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Non-invasive assessment for therapeutic response to gene therapy using redox imaging and MALDI-TOF mass-spectrometry

Research Project

Project/Area Number 22659111
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Applied pharmacology
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) HYOUDOU Fuminori  九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (10380693)
FUJIMURA Yoshinori  九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (20390304)
MIURA Daisuke  九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (40532627)
Co-Investigator(Renkei-kenkyūsha) UTSUMI Hideo  九州大学, 先端融合医療レドックスナビ研究拠点, 特任教授 (20101694)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,220,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords非侵襲的治療応答性アッセイ / レドックスイメージング / メタボリック・プロフ ァイリング / 遺伝子治療 / 非侵襲的治療応答アッセイ / メタボリック・プロファイリング / 核酸治療 / レドックスイメージ / OMRI
Research Abstract

The purpose of this study is to develop the non-invasive assays to evaluate therapeuticresponse to gene therapy, as the indexes of redox state assessed by Overhauser MRI(OMRI) and metabolic profiling analyzed by MALDI-TOF mass-spectrometry. The ratio of radical disappearance curve analyzed by OMRI was increased for the TNF-αgene therapy compared with the control in subcutaneous tumor model. However, there was no significant difference between two groups in peritoneal dissemination, wherethe heterogeneity of tumor and normal tissues was present, suggesting the gating technology of redox imaging restricting tumor area may be necessary to improve the assay. In a separate experiment, the microanalysis of metabolites in endothelial cells post-transfection of redox-related transcription factor: YB-1-targeting siRNA using MALDI-TOF mass-spectrometry revealed the reduction of NAD and the increase of Histidine and Aspartate in cells with YB-1-siRNA. These results suggest that the improvement of visualizing (gating) ability of OMRI for tumor area could potentiate the redox imaging-based non-invasive assay to estimate the response to gene therapy.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (34 results)

All 2012 2011 2010 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (17 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Journal Article] Effective transgene expression without toxicity by intraperitoneal administration of PEG-detachable polyplex micelles in mice with peritoneal dissemination2012

    • Author(s)
      M.Kumagai, N.Nishiyama, et al.
    • Journal Title

      J.Control.Release

      Volume: (in press)(印刷中)(掲載確定) Issue: 3 Pages: 542-551

    • DOI

      10.1016/j.jconrel.2012.03.021

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] In situ metabolomic mass spectrometry imaging : Recent advances and difficulties2012

    • Author(s)
      Miura D, Fujimura Y, Wariishi H
    • Journal Title

      J.Proteomics

      Volume: (In press) Issue: 16 Pages: 5052-5060

    • DOI

      10.1016/j.jprot.2012.02.011

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The relationship between tissue oxygenation and redox status using magnetic resonance imaging2012

    • Author(s)
      Hyodo F, Davis RM, Hyodo E, Matsumoto S, Krishna MC, Mitchell JB
    • Journal Title

      Int J Oncol.

      Volume: - Issue: 6 Pages: 2103-8

    • DOI

      10.3892/ijo.2012.1638

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo toxicity and antitumor activity of mangosteen extract2012

    • Author(s)
      Kosem N, Ichikawa K, Utsumi H, Moongkarndi P
    • Journal Title

      J Nat Med

      Volume: 67(2) Issue: 2 Pages: 255-63

    • DOI

      10.1016/j.freeradbiomed.2012.04.026

    • NAID

      40019608907

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired activities of cyclic adenosine monophosphate (cAMP)-responsive element binding protein, protein kinase A and calcium-independent phospholipase A2 are involved in deteriorated regeneration of cirrhotic liver after partial hepatectomy in rats2011

    • Author(s)
      Zhao G, Wakabayashi R, Shimoda S, Fukunaga Y, Kumagai M, Tanaka M, Nakano K
    • Journal Title

      Hepatology Res

      Volume: 41 Pages: 1110-9

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transforming Growth Factor β1 Contributes to the Invasiveness of Pancreatic Ductal Adenocarcinoma Cells Through the Regulation of CD24 Expression2011

