Suzuki Y, Nishida H, Hiwatashi N, Saito H, Watanabe M, Sugano K, and Shimosegawa T
  • Journal Title: J Gastroenterol Volume: 50 Pages: 252-60
  • DOI: 10.1007/s00535-014-1021-4.
  • Peer Reviewed / Open Access
• [Journal Article] Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study. (2015)
  • Author(s): Wada Y, Hisamatsu T, Naganuma M, Matsuoka K, Okamoto S, Inoue N, Yajima T, Kouyama K, Iwao Y, Ogata H, Hibi T, Abe T, Kanai T
  • Journal Title: Clin Nutr Volume: 34 Pages: 1202-9
  • DOI: 10.1016/j.clnu.2015.01.003
  • Peer Reviewed / Open Access
• [Journal Article] Combination Therapy with Infliximab and Thiopurine Compared to Infliximab Monotherapy in Maintaining Remission of Postoperative Crohn's Disease (2015)
  • Author(s): Sakuraba A, Okamoto S, Matsuoka K, Sato T, Naganuma M, Hisamatsu T, Iwao Y, Ogata H, Kanai T, Hibi T
  • Journal Title: Digestion. Volume: 91 Pages: 233-8
  • DOI: 10.1159/000375302
  • Peer Reviewed / Open Access
• [Journal Article] Association of Visceral Fat Area, Smoking, and Alcohol Consumption with Reflux Esophagitis and Barrett's Esophagus in Japan. (2015)
  • Author(s): Matsuzaki J, Suzuki H, Kobayakawa M, Inadomi JM, Takayama M, Makino K, Iwao Y, Sugino Y, Kanai T
  • Journal Title: PLoS One. Volume: 10 Pages: 1-15
  • DOI: 10.1371/journal.pone.0133865.
  • Peer Reviewed / Open Access
• [Journal Article] Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission. (2015)
  • Author(s): Hisamatsu T, Ono N, Imaizumi A, Mori M, Suzuki H, Uo M, Hashimoto M, Naganuma M, Matsuoka K, Mizuno S, Kitazume MT, Yajima T, Ogata H, Iwao Y, Hibi T, Kanai T
  • Journal Title: PLoS One. Volume: 10 Pages: 1-10
  • DOI: 10.1371/journal.pone.0140716.
  • Peer Reviewed / Open Access
• [Presentation] 小腸pyogenic granuloma4例の臨床的検討． (2015)
  • Author(s): 宮永亮一、細江直樹、平田賢郎、中里圭宏、長沼誠、岩男泰、緒方晴彦、金井隆典
  • Organizer: 第101回日本消化器内視鏡学会関東支部例会
  • Place of Presentation: シェーンバッハ・サボー(東京都千代田区)
  • Year and Date: 2015-12-12 – 2015-12-13
• [Presentation] Prokinetics, mosapride citrate, is useful adjunction in a morning-only bowel preparation using polyethylene glycol and electrolyte solution (PEG-ELS) plus ascorbic acid for screening colonoscopy (2015)
  • Author(s): Inoue N, Yoshida T, Kashiwagi K, Sugino Y, Iwao Y
  • Organizer: Asian Pacific Digestive Week
  • Place of Presentation: 台北(台湾)
  • Year and Date: 2015-12-03 – 2015-12-06
  • Int'l Joint Research
• [Presentation] Aging, Smoking, Dyslipidemia, and Obesity Are Independently Associated With the Prevalence of Colorectal Neoplasia in Japan: Analyses of Comprehensive Health Checkup Data (2015)
  • Author(s): Inoue N, Takayama M, Makino K, Matsuzaki J, Shiomi E, Shimizu R, Yoshida T, Kashiwagi K, Hirose H, Momoshima S, Sugino Y, Iwao Y
  • Organizer: Annual Scientific Meeting of the American College of Gastroenterology.
  • Place of Presentation: ハワイ(アメリカ)
  • Year and Date: 2015-10-16 – 2015-10-21
  • Int'l Joint Research
• [Presentation] Prokinetics, Mosapride Citrate, Is Useful Adjunction in a Morning-Only Bowel Preparation Using Polyethylene Glycol and Electrolyte Solution (PEG-ELS) Plus Ascorbic Acid for Screening Colonoscopy. (2015)
  • Author(s): Inoue N, Matsuzaki J, Yoshida T, Kashiwagi K, Sugino Y, Iwao Y
  • Organizer: Annual Scientific Meeting of the American College of Gastroenterology.
  • Place of Presentation: ハワイ(アメリカ)
  • Year and Date: 2015-10-16 – 2015-10-21
  • Int'l Joint Research
• [Presentation] 潰瘍性大腸炎合併大腸癌初期病変の内視鏡像の検討 (2015)
  • Author(s): 長沼誠，岩男泰，金井隆典
  • Organizer: 第89回日本消化器内視鏡学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2015-05-29 – 2015-05-31
• [Presentation] モサプリドクエン酸塩を併用したアスコルビン酸加ポリエチレングリコール含有電解質溶液による大腸内視鏡前処置法の工夫 (2015)
  • Author(s): 井上詠，岩男泰，松崎潤太郎，吉田諭史，杉野吉則
  • Organizer: 第89回日本消化器内視鏡学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋)
  • Year and Date: 2015-05-29 – 2015-05-31
• [Presentation] 潰瘍性大腸炎合併大腸癌・dysplasia の内視鏡的危険因子の検討 (2015)
  • Author(s): 長沼誠，松岡克善，岩男泰
  • Organizer: 第101回日本消化器病学会総会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
  • Year and Date: 2015-04-23 – 2015-04-25