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Development of novel microRNA-based therapy against KRAS/BRAF-mutant colorectal cancer

Research Project

Project/Area Number 25462057
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionOkayama University

Principal Investigator

TAZAWA HIROSHI  岡山大学, 大学病院, 助教 (90415513)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsマイクロRNA / 大腸癌 / KRAS / BRAF / EGFR
Outline of Final Research Achievements

KRAS/BRAF-mutant colorectal cancer is an intractable disease that frequently shows the refractory to chemotherapy, recurrence and metastatic progression. Since EGFR signaling pathway is constitutively activated in KRAS/BRAF-mutant colorectal cancer, the development of novel therapy for strongly suppressing EGFR signaling pathway is important issue. Here we show that oncolytic adenoviruses have profound antitumor effect through activation of EGFR-suppressive microRNA and induction of apoptosis- and autophagy-related cell death against KRAS/BRAF-mutant colorectal cancer.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (22 results)

All 2015 2014 2013

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Acknowledgement Compliant: 3 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.2015

    • Author(s)
      Kikuchi S, et al.
    • Journal Title

      Molecular Therapy

      Volume: 23 Issue: 3 Pages: 501-509

    • DOI

      10.1038/mt.2014.244

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.2015

    • Author(s)
      Kikuchi S, Kishimoto H, Tazawa H, Hashimoto Y, Kuroda S, Nishizaki M, Nagasaka T, Shirakawa Y, Kagawa S, Urata Y, Hoffman RM, Fujiwara T.
    • Journal Title

      Mol Ther.

      Volume: 23(3) Issue: 4 Pages: 501-509

    • DOI

      10.1136/gutjnl-2014-306957

    • NAID

      120005537574

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells2015

    • Author(s)
      Shimoyama K, Kagawa S, Ishida M, Watanabe S, Noma K, Takehara K, Tazawa H, Hashimoto Y, Tanabe S, Matsuoka J, Kobayashi H, Fujiwara T
    • Journal Title

      Breast Cancer Reseach and Treatment

      Volume: 149 Issue: 3 Pages: 597-605

    • DOI

      10.1007/s10549-015-3265-y

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional gelfoam histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging2015

    • Author(s)
      Yano S, Miwa S, Mii S, Hiroshima Y, Uehara F, Kishimoto H, Tazawa H, Zhao M, Bouvet M, Fujiwara T, Hoffman RM
    • Journal Title

      Cell Cycle

      Volume: 14 Issue: 6 Pages: 808-819

    • DOI

      10.1080/15384101.2014.1000685

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Experimental curative fluorescence-guided surgery of highly-invasive glioblastoma multiforme selectively labeled with a killer-reporter adenovirus2015

    • Author(s)
      Yano S, Miwa S, Kishimoto H, Toneri M, Hiroshima Y, Yamamoto M, Bouvet M, Urata Y, Tazawa H, Kagawa S, Fujiwara T, Hoffman RM
    • Journal Title

      Mol Ther

      Volume: 23 Issue: 7 Pages: 1182-1188

    • DOI

      10.1038/mt.2015.63

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma2015

    • Author(s)
      Yano S, Miwa S, Kishimoto H, Uehara F, Tazawa H, Toneri M, Hiroshima Y, Yamamoto M, Urata Y, Kagawa S, Bouvet M, Fujiwara T
    • Journal Title

      Oncotarget

      Volume: 6 Pages: 13133-13148

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery.2015

    • Author(s)
      Yano S, Hiroshima Y, Maawy A, Kishimoto H, Suetsugu A, Miwa S, Toneri M, Yamamoto M, Katz MH, Fleming JB, Urata Y, Tazawa H, Kagawa S, Bouvet M, Fujiwara T, Hoffman RM.
    • Journal Title

      Cancer Gene Ther

      Volume: 22 Issue: 7 Pages: 344-50

    • DOI

      10.1038/cgt.2015.26

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Genetic and epigenetic alterations of netrin-1 receptors in gastric cancer with chromosomal instability.2015

    • Author(s)
      Toda K, Nagasaka T, Umeda Y, Tanaka T, Kawai T, Fuji T, Taniguchi F, Yasui K, Kubota N, Takehara Y, Tazawa H, Kagawa S, Sun DS, Nishida N, Goel A, Fujiwara T.
    • Journal Title

      Clin Epigenetics

      Volume: 7 Issue: 1 Pages: 73-73

    • DOI

      10.1186/s13148-015-0096-y

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Invading cancer cells are predominantly in G0/G1 resulting in chemoresistance demonstrated by real-time FUCCI imaging2014

    • Author(s)
      Yano S, Miwa S, Mii S, Hiroshima Y, Uehara F, Yamamoto M, Kishimoto H, Tazawa H, Bouvet M, Fujiwara T, Hoffman RM
    • Journal Title

