The effect of local reactivation of cytomegalovirus in ulcerative colitis-related colorectal cancer

• Project/Area Number: 18K07947
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kawakami Kentaro 札幌医科大学, 医学部, 研究員 (60758712)
• Co-Investigator(Kenkyū-buntansha): 仲瀬 裕志 札幌医科大学, 医学部, 教授 (60362498)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 潰瘍性大腸炎 / サイトメガロウイルス / 炎症性発癌 / サイトメガロウィルス

Outline of Final Research Achievements

Our goal was to elucidate the role of cytomegalovirus (CMV) in ulcerative colitis-related carcinogenesis. (1) In experiments using mouse CMV latently infected mice, it was difficult to obtain sufficient numbers of mice due to the frequent occurrence of early death in the mouse CMV-administered group. With the study of Wild Type mice that have survived, we confirmed that the expression of IFN-γ was increased in real-time PCR. However, it is a crucial task that obtain sufficient mice by improving the breeding conditions. (2) CMV immunostaining was performed on human colitic cancer specimens, but CMV positive cells could not be detected in both neoplastic lesions and non-neoplastic mucosa. We considered that it would be insufficient to detect the reactivation of CMV with immunohistological evaluation.

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎の長期経過症例では、腸炎を背景とした大腸癌を合併するリスクが高くなる。一方、CMV感染は潰瘍性大腸炎の難治および慢性炎症持続に寄与する要因の１つであることが知られている。したがって、CMV感染による慢性炎症の持続は、潰瘍性大腸炎関連大腸発癌と関連するものと推測され、マウスCMV潜伏感染モデルを作成し検討を行うことを目標としてきた。現段階で得られている成果は、CMVと炎症性発癌の相関関係を根本的に解明するものではない。今後も実験を継続し、潰瘍性大腸炎関連発癌の予測の観点から、CMV治療を行う意義について明らかにしたい。

Research Products

• [Journal Article] New paradigm of B-cell biology regarding the elucidation of a new mechanism of tissue fibrosis in IgG4-related disease. (2020)
  • Author(s): Nakase H, Ishigami K.
  • Journal Title: J Allergy Clin Immunol Volume: 145 Issue: 3 Pages: 785-787
  • DOI: 10.1016/j.jaci.2020.01.004
  • Peer Reviewed / Open Access
• [Journal Article] The shining DIAMOND for evidence-based treatment strategies for Crohn’s disease. (2020)
  • Author(s): Nakase H, Matsumoto T, Watanabe K, Hisamatsu T.
  • Journal Title: J Gastroenterol Volume: 55 Issue: 9 Pages: 824-832
  • DOI: 10.1007/s00535-020-01702-x
  • Peer Reviewed / Open Access
• [Journal Article] Contradictory effects of NLRP3 inflammasome regulatory mechanisms in colitis. (2020)
  • Author(s): Wagatsuma K, Nakase H.
  • Journal Title: Int J Mol Sci Volume: 21 Issue: 21 Pages: 8145-8145
  • DOI: 10.3390/ijms21218145
  • Peer Reviewed / Open Access
• [Journal Article] Immunological mechanisms in inflammation-associated colon carcinogenesis. (2020)
  • Author(s): Hirano T, Hirayama D, Wagatsuma K, Yamakawa T, Yokoyama Y, Nakase H.
  • Journal Title: Int J Mol Sci Volume: 21 Issue: 9 Pages: 3062-3062
  • DOI: 10.3390/ijms21093062
  • Peer Reviewed / Open Access
• [Journal Article] Expert opinions on the current therapeutic management of inflammatory bowel disease during the COVID-19 pandemic: Japan IBD COVID-19 taskforce, intractable diseases, the health and labor sciences research. (2020)
  • Author(s): akase H, Matsumoto T, Matsuura M, Iijima H, Matsuoka K, Ohmiya N, Ishihara S, Hirai F, Wagatsuma K, Yokoyama Y, Hisamatsu T.
  • Journal Title: Digestion Volume: - Issue: 5 Pages: 1-9
  • DOI: 10.1159/000510502
  • Peer Reviewed / Open Access
• [Journal Article] Influence of Pharmaceutical Formulation on the Mucosal Concentration of 5-Aminosalicylic Acid and <i>N</i>-Acetylmesalamine in Japanese Patients with Ulcerative Colitis (2019)
  • Author(s): Yamamoto Y, Masuda S, Nakase H, Matsuura M, Maruyama S, Hisamatsu T, Suzuki Y, Matsubara K.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 42 Issue: 1 Pages: 81-86
  • DOI: 10.1248/bpb.b18-00561
  • NAID: 130007542208
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2019-01-01
  • Peer Reviewed / Open Access
• [Journal Article] Chronic Intestinal Pseudo-Obstruction Due to Al Amyloidosis: A Case Report and Literature Review (2019)
  • Author(s): Iida Tomoya, Hirayama Daisuke, Sudo Gota, Mitsuhashi Kei, Igarashi Hisayoshi, Yamashita Kentaro, Yamano Hiroo, Nakase Hiroshi.