    • Author(s)
      Kitaura Y, Chikazawa N, Tasaka T, Nakano K, Tanaka M, Onishi H, Katano M
    • Journal Title

      Pancreas

      Volume: 40 Pages: 1034-1042

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual blockade of phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways overcomes paclitaxel-resistance in colorectal cancer2011

    • Author(s)
      Xu R, Nakano K, Iwasaki H, Kumagai M, Wakabayashi R, Suzuki H, Yamasaki A, Mibu R, Onishi H, Katano M
    • Journal Title

      Cancer Lett

      Volume: 306 Pages: 151-160

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor2011

    • Author(s)
      Nakano K, Kobayashi M, Nakamura K, Nakanishi T, Asano R, Kumagai I, Tahara H, Kuwano M, Cohen JB, Glorioso JC
    • Journal Title

      Virology

      Volume: 413 Pages: 12-18

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Y-box binding protein-1 (YB-1) promotes cell cycle progression through CDC6-dependent pathway in human cancer cells.2010

    • Author(s)
      Basaki Y, Nakano K (8), 他11名
    • Journal Title

      Eur J Cancer

      Volume: 46 Pages: 945-965

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] VEGFR2 is selectively expressed by FOXP3high CD4+ Treg.2010

    • Author(s)
      Suzuki H, Nakano K (6), 他6名
    • Journal Title

      Eur J Immunol

      Volume: 40 Pages: 197-203

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor.2010

    • Author(s)
      Nakano K (1), 他9名
    • Journal Title

      Virology

      Volume: 413 Pages: 12-18

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual blockade of phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways overcomes paclitaxel-resistance in colorectal cancer.

    • Author(s)
      Xu R, Nakano K (2), 他8名
    • Journal Title

      Cancer Letters

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 磁気共鳴イメージング法を用いたレドックス疾患の解析と抗酸化物質の評価2012

    • Author(s)
      兵藤文紀
    • Organizer
      第51回電子スピンサイエンス学会年会
    • Place of Presentation
      北海道
    • Year and Date
      2012-11-03
    • Related Report
      2012 Final Research Report
  • [Presentation] 酸化ストレス疾患解明のための生態レドックスイメージング法の開発2012

    • Author(s)
      兵藤文紀
    • Organizer
      第51回日本生体医工学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-05-11
    • Related Report
      2012 Final 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 monkeys2012

    • 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
      Miami, FL
    • Related Report
      2012 Final 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、古垣浩一、新海健太郎、国沢裕美、片岡一則、中野賢二
    • Organizer
      第25回日本バイオセラピィ学会学術集会総会(倉敷)
    • Place of Presentation
      ワークショップ
    • Related Report
      2012 Final Research Report
  • [Presentation] Metabolome early response to hydrogen peroxide-induced oxidative stress in mammalian cell2012

    • Author(s)
      Setoyama D, Fujimura Y, Miura D
    • Organizer
      19 th Annual Meeting of SFRBM
    • Place of Presentation
      Hilton San Diego Bayfront, San Diego, CA
    • Related Report
      2012 Final Research Report
  • [Presentation] Non-invasive analysis of redox status and antioxidant efficacy using Overhauser - MRI2012

    • Author(s)
      Fuminori Hyodo
    • Organizer
      Oxidative stress in Congenital and Acquired Hemolytic Anemia, Thaikand
    • Related Report
      2012 Final 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)
    • 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(Miami, FL)
    • Related Report
      2012 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
      倉敷芸文館(倉敷市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 非ウイルスベクターを用いた癌遺伝子・核酸治療:臨床試験への展開.2011

    • Author(s)
      中野 賢二
    • Organizer
      第24回日本バイオセラピィ学会学術集会総会.
    • Place of Presentation
      和歌山
    • Year and Date
      2011-12-01
    • Related Report
      2012 Final Research Report
  • [Presentation] 非ウイルスベクターを用いた癌遺伝子・核酸治療:臨床試験への展開2011

