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Reconstruction of the normal vasculature for the strategy of new cancer therapy.

Research Project

Project/Area Number 24659904
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Surgical dentistry
Research InstitutionTokyo Women's Medical University

Principal Investigator

EZAKI Taichi  東京女子医科大学, 医学部, 教授 (10128259)

Co-Investigator(Kenkyū-buntansha) KITAHARA Shuji  東京女子医科大学, 医学部, 助教 (40510235)
MORISHIMA Masae  東京女子医科大学, 医学部, 助教 (00241068)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腫瘍血管 / 血管正常化 / 血管再構築 / 再生医療 / Normalization / ドラッグデリバリーシステム / ES細胞 / scaffold / 血管新生
Research Abstract

We hypothesized that reconstruction of normal blood vessels in tumors may lead to improvement of hypoxic conditions, contributing to potential improvements in the delivery of anticancer drugs. Tumor cells were injected into the dorsal subcutis of SCID mice. After 2 weeks, the tumor-bearing mice were injected cisplatin intraperitoneally to regress tumors and tumor vessels for the first step. Two weeks later, human ECs or human ES-derived ECs were transplanted into necrotic regions of the tumor to induce normal angiogenesis for the second step. Microscopic observations revealed that the transplanted ECs formed anastomoses with the host mouse vasculature. Blood vessels reconstituted by ECs exhibited the normalization of tumor vasculature, resulting in a significant reduction in the tumor volume. Thus, this model is a useful model for the future development of new cancer therapies by the construction of reliable drug delivery systems and the improvement of hypoxic conditions.

Report

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

    (24 results)

All 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (16 results) (of which Invited: 2 results)

  • [Journal Article] Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors2014

    • Author(s)
      Kuwahara Y, Mori M, Kitahara S, Fukumoto M, Ezaki T,(他3名)
    • Journal Title

      Cancer Med. 3

      Volume: 2 Pages: 310-21

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a normalized revascularization mouse model using tumor transplantation, Journal of Oral and Maxillofacial Surgery2014

    • Author(s)
      Momoki Y, Kitahara S,(他3名)
    • Journal Title

      Medicine, and Pathology 26

      Volume: 1 Pages: 80-88

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors2014

    • Author(s)
      Kuwahara Y, Mori M, Kitahara S, Fukumoto M, Ezaki T, Mori S, Echigo S, Ohkubo Y, Fukumoto M.
    • Journal Title

      Cancer Med

      Volume: 3(2) Issue: 2 Pages: 310-21

    • DOI

      10.1002/cam4.185

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a normalized revascularization mouse model using tumor transplantation. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology2014

    • Author(s)
      Momoki Y, Kitahara S, Kuwahara K, Sasaki R, Ando T
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: 26 Pages: 80-88

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction2013

    • Author(s)
      Shimizu K, Asakura M, Shinga J, Sato Y, Kitahara S, Hoshino K, Kaisho T, Schoenberger SP, Ezaki T, (他1名)
    • Journal Title

      J Immunol

      Volume: 190 Pages: 5609-19

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Invariant NKT cells induce plasmacytoid DC cross-talk with conventional DCs for efficient memory CD8+ T cell induction2013

    • Author(s)
      Shimizu K, Asakura M, Shinga J, Sato Y, Kitaha Hoshino K, Kaisho T, Schoenberger SP, Ezaki T, Fujii S
    • Journal Title

      J Immunol

      Volume: 190 Issue: 11 Pages: 5609-5619

    • DOI

      10.4049/jimmunol.1300033

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a normalized revascularization mouse model using tumor transplantation2013

    • Author(s)
      Yumiko Momokia
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: 未定 Issue: 1 Pages: 80-88

    • DOI

      10.1016/j.ajoms.2013.02.004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor-Derived Microvesicles Induce Proangiogenic Phenotype in Endothelial Cells via Endocytosis2012

    • Author(s)
      T. Kawamoto, et al.
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 3 Pages: e34045-e34045

    • DOI

      10.1371/journal.pone.0034045

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 腫瘍の増殖環境変化にともなう腫瘍血管の形態的機能的変化2014

    • Author(s)
      北原秀治
    • Organizer
      第119回日本解剖学会総会
    • Place of Presentation
      栃木
    • Related Report
      2013 Final Research Report
  • [Presentation] Neoplastic transformation sequence in Apc^<Min/+>mice depends on prior microvascular changes and vasohibin-2 expression2014

