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Analysis of the expression of drug resistance-related genes in tumor blood vessels

Research Project

Project/Area Number 25462846
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphological basic dentistry
Research InstitutionHokkaido University

Principal Investigator

SUZUKI Yuko  北海道大学, 遺伝子病制御研究所, 学術研究員 (90646118)

Co-Investigator(Kenkyū-buntansha) OHGA Noritaka  北海道大学, 大学院歯学研究科, 助教 (40548202)
AKIYAMA Kosuke  北海道大学, 遺伝子病制御研究所, 客員研究員 (10609100)
MAISHI Nako  北海道大学, 遺伝子病制御研究所, 助教 (00632423)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords腫瘍血管 / 薬剤抵抗性 / トランスポーター / がん幹細胞
Outline of Final Research Achievements

We have reported that drug resistance-related gene, P-glycoprotein (P-gp) is upregulated in tumor endothelial cells (TECs). In this study, we examined the involvement of P-gp expression of TEC in cancer refractory. When TECs were treated with both paclitaxel and P-gp inhibitor, TEC proliferation was inhibited compared to paclitaxel alone group. Combination treatment with paclitaxel and P-gp inhibitor abrogated TEC resistance in mouse tumor model. These results suggested that inhibiting P-gp in TECs may be a good strategy for cancer therapy.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (35 results)

All 2016 2015 2014 2013

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Evaluation of the level of progression of extracapsular spread for cervical lymph node metastasis in oral squamous cell carcinoma.2016

    • Author(s)
      Yamada S, Yanamoto S, Otani S, Hasegawa T, Miyakoshi M, Minamikawa T, Ohga N, Kamata T, Komori T, Kitagawa Y, Kurita H, Umeda M.
    • Journal Title

      Int J Oral Maxillofac Surg

      Volume: 45(2) Issue: 2 Pages: 141-6

    • DOI

      10.1016/j.ijom.2015.09.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CXCL 12-CXCR7 axis is important for tumor endothelial cell angiogenic property2015

    • Author(s)
      Yamada K., Maishi N., Akiyama K., Alam Mohammad Towfik, Ohga N., Kawamoto T., Shindoh M. Takahashi N., Kamiyama T., Hida Y., Taketomi A. and Hida K.
    • Journal Title

      Int J Cancer

      Volume: 137(12) Issue: 12 Pages: 2825-2836

    • DOI

      10.1002/ijc.29655

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel2015

    • Author(s)
      1.Akiyama K., Maishi N., Ohga N., Hida Y., Ohba Y., Alam Mohammad Towfik, Kawamoto T., Ohmura H., Yamada K., Torii C., Shindoh M. and *Hida K.
    • Journal Title

      Am J Pathol

      Volume: 185(2) Issue: 2 Pages: 572-580

    • DOI

      10.1016/j.ajpath.2014.10.017

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differences in sequential posttreatment salivary IL-6 levels between patients with and patients without locoregional recurrences of oral squamous cell carcinoma: Part III of a cohort study.2015

    • Author(s)
      Sato J, Ohuchi M, Wada M, Ohga N, Asaka T, Yoshikawa K, Miyakoshi M, Hata H, Satoh A, Kitagawa Y.
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol

      Volume: 120 Issue: 6 Pages: 751-60

    • DOI

      10.1016/j.oooo.2015.08.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Marked bone production from the mandibular head to the reconstructed fibula after chemoradiotherapy for the recurrent tumor2015

    • Author(s)
      Satoh.A, Ohga.N*, Asaka.T, Kitagawa.Y
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: 27(6) Pages: 829-833

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dose escalation effectiveness and tolerability of paroxetine in patients with burning mouth syndrome and depressive conditions.2015

    • Author(s)
      Ohga.N*, Yamazaki.Y, Sato.J, Hata.H, Murata.T, Sakata.K, Inoue.T, Kitagawa.Y
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: 27(3) Pages: 402-406

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Healing of osteonecrosis of the jaw (ONJ) after discontinuation of denosumab in a patient with bone metastases of colorectal cancer: a case report and hypothesis.2015

    • Author(s)
      Ohga N*, Yamazaki Y, Tsuboi K, Kitagawa Y
    • Journal Title

      Quintessence Int.

      Volume: 46(7) Pages: 621-626

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CRK adaptor protein induces epithelial-mesenchymal transition and metastasis of bladder cancer cells via HGF/c-Met feedback loop.2015

    • Author(s)
      Matsumoto R, Tsuda M, Wang L, Maishi N, Abe t, Kimura T, Tanino M, Nishihara H, Hida K, Ohba Y, Shinohara N, Nonomura K, Tanaka S.
    • Journal Title

      Cancer Sci

      Volume: in press Issue: 6 Pages: 709-17

    • DOI

      10.1111/cas.12662

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype2014

    • Author(s)
      2.Ohmura-Kakutani H., Akiyama K., Maishi N., Ohga N., Hida Y., Kawamoto T., Iida J., Shindoh M., Tsuchiya K., Shinohara N., *Hida K
    • Journal Title

