Analyses of epigenomic variation such as DNA methylation due to obesity conditions by high nutrient intake.

• Project/Area Number: 26430139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan
• Principal Investigator: FUJII GEN 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (90321877)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 遺伝子環境交互作用 / 肥満 / DNAメチル化 / 遺伝子環境相互作用 / エピゲノム / ヒストン修飾

Outline of Final Research Achievements

Cancer is a disease of genes, and also is a disease strongly influenced from the environment. In recent years, obesity has formed an environment called mild chronic inflammation, and the mechanism by which cancer develops from it has drawn attention.
Therefore, in this study, we verified high nutrient intake in cultured cells or in mice brought into obesity conditions can evoke epigenomic changes such as DNA methylation occur at such frequencies as to explain the carcinogenic processes.
As a result, it was revealed that the DNA methylation state could be changed depending on the nutrient condition by long-term cultivation in the sugar-rich medium / lipid-rich medium in the experiment on the cultured cell level. We continue to conduct similar experiments and measurements also at the animal individual level.

Research Products

• [Journal Article] Colorectal cancer prevention using endoscopic polypectomy in familial adenomatous polyposis (a retrospective study) (2016)
  • Author(s): Ishikawa H, Mutoh M, Iwama T, Suzuki S, Abe T, Takeuchi Y, Nakamura T, Ezoe Y, Fujii G, Nakajima T, Wakabayashi K, Sakai T.
  • Journal Title: Endoscopy Volume: 48 Issue: 01 Pages: 51-55
  • DOI: 10.1055/s-0034-1392774
  • Peer Reviewed
• [Journal Article] Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice. (2016)
  • Author(s): Onuma W, Tomono S, Miyamoto S, Fujii G, Hamoya T, Fujimoto K, Miyoshi N, Fukai F, Wakabayashi K, Mutoh M.
  • Journal Title: Oncotarget Volume: 7 Issue: 8 Pages: 8640-52
  • DOI: 10.18632/oncotarget.7082
  • Peer Reviewed / Open Access
• [Journal Article] Effects of NSAIDs on the risk factors of colorectal cancer: a mini review (2016)
  • Author(s): Takahiro Hamoya, Gen Fujii, Shingo Miyamoto, Mami Takahashi, Yukari Totsuka, Keiji Wakabayashi, Jiro Toshima, Michihiro Mutoh
  • Journal Title: Genes and Environment Volume: 38 Issue: 1 Pages: 1-7
  • DOI: 10.1186/s41021-016-0033-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intestinal Peyer’s patches prevent tumorigenesis in <i>Apc</i>^Min/+ mice (2015)
  • Author(s): Fujimoto K, Fujii G, Sakurai H, Yoshitome H, Mutoh M, Wada M.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 56 Issue: 1 Pages: 43-48
  • DOI: 10.3164/jcbn.14-115
  • NAID: 130004704978
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of NADPH oxidases in suppression of cyclooxygenase-2 promoter-dependent transcriptional activities by sesamol (2015)
  • Author(s): Shimizu S, Ishigamori R, Fujii G, Takahashi M, Onuma W, Terasaki M, Yano T, Mutoh M.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 56 Issue: 2 Pages: 118-122
  • DOI: 10.3164/jcbn.14-89
  • NAID: 130004879380
