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Development of gene therapy of liver and bladder cancer by using nanobubbles and ultrasound

Research Project

Project/Area Number 20300173
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical systems
Research InstitutionTohoku University

Principal Investigator

KODAMA Tetsuya  東北大学, 大学院・医工学研究科, 教授 (40271986)

Co-Investigator(Kenkyū-buntansha) FUJIKAWA Shigeo  北海道大学, 大学院・工学研究科, 教授 (70111937)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2009: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2008: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywordsドラッグデリバリーシステム / ナノバブル / 超音波 / 遺伝子治療 / 肝がん / 膀胱がん
Research Abstract

The present research was aimed to develop a new gene therapy method of bladder and liver cancer by using nanobubbles (NBs)and ultrasound (US). The former was based on regional cancer therapy, and the later on the enhanced permeability and retention (EPR)effect. We developed acoustic liposome (NBs)(<200nm in diameter)as drug carrier and ultrasound contrast agent, dual ultrasound exposure system with high/low acoustic intensity pulses for effective delivery of fluorescent molecules and naked plasmid DNA to the bladder wall in the presence of NBs. In addition, we achieved therapeutic level by delivering tumor necrosis factor (TNF)-alpha expressing plasmid DNA to solid tumors of mice with NBs and US. Furthermore, we established a two/three-dimensional (2/3D)vascular construction method to evaluate therapeutic effects on liver cancer by using NBs and US. Our results demonstrate that the combination of these established materials and methodology can be used for a new gene therapy of bladder and liver cancer.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (69 results)

All 2010 2009 2008 Other

All Journal Article (14 results) (of which Peer Reviewed: 13 results) Presentation (53 results) Remarks (2 results)

  • [Journal Article] Investigating the effect of polymeric approaches on circulation time and physical properties of nanobubbles.2010

    • Author(s)
      du Toit LC, Govender T, Pillay V, Choonara YE, Kodama T
    • Journal Title

      Pharmaceutical Research

      Volume: 28 Pages: 494-504

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Morphological study of acoustic liposome using transmission electron microscopy2010

    • Author(s)
      Kodama T, Tomita N, Horie S, Sax N, Iwasaki H, Suzuki R, Maruyama K, Mori S, Fukumoto M
    • Journal Title

      Journal of Electron Microscopy

      Volume: 59(3) Pages: 187-196

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Investigating the effect of polymeric approaches on circulation time and physical properties of nanobubbles2010

    • Author(s)
      du Toit LC.
    • Journal Title

      Pharmaceutical Research

      Volume: 28 Pages: 494-504

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of localized gene delivery using a dual-intensity ultrasound system in the bladder2010

    • Author(s)
      Horie S.
    • Journal Title

      Ultrasound in Medicine and Biology

      Volume: 36 Pages: 1867-1875

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimum conditions of ultrasound-mediated destruction of bubble liposome for siRNA transfer in bladder cancer2010

    • Author(s)
      Fujisawa S.
    • Journal Title

      Therapeutic Delivery

      Volume: 1 Pages: 237-245

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological study of acoustic liposome using transmission electron microscopy2010

    • Author(s)
      Kodama T.
    • Journal Title

      Journal of Electron Microscopy

      Volume: 59 Pages: 187-196

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cavitation bubbles mediated molecular delivery during sonoporation2009

    • Author(s)
      Kodama T, Tomita Y, Watanabe Y, Koshiyama K, Yano T, Fujikawa S
    • Journal Title

      Journal of Biomechanical Science and Engineering

      Volume: 4 Pages: 124-140

    • NAID

      130000107450

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Morphological study on acoustic liposome using transmission electron microscopy.2009

    • Author(s)
      Kodama T.
    • Journal Title

      Journal of Electron Microscopy (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cavitation bubbles mediated molecular delivery during sonoporation.2009

    • Author(s)
      Kodama T.
    • Journal Title

      Journal of Biomechanical Science and Engineering 4

      Pages: 124-140

    • NAID

      130000107450

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel strategy utilizing ultrasound for antigen delivery in dendritic cell-based cancer immunotherapy.2009

    • Author(s)
      Suzuki R.
    • Journal Title

      Journal of Controlled Release. 133

      Pages: 198-205

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 音響性リポソームと超音波を利用した遺伝子薬物デリバリー2009

    • Author(s)
      柳下陽子
    • Journal Title

      血管医学 10巻4号

      Pages: 91-98

    • Related Report
      2009 Annual Research Report
  • [Journal Article] A novel strategy utilizing ultrasound for antigen delivery in dendritic cell-based cancer immunotherapy2009

    • Author(s)
      Suzuki R.
    • Journal Title

      Journal of Controlled Release 133

      Pages: 198-205

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cavitation bubbles mediated molecular delivery during sonoporation2009

