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Elucidation of the mechanism for regulating microenvironment and cancer development by mutant KRAS

Research Project

Project/Area Number 15K06847
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionFukuoka University

Principal Investigator

Tsunoda Toshiyuki  福岡大学, 医学部, 准教授 (70444817)

Co-Investigator(Renkei-kenkyūsha) KOTAKE Yojiro  近畿大学, 産業理工学部, 准教授 (90531963)
SHIRASAWA Senji  福岡大学, 医学部, 教授 (10253535)
SASAKI Takamitsu  福岡大学, 医学部, 講師 (00382284)
Research Collaborator HIROSE Yumiko  
ISOYAMA Chiyo  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsKRAS / 3次元培養 / 低分子化合物 / 3次元培養 / 化合物スクリーニング
Outline of Final Research Achievements

In this study, we tried to find the compounds through the elucidation of the mechanism for regulating microenvironment and cancer development by the mutated KRAS. Three-dimensional (3D) floating culture system using the isogenic cell lines expressing wild-type KRAS or mutant (mt) KRAS were established from HKe3 cells, derived from colorectal cancer (CRC) HCT116 cells and disrupted at mtKRAS gene, and employed for the drug screening. During screening for 400 core-compounds from natural products which selectively suppress growth of human CRC spheroids with mtKRAS, we found 121 derivatives from 8 core-compounds and obtain a patent as inhibitors for signalling pathway associated with mtKRAS.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (5 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (8 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Glasgow(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Glasgow University/College of Medical/Department of Molecular Pharmacology(英国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Blokhin Cancer Center(ロシア連邦)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Glasgow University/College of Medical/Department of Molecular Pharmacology(英国)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Blokhin Cancer Center(ロシア連邦)

    • Related Report
      2015 Research-status Report
  • [Journal Article] The Long Noncoding RNA OIP5-AS1 Is Involved in the Regulation of Cell Proliferation2018

    • Author(s)
      Naemura M, Kuroki M, Tsunoda T, Arikawa N, Sawata Y, Shirasawa S, Kotake Y.
    • Journal Title

      Anticancer Research

      Volume: 38 Issue: 1 Pages: 77-81

    • DOI

      10.21873/anticanres.12194

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apremilast Induces Apoptosis of Human Colorectal Cancer Cells with Mutant KRAS2017

    • Author(s)
      Nishi K, Luo H, Ishikura S, Doi K, Iwaihara Y, Wills L, Baillie GS, Sakata T, Shirasawa S, Tsunoda T.
    • Journal Title

      Anticancer Research

      Volume: 37 Issue: 7 Pages: 3833-3839

    • DOI

      10.21873/anticanres.11762

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Alpha-kinase 2 Gene Variant Disrupts Filamentous Actin Localization in the Surface Cells of Colorectal Cancer Spheroids2017

    • Author(s)
      12.Nishi K, Luo H, Nakabayashi K, Doi K, Ishikura S, Iwaihara Y, Yoshida Y, Tanisawa K, Arai T, Mori S, Sawabe M, Muramatsu M, Tanaka M, Sakata T, Shirasawa S, Tsunoda T
    • Journal Title

      Anticancer Research

      Volume: 37 Issue: 7 Pages: 3855-3862

    • DOI

      10.21873/anticanres.11765

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ROS-induced cleavage of NHLRC2 by caspase-8 leads to apoptotic cell death in the HCT116 human colon cancer cell line2017

    • Author(s)
      Nishi Kensuke、Iwaihara Yuri、Tsunoda Toshiyuki、Doi Keiko、Sakata Toshifumi、Shirasawa Senji、Ishikura Shuhei
    • Journal Title

      Cell Death & Disease

      Volume: 8 Issue: 12 Pages: 3218-3231

    • DOI

      10.1038/s41419-017-0006-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ANRIL regulates the proliferation of human colorectal cancer cells in both two- and three-dimensional culture2016

    • Author(s)
      Naemura M, Tsunoda T, Inoue Y, Okamoto H, Shirakawa S, and Kotake Y
    • Journal Title

      Molecular and cellular biochemistry.

      Volume: 412 Issue: 1-2 Pages: 141-146

    • DOI

      10.1007/s11010-015-2618-5

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of New Congeners of 1-methyl-3-aminoisoquinolines, Evaluation of Their Cytotoxic Activity, In Silico and In Vitro Study of Their Molecular Targets as PDE4B.2016

    • Author(s)
      Lapa GB, Tsunoda T, Shirasawa S, Baryshnikova MA, Evseev GG, Afanasyeva DA, Chigorina EA.
    • Journal Title

      Chem Biol Drug Des.