    • Author(s)
      中野賢二
    • Organizer
      第24回日本バイオセラピィ学会学術集会総会
    • Place of Presentation
      和歌山
    • Year and Date
      2011-12-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Block co-polymer based gene therapy for disseminated cancer: Perspective to Clinical Trials2011

    • Author(s)
      Nakano K, Kumagai M, Shimoda S, Wakabayashi R, Nishiyama N, Kataoka K
    • Organizer
      17thAnnual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Fukuoka
    • Year and Date
      2011-07-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Block co-polymer based gene therapy for disseminated cancer : Perspective to Clinical Trials2011

    • Author(s)
      Nakano K, Kumagai M, Shimodas, Wakabayashi R, Nishiyama N, Kataoka K
    • Organizer
      17^<th> Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Fukuoka
    • Year and Date
      2011-07-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Molecular Imaging of Oxidative Stress using NitroxylRadical Compounds2011

    • Author(s)
      Oxidative stress in Congenital and Acquired Hemolytic Anemia, Thaikand
    • Organizer
      Symposium "Taiload materials for pharmacy" onWeinberg-Campus, Pharmazie-Horaal
    • Place of Presentation
      Martin-Luther University Halle Wittenberg
    • Year and Date
      2011-06-30
    • Related Report
      2012 Final Research Report
  • [Presentation] High-throughput Metabolic Profiling and in situ Metabolite Imaging by MALDI mass spectrometry2011

    • Author(s)
      Miura D, Yukihira D, Fujimura Y, Wariishi H
    • Organizer
      59thASMS Conference on Mass Spectrometry and Allied Topics
    • Place of Presentation
      Colorado Convention Centre, Denver, Colorado
    • Related Report
      2012 Final Research Report
  • [Presentation] Disclosing Oxidatively Damaged Metabolites under Homeostatic Control of Mammalian Cells by LC-MS-based Metabolomics.2011

    • Author(s)
      Setoyama D, Fujimura Y, Sakai K, Ichikawa K, Wariishi H, Miura D
    • Organizer
      59thASMS Conference on Mass Spectrometry and Allied Topics
    • Place of Presentation
      Colorado Convention Centre, Denver, Colorado
    • Related Report
      2012 Final Research Report
  • [Presentation] New insights into anticancer effect of green tea polyphenol epigallocatechin-3-gallate in hypoxia by metabolic profiling2010

    • Author(s)
      Fujimura Y, Miura D, Hyodo F, Yasukawa K, Tachibana H, Utsumi H, Wariishi H.
    • Organizer
      17 th Annual Meeting of SFRBM
    • Place of Presentation
      Caribe Royale All-Suite Hotel & Convention Center, Orlando, Florida
    • Related Report
      2012 Final Research Report
  • [Remarks] Control of Mammalian Cells by LC-MS-based Metabolomics. 59thASMS Conference on Mass Spectrometry and Allied Topics (June 5-9, 2011, Colorado Convention Centre, Denver, Colorado)8. Fujimura Y, Miura D, Hyodo F, Yasukawa K, Tachibana H, Utsumi H, Wariishi H

    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] TNF-a, CD40L及びGM-CSF併用遺伝子治療剤2011

    • Inventor(s)
      中野賢二、西山伸宏、片岡一則.
    • Filing Date
      2011-12-28
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] TNF-a,CD40L及びGM-CSF併用遺伝子治療剤2011

    • 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
    • Filing Date
      2011-12-28
    • Related Report
      2011 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 高分子ミセル内包TNF-α遺伝子治療剤2010

    • Inventor(s)
      中野賢二、西山伸宏、片岡一則.
    • Filing Date
      2010-07-02
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 高分子ミセル内包TNF-α遺伝子治療剤2010

    • Inventor(s)
      中野賢二、片岡一則、西山伸宏
    • Industrial Property Rights Holder
      東京大学
    • Filing Date
      2010-07-02
    • Related Report
      2010 Annual Research Report
    • Overseas

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Published: 2010-08-23   Modified: 2019-07-29  

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