    • Author(s)
      Kodama T.
    • Journal Title

      Journal of Biomechanical Science and Engineering 4

      Pages: 124-140

    • NAID

      130000107450

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low-intensity ultrasound and microbubbles enhance the antitumor effect of cisplatin2008

    • Author(s)
      Watanabe Y.
    • Journal Title

      Cancer Science 99(12)

      Pages: 2525-2531

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] マイクロバブルと高周波超音波を用いた三次元イメージング法による転移リンパ節の血管密度の評価2010

    • Author(s)
      小玉哲也
    • Organizer
      日本超音波医学会東北地方会第40回学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 音響性リポソームの減衰特性における実験的かつ論理的解析2010

    • Author(s)
      小玉哲也
    • Organizer
      日本超音波医学会東北地方会第40回学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ultrasound molecular imaging of lymph node metastasis with nano/microbubbles.2010

    • Author(s)
      小玉哲也
    • Organizer
      International Symposium of AIDS and Tuberculosis (ISAT2010)
    • Place of Presentation
      Sendai
    • Year and Date
      2010-01-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] Physical characterization of acoustic liposomes.2010

    • Author(s)
      小玉哲也
    • Organizer
      International Symposium of AIDS and Tuberculosis (ISAT2010)
    • Place of Presentation
      Sendai
    • Year and Date
      2010-01-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] 三次元高周波超音波およびナノバブルを用いた肝転移の非侵襲的観察2010

    • Author(s)
      小玉哲也
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Longitudinal three-dimensional noninvasive imaging analysis and quantification of anti-tumor effects of TNF-alpha gene for small tumor2010

    • Author(s)
      Kodama T
    • Organizer
      2010 World Molecular Imaging Congress
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Developement and characterization of echogenic pogylated liposomes2010

    • Author(s)
      Kodama T
    • Organizer
      第26回日本DDS学会学術集会
    • Place of Presentation
      大阪国際交流センター
    • Related Report
      2010 Final Research Report
  • [Presentation] Longitudinal three-dimensional noninvasive imaging analysis and quantification of anti-tumor effects of TNF-alpha gene for small tumor2010

    • Author(s)
      Kodama T.
    • Organizer
      2010 World Molecular Imaging Congress
    • Place of Presentation
      Kyoto
    • Related Report
      2010 Annual Research Report
  • [Presentation] In vivo detection of cancer metastases at an early stage by vessel density with ultrasound and nano/microbubbles2010

    • Author(s)
      森士朗
    • Organizer
      第52回歯科基礎医学会学術大会ならびに総会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report
  • [Presentation] Developement and characterization of echogenic pogylated liposomes2010

    • Author(s)
      Kodama T.
    • Organizer
      第26回日本DDS学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] ナノバブルと高周波超音波を用いた腫瘍血管構築法の開発2010

    • Author(s)
      小玉哲也
    • Organizer
      第26回日本DDS学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] ナノバブルと超音波を用いたTNF-α遺伝子導入による抗腫瘍効果の評価2010

    • Author(s)
      小玉哲也
    • Organizer
      第26回日本DDS学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] 表在性膀胱がんに対する再発防止法の開発2010

    • Author(s)
      松村保広
    • Organizer
      第26回日本DDS学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] In vivo detection of cancer raetastases at an early stage by vessel density with ultrasound and nano/microbubbles2010

    • Author(s)
      森士朗
    • Organizer
      第52回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膀胱がん治療に向けた二重超音波照射法の数値的至適化2010

    • Author(s)
      小玉哲也
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] 表在性膀胱がんに対する膀胱内注入遺伝子治療2010

    • Author(s)
      松村保広
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] ナノバブルと超音波を用いたTNF-a遺伝子導入による抗腫瘍効果の評価2010

    • Author(s)
      小玉哲也
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] ナノバブルと二重超音波を用いた膀胱がん治療の基礎研究2010

    • Author(s)
      小玉哲也
    • Organizer
      第15回キャビテーションシンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] Targeted gene delivery using nanobubble and ultrasound.2010

    • Author(s)
      小玉哲也
    • Organizer
      The 5th International Symposium on Medical, Bio-and Nano-Electronics.
    • Place of Presentation
      Sendai
    • Related Report
      2009 Annual Research Report
  • [Presentation] Observation for angiogenesis of liver metastases in preclinical models.2010

    • Author(s)
      小玉哲也
    • Organizer
      The 5th International Symposium on Medical, Bio- and Nano-Electronics.
    • Place of Presentation
      Sendai
    • Related Report
      2009 Annual Research Report
  • [Presentation] Four-dimensional high-frequency ultrasound imaging system for early detection of lymph node micro-metastasis.2010