      Volume: 87(4) Issue: 4 Pages: 575-82

    • DOI

      10.1111/cbdd.12691

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Nuclear Zinc Finger Protein Zfat Maintains FoxO1 Protein Levels in Peripheral T Cells by Regulating the Activities of Autophagy and the Akt Signaling Pathway.2016

    • Author(s)
      Ishikura S, Iwaihara Y, Tanaka Y, Luo H, Nishi K, Doi K, Koyanagi M, Okamura T, Tsunoda T, Shirasawa S.
    • Journal Title

      J Biol Chem.

      Volume: 291(29) Issue: 29 Pages: 15282-91

    • DOI

      10.1074/jbc.m116.723734

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Resveratrol Overcomes Cellular Resistance to Vemurafenib Through Dephosphorylation of AKT in BRAF-mutated Melanoma Cells.2016

    • Author(s)
      Luo H, Umebayashi M, Doi K, Morisaki T, Shirasawa S, Tsunoda T.
    • Journal Title

      Anticancer Res.

      Volume: 36(7) Pages: 3585-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular mechanisms of transcriptional regulation by the nuclear zinc-finger protein Zfat in T cells.2016

    • Author(s)
      Ishikura S, Tsunoda T, Nakabayashi K, Doi K, Koyanagi M, Hayashi K, Kawai T, Tanaka Y, Iwaihara Y, Luo H, Nishi K, Okamura T, Shirasawa S.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1859(11) Issue: 11 Pages: 1398-1410

    • DOI

      10.1016/j.bbagrm.2016.08.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Establishment of a Three-dimensional Floating Cell Culture System for Screening Drugs Targeting KRAS-mediated Signaling Molecules.2015

    • Author(s)
      Tsunoda T, Ishikura S, Doi K, Iwaihara Y, Hidesima H, Luo H, Hirose Y, Shirasawa S.
    • Journal Title

      Anticancer Res.

      Volume: 35(8) Pages: 4453-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Marked Reduction in FoxO1 Protein by its Enhanced Proteasomal Degradation in Zfat-deficient Peripheral T-Cells.2015

    • Author(s)
      Iwaihara Y, Ishikura S, Doi K, Tsunoda T, Fujimoto T, Okamura T, Shirasawa S.
    • Journal Title

      Anticancer Res.

      Volume: 35(8) Pages: 4419-23

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] PDE4 阻害剤アプレミラストは変異KRAS 陽性大腸癌細胞株にアポトーシスを誘導する.2017

    • Author(s)
      角田俊之, 白澤専二
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 三次元共培養法を用いた、KRAS変異大腸癌に対するCytokine-activated killer細胞と免疫チェックポイント阻害薬併用効果の検討2017

    • Author(s)
      西 憲祐、羅 昊、梅林 雅代、森崎 隆、白澤 専二、角田 俊之
    • Organizer
      第21回バイオ治療法研究会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] PDE4阻害剤Apremilastの抗腫瘍効果の検討2016

    • Author(s)
      羅 昊、西 憲祐、角田 俊之、白澤 専二
    • Organizer
      第20回バイオ治療法研究会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2016-12-10
    • Related Report
      2016 Research-status Report
  • [Presentation] ALPK2のQ1853E変異は大腸癌の造腫瘍活性を促進する2016

    • Author(s)
      西 憲祐、羅 昊、角田 俊之、白澤 専二
    • Organizer
      第20回バイオ治療法研究会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2016-12-10
    • Related Report
      2016 Research-status Report
  • [Presentation] レスベラトロールはAKTを脱リン酸化しBRAF変異メラノーマのベムラフェニブ耐性化を抑制する2016

    • Author(s)
      角田俊之, 白澤専二
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 3次元特異的変異KRAS制御分子KRAPの造腫瘍メカニズムの解明2015

    • Author(s)
      角田俊之,土井佳子, 白澤専二
    • Organizer
      第19回バイオ治療法研究会学術集会
    • Place of Presentation
      東京 東京理科大学 森戸記念館
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 大腸癌造腫瘍能におけるALPK2遺伝子変異の機能的解析2015

    • Author(s)
      角田俊之, 新井冨生、森聖二郎、沢辺元司、村松正明、田中雅嗣、白澤専二
    • Organizer
      日本人類遺伝学会第60回大会
    • Place of Presentation
      東京 新宿 京王プラザホテル
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] 変異KRAS制御シグナル関連分子を標的とする薬剤をスクリーニングするための3次元浮遊培養システムの構築2015

    • Author(s)
      角田俊之, 白澤専二
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Remarks] 福岡大学医学部 細胞生物学教室

    • URL

      http://www.med.fukuoka-u.ac.jp/cellbio/top.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] Butterfield Awards

    • URL

      http://www.gla.ac.uk/researchinstitutes/icams/staff/georgebaillie/#/grants

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Patent(Industrial Property Rights)] 変異KRAS関連シグナル阻害用組成物2017

    • Inventor(s)
      白澤専二、角田俊之
    • Industrial Property Rights Holder
      白澤専二、角田俊之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-140139
    • Filing Date
      2017
    • Acquisition Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2022-06-16  

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