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Suppressive effects of the NADPH oxidase inhibitor apocynin on intestinal tumorigenesis in obese KK-Ay and Apc mutant Min mice (2015)
  • Author(s): Komiya M, Fujii G, Miyamoto S, Takahashi M, Ishigamori R, Onuma W, Ishino K, Totsuka Y, Fujimoto K, Mutoh M
  • Journal Title: Cancer Sci Volume: 106 Pages: 1499-1505
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of intestinal carcinogenesis in <i>Apc</i>-mutant mice by limonin (2015)
  • Author(s): Shimizu S, Miyamoto S, Fujii G, Nakanishi R, Onuma W, Ozaki Y, Fujimoto K, Yano T, Mutoh M.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 57 Issue: 1 Pages: 39-43
  • DOI: 10.3164/jcbn.15-28
  • NAID: 130005085265
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of trefoil factor family 2 in the enlargement of intestinal tumors in ApcMin/+ mice. (2015)
  • Author(s): Fujimoto K, Fujii G, Taniguchi K, Yasuda K, Matsuo Y, Hashiyama A, Mutoh M, Tanaka H, Wada M,
  • Journal Title: Biochem Biophys Res Commun. Volume: 463 Issue: 4 Pages: 859-863
  • DOI: 10.1016/j.bbrc.2015.06.025
  • Peer Reviewed / Open Access
• [Journal Article] Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in <i>Apc</i>^Min/+ mice (2014)
  • Author(s): Shimizu S, Fujii G, Takahashi M, Nakanaishi R, Komiya M, Shimura M, Noma N, Onuma W, Yano T, Mutoh M.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 54 Issue: 2 Pages: 95-101
  • DOI: 10.3164/jcbn.13-91
  • NAID: 130004879356
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Bi-directional regulation between adiponectin and plasminogen activator-inhibitor-1 in 3T3-L1 cells. (2014)
  • Author(s): Komiya M, Fujii G, Takahashi M, Shimura M, Noma N, Shimizu S, Onuma W, Mutoh M.
  • Journal Title: IN VIVO Volume: 28 Pages: 13-19
  • Peer Reviewed
• [Journal Article] Potential of drug repositioning for colorectal cancer prevention: Inhibition of colorectal polyp recurrence by aspirin. (2014)
  • Author(s): Mutoh M, Fujii G.
  • Journal Title: BioIndustry Volume: 31 Pages: 29-34
  • NAID: 40020263479
• [Journal Article] Potential ability of xanthophylls to prevent obesity-associated cancer. (2014)
  • Author(s): Terasaki M, Mutoh M, Fujii G, Takahashi M, Ishigamori R, Masuda S.
  • Journal Title: World J Pharmcol Volume: 3 Pages: 140-152
  • Peer Reviewed
• [Presentation] 分子推論により得られる新規がん化学予防剤の候補 (2016)
  • Author(s): 武藤倫弘、藤井 元、宮本真吾、高山哲治
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-06
• [Presentation] 既承認薬ライブラリを用いた大腸がん化学予防剤スクリーニング (2016)
  • Author(s): 宮本真吾、藤井 元、武藤倫弘
  • Organizer: 第69回日本酸化ストレス学会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-08-30
• [Presentation] パイエル板数の増加が腸管腫瘍発生数の減少をもたらす (2016)
  • Author(s): 藤本京子、藤井元、桜井瞳、吉留弘子、 小宮 雅美、和田守、武藤倫弘
  • Organizer: 第32回発癌病理研究会
  • Place of Presentation: 信州松代ロイヤルホテル（長野県・長野市）
  • Year and Date: 2016-08-23
• [Presentation] 高脂肪食による発育期ラット乳腺における平面極性関連遺伝子のメチル化異常 (2016)
  • Author(s): 今井俊夫、藤井 元、武藤倫弘、高橋真美
  • Organizer: がん予防学術大会2016名古屋
  • Place of Presentation: 名古屋大学医学部（愛知県・名古屋市）
  • Year and Date: 2016-07-01
• [Presentation] Establishment of desmoid-ike cell lines by an intestinal tumor-derived xenograft model. (2016)
  • Author(s): Shingo Miyamoto, Wakana Onuma, Gen Fujii, Michihiro Mutoh.