    • Author(s)
      小玉哲也
    • Organizer
      The 5th International Symposium on Medical, Bio- and Nano-Electronics.
    • Place of Presentation
      Sendai
    • Related Report
      2009 Annual Research Report
  • [Presentation] TEM observation and analysis of echogenic nano-bubbles.2010

    • Author(s)
      小玉哲也
    • Organizer
      The 5th International Symposium on Medical, Bio- and Nano-Electronics.
    • Place of Presentation
      Sendai
    • Related Report
      2009 Annual Research Report
  • [Presentation] Volumetric and angiogenetic imaging system by using nanobubbles and high-frequency ultrasound for evaluation of the antitumor effect by cisplatin.2010

    • Author(s)
      小玉哲也
    • Organizer
      The 5th International Symposium on Medical, Bio- and Nano-Electronics.
    • Place of Presentation
      Sendai
    • Related Report
      2009 Annual Research Report
  • [Presentation] Three-dimentional high-frequency ultrasound imaging for early diagnosis of lymph node metastasis combined with microbubbles.2009

    • Author(s)
      小玉哲也
    • Organizer
      The 3rd East Asian Pacific Student Workshop on Nano-Biomedical Engineering.
    • Place of Presentation
      Engineering Auditorium, National University Of Singapore, Singapore
    • Year and Date
      2009-12-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 超音波分子イメージングによるリンパ節転移早期診断法の開発2009

    • Author(s)
      小玉哲也
    • Organizer
      第68回日本日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 表在性膀胱がんに対する膀胱内注入遺伝子療法2009

    • Author(s)
      小玉哲也
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 表在性膀胱がんに対する薬剤送達法の開発2009

    • Author(s)
      小玉哲也
    • Organizer
      日本機械学会2009年度年次大会
    • Place of Presentation
      岩手
    • Year and Date
      2009-09-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] 前臨床試験を目指した肝転移モデルの非侵襲的観察2009

    • Author(s)
      小玉哲也
    • Organizer
      日本機械学会2009年度年次大会
    • Place of Presentation
      岩手
    • Year and Date
      2009-09-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] Microbubble Disruption by Ultrasound and Induced Cavitation Phenomena.2009

    • Author(s)
      小玉哲也
    • Organizer
      The 7th International Symposium on Cavitation.
    • Place of Presentation
      Ann Arbor, Michigan, USA
    • Year and Date
      2009-08-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] Molecular delivery system by using nanobubbles and ultrasound.2009

    • Author(s)
      小玉哲也
    • Organizer
      International Symposium on HIV/AIDS, Medicinal Plants and Geophagia, Advancing the frontiers of Research on HIV/AIDS Medicinal Plants and Geophagia
    • Place of Presentation
      Walter Sisulu University Health Resource Centre Mthatha, Eastern Cape, South Africa
    • Year and Date
      2009-07-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 音響照射圧を用いたターゲッティング分子導入法の開発2009

    • Author(s)
      小玉哲也
    • Organizer
      第6回東北大学バイオサイエンスシンポジウムおよび第14回学際ライフサイエンスシンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2009-06-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 表在性膀胱がんに対する新しい遺伝子治療法の開発2009

    • Author(s)
      小玉哲也
    • Organizer
      第48回日本生体医工学会大会
    • Place of Presentation
      東京
    • Year and Date
      2009-04-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] Three-dimentional high-frequency ultrasound imaging for early diagnosis of lymph node metastasis combined with microbubbles2009

    • Author(s)
      Kodama T
    • Organizer
      The 3rd East Asian Pacific Student Workshop on Nano-Biomedical Engineering
    • Place of Presentation
      Engineering Auditorium, National University Of Singapore, Singapore
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular delivery system by using nanobubbles and ultrasound2009

    • Author(s)
      Tetsuya Kodama
    • Organizer
      International Symposium on HIV/AIDS
    • Place of Presentation
      Medicinal Plants and Geophagia, Advancing the frontiers of Research on HIV/AIDS, Medicinal Plants and Geophagia at Walter Sisulu University Health Resource Centre Mthatha, Eastern Cape, South Africa
    • Related Report
      2010 Final Research Report
  • [Presentation] ナノバブルと高周波超音波を用いた血管抽出法の開発2009

    • Author(s)
      小玉哲也
    • Organizer
      第25回日本DDS学会
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] 超音波の作用によるマイクロバブルの破壊とキャビテーション気泡の挙動2009

    • Author(s)
      小玉哲也
    • Organizer
      日本混相流学会 年会講演会 2009
    • Place of Presentation
      熊本
    • Related Report
      2009 Annual Research Report
  • [Presentation] 口腔癌治療のためのナノバブルと超音波を用いた抗腫瘍効果増強法に関する検討2009

