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Determining the driver gene for colon carcinogenesis accelerated by chronic inflammation

Research Project

Project/Area Number 17K08761
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionTottori University

Principal Investigator

OKADA Futoshi  鳥取大学, 医学部, 教授 (00250423)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords炎症発癌 / ドライバー遺伝子 / 大腸発癌 / 腸管発癌 / 炎症発がん / 大腸がん
Outline of Final Research Achievements

We investigated which genetic alterations observed in human colorectal carcinogenesis are critical in the inflammation-related bowel carcinogenesis. The inflammation was evoked by implantation of foreign substances such as plastic plate. Male mouse intestinal organoids with K-ras activation and APC knockdown were grew lethally in the inflammation formed in female nude mice. When an organoid obtained from a homozygous p53 gene-deficient mouse and implanted them into the inflammatory region, they formed fibrous tumors. Organoids obtained from a heterozygous p53 gene-deficient mouse, they did not grow under the inflammation. Organoid obtained from a p53 gene homozygous mouse with APC knockdown formed tumors in mice, however, the histological type were fibrous ones.

Academic Significance and Societal Importance of the Research Achievements

慢性炎症による大腸発癌のdriver遺伝子として,p53遺伝子に加えてどの大腸癌関連遺伝子が,どのような組合せで,真の“癌腫発生に必要なdriver遺伝子”となるのかを決定する.これにより,大腸の炎症発癌に対する新規の治療・予防のための標的遺伝子を明らかにすることができる.今後の炎症性腸疾患に対する創薬研究開発等への波及効果が望める.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2020 2019 2018 2017 Other

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) Remarks (1 results)

  • [Journal Article] Pretreatment with cilnidipine attenuates hypoxia/reoxygenation injury in HL-1 cardiomyocytes through enhanced NO production and action potential shortening2020

    • Author(s)
      Minato Hiroyuki、Hisatome Ichiro、Kurata Yasutaka、Notsu Tomomi、Nakasone Naoe、Ninomiya Haruaki、Hamada Toshihiro、Tomomori Takuya、Okamura Akihiro、Miake Junichiro、Tsuneto Motokazu、Shirayoshi Yasuaki、Endo Ryo、Otsuki Akihiro、Okada Futoshi、Inagaki Yoshimi
    • Journal Title

      Hypertension Research

      Volume: 43 Issue: 5 Pages: 380-388

    • DOI

      10.1038/s41440-019-0391-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-based diagnosis and treatment of metastatic human osteosarcoma2019

    • Author(s)
      Sasaki R, Osaki M, Okada F
    • Journal Title

      Cancers

      Volume: 11 Issue: 4 Pages: 553-553

    • DOI

      10.3390/cancers11040553

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and biological evaluation of glucose conjugated phthalocyanine as a second-generation photosensitizer.2019

    • Author(s)
      Uruma Y, Sivasany L, Yen PYM, Onuma K, Omura Y, Doe M, Osaki M, and Okada F.
    • Journal Title

      Bioorgan Med Chem

      Volume: 27 Issue: 15 Pages: 3279-3284

    • DOI

      10.1016/j.bmc.2019.06.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The circadian rhythm of bladder clock genes in the spontaneously hypersensitive rat.2019

    • Author(s)
      Kimura Y, Honda M, Sasaki R, Yumioka T, Iwamoto H, Tsounapi P, Morizane S, Hikita K, Osaki M, Okada F, and Takenaka A.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 12 Pages: e0227321-e0227321

    • DOI

      10.1371/journal.pone.0227321

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PITX1 protein interacts with ZCCHC10 to regulate hTERT mRNA transcription.2019

    • Author(s)
      Ohira T, Kojima H, Kuroda Y, Aoki S, Inaoka D, Osaki M, Wanibuchi H, Okada F, Oshimura M, Kugoh H.
    • Journal Title

      Plos one

      Volume: 12 Issue: 8 Pages: e0217605-e0217605

    • DOI

      10.1371/journal.pone.0217605

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bisphosphonates induced reactive oxygen species inhibit proliferation and migration of oral fibroblast: A pathogenesis of bisphosphonate-related osteonecrosis of the jaw.2019

    • Author(s)
      Taniguchi N, Osaki M, Onuma K, Ishikawa M, Ryoke K, Kotani I, and Okada F.
    • Journal Title

      J Periodontol

      Volume: in press Issue: 7 Pages: 947-955

    • DOI

      10.1002/jper.19-0385

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fascin protein stabilization by miR-146a implicated in the process of a chronic inflammation-related colon carcinogenesis model.2018

    • Author(s)
      Kanda Y, Kawaguchi T, Osaki M, OnumaK, Ochiya T, Kitagawa T and Okada F.
    • Journal Title

      Inflamm Res

      Volume: 67 Issue: 10 Pages: 839-846

    • DOI

      10.1007/s00011-018-1175-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ozone augments interleukin-8 production induced by ambient particulate matter.2018

    • Author(s)
      Kurai J, Onuma K, Sano H, Okada F and Watanabe M.
    • Journal Title

      Genes & Environment

      Volume: 40 Issue: 1 Pages: 14-14

    • DOI

      10.1186/s41021-018-0102-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SK-216, a Novel Inhibitor of Plasminogen Activator Inhibitor-1, Suppresses Lung Metastasis of Human Osteosarcoma2018

    • Author(s)
      Tsuge Minori、Osaki Mitsuhiko、Sasaki Ryo、Hirahata Mio、Okada Futoshi
    • Journal Title