  • Organizer: Tenth AACR-JCA Joint Conference
  • Place of Presentation: Maui（USA)
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Minマウス腸ポリープからのデスモイド腫瘍細胞株樹立の試み (2015)
  • Author(s): 宮本真吾、武藤倫弘、尾沼若奈、藤井元、鱧屋隆博、高橋真美。
  • Organizer: 第26回日本消化器癌発生学会
  • Place of Presentation: 米子（鳥取）
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] Inhibition of intestinal polyp formation in Min mice by erythromycin. (2015)
  • Author(s): Miyamoto S, Fujii G, Komiya M, Takahashi M, Ishigamori R, Onuma W, Mutoh M.
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋（愛知）
  • Year and Date: 2015-10-08
• [Presentation] Citrus limonoid limonin suppressed intestinal polyp development in ApcMin/+ mice. (2015)
  • Author(s): Mutoh M, Miyamoto S, Komiya M, Ishigamori R, Imai T, Takahashi M, Fujii G
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋（愛知）
  • Year and Date: 2015-10-08
• [Presentation] Azoxymethane誘発マウス大腸aberrant crypt foci生成における低用量azoxymethane前日投与の影響 (2015)
  • Author(s): 長野愛矢、藤井 元、宮本真吾、中西るり、小宮雅美、三浦彩華、尾沼若奈、鱧屋隆博、高橋真美、今井俊夫、高橋 智、武藤倫弘
  • Organizer: がん予防学術大会
  • Place of Presentation: さいたま（埼玉）
  • Year and Date: 2015-06-05
• [Presentation] Irsogladine maleateによるマウス腸発がん抑制効果（第２報） (2015)
  • Author(s): 尾沼若奈、藤井 元、宮本真吾、中西るり、小宮雅美、三浦彩華、鱧屋隆博、高橋真美、今井俊夫、深井文雄、武藤倫弘
  • Organizer: がん予防学術大会
  • Place of Presentation: さいたま（埼玉）
  • Year and Date: 2015-06-05
• [Presentation] 胡麻成分Sesamolによる腸発がん抑制機構の解明（第２報） (2015)
  • Author(s): 宮本真吾、清水聡美、藤井 元、中西るり、小宮雅美、尾沼若奈、鱧屋隆博、高橋真美、矢野友啓、武藤倫弘
  • Organizer: がん予防学術大会
  • Place of Presentation: さいたま（埼玉）
  • Year and Date: 2015-06-05
• [Presentation] Suppressive effects of irsogladine, a gastric mucosal protectant, on intestinal polyp development in Apc-mutant Min mice. (2015)
  • Author(s): Mutoh M, Onuma W, Fujii G, Fukai F, Sasazuki S.
  • Organizer: Digestive Disease Week
  • Place of Presentation: Washington DC (USA)
  • Year and Date: 2015-05-16
  • Int'l Joint Research
• [Presentation] ゴマ由来成分セサモールによる腸発がん抑制機構 (2014)
  • Author(s): 清水聡美、石ヶ守 里加子、藤井元、高橋真美、中西るり、尾沼若奈、矢野友啓、武藤倫弘
  • Organizer: 第8回国際消化器病発生会議
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] Irsogladine maleateによるマウス腸発がん抑制効果 (2014)
  • Author(s): 尾沼若奈、藤井元、高橋真美、中西るり、石ヶ守 里加子、清水聡美、深井文雄、武藤倫弘
  • Organizer: 第8回国際消化器病発生会議
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] Inhibition of intestinal polyp formation in Min mice by acetazolamide. (2014)
  • Author(s): Mutoh M, Takahashi M, Ishigamori R, Shimizu S, Onuma W, Imai T, Fujii G.
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Sesamol suppresses COX-2 transcriptional activity via inhibition of NADPH oxidases in colon cancer cells. (2014)
  • Author(s): Shimizu S, Ishigamori R, Fujii G, Takahashi M, Onuma W, Yano T, Mutoh M.
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Long-term culture method for precancerous lesion-derived cells. (2014)
  • Author(s): Onuma W, Fujii G, Shimizu S, Ishigamori R, Takahashi M, Imai T, Fukai F, Mutoh M.
