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Development of combination therapy with hyperthermia and targeted therapy

Research Project

Project/Area Number 24792006
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionYokohama City University

Principal Investigator

NAKASHIMA Hideyuki  横浜市立大学, 附属病院, 助教 (30437032)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords温熱療法 / 分子標的薬 / 併用療法 / 口腔癌 / 口腔扁平上皮癌
Research Abstract

Interleukin-13 receptor alpha 2 chain (IL-13Ra2), a unique tumor-associated antigen, is a promising target for cancer immunotherapy. IL13-PE, a targeted cytotoxin composed of IL-13 and mutated Pseudomonas exotoxin, induces specific killing of IL-13Ra2 positive tumor cells. Our objective is whether hyperthermia treatment of oral squamous cell carcinoma (OSCC) can modulate the expression of IL-13Ra2 and increase their sensitivity to IL13-PE.
OSCC cell lines, HSC-3 and SCC-25 cells were heated with 43 degree for 1 hour. The proliferation of heat-stressed OSCC cells showed more than 50% growth inhibition compared to control cells. IL-13Ra2 was up-regulated after heating of OSCC cells. Protein synthesis inhibition assay with IL13-PE showed that heat-stressed OSCC cells decreased the number of IC50 compared to that of without heated OSCC cells. The percentages of apoptotic cells increased in OSCC cells treated with IL13-PE after hyperthermia compared with controls.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2014 2013 2012

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (8 results) (of which Invited: 2 results)

  • [Journal Article] Targeting of interleukin-13 receptor α2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-β and PTEN signaling.2013

    • Author(s)
      Hall B, Nakashima H, Sun ZJ, Sato Y, Bian Y, Husain SR, Puri RK, Kulkarni AB.
    • Journal Title

      J Transl Med.

      Volume: 11 Pages: 45-45

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Review: IL-13 receptor-directed cancer vaccines and immunotherapy.2012

    • Author(s)
      Nakashima H, Husain SR, Puri RK.
    • Journal Title

      Immunotherapy

      Volume: 4 Issue: 4 Pages: 443-451

    • DOI

      10.2217/imt.12.28

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] A Combination therapy with hyperthermia and immunotoxin targeted IL-13 receptor alpha2 for human oral cancer cells2014

    • Author(s)
      M. Okubo, H. Nakashima, M. Kioi, T. Sakaguchi, H. Umemura, K. Sugiura, I. Sato, M. Iida, K. Mitsudo and I. Tohnai
    • Organizer
      第6回アジアハイパーサーミア腫瘍学会・第31回日本ハイパーサーミア学会合同大会
    • Place of Presentation
      AOSSA (福井県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 口腔扁平上皮癌における分子標的薬と温熱療法との併用療法の開発. シンポジウム2013

    • Author(s)
      中島 英行, 來生 知, 大久保牧子, 杉浦 圭, 佐藤 格, 飯田 昌樹, 佐藤 有紀, 光藤 健司, 藤内 祝
    • Organizer
      第30回日本ハイパーサーミア学会・学術大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-08-31
    • Related Report
      2013 Final Research Report
  • [Presentation] 口腔扁平上皮癌における分子標的薬と温熱療法との併用療法の開発2013

    • Author(s)
      中島 英行,來生 知,大久保牧子,杉浦 圭,佐藤 格,飯田 昌樹,佐藤 有紀,光藤 健司,藤内 祝
    • Organizer
      第30回 日本ハイパーサーミア学会・学術大会
    • Place of Presentation
      横浜シンポジア(神奈川県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Interleukin-13 Receptor α2 chain Regulation in Human Head and Neck by Hyperthermia in vitro2012

    • Author(s)
      Sugiura K, Nakashima H, Okubo M, Sato I, Iida M, Sato Y, Kioi M, Mitsudo K, Husain SR, Tohnai, Puri RK
    • Organizer
      International Conference on Diabetes Mellitus and Cancer (Dia-Can' 12)
    • Place of Presentation
      Tamil Nadu, India
    • Year and Date
      2012-12-15
    • Related Report
      2013 Final Research Report
  • [Presentation] A Novel Combination Immunotherapy for Targeting Murine Breast Cancer with IL-13 Receptor alpha 2 DNA Vaccine and an Immunotoxin2012

    • Author(s)
      Nakashima H, Husain SR, Sato Y. Kioi M. Tohnai I, Puri RK
    • Organizer
      International Conference on Diabetes Mellitus and Cancer (Dia-Can' 12)
    • Place of Presentation
      Tamil Nadu, India
    • Year and Date
      2012-12-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Hyperthermia sensitizes resistant human oral cancer cells to IL-13 cytotoxin2012

    • Author(s)
      Nakashima H, Kioi M, Okubo M, Sugiura K, Sato I, Iida M, Mitsudo K, Husain SR, Puri RK, Tohnai I
    • Organizer
      ICHO & JCTM 2012 meeting
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2012-08-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Hyperthermia sensitizes resistant human oral cancer cells to IL-13 cytotoxin2012

    • Author(s)
      H. Nakashima, M. Kioi, M. Okubo, K. Sugiura, I. Sato, M. Iida, K. Mitsudo, S. R. Husain, R. K. Puri and I. Tohnai
    • Organizer
      ICHO & JCTM 2012 meeting
    • Place of Presentation
      ハイアットリージェンシー(京都府)
    • Related Report
      2012 Research-status Report
  • [Presentation] Interleukin-13 Receptor α2 chain Regulation in Human Head and Neck by Hyperthermia in vitro2012

    • Author(s)
      Kei Sugiura, Hideyuki Nakashima, Makiko Okubo, Itaru Sato, Masaki. Iida, Yuki Sato, Mitomu Kioi, Kenji Mitsudo, Syed R. Husain, Iwai Tohnai and Raj K. Puri
    • Organizer
      International Conference on Diabetes Mellitus and Cancer (Dia-Can’ 12)
    • Place of Presentation
      Tamil Nadu, India
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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