      Int J Mol Sci

      Volume: 19 Issue: 3 Pages: 736-736

    • DOI

      10.3390/ijms19030736

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protoporphyrinogen oxidase is involved in the fluorescence intensity of 5-aminolevulinic acid-mediated laser-based photodynamic endoscopic diagnosis for early gastric cancer2018

    • Author(s)
      Kurumi Hiroki、Kanda Tsutomu、Kawaguchi Koichiro、Yashima Kazuo、Koda Hiroki、Ogihara Kumi、Matsushima Kayoko、Nakao Kazuhiko、Saito Hiroaki、Fujiwara Yoshiyuki、Osaki Mitsuhiko、Okada Futoshi、Isomoto Hajime
    • Journal Title

      Photodiagnosis Photodyn Ther

      Volume: S1572-1000(17) Pages: 1-2

    • DOI

      10.1016/j.pdpdt.2018.02.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protective Effects of Topiroxostat on an Ischemia-Reperfusion Model of Rat Hearts2018

    • Author(s)
      Tanno S. et al.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 4 Pages: 1101-1111

    • DOI

      10.1253/circj.CJ-17-1049

    • NAID

      130006528600

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysosome-associated membrane protein 2 (LAMP-2) expression induced by miR-194-5p down-regulation contributes to sunitinib resistance in human renal cell carcinoma cells.2017

    • Author(s)
      Yumioka T, Osaki M, Sasaki R, Yamaguchi N, Onuma K, Iwamoto H, Morizane S, Honda M, Takenaka A and Okada F.
    • Journal Title

      Oncol Lett

      Volume: 15 Pages: 893-900

    • DOI

      10.3892/ol.2017.7423

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of microRNAs involved in resistance to Sunitinib in renal cell carcinoma cells.2017

    • Author(s)
      Yamaguchi N, Osaki M, Onuma K, Yumioka T, Iwamoto H, Sejima T, Kugoh H, Takenaka A and Okada F.
    • Journal Title

      Anticancer Res

      Volume: 37 Issue: 6 Pages: 2985-2992

    • DOI

      10.21873/anticanres.11652

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction2017

    • Author(s)
      Kanda Y, Osaki M, Okada F.
    • Journal Title

      Int J Mol Sci

      Volume: 18 Issue: 4 Pages: 867-867

    • DOI

      10.3390/ijms18040867

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Design, synthesis, and biological evaluation of a highly water-soluble psoralen-based photosensitizer.2017

    • Author(s)
      Uruma Y, Nonomura T, Yen PYM, Edatani M, Yamamoto R, Onuma K and Okada F.
    • Journal Title

      Bioorgan Med Chem

      Volume: 25 Issue: 8 Pages: 2372-2377

    • DOI

      10.1016/j.bmc.2017.02.050

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amigo2-upregulation in Tumour Cells Facilitates Their Attachment to Liver Endothelial Cells Resulting in Liver Metastases2017

    • Author(s)
      Kanda Y, Osaki M, Onuma K, Sonoda A, Kobayashi M, Hamada J, Nicolson GL, Ochiya T, Okada F
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 43567-43567

    • DOI

      10.1038/srep43567

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] AMIGO2は肝血管内皮細胞への接着を介して大腸癌肝転移形成に関与する2019

    • Author(s)
      谷尾彬充,齊藤博昭,植嶋千尋,多田陽一郎,山本 学,藤原義之,尾﨑充彦,岡田 太
    • Organizer
      第28回日本がん転移学会学術集会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 骨肉腫の肺転移に対する予防標的分子の探索2019

    • Author(s)
      尾﨑充彦,岡田 太
    • Organizer
      第26回日本がん予防学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 血管内皮細胞におけるMTA1発現の抑制はS100A4発現抑制を介した血管新生阻害による抗腫瘍効果を引き起こす.2018

    • Author(s)
      石川瑞穂,尾﨑充彦,山岸 誠,小沼邦重,井藤久雄,岡田 太,遠藤英也.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 炎症による発がん・悪性化の発酵玄米食品による予防2018

    • Author(s)
      小沼邦重,尾﨑充彦,鹿内正孝,小林 博,岡田 太.
    • Organizer
      第25回日本がん予防学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肝転移に必要な新規分子の同定2017

    • Author(s)
      神田裕介,小沼邦重,園田彩奈,尾崎充彦,岡田 太
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん予防基礎研究者が思う出口戦略2017

    • Author(s)
      岡田 太
    • Organizer
      第24回日本がん予防学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝転移のドライバー分子としてのAmigo2の同定2017

    • Author(s)
      神田裕介,小沼邦重,園田彩奈,濱田淳一,小林正伸,尾﨑充彦,岡田 太
    • Organizer
      第26回日本がん転移学会学術集会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 血管内皮細胞に発現するMTA1は血管新生阻害の標的分子となりうる2017

    • Author(s)
      石川瑞穂,尾﨑充彦,小沼邦重,神田裕介,岡田 太
    • Organizer
      第26回日本がん転移学会学術集会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] MTA1 expressed in endothelial cells is a candidate target molecule for inhibiting angiogenesis2017

    • Author(s)
      石川瑞穂,尾﨑充彦,山岸 誠,岡田 太,遠藤英也
    • Organizer
      第9回日本RNAi研究会・第4回日本細胞外小胞学会
    • Related Report
      2017 Research-status Report
  • [Remarks] 鳥取大学医学部病態生化学分野

    • URL

      https://byoutaiseikagaku.jimdo.com/

    • Related Report
      2018 Research-status Report 2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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