Identification of driver genes in inflammation-related intestinal tract carcinogenesis

• Project/Area Number: 26460472
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tottori University
• Principal Investigator: Okada Futoshi 鳥取大学, 医学部, 教授 (00250423)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症発癌 / 慢性炎症 / ドライバー遺伝子 / 発癌

Outline of Final Research Achievements

I tried to determine driver genes in inflammation-related intestinal tract carcinogenesis by using three-dimentional tissue culture system. Solid surface foreign-body such as plastic plate was used to induce inflammation. Reconstitive intestinal tract obtained from K-ras mutant mice formed dormant tumors under chronic inflammation in mice. Intestinal tissue obtained from p53-/- mice developed lethal tumors under chronic inflammation; however, the tissue spontaneously regressed under acute inflammation. Moreover, intestinal tissue obtained from p53+/- mice does not form tumors in the chronic inflammatory environment. I found that p53 gene mutation has a role in the development of inflammation-related intestinal carcinogenesis.

Research Products

• [Journal Article] IL-17A-producing CD30(+) Vδ1 T cells drive inflammation-induced cancer progression. (2016)
  • Author(s): Kimura Y, Nagai N, Tsunekawa N, Sato-Matsushita M, Yoshimoto T, Cua DJ, Iwakura Y, Yagita H, Okada F, Tahara H, Saiki I, Irimura T, Hayakawa Y.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 9 Pages: 1206-14
  • DOI: 10.1111/cas.13005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The SOD1 transgene expressed in erythroid cells alleviates fatal phenotype in congenic NZB/NZW-F1 mice (2016)
  • Author(s): Otsuki N, Konno T, Kurahashi T, Suzuki S, Lee J, Okada F, Iuchi Y, Homma T and Fujii J
  • Journal Title: Free Radic Res Volume: 50 Pages: 793-800
  • Peer Reviewed / Open Access
• [Journal Article] PAI-1, a target gene of miR-143, regulates invasion and metastasis by upregulating MMP-13 expression of human osteosarcoma. (2016)
  • Author(s): Hirahata M, Osaki M, Kanda Y, Sugimoto Y, Yoshioka Y, Kosaka N, Takeshita F, Fujiwara T, Kawai A, Ito H, Ochiya T, Okada F.
  • Journal Title: Cancer Med Volume: - Issue: 5 Pages: 892-902
  • DOI: 10.1002/cam4.651
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PITX1 is a possible predictor of the response to chemotherapy in head and neck squamous cell carcinoma (2016)
  • Author(s): Takenobu M, Osaki M, Fujiwara K, Fukuhara T, Kitano H, Kugoh H and Okada F
  • Journal Title: Mol Clin Oncol Volume: 5 Issue: 1 Pages: 89-94
  • DOI: 10.3892/mco.2016.880
  • Peer Reviewed / Open Access
• [Journal Article] Host stromal versican is essential for cancer-associated fibroblast function to inhibit cancer growth. (2015)
  • Author(s): Fanhchaksai K, Okada F, Nagai N, Pothacharoen P, Kongtawelert P, Hatano S, Makino S, Nakamura T and Watanabe H
  • Journal Title: International Journal of Cancer Volume: 138 Issue: 3 Pages: 630-641
  • DOI: 10.1002/ijc.29804
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fermented brown rice and rice bran with Aspergillus oryzae (FBRA) prevents inflammation-related carcinogenesis in mice, by inhibiting infiltration of inflammatory cells (2015)
  • Author(s): Onuma K, Kanda Y, Suzuki Ikeda S, Sakaki R, Nonomura T, Kobayashi M, Osaki M, Shikanai M, Kobayashi H and Okada F.
  • Journal Title: Nutrients Volume: 7 Issue: 12 Pages: 10237-10250
  • DOI: 10.3390/nu7125531
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inflammation-related tumor progression in murine fibrosarcoma exhibited over-expression of sex-determining region Y-box 2 (Sox2) compared to parental regressor cells (2015)
  • Author(s): Kuramitsu Y, Tanaka I, Wang Y, Okada F, Tokuda K, Kitagawa T, Akada J and Nakamura K
  • Journal Title: Anticancer Res Volume: 35 Pages: 3217-3221
  • Peer Reviewed
• [Journal Article] Cystathionine is a novel substrate of cystine/glutamate transporter: implications for immune function (2015)
  • Author(s): Kobayashi, S., Sato, M., Kasakoshi, T., Tsutsui, T., Sugimoto, M., Osaki, M., Okada, F., Igarashi, K., Hiratake, J., Homma, T., Conrad, M., Fujii, J., Soga, T., Bannai, S., Sato, H.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 14 Pages: 8778-8788
  • DOI: 10.1074/jbc.m114.625053
  • Peer Reviewed / Open Access