  • Journal Title: Clinical journal of gastroenterology Volume: 12 Issue: 2 Pages: 176-181
  • DOI: 10.1007/s12328-018-0909-6
  • Peer Reviewed
• [Journal Article] The Etiology of Pancreatic Manifestations in Patients with Inflammatory Bowel Disease (2019)
  • Author(s): Iida Tomoya、Wagatsuma Kohei、Hirayama Daisuke、Yokoyama Yoshihiro、Nakase Hiroshi
  • Journal Title: Journal of Clinical Medicine Volume: 8 Issue: 7 Pages: 916-916
  • DOI: 10.3390/jcm8070916
  • Peer Reviewed
• [Journal Article] Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2) (2019)
  • Author(s): Hisamatsu Tadakazu、DIAMOND2 Study Group、Kato Shingo、Kunisaki Reiko、Matsuura Minoru、Nagahori Masakazu、Motoya Satoshi、Esaki Motohiro、Fukata Norimasa、Inoue Satoko、Sugaya Takeshi、Sakuraba Hirotake、Hirai Fumihito、Watanabe Kenji、Kanai Takanori、Naganuma Makoto、Nakase Hiroshi、et al.
  • Journal Title: Journal of Gastroenterology Volume: 54 Issue: 10 Pages: 860-870
  • DOI: 10.1007/s00535-019-01582-w
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic Efficacy and Adverse Events of Tacrolimus in Patients with Crohn’s Disease: Systematic Review and Meta-Analysis (2019)
  • Author(s): Iida Tomoya、Nojima Masanori、Nakase Hiroshi
  • Journal Title: Digestive Diseases and Sciences Volume: 64 Issue: 10 Pages: 2945-2954
  • DOI: 10.1007/s10620-019-05619-1
  • Peer Reviewed / Open Access
• [Journal Article] Diversity of Gut Microbiota Affecting Serum Level of Undercarboxylated Osteocalcin in Patients with Crohn’s Disease (2019)
  • Author(s): Wagatsuma Kohei、Yamada Satoshi、Ao Misora、Matsuura Minoru、Tsuji Hidemi、Iida Tomoya、Miyamoto Kentaro、Oka Kentaro、Takahashi Motomichi、Tanaka Kiyoshi、Nakase Hiroshi
  • Journal Title: Nutrients Volume: 11 Issue: 7 Pages: 1541-1541
  • DOI: 10.3390/nu11071541
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MEFV Gene-Related Enterocolitis Account for Some Cases Diagnosed as Inflammatory Bowel Disease Unclassified (2019)
  • Author(s): Saito Daisuke、Hibi Noritaka、Ozaki Ryo、Kikuchi Oki、Sato Taro、Tokunaga Sotaro、Minowa Shintaro、Ikezaki Osamu、Mitsui Tatsuya、Miura Miki、Sakuraba Akihito、Hayashida Mari、Miyoshi Jun、Matsuura Minoru、Nakase Hiroshi、Hisamatsu Tadakazu
  • Journal Title: Digestion Volume: 1 Issue: 6 Pages: 1-9
  • DOI: 10.1159/000502640
  • Peer Reviewed
• [Journal Article] Concerns and side effects of azathioprine during adalimumab induction and maintenance therapy for Japanese patients with Crohn's disease: a sub-analysis of a prospective randomized clinical trial (DIAMOND study). (2019)
  • Author(s): Hisamatsu T, Matsumoto T, Watanabe K,;Nakase H, Motoya S, Yoshimura N, Ishida T, Kato S, Nakagawa T, Esaki M, Nagahori M, Matsui T, Naito Y, Kanai T, Suzuki Y, Nojima M, Watanabe M, Hibi T; DIAMOND study group.
  • Journal Title: J Crohns Colitis. Volume: 印刷中 Issue: 9 Pages: 1097-1104
  • DOI: 10.1093/ecco-jcc/jjz030
  • Peer Reviewed / Open Access
• [Journal Article] Evidence-based clinical practice guidelines for inflammatory bowel disease. (2018)
  • Author(s): Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, Kato J, Kobayashi K, Kobayashi K, Koganei K, Kunisaki R, Motoya S, Nagahori M, Nakase H, Omata F, Saruta M, Watanabe T, Tanaka T, Kanai T, Noguchi Y, Takahashi K, Watanabe K, Hibi T, Suzuki Y, Watanabe M, Sugano K, Shimosegawa T.
