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Development of YB-1-silencing miRNA/ decoy gene therapy against intractable solid tumor to regulate malignant microcircumstances

Research Project

Project/Area Number 24390322
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

NAKANO Kenji  九州大学, 先端融合医療レドックスナビ研究拠点, 教授 (00315061)

Co-Investigator(Kenkyū-buntansha) KATANO Mitsuo  九州大学, 大学院医学研究院, 教授 (10145203)
KATAOKA Kazunori  東京大学, 大学院工学研究科, 教授 (00130245)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
KeywordsYB-1 / miRNA / デコイ / 癌微小環境 / 血管新生 / 遺伝子治療
Outline of Final Research Achievements

The purpose of this study is to develop YB-1 silencing miRNA/ decoy gene therapy against intractable solid tumors to regulate tumor angiogenesis. Block/homo-polyplex micelles, which encapsulate YB-1 miRNA/decoy expression plasmid with and without exportin-5 (Xpo-5) and argonaoute-2 (Ago-2) plasmids, were intraperitoneally administered in nude mice harboring disseminated pancreatic cancer. The disseminated tumors were inhibited in the YB-1 miRNA/decoy alone and the combination treatment groups compared with the controls, but there was no significant prolongation of survival between the treatment and control groups. The microvascular density was decreased in tumor tissues treated with miRNA/decoy compared with the controls. However, the localization of micelles was limitedlly detected in the peripheral area of tumor tissues. These results suggest that YB-1 silencing is promising strategy for antiangiogenesis treatment and more efficient transduction devices may resolve the issues.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (22 results)

All 2015 2014 2013 2012

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) Book (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Feasibility of a subcutaneously administered block/homo-mixed polyplex micelle as a carrier for DNA vaccination in a mouse tumor model.2015

    • Author(s)
      Cui L, Osada K, Imaizumi A, Kataoka K, Nakano K
    • Journal Title

      J Control Release

      Volume: 206 Pages: 220-231

    • DOI

      10.1016/j.jconrel.2015.03.029

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intraperitoneal transduction of tumor-associated antigen, CD40L and GM-CSF genes by polyplex micelle elicits vaccine effect in mouse tumor models.2014

    • Author(s)
      Furugaki K, Cui L, Kunisawa Y, Shinkai K, Tanaka M, Kataoka K, Nakano K
    • Journal Title

      Plos One

      Volume: 9(7) Issue: 7 Pages: e101854-e101854

    • DOI

      10.1371/journal.pone.0101854

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer.2014

    • Author(s)
      Matsushita S, Onishi H, Nakano K, Nagamatsu I, Imaizumi A, Hattori M, Oda Y, Tanaka M, Katano M.
    • Journal Title

      Cancer Sci

      Volume: 105(3) Issue: 3 Pages: 272-280

    • DOI

      10.1111/cas.12354

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reoxygenation from chronic hypoxia promotes metastatic processes in pancreatic cancer through the Hedgehog signaling.2014

    • Author(s)
      Morifuji Y, Onishi H, Iwasaki H, Imaizumi A, Nakano K, Tanaka M, Katano M.
    • Journal Title

      Cancer Sci

      Volume: 105(3) Issue: 3 Pages: 324-333

    • DOI

      10.1111/cas.12348

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Notch4 is a potential therapeutic target for triple-negative breast cancer.2014

    • Author(s)
      Nagamatsu I, Onishi H, Matsushita S, Kubo M, Kai M, Imaizumi A, Nakano K, Hattori M, Oda Y, Tanaka M, Katano M.
    • Journal Title

      Anticancer Res

      Volume: 34 Pages: 69-80

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hedgehog G113 act ivator signal augments tumorigenicity of colorectal cancer via up-regulation of adherence-related genes.2013

    • Author(s)
      Iwasaki H. Katano M, et al.
    • Journal Title

      Cancer Sci

      Volume: 104 (3) Issue: 3 Pages: 328-336

    • DOI

      10.1111/cas.12073

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and cynomolgus monkeys.2013

    • Author(s)
      Ohgidani M, Furugaki K, Shinkai K, Kunisawa Y, Itaka K, Kataoka K, Nakano K.
    • Journal Title

      J Control Release

      Volume: 167 Issue: 3 Pages: 238-247

    • DOI

      10.1016/j.jconrel.2013.02.006

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Tumor-associated antigen gene-loading polyplex micelle is a promising platform for anti-cancer DNA vaccine2015