• [Journal Article] Inhibitor of apoptosis proteins (IAPs) may be effective therapeutic targets for treating endometriosis (2015)
  • Author(s): Ueagaki T, Taniguchi F, Nakamura K, Osaki M, Okada F, Yamamoto O, Harada T
  • Journal Title: Hum Reprod Volume: 30 Issue: 1 Pages: 149-158
  • DOI: 10.1093/humrep/deu288
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MicroRNA therapy targeting cancer stem cells: A new paradigm for cancer treatment and prevention of tumor recurrence (2015)
  • Author(s): Osaki M, Okada F and Ochiya T
  • Journal Title: Ther Deliv Volume: 6 Issue: 3 Pages: 323-337
  • DOI: 10.4155/tde.14.122
  • Peer Reviewed
• [Journal Article] Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis (2014)
  • Author(s): Kanda Y, Kawaguchi T, Kuramitsu Y, Kitagawa T, Kobayashi T, Takahashi N, Tazawa H, Habelhah H, Hamada J-I, Kobayashi M, Hirahata M, Onuma K, Osaki M, Nakamura K, Kitagawa T, Hosokawa M and Okada F.
  • Journal Title: Proteomics Volume: 14 Issue: 9 Pages: 1031-1041
  • DOI: 10.1002/pmic.201300414
  • Peer Reviewed
• [Journal Article] Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma (2014)
  • Author(s): Iwamoto H, Kanda Y, Sejima T, Osaki M, Okada F and Takenaka A.
  • Journal Title: Int J Oncol Volume: 44 Issue: 1 Pages: 53-58
  • DOI: 10.3892/ijo.2013.2169
  • Peer Reviewed
• [Journal Article] Proteomic analysis indicates that overexpression and nuclear translocation of lactoylglutathione lyase (GLO1) is associated with tumor progression in murine fibrosarcoma (2014)
  • Author(s): Wang Y, Kuramitsu Y, Tokuda K, Okada F, Baron B, Akada J, Kitagawa T, Nakamura K.
  • Journal Title: Electrophoresis Volume: 印刷中 Issue: 15 Pages: 3661-3665
  • DOI: 10.1002/elps.201300497
  • Peer Reviewed
• [Journal Article] Circulating miRNAs in drug safety assessment for hepatic and cardiovascular toxicity: the latest biomarker frontier? (2014)
  • Author(s): Osaki M, Kosaka N, Okada F and Ochiya T
  • Journal Title: Mol Diagn Ther Volume: 18 Issue: 2 Pages: 121-126
  • DOI: 10.1007/s40291-013-0065-0
  • Peer Reviewed
• [Journal Article] PITX1 is reliable biomarker for predicting prognosis in patients with oral epithelial dysplasia (2014)
  • Author(s): Nakabayashi M, Osaki M, Kodani I, Okada F, Ryoke K, Oshimura M, Ito H and Kugoh H
  • Journal Title: Oncol Lett Volume: 7 Pages: 750-754
  • Peer Reviewed
• [Journal Article] Inflammation-related carcinogenesis: current findings in epidemiological trends, causes and mechanisms (2014)
  • Author(s): Okada F
  • Journal Title: Yonago Acta Med Volume: 57 Pages: 65-72
  • NAID: 120005463510
  • Peer Reviewed
• [Presentation] 異物誘発炎症による発癌・悪性化進展 (2016)
  • Author(s): 岡田 太
  • Organizer: 第25回日本がん転移学会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2016-07-21
• [Presentation] 炎症発がん予防への実験的挑戦 (2016)
  • Author(s): 岡田 太
  • Organizer: 第23回日本がん予防学会総会
  • Place of Presentation: 名古屋大学大学院医学系研究科基礎研究棟第４講義室（愛知県名古屋市）
  • Year and Date: 2016-07-01
• [Presentation] ヒト大腸腺腫細胞の慢性炎症による癌化機構の解析 (2015)
  • Author(s): 佐々木 諒，河口徳一，神田裕介，平畑美緒，小沼邦重，尾﨑充彦，北川知行，岡田 太
  • Organizer: 第26回日本消化器癌発生学会総会
  • Place of Presentation: 米子全日空ホテル（鳥取県米子市）
  • Year and Date: 2015-11-19
• [Presentation] 慢性炎症を背景としたヒト大腸発癌を規定するマイクロRNAの探索 (2015)
  • Author(s): 神田裕介，佐々木 諒，平畑美緒，小沼邦重，尾﨑充彦，河口徳一，北川知行，岡田 太
  • Organizer: 第7回日本RNAi研究会
  • Place of Presentation: グランドプリンスホテル広島（広島県広島市）
  • Year and Date: 2015-08-26
• [Presentation] 発酵玄米による炎症細胞の浸出抑制を介したマウス炎症発癌の予防 (2015)
  • Author(s): 神田裕介，平畑美緒，小沼邦重，尾﨑充彦，小坂弘明，鹿内正孝，小林 博，岡田 太
  • Organizer: 第22回日本がん予防学会総会
  • Place of Presentation: ラフレさいたま （埼玉県さいたま市）
  • Year and Date: 2015-06-05
• [Presentation] 転移先臓器の指向性を規定する分子探索のためのがん細胞株樹立の試み (2015)
  • Author(s): 神田裕介，平畑美緒，小沼邦重，尾﨑充彦，岡田 太
  • Organizer: 平成26年度文部科学省科学研究費補助金新学術領域研究「がん研究分野の特性等を踏まえた支援活動」平成26年度「個体レベルでのがん研究支援活動」ワークショップ
  • Place of Presentation: 琵琶湖ホテル（大津市）
  • Year and Date: 2015-02-05 – 2015-02-06
• [Presentation] ヒト大腸腺腫細胞の大腸癌細胞への進展における慢性炎症由来一酸化窒素の証明とfascinの同定 (2014)
  • Author(s): 神田裕介，河口徳一，田澤 大，平畑美緒，小沼邦重，北川知行，尾﨑充彦，岡田 太
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 慢性炎症に伴う一酸化窒素生成はヒト大腸腺腫細胞から大腸癌細胞を誘導する (2014)
  • Author(s): 田澤 大，河口徳一，蔵満保宏，神田裕介，尾崎充彦，藤原俊義，北川知行，岡田 太．
  • Organizer: 第14回日本NO学会学術集会
  • Place of Presentation: ホテルニューオータニ佐賀（佐賀市）
  • Year and Date: 2014-05-16 – 2014-05-17
• [Remarks] 鳥取大学医学部病態生化学分野
  • URL: http://byoutaiseikagaku.jimdo.com/