  • Journal Title: J Gastroenterol. Volume: 53 Issue: 3 Pages: 305-353
  • DOI: 10.1007/s00535-018-1439-1
  • Peer Reviewed / Open Access
• [Journal Article] Clinical and pharmacokinetic factors associated with adalimumab-induced mucosal healing in patients with Crohn’s disease. (2018)
  • Author(s): Watanabe K, Matsumoto T, Hisamatsu T, Nakase H, Motoya S, Yoshimura N, Ishida T, Kato S, Nakagawa T, Esaki M, Nagahori M, Matsui T, Naito Y, Kanai T, Suzuki Y, Nojima M, Watanabe M, Hibi T.
  • Journal Title: Clin Gastroenterol Hepatol. Volume: 16 Pages: 542-549
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of endoscopic balloon dilation for small bowel strictures in patients with Crohn’s disease: a nationwide, multi-centre, open-label, prospective cohort study. (2018)
  • Author(s): Hirai F, Andoh A, Ueno F, Watanabe K, Ohmiya N, Nakase H, Kato S, Esaki M, Endo Y, Yamamoto H, Matsui T, Iida M, Hibi T, Watanabe M, Suzuki Y, Matsumoto T.
  • Journal Title: J Crohns Colitis. Volume: 12 Issue: 4 Pages: 394-401
  • DOI: 10.1093/ecco-jcc/jjx159
  • Peer Reviewed
• [Journal Article] Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries. (2018)
  • Author(s): Kobayashi T, Hisamatsu T, Suzuki Y, Ogata H, Andoh A, Araki T, Hokari R, Iijima H, Ikeuchi H, Ishiguro Y, Kato S, Kunisai R, Matsumoto T, Motoya S, Nagahori M, Nakamura S, Nakase H, Tsujikawa T, Sasaki M, Yokoyama K, Yoshimura N, Watanabe K, Katafuchi M, Watanabe M, Hibi T.
  • Journal Title: Intest Res. Volume: 16 Issue: 2 Pages: 168-177
  • DOI: 10.5217/ir.2018.16.2.168
  • Peer Reviewed / Open Access
• [Journal Article] Effect of elemental diet combined with infliximab dose escalation in patients with Crohn’s disease with loss of response to infliximab: CERISIER trial. (2018)
  • Author(s): Hisamatsu T, Kunisaki R, Nakamura S, Tsujikawa T, Hirai F, Nakase H, Watanabe K, Yokoyama K, Nagahori M, Kanai T, Naganuma M, Michimae H, Andoh A, Yamada A, Yokoyama T, Kamata N, Tanaka S, Suzuki Y, Hibi T, Watanabe M.
  • Journal Title: Intest Res. Volume: 16 Issue: 3 Pages: 494-498
  • DOI: 10.5217/ir.2018.16.3.494
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of fecal calprotectin by monoclonal antibody testing in adult Japanese with inflammatory bowel diseases: a prospective multicenter study. (2018)
  • Author(s): Nakamura S, Imaeda H, Nishikawa H, Iimuro M, Matsuura M, Oka H, Oku J, Miyazaki T, Honda H, Watanabe K, Nakase H, Andoh A.
  • Journal Title: Intest Res. Volume: 16 Issue: 4 Pages: 554-562
  • DOI: 10.5217/ir.2018.00027
  • Peer Reviewed / Open Access
• [Journal Article] The Incidence and Risk Factors of Venous Thromboembolism in Patients with Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study (2018)
  • Author(s): Ando Katsuyoshi、Fujiya Mikihiro、Nomura Yoshiki、Inaba Yuhei、Sugiyama Yuya、Kobayashi Yu、Iwama Takuya、Ijiri Masami、Takahashi Keitaro、Ueno Nobuhiro、Kashima Shin、Moriichi Kentaro、Tanabe Hiroki、Mizukami Yusuke、Akasaka Kazumi、Fujii Satoshi、Yamada Satoshi、Nakase Hiroshi、Okumura Toshikatsu
  • Journal Title: Digestion Volume: NA Issue: 4 Pages: 1-9
  • DOI: 10.1159/000495289
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy of Indigo naturalis in a Multicenter Randomized Controlled Trial of Patients with Ulcerative Colitis (2017)
  • Author(s): .Naganuma M, Sugimoto S, Mitsuyama K, Kobayashi T, Yoshimura N, Ohi H, Tanaka S, Andoh A, Ohmiya N, Saigusa K, Yamamoto T, Morohoshi Y, Ichikawa H, Matsuoka K, Hisamatsu T, Watanabe K, Mizuno S, Suda W, Hattori M, Fukuda S, Hirayama A, Abe T, Watanabe M, Hibi T, Suzuki Y, Kanai T
  • Journal Title: Gastroenterology Volume: 4 Issue: 4 Pages: 935-947
  • DOI: 10.1053/j.gastro.2017.11.024
  • Peer Reviewed / Open Access
• [Presentation] 炎症性腸疾患の鑑別診断としてのMEFV遺伝子関連腸炎． (2020)
  • Author(s): 仲瀬裕志
  • Organizer: 第3回日本免疫不全自己炎症学会総会学術集会
• [Presentation] 実地診療における進行消化管癌に対するMSI検査 (2020)
  • Author(s): 川上賢太郎，奥田博介，山下健太郎，大内知之，武内利直，坂下啓太，澄川宗祐，佐々木邦明，西田靖仙，久須美貴哉，細川正夫.