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Agoutiによるマウス膵臓発がん促進メカニズム (2014)
  • Author(s): 高橋真美、石ヶ守里加子、藤井元、武藤倫弘、今井俊夫
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 高脂肪食によるラット乳腺発がんの促進に対する細胞接着分子の関与 (2014)
  • Author(s): 今井俊夫、藤井元、武藤倫弘、高橋真美
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Effect of cytokines on human primary hepatic stellate cell. (2014)
  • Author(s): Asami Inoue, Kenichi Obayashi, Fumihiko Ogasawara, Anna Nakamura, Takato Ueno, Gen Fujii, Michihiro Mutoh, Satoru Kuhara, Kosuke Tashiro.
  • Organizer: the FEBS-EMBO 2014 congress
  • Place of Presentation: パリ
  • Year and Date: 2014-08-30 – 2014-09-04
• [Presentation] 腸前がん病変由来細胞の長期培養方法の確立 (2014)
  • Author(s): 尾沼 若奈、中西 るり、藤井 元、清水 聡美、石ヶ守 里加子、武藤 倫弘、高橋 真美、今井 俊夫、深井 文雄
  • Organizer: がん予防学術大会2014東京
  • Place of Presentation: 東京
  • Year and Date: 2014-06-13 – 2014-06-14
• [Presentation] ゴマ由来成分 sesamol によるアラキドン酸カスケード及びPGE2関連分子の抑制 (2014)
  • Author(s): 清水 聡美、 石ヶ守 里加子、 藤井 元、 小宮 雅美、 中西 るり、 尾沼 若奈、 矢野 友啓、 武藤 倫弘
  • Organizer: がん予防学術大会2014東京
  • Place of Presentation: 東京
  • Year and Date: 2014-06-13 – 2014-06-14
• [Presentation] ポンカン果皮粉末によるazoxymethane誘発F344ラット大腸aberrant crypt foci生成の抑制 (2014)
  • Author(s): 浅井大智、小林 亜里子、中西 るり、藤井 元、清水 聡美、尾沼 若奈、石ヶ守 里加子、武藤 倫弘、高橋 智、若林敬二
  • Organizer: がん予防学術大会2014東京
  • Place of Presentation: 東京
  • Year and Date: 2014-06-13 – 2014-06-14
• [Presentation] 高脂肪食による乳腺発がん促進に関与する発現遺伝子の探索 (2014)
  • Author(s): 今井 俊夫、打屋尚章、高橋真美、藤井 元、武藤倫弘
  • Organizer: がん予防学術大会2014東京
  • Place of Presentation: 東京
  • Year and Date: 2014-06-13 – 2014-06-14
• [Presentation] ラット若齢期乳腺に対する高脂肪食の影響と発がん促進 (2014)
  • Author(s): 今井俊夫、打屋尚章、藤井 元、武藤倫弘、高橋真美
  • Organizer: 第61回日本実験動物学会
  • Place of Presentation: 札幌
  • Year and Date: 2014-05-15 – 2014-05-17
• [Book] Critical Dietary Factors in Cancer Chemoprevention (2015)
  • Author(s): Miyamoto S, Fujii G, Komiya M, Terasaki M and Mutoh M
  • Total Pages: 373
  • Publisher: Springer Publishers
• [Book] 次世代のがん治療・診断のための研究開発～免疫療法・遺伝子治療・がん幹細胞～ (2015)
  • Author(s): 武藤倫弘、石川秀樹、藤井元、宮本真吾、若林敬二
  • Total Pages: 400
  • Publisher: 技術情報協会
• [Book] Critical Dietary Factors in Cancer Chemoprevention (2015)
  • Author(s): Miyamaoto S, FujiiG, Komiya M, Terasaki M, and Mutoh M
  • Publisher: Springer Publishers (Basel, Switzerland)