    • Author(s)
      Cui L, Fukugaki K, Osada K, Kataoka K, Nakano K
    • Organizer
      AACR Annual Meeting 2015
    • Place of Presentation
      Philladelphia, USA
    • Year and Date
      2015-04-18 – 2015-04-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 非ウイルスベクターを用いたDNAワクチンによる難治癌に対する集学的治療への試み2015

    • Author(s)
      崔林、古垣浩一、新海健太郎、田中雅夫、中野賢二
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-16 – 2015-04-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膵癌におけるYB-1高発現の生物学的意義に関する検討2014

    • Author(s)
      新海健太郎、中野賢二、大西秀哉、田中雅夫、片野光男
    • Organizer
      第27回日本バイオセラピィ学会学術集会総会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規癌遺伝子ワクチンとしての腫瘍関連抗原遺伝子を内包した高分子ミセルの 安全性と治療効果の検討2014

    • Author(s)
      崔林、新海健太郎、岩崎寛智、片野光男、田中雅夫、片岡一則、中野賢二
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 固形腫瘍の血管新生に寄与するYB-1の治療標的としての有用性2014

    • Author(s)
      新海健太郎、中野賢二、岩崎寛智、大西秀也、田中雅夫、片野光男
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] :膵癌の腫瘍形成能および血管新生におけるY-box binding protein-1の意義:膵癌と癌周囲微小環境の多角的制御による治療への展開.2013

    • Author(s)
      新海健太郎、岩崎寛智、大西秀也、田中雅夫、片野光男、中野賢二
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] 非ウイルスベクターを用いた消化器がんに対する新規遺伝子ワクチン療法の開発.2013

    • Author(s)
      古垣浩一、国澤由美、扇谷昌宏、新海健太郎、坂井綾、片野光男、田中雅夫、中野賢二
    • Organizer
      第68回日本消化器外科学会総会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Annual Research Report
  • [Presentation] 非ウイルス型遺伝子キャリアを用いた新規がん治療ワクチンの開発.2013

    • Author(s)
      崔林、新海健太郎、岩崎寛智、片野光男、田中雅夫、片岡一則、中野賢二
    • Organizer
      第26回日本バイオセラピィ学会学術集会総会
    • Place of Presentation
      盛岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] 非ウイルス型ベクター高分子ミセルの腹腔内投与による膵癌に対するGM-CSF遺伝子治療.2012

    • Author(s)
      扇谷昌宏、中野賢二、他
    • Organizer
      第25回日本バイオセラピィ学会学術集会総会(ワークショップ)
    • Place of Presentation
      倉敷市芸文館(倉敷市)
    • Year and Date
      2012-12-13
    • Related Report
      2012 Annual Research Report
  • [Presentation] Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and cynomolgus monkeys.2012

    • Author(s)
      Ohgidani M, Furugaki K, Shinkai K, Kunisawa Y, Itaka K, Kataoka K, Nakano K
    • Organizer
      AACR Special Conference : Tumor Immunology
    • Place of Presentation
      Intercontinental Miami (Maiami, FL, USA)
    • Year and Date
      2012-12-03
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腫瘍血管を標的とする非ウイルス型デリバリーシステムを用いたmiRNA治療 : 治療抵抗性の腹膜播種・膵臓癌に対する新たな治療戦略.2012

    • Author(s)
      中野賢二
    • Organizer
      第112回日本外科学会定期学術集会(シンポジウム)
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2012-04-13
    • Related Report
      2012 Annual Research Report
  • [Book] 分子細胞治療フロンティア2015 ”次世代の難治癌個別化治療に向けたDDS搭載遺伝子ワクチンの開発”2014

    • Author(s)
      中野賢二
    • Total Pages
      10
    • Publisher
      飯田橋パピルス(東京)
    • Related Report
      2014 Annual Research Report
  • [Book] 分子細胞治療フロンティア 2015 "次世代の難治癌個別化治療に向けたDDS搭載遺伝子ワクチンの開発"2014

    • Author(s)
      中野賢二
    • Total Pages
      10
    • Publisher
      飯田橋パピルス(東京)
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] Anti-tumor DNA vaccine2014

    • Inventor(s)
      Kenji Nakano
    • Industrial Property Rights Holder
      Kenji Nakano
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-04-05
    • Related Report
      2014 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アポトーシス誘導剤及び癌治療薬2012

    • Inventor(s)
      中野賢二、片岡一則、西山伸宏
    • Industrial Property Rights Holder
      九州大学/東京大学
    • Industrial Property Number
      2012-089772
    • Filing Date
      2012-04-10
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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