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Development of new screening system for anti-angiogenic drugs using tumor associated endothelial cells derived from renal cell carcinoma

Research Project

Project/Area Number 20591847
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionHokkaido University

Principal Investigator

SHINOHARA Nobuo  Hokkaido University, 大学院・医学研究科, 准教授 (90250422)

Co-Investigator(Kenkyū-buntansha) HIDA Kyoko  北海道大学, 大学院・歯学研究科, 准教授 (40399952)
NONOMURA Katsuya  北海道大学, 大学院・医学研究科, 教授 (60113750)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords腫瘍血管内皮 / スクリーニング / 薬剤感受性 / 抗がん剤 / 腎癌治療 / 血管新生阻害剤 / 腫瘍血管内皮細胞 / 血管内皮細胞マーカー / 染色体異常
Research Abstract

To develope new screening system for anti-angiogenic drugs, we isolated normal endothelial cell (NEC) and tumor endothelial cell (TEC) from human renal cell carcinoma xenografts and from dermis of normal mice, respectively. We analyzed the difference between TEC and NEC and investigate the potential of TEC for the screening system which reflect tumor microenvironment.
Especially, we focused on several genes which were upregulated in TEC compared to NEC by DNA microarray analysis.
We found these genes had strong association with abnormal phenotypes of TECs such as drug resistance, high viability, and migration.
The specific phenotype in mouse TEC were also found in human TEC isolated from human renal cell carcinoma.
These results enable us to approach new anti-angiogenic drug screening system and new anti-angiogenic therapy.

Report

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

    (27 results)

All 2011 2010 2009 2008

All Journal Article (18 results) (of which Peer Reviewed: 16 results) Presentation (4 results) Book (5 results)

  • [Journal Article] HuR keeps an angiogenic switch on by stabilizing mRNA of VEGF and COX-2 in tumor endothelium2011

    • Author(s)
      Kurosu T, Ohga N, Hida Y, Maishi N, Akiyama K, Kakuguchi W, Kuroshima T, Kondo M, Akino T, Totsuka Y, Shindoh M, Higashino F., Hida K.
    • Journal Title

      Br J Cancer. 104(5)

      Pages: 819-829

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The incidence and the mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma.2011

    • Author(s)
      Shinohara N, Takahashi M, Kamishima T, Ikushima H, Otsuka N, Ishizu A, Shi mazu C, Kanayama H, Nonomura K.
    • Journal Title

      Br J Cancer

      Volume: 104 Pages: 241-247

    • NAID

      120003169038

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolated tumor endothelial cells maintain specific character during long-term culture2010

    • Author(s)
      Matsuda K, Ohga N, Hida Y, Muraki C, Kurosu T, Tsuchiya K, Akino T, Shih SC, Totsuka Y, Klagsbrun M, Shindoh M., Hida K.
    • Journal Title

      Biochem Biophys Res Commun. 394

      Pages: 947-954

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma : insights into the treatment, efficacy and safety.2010

    • Author(s)
      Uemura H, Shinohara N, Yuasa T, Tomita Y, Fujimoto H, Niwakawa M, Mugiya S, Miki T, Nonomura N, Takahashi M, Hasegawa Y, Agata N, Houk B, Naito S, Akaza H
    • Journal Title

      Jap J Clin Oncol 40

      Pages: 194-202

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization.2010

    • Author(s)
      Tsuchiya K, Hida K, Hida Y, Muraki C, Ohga N, Akino T, Kondo T, Miseki T, Nakagawa K, Shindoh M, Harabayashi T, Shinohara N, Nonomura K, Kobayashi M
    • Journal Title

      Int J Oncol. 36(6)

      Pages: 1379-86

    • NAID

      120003370695

    • Related Report
      2010 Final Research Report
  • [Journal Article] The incidence and the mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma.2010

    • Author(s)
      Shinohara N, Takahashi M, Kamishima T, Ikushima H, Otsuka N, Ishizu A, Shimazu C, Kanayama H, Nonomura K
    • Journal Title

      Br J Cancer 104

      Pages: 241-247

    • NAID

      120003169038

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overall survival and updated results from a Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cwll Carcinoma.2010

    • Author(s)
      Tomita Y, Shinohara N, Yuasa T, Fujimoto H, Niwakawa M, Mugiya S, Miki T, Uemura H, Nonomura K, Takahashi M, Hasegawa Y, Agata N, Houk B, Naito S, Akaza H
    • Journal Title

      Jpn J Clin Oncol. 40(12)

      Pages: 1166-72

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma.2010

    • Author(s)
      Naito S, Eto M, Shinohara N, Tomita Y, Fujisawa M, Namiki M, Nishikido M, Usami M, Tsukamoto T, Akaza H
    • Journal Title

      J Clin Oncol 28

      Pages: 5022-5028

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overall survival and updated results from a Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cwll Ca rcinoma.2010

    • Author(s)
      Tomita Y, Shinohara N, Yuasa T, Fujimo to H, Niwakawa M, Mugiya S, Mild T, Uemura H, Nonomura K, Takahashi M, Hasegawa Y, Agata N, Houk B, Naito S, Akaza H.
    • Journal Title

      Jpn J Clin Oncol.