      Cell Cycle

      Volume: 13 Issue: 6 Pages: 953-960

    • DOI

      10.4161/cc.27818

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chronic inflammation-derived nitric oxide causes conversion of human colonic adenoma cells into adenocarcinoma cells2013

    • Author(s)
      Tazawa H, Kawaguchi T, Kobayashi T, Kuramitsu Y, Wada S, Satomi Y, Nishino H, Kobayashi M, Kanda Y, Osaki M, Kitagawa T, Hosokawa M and Okada F
    • Journal Title

      Exp Cell Res

      Volume: 319 Issue: 18 Pages: 2835-2844

    • DOI

      10.1016/j.yexcr.2013.08.006

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent cancer stem-like cells into S/G2/M-phases.2013

    • Author(s)
      Yano S, Tazawa H, Hashimoto Y, Shirakawa Y, Kuroda S, Nishizaki M, Kishimoto H, Uno F, Nagasaka T, Urata Y, Kagawa S, Hoffman RM, Fujiwara T
    • Journal Title

      Clin Cancer Res

      Volume: 19 Issue: 23 Pages: 6495-6505

    • DOI

      10.1158/1078-0432.ccr-13-0742

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advances in adenovirus-mediated p53 cancer gene therapy.2013

    • Author(s)
      Tazawa H, Kagawa S, Fujiwara T
    • Journal Title

      Expert opinion on biological therapy.

      Volume: 13 Issue: 11 Pages: 1569-1583

    • DOI

      10.1517/14712598.2013.845662

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oncolytic adenovirus-induced autophagy: tumor-suppressive effect and molecular basis2013

    • Author(s)
      Tazawa H, Kagawa S, Fujiwara T
    • Journal Title

      Acta Medica Okayama

      Volume: 67 Pages: 333-342

    • NAID

      120005353344

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] KRAS/BRAF変異を持つ大腸癌に対する新たな腫瘍融解ウイルス療法の開発2015

    • Author(s)
      田村周太、田澤 大、堀 直人、國府島 健、菊地覚次、黒田新士、岸本浩行、永坂岳司、西崎正彦、浦田泰生、香川俊輔、藤原俊義
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Preclinical evaluation of tumor-specific oncolytic virotherapy against human colorectal cancer cells with different KRAS/BRAF mutation and microsatellite stability2015

    • Author(s)
      Tamura S, Tazawa H, Hori N, Koujima T, Kikuchi S, Kuroda S, Kishimoto H, Nagasaka T, Nishizaki M, Urata Y, Kagawa S, Fujiwara T
    • Organizer
      第21回日本遺伝子治療学会
    • Place of Presentation
      大阪
    • Year and Date
      2015-07-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Companion diagnostics-based telomerase-specific oncolytic virotherapy: preclinical evaluation in human colorectal cancer cell lines differentially affected in the RAS/RAF/MEK signaling pathway2015

    • Author(s)
      Tamura S, Tazawa H, Hori N, Koujima T, Kikuchi S, Kuroda S, Kishimoto H, Nagasaka T, Nishizaki M, Urata Y, Kagawa S, Fujiwara T
    • Organizer
      106th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cytotoxic effect of photosensitive fluorescent protein KillerRed-expressing adenovirus against human cancer cells2013

    • Author(s)
      Takehara K, Tazawa H, Hashimoto Y, Kishimoto H, Narii N, Mizuguchi H, Fujiwara T
    • Organizer
      104th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Telomerase-specific oncolytic adenovirus OBP-301 kills quiescent peritonially disseminated cancer cells2013

    • Author(s)
      Yano S, Tazawa H, Kishimoto H, Fujiwara T, Hoffman RM
    • Organizer
      104th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel adenovirus-based CTC detection technique and its clinical applications2013

    • Author(s)
      Tazawa H, Takakura M, Katagiri N
    • Organizer
      第19回日本遺伝子治療学会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumor-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression2013

    • Author(s)
      Tazawa H, Yamasaki Y, Hashimoto Y, Kuroda S, Yano S, Yoshida R, Uno F, Mizuguchi H, Ohtsuru A, Urata Y, Kagawa S, Fujiwara T
    • Organizer
      第19回日本遺伝子治療学会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
  • [Presentation] 腫瘍融解ウイルス療法におけるE2F1誘導性マイクロRNAの腫瘍抑制的機能2013

    • Author(s)
      田澤 大、長谷井 嬢、大西哲平、矢野修也、香川俊輔、藤原俊義
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Book] Tumor Suppressor Genes: Functions, Regulation and Health Effects2013

    • Author(s)
      Tazawa H, Kagawa S, Fujiwara T
    • Total Pages
      373
    • Publisher
      Nova Science Publishers
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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