    • Author(s)
      小玉哲也
    • Organizer
      日本口腔外科学会
    • Place of Presentation
      札幌
    • Related Report
      2009 Annual Research Report
  • [Presentation] ナノバブルと超音波を用いた高周波超音波診断装置による微小転移検出に関する検討2009

    • Author(s)
      小玉哲也
    • Organizer
      日本口腔外科学会
    • Place of Presentation
      札幌
    • Related Report
      2009 Annual Research Report
  • [Presentation] ナノバブルを用いたリンパ節転移診断に関する三次元高周波超音波イメージング法の開発2009

    • Author(s)
      小玉哲也
    • Organizer
      日本機械学会第21回バイオエンジニアリング講演会
    • Place of Presentation
      札幌コンベンションセンター
    • Related Report
      2008 Annual Research Report
  • [Presentation] 高周波超音波を用いたリンパ節早期転移の画像診断システムの開発2008

    • Author(s)
      小玉哲也
    • Organizer
      第42回日本生体医工学会東北支部大会
    • Place of Presentation
      東北大学青葉記念会館
    • Year and Date
      2008-12-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] がんの早期診断と治療を目指したナノバブルと超音波を用いた分子デリバリーシステムの開発2008

    • Author(s)
      小玉哲也
    • Organizer
      東北大学イノベーションフェア2008in仙台
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2008-09-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 膀胱がん治療のための分子デリバリーシステムの開発2008

    • Author(s)
      小玉哲也
    • Organizer
      東北大学イノベーションフェア2008in仙台
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2008-09-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] ナノ・マイクロバブルと超音波によるシスプラチンの抗腫瘍効果の増強2008

    • Author(s)
      小玉哲也
    • Organizer
      日本超音波医学会第36回東北地方会学術集会
    • Place of Presentation
      山形テルサ
    • Year and Date
      2008-09-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] Contrast-Enhanced High-Frequency Ultrasound Imaging of Liver Metastases in preclinical models2008

    • Author(s)
      Kodama T
    • Organizer
      2008 IEEE International Ultrasonics Symposium (IUS)
    • Place of Presentation
      Beijing International Convention Center (BICC), Beijing, China
    • Related Report
      2010 Final Research Report
  • [Presentation] Peeling off effect and damage pit formation by ultrasonic cavitation2008

    • Author(s)
      Kodama T
    • Organizer
      The International Conference on Hydraulic Machinery and Equipments Timisoara
    • Place of Presentation
      Romania
    • Related Report
      2010 Final Research Report
  • [Presentation] Peeling off effect and, damage pit formation by ultrasonic cavitation2008

    • Author(s)
      Kodama T.
    • Organizer
      The International Conference on Hydraulic Machinery and Equipments Timisoara
    • Place of Presentation
      Politehnica University of Timisoara, Timisoara, Romania
    • Related Report
      2008 Annual Research Report
  • [Presentation] Bladder cancer therapy using nanobubbles and two different intensities of ultrasound2008

    • Author(s)
      Kodama T.
    • Organizer
      The 2008 Nanomedicine Conference
    • Place of Presentation
      Hotel Eden Roc, Sant Feliude Guixols, Spain
    • Related Report
      2008 Annual Research Report
  • [Presentation] Development of diagnostic imaging system for regional lymph node micrometastasis with high-frequency ultrasound2008

    • Author(s)
      Kodama T.
    • Organizer
      2008 IEEE International Ultrasonics Symposium (US)
    • Place of Presentation
      Beijing International Convention Center (BICC), Beijing, China
    • Related Report
      2008 Annual Research Report
  • [Presentation] Contrast-Enhanced High-Frequency Ultrasound Imaging of Liver Metastases in oreclinical models2008

    • Author(s)
      Kodama T.
    • Organizer
      2008 IEEE International Ultrasonics Symposium (IUS)
    • Place of Presentation
      Beijing International Convention Center (BICC), Beijing, China
    • Related Report
      2008 Annual Research Report
  • [Presentation] ナノバブルを用いた肝転移診断に関する三次元高周波超音波イメージング2008

    • Author(s)
      小玉哲也
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2008 Annual Research Report
  • [Presentation] 膀胱がん治療のための新しい薬剤到達法の開発2008

    • Author(s)
      小玉哲也
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2008 Annual Research Report
  • [Presentation] 表在性膀胱がんに対する膀胱内注入遺伝子治療2008

    • Author(s)
      小玉哲也
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2008 Annual Research Report
  • [Presentation] ナノバブルと超音波を用いた膀胱がんへの遺伝子導入法の開発2008

    • Author(s)
      小玉哲也
    • Organizer
      第46回日本癌治療学会総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.ecei.tohoku.ac.jp/kodama/index.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.ecei.tohoku.ac.jp/kodama/index.html

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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