      PLoS ONE

      Volume: 9(12) Issue: 12 Pages: e113910-e113910

    • DOI

      10.1371/journal.pone.0113910

    • NAID

      120005540289

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suprabasin as a novel tumor endothelial cell marker2014

    • Author(s)
      3.Alam Mohammad Towfik,Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Taketomi A., Shindoh M., Hida Y. and *Hida K
    • Journal Title

      Cancer Sci

      Volume: 105(12) Issue: 12 Pages: 1533-1540

    • DOI

      10.1111/cas.12549

    • NAID

      120005539218

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Novel Targets for Antiangiogenic Therapy by Comparing the Gene Expressions of Tumor and Normal Endothelial Cells2014

    • Author(s)
      Otsubo T., et al., Hida Y., Ohga N., Sato H., Kai T., Matsuki Y., Takasu H., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Nonomura K., Hida K.
    • Journal Title

      Cancer Sci.

      Volume: (印刷中) Issue: 5 Pages: 560-567

    • DOI

      10.1111/cas.12394

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Novel Targets for Antiangiogenic Therapy by Comparing the Gene Expressions of Tumor and Normal Endothelial Cells2014

    • Author(s)
      Otsubo T., Hida Y., Ohga N., Sato H., Kai T., Matsuki Y., Takasu H., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Nonomura K., Hida K
    • Journal Title

      Cancer Sci,

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The F-prostaglandin receptor is a novel marker for tumor endothelial cells in renal cell carcinoma2013

    • Author(s)
      Akiyama K., Ohga N., Maishi N., Hida Y., Kitayama K., Kawamoto T., Osawa T., Suzuki Y., Shinohara N., Nonomura K., Shindoh M., Hida K.
    • Journal Title

      Pathol. Int.

      Volume: 63(1) Issue: 1 Pages: 37-44

    • DOI

      10.1111/pin.12031

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lysyl oxidase secreted by tumour endothelial cells Promotes angiogenesis and metastasiso2013

    • Author(s)
      Osawa T., et al., Ohga N., Akiyama K., Hida Y., Kitayama K., Kawamoto T, , Yamamoto K., Maishi N., Kondoh M., Onodera Y., Fujie M., Nonomura K., Shindoh M., Hida K.
    • Journal Title

      Br. J. Cancer

      Volume: 109(8) Issue: 8 Pages: 2237-2247

    • DOI

      10.1038/bjc.2013.535

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment2013

    • Author(s)
      Kondoh M., Ohga N., Akiyama K., Hida Y., Maishi N., Alam Mohammad Towfik, Inoue N., Shindoh M. and Hida K
    • Journal Title

      PLoS ONE

      Volume: 8(11) Issue: 11 Pages: e80349-e80349

    • DOI

      10.1371/journal.pone.0080349

    • NAID

      120005367415

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Tumor Endothelial Cells Promote Metastasis via Biglycan2016

    • Author(s)
      Maishi N.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Breckenridge (USA)
    • Year and Date
      2016-03-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腫瘍分泌小胞miRNAによる血管内皮の薬剤耐性誘2016

    • Author(s)
      鳥居ちさほ,間石奈湖,樋田京子
    • Organizer
      第2回血管生物若手研究会
    • Place of Presentation
      東北大学加齢医学研究所スマートエージング国際共同研究センター国際会議室(宮城県・仙台市)
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion2016

    • Author(s)
      Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Mohammad Towfik Alam, Shindoh M., Hida Y., Hida K
    • Organizer
      Tenth AACR-JCA Joint Conference “Breakthroughs in Cancer Research: From Biology to Therapeutics”
    • Place of Presentation
      Maui (USA)
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ROS によるbiglycan 発現誘導を介した腫瘍血管内皮細胞の血管新生能亢進2015

    • Author(s)
      北條敬之,間石奈湖,Mohammad T Alam,秋山廣輔,大賀則孝,進藤正信,樋田泰浩,藤澤俊明,樋田京子
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 高転移性腫瘍miRNA はIL-6 ならびにALDH の発現亢進を介して血管内皮に薬剤耐性を誘導する2015

    • Author(s)
      鳥居ちさほ,秋山廣輔,川本泰輔,間石奈湖,鄭漢忠,戸塚靖則,進藤正信,樋田泰浩,南敬,小坂展慶,落谷孝広,樋田京子
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍血管内皮細胞はbiglycan の分泌を介してがんの転移を促進する2015

    • Author(s)
      間石奈湖,大場雄介,秋山廣輔,大賀則孝,浜田淳一,北本(永尾)宗子,Mohammad Alam T.,進藤正信,樋田泰浩,樋田京子
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion2015

    • Author(s)
      Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Mohammad Towfik Alam, Shindoh M., Hida Y., Hida K
    • Organizer
      The European Cancer Congress 2015
    • Place of Presentation
      Vienna (Austria)
    • Year and Date
      2015-09-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tumor Endothelial cell-secreted protein activates a DNA damage response2015

