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

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591847
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Hokkaido 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
• Keywords: 腫瘍血管内皮 / スクリーニング / 薬剤感受性 / 抗がん剤

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.

Research Products

• [Journal Article] HuR keeps an angiogenic switch on by stabilizing mRNA of VEGF and COX-2 in tumor endothelium (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Isolated tumor endothelial cells maintain specific character during long-term culture (2010)
  • 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
  • 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
  • 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
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
  • Total Pages: 54-57
  • Publisher: 医薬ジャーナル社
• [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
  • Total Pages: 149-155
  • Publisher: 羊土社
• [Book] Year Book of RCC 2009 (2009)
  • Author(s): 冨田善彦、金山博臣、植村天受、篠原信雄
  • Total Pages: 1-256
  • Publisher: メディカルレビュー社