      Volume: 40(12) Pages: 1166-72

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multicenter phase II trial of S-1 in patients with cytokine-refra ctory metastatic renal cell carcinoma.2010

    • Author(s)
      Naito S, Eto M, Shinohara N, Tomita Y, Fujisawa M, Namiki M, Nishikido M, Usami M, Tsukamoto T, Akaza H.
    • Journal Title

      J Clin Onool

      Volume: 28 Pages: 5022-5028

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma : insights into the treatment, efficacy and safety.2010

    • Author(s)
      Uemura H, Shinohara N, Yuasa T, Tomita Y, Fujimoto H, Niwakawa M, Mugiya S, Miki T, Nonomura N, Takahashi M, Hasegawa Y, Agata N, Houk B, Naito S, Akaza H.
    • Journal Title

      Jap J Clin Oncol 40

      Pages: 194-202

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multi-center phase II trial of combination therapy with meloxicam, a COX-2 inhibitor, and natural interferon alfa for metastatic renal cell carcinoma.2009

    • Author(s)
      Shinohara N, Kumagai A, Kanagawa K, Maruyama S, Abe T, Sazawa A, Nonomura K
    • Journal Title

      Jap J Clin Oncol 39

      Pages: 720-726

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors.2009

    • Author(s)
      Akino T, Hida K, Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, Matsuda K, Akiyama K, Harabayashi T, Shinohara N, Nonomura K, Klagsbrun M, Shindoh M
    • Journal Title

      Am J Pathol 175

      Pages: 2657-2667

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multi-center phase II trial of combination therapy with meloxicam, a COX-2 inhibitor, and natural interferon alfa for metastatic renal cell carcinoma.2009

    • Author(s)
      Shinohara N, Kumagai A, Kanagawa K, Maruyama S, Abe T, Sazawa A, Nonomura K.
    • Journal Title

      Jap J Clin Oncol 39

      Pages: 720-726

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors.2009

    • Author(s)
      Akino T, Hida K, Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, Matsuda K, Akiyama K, Harabayashi T, Shinohara N, Nonomura K, Klagsbrun M, Shindoh M.
    • Journal Title

      Am J Pathol 175

      Pages: 2657-2667

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      冨田善彦, 金山博臣, 植村天受, 篠原信雄
    • Journal Title

      Year Book of RCC 2009(メディカルレビュー社)

      Pages: 1-256

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Adrenomedullin antagoniustのヌードマウス移植腎細胞癌に対する血管新生抑制を介した増殖抑制効果-腎細胞癌組織由来腫瘍血管内皮細胞を用いたメカニズム解析-2008

    • Author(s)
      土屋邦彦
    • Journal Title

      北海道医学雑誌 83

      Pages: 369-376

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Understanding Abnormality of Tumor Endothelial Cells to Develop Ideal Anti-angiogenic Therapies2008

    • Author(s)
      Hida K, Hida Y. and Shindoh M.
    • Journal Title

      Can Sci 99(3)

      Pages: 459-466

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Gene expression analysis of circulating endothelial cells in cancer patients.2010

    • Author(s)
      Kondoh M, Ohga N, Kurosu T, Kitayama K, Akiyama K, Maishi N, Kawamoto T, Ohsawa T, Yamamoto K, Hida Y, Shindoh M., Hida K.
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Final Research Report
  • [Presentation] The role of cytoreductive nephrectomy for patients with metastatic renal cell cartinoma.2010

    • Author(s)
      Shinohara N
    • Organizer
      27^<th> Japan-Korea Urological Congress
    • Place of Presentation
      ウエスティン都ホテル京都
    • Year and Date
      2010-09-11
    • Related Report
      2010 Final Research Report
  • [Presentation] The role of cytoreductive nephrectomy for patients with metast atic renal cell cartinoma.2010

    • Author(s)
      Shinohara N.
    • Organizer
      27th Japan-Korea Urological Congress
    • Place of Presentation
      ウエスティン都ホテル京都 招待講演
    • Year and Date
      2010-09-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cytogenetic Abnormalities of Tumor Endothelial Cells in Human Malignant Tumors.2010

    • Author(s)
      Hida K, Akino T., Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, Matsuda K, Akiyama K, Kurosu T, Kondo M, Maishi N, Harabayashi T, Shinohara N, Nonomura K, Klagsbrun M., Shindoh M.
    • Organizer
      AACR 101st ANNUAL MEETING 2010.
    • Place of Presentation
      Washington DC
    • Year and Date
      2010-04-17
    • Related Report
      2010 Final Research Report
  • [Book] 膀胱がん(吉田修、大園誠一郎、赤座英之編)(インフォームドコンセントのための図解シリーズ)2010

    • Author(s)
      篠原信雄
    • Publisher
      医薬ジャーナル社
    • Related Report
      2010 Final Research Report
  • [Book] 膀胱がん(吉田修、大園誠一郎、赤座英之編)インフォームドコンセントのための図解シリーズ2010

    • Author(s)
      篠原信雄
    • Publisher
      医薬ジャーナル社
    • Related Report
      2010 Annual Research Report
  • [Book] がん組織中の血管内皮細胞の異常性-遺伝子発現から染色体異常まで2009

    • Author(s)
      樋田京子、秋野文臣、樋田泰浩
    • Publisher
      羊土社
    • Related Report
      2010 Final Research Report
  • [Book] Year Book of RCC 20092009

    • Author(s)
      冨田善彦、金山博臣、植村天受、篠原信雄
    • Publisher
      メディカルレビュー社
    • Related Report
      2010 Final Research Report
  • [Book] がん組織中の血管内皮細胞の異常性一遺伝子発現から染色体異常まで2009

    • Author(s)
      樋田京子、秋野文臣、樋田泰浩
    • Publisher
      羊土社
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2021-12-20  

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