    • Author(s)
      Annan Dorcas A., 間石奈湖,北條敬之,鳥居ちさほ,Mohammad T Alam.,Habiba Umma,樋田泰浩,樋田京子
    • Organizer
      第112回北海道癌談話会例会
    • Place of Presentation
      北海道大学医学部学友会館[フラテ」(北海道・札幌市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 高転移性腫瘍miRによらう血管内皮におけるIL-6を介した薬剤耐性誘導2015

    • Author(s)
      鳥居ちさほ,秋山廣輔,川本泰輔,間石奈湖,Alam Mohammad Towfik,鄭 漢忠,戸塚靖則,進藤正信,樋田泰浩,南 敬,小坂展慶,落谷孝広,樋田京子
    • Organizer
      第112回北海道癌談話会例会
    • Place of Presentation
      北海道大学医学部学友会館[フラテ」(北海道・札幌市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍血管内皮細胞はbiglycanの分泌を介してがんの転移を促進する2015

    • Author(s)
      間石奈湖,大場雄介,秋山廣輔,大賀則孝,浜田淳一,北本宗子,Alam Mohammad Towfik,進藤正信,樋田泰浩,樋田京子
    • Organizer
      第26回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      北海道大学学術交流会館(北海道・札幌市)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] 高転移性腫瘍miRNAはIL-6ならびにALDHの発現亢進を介して血管内皮に薬剤耐性を誘導する2015

    • Author(s)
      鳥居ちさほ,秋山廣輔,川本泰輔,間石奈湖,鄭 漢忠,戸塚靖則,進藤正信,樋田泰浩,樋田京子
    • Organizer
      第26回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      北海道大学学術交流会館(北海道・札幌市)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] Suprabasin as a novel tumor endothelial cell marker2015

    • Author(s)
      Alam Mohammad Towfik,Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T, Shinohara N., Taketomi A., Shindoh M, Hida Y, Hida K
    • Organizer
      第26回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      北海道大学学術交流会下院(北海道・札幌市)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] 活性酸素種によるBiglycan発現誘導を介した腫瘍血管内皮細胞の血管新生能亢進2015

    • Author(s)
      北條敬之,間石奈湖,秋山廣輔,大賀則孝,進藤正信,樋田泰浩,藤澤俊明,樋田京子
    • Organizer
      第26回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      北海道大学学術交流会館(北海道・札幌市)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍血管内皮細胞はbiglycanの分泌を介してがんの転移を促進する2015

    • Author(s)
      間石奈湖
    • Organizer
      第24回日本がん転移学会学術集会・総会
    • Place of Presentation
      シティプラザ大阪(大阪府・大阪市)
    • Year and Date
      2015-07-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍微小環境において,腫瘍由来のmiRX により血管内皮はIL-6 をオートクラインで利用し,薬剤耐性や幹細胞性を獲得している2015

    • Author(s)
      鳥居ちさほ,秋山廣輔,川本泰輔,間石奈湖,鄭 漢忠,進藤正信,樋田泰浩,樋田京子
    • Organizer
      第69回日本口腔科学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2015-05-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tumor endothelial cells instigate metastasis of indolent tumors2015

    • Author(s)
      Maishi N., Hida K.
    • Organizer
      Spring Special Symposium of the Japanese Vascular Biology and Medicine Organization
    • Place of Presentation
      大阪大学微生物病研究所谷口記念講堂(大阪府・吹田市)
    • Year and Date
      2015-05-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腫瘍血管内皮細胞を標的としたメトロノミックケモセラピーとP-gp阻害剤の併用療法の有効性の検討2013

    • Author(s)
      秋山廣輔,大賀則孝,樋田泰浩,間石奈湖,Alam Mohammad Towfik, 川本泰輔,大村 瞳,山田健司,鳥居ちさほ,進藤正信,大場雄介,樋田京子
    • Organizer
      第46回北海道病理談話会
    • Place of Presentation
      北海道大学医学部学友会館(札幌市)
    • Related Report
      2013 Research-status Report
  • [Presentation] P-gp阻害剤はメトロノミックケモセラピーの血管新生阻害効果を強める2013

    • Author(s)
      秋山廣輔,大賀則孝,樋田泰浩,間石奈湖,Alam MohammadTowfik,川本泰輔,大村瞳,山田健司,鳥居ちさほ,進藤正信,大場雄介,樋田京子
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 腫瘍血管を標的としたMetronomic ChemotherapyとP-gp阻害剤の併用療法の有効性の検討2013

    • Author(s)
      秋山廣輔,大賀則孝,樋田泰浩,間石奈湖,Alam MohammadTowfik,川本泰輔,大村瞳,山田健司,鳥居ちさほ,進藤正信,大場雄介,樋田京子
    • Organizer
      第108回北海道癌談話会例会
    • Place of Presentation
      旭川グランドホテル(旭川市)
    • Related Report
      2013 Research-status Report
  • [Book] 別冊BIO Clinica 慢性炎症と疾患~慢性炎症とがん2016

    • Author(s)
      樋田京子,大賀則孝,間石奈湖,秋山廣輔,樋田泰浩
    • Total Pages
      172
    • Publisher
      北隆館
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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