    • Author(s)
      Shuji KITAHARA
    • Organizer
      5^<th> International meeting of Angiogenesis
    • Place of Presentation
      Amsterdam
    • Related Report
      2013 Final Research Report
  • [Presentation] Neoplastic transformation sequence in ApcMin/+ mice depends on prior microvascular changes and vasohibin-2 expression2014

    • Author(s)
      Shuji Kitahara, Yasuhiro Suzuki, Asuka Yoshii, Yasufumi Sato, Taichi Ezaki
    • Organizer
      5th International Meeting Of Angiogenesis
    • Place of Presentation
      オランダ
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腫瘍の増殖環境変化にともなう腫瘍血管系の形態的・機能的変化2014

    • Author(s)
      北原秀治、菊田幸子、山田翔子、前田有貴子、森島正恵、江崎太一
    • Organizer
      第119回日本解剖学会総会
    • Place of Presentation
      栃木
    • Related Report
      2013 Annual Research Report
  • [Presentation] シンポジウム「頭頚部の微小循環」腫瘍微小循環系の制御による腫瘍増殖抑制の試み?2013

    • Author(s)
      北原秀治
    • Organizer
      第55回歯科基礎医学会
    • Place of Presentation
      岡山
    • Related Report
      2013 Final Research Report
  • [Presentation] Transplanting normal endothelial cells into tumor mass retards the tumor growth by vascular reconstruction and vascular normalization2013

    • Author(s)
      Shuji KITAHARA
    • Organizer
      Experimental Biology 2013
    • Place of Presentation
      Boston
    • Related Report
      2013 Final Research Report
  • [Presentation] Transplanting normal endothelial cells into tumor mass retards the tumor growth by vascular reconstruction and vascular normalization2013

    • Author(s)
      Kitahara S, Nishio M, Morikawa S, Nakada K, Yoshii A, Saeki K, Ezaki T
    • Organizer
      EXPERIMENTAL BIOLOGY 2013
    • Place of Presentation
      Boston
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腫瘍微小循環系の制御による腫瘍増殖抑制の試み2013

    • Author(s)
      北原秀治
    • Organizer
      第55回歯科基礎医学会
    • Place of Presentation
      岡山
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Vasohibin-2の抑制が消化管における自然発症腫瘍に影響を及ぼすか?2013

    • Author(s)
      北原秀治、鈴木康弘、森島正恵、吉井明日香、松居彩、佐藤靖史、江崎太一
    • Organizer
      第21回日本血管生物医学会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] シンポジウム「遺伝子異常vs微小循環の異常」微小循環系の制御が腫瘍の悪性化抑制につながるか?2012

    • Author(s)
      北原秀治
    • Organizer
      第23回消化器癌発生学会
    • Place of Presentation
      徳島
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] サテライトシンポジウム, [頭頚部領域の微小循環系]、腫瘍における微小循環系の多様性2012

    • Author(s)
      北原秀治
    • Organizer
      第54回歯科基礎医学会総会
    • Place of Presentation
      福島
    • Year and Date
      2012-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 臨床的放射線耐性腫瘍を用いた新たな癌治療モデルの確立2012

    • Author(s)
      北原秀治
    • Organizer
      第55回日本放射線影響学会
    • Place of Presentation
      仙台
    • Year and Date
      2012-09-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Transplanting normal endothelial cells to tumor-bearing mice triggers vascular remodeling and reduces tumor volume2012

    • Author(s)
      Shuji KITAHARA
    • Organizer
      14th INTERNATIONAL HISTOCHEMISTRY AND CUTOCHEMISTRY
    • Place of Presentation
      Kyoto, japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Does the regeneration of the normal vasculature in tumors suppress the tumor growth?2012

    • Author(s)
      Shuji KITAHARA
    • Organizer
      International Vascular Biology Meeting
    • Place of Presentation
      Germany
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Transplanting normal endothelial cells to tumor-bearing mice triggers vascular remodeling and reduces tumor volume2012

    • Author(s)
      Shuji Kitahara
    • Organizer
      INTERNATIONAL HISTOCHEMISTRY AND CUTOCHEMISTRY
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] 腫瘍における微小循環系の多様性2012

    • Author(s)
      北原秀治
    • Organizer
      第54回歯科基礎医学会総会
    • Place of Presentation
      福島
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2023-03-16  

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