  • Organizer: 第16回日本消化管学会総会学術集会
• [Presentation] The treatment goal of Crohn’s disease based on the new therapeutic strategy． (2020)
  • Author(s): 仲瀬裕志．
  • Organizer: 第62回日本消化器病学会大会
  • Int'l Joint Research
• [Presentation] 北海道内のIBD患者におけるIFX-BS治療のReal world data～Phoenix cohortより～ (2020)
  • Author(s): 風間友江，横山佳浩，平山大輔，我妻康平，安藤勝祥，上野伸展，藤谷幹浩，伊藤貴博，前本篤男，仲瀬裕志．
  • Organizer: 第11回日本炎症性腸疾患学会学術集会
• [Presentation] JAPAN IBD COVID-19 Taskforceの現在、そして今後の課題 (2020)
  • Author(s): 仲瀬裕志．
  • Organizer: 第11回日本炎症性腸疾患学会学術集会
• [Presentation] 炎症性大腸発癌の深部浸潤機序における低分子量GTP蛋白質Ralの機能解析 (2019)
  • Author(s): 飯田智哉，川上賢太郎，仲瀬裕志
  • Organizer: 第15回日本消化管学会総会学術集会
• [Presentation] 炎症性腸疾患治療―過去・現在・そして未来― (2019)
  • Author(s): 仲瀬裕志
  • Organizer: 第15回日本消化管学会総会学術集会
  • Invited
• [Presentation] 炎症性腸疾患鑑別診断としての家族性地中海熱遺伝子関連腸炎 (2019)
  • Author(s): 仲瀬裕志
  • Organizer: 第47回日本臨床免疫学会総会
• [Presentation] Role of biosimilars in IBD : What you need to know now (2019)
  • Author(s): 仲瀬裕志
  • Organizer: 第61回日本消化器病学会大会
• [Presentation] Can TDM guide us to de-escalate? (2019)
  • Author(s): Nakase H.
  • Organizer: The 7th Annual Meeting of Asian Organization for Crohn’s & Colitis.
  • Int'l Joint Research
• [Presentation] Therapeutic efficacy and adverse events of tacrolimus in patients with Crohn’s disease : a systematic review and meta-analysis. (2018)
  • Author(s): Iida T, Nojima M, Nakase H.
  • Organizer: Digestive Disease Week2018．
  • Int'l Joint Research
• [Presentation] 潰瘍性大腸炎の最適治療を模索する―ブデソニド注腸フォーム剤の可能性を含めて―． (2018)
  • Author(s): 仲瀬裕志．
  • Organizer: 第14回日本消化管学会総会学術集会．
  • Invited
• [Presentation] 炎症性腸疾患に合併する肺病変の発症機序―免疫学的観点からのアプローチ―． (2018)
  • Author(s): 仲瀬裕志．
  • Organizer: 第95回日本消化器内視鏡学会総会．
  • Invited
• [Presentation] Ral-NLRP3インフラマソーム経路は炎症性大腸発癌を促進する． (2018)
  • Author(s): 飯田智哉，野島正寛，堀内久徳，仲瀬裕志．
  • Organizer: 第77回日本癌学会学術総会．
  • Invited
• [Presentation] 潰瘍性大腸炎新規内視鏡粘膜評価法を目指したReal-time automated calculating systemの開発． (2018)
  • Author(s): 仲瀬裕志，Peter B，Raf B．
  • Organizer: 第60回日本消化器病学会大会．
  • Invited
• [Presentation] 炎症性腸疾患領域における生物学的製剤の位置付け． (2018)
  • Author(s): 仲瀬裕志．
  • Organizer: 第46回日本臨床免疫学会総会．
  • Invited
• [Presentation] Understanding current treatment of ulcerative colitis based on mode of action． (2018)
  • Author(s): 仲瀬裕志．
  • Organizer: 第55回日本消化器免疫学会総会．
• [Book] 最適治療を極める！クローン病 (2019)
  • Author(s): 仲瀬裕志
  • Total Pages: 80
  • Publisher: 医学と看護社
  • ISBN: 9784909888044
• [Book] 最適治療を極める！潰瘍性大腸炎 (2018)
  • Author(s): 仲瀬裕志
  • Total Pages: 82
  • Publisher: 医学と看護社
  • ISBN: 9784906829873