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

使用源自肾细胞癌的肿瘤相关内皮细胞开发新的抗血管生成药物筛选系统

• 批准号: 20591847
• 负责人: SHINOHARA Nobuo
• 金额: $ 2.91万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591847/
• 关键词: 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

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.

为了建立新的抗血管生成药物筛选体系，我们分别从人肾癌移植瘤和正常小鼠真皮中分离正常内皮细胞（NEC）和肿瘤内皮细胞（TEC）。我们分析了TEC与NEC的差异，探讨了TEC作为反映肿瘤微环境的筛选系统的潜力，特别是通过DNA微阵列分析了TEC与NEC相比表达上调的几个基因，发现这些基因与TEC的异常表型如耐药性、高活力、这些结果为我们探索新的抗血管生成药物筛选体系和新的抗血管生成治疗方法提供了可能。

项目成果

Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumors

• DOI: 10.2353/ajpath.2009.090202
• 发表时间: 2009-12-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Akino, Tomoshige;Hida, Kyoko;Shindoh, Masanobu
• 通讯作者: Shindoh, Masanobu

Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization.

• DOI: 10.3892/ijo_00000622
• 发表时间: 2010-06
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: K. Tsuchiya;K. Hida;Y. Hida;C. Muraki;N. Ohga;T. Akino;T. Kondo;T. Miseki;K. Nakagawa;M. Shindoh;T. Harabayashi;N. Shinohara;K. Nonomura;Masanobu Kobayashi

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)

膀胱癌（吉田修、大园精一郎、赤座英幸主编）（知情同意图系列）

• 发表时间: 2010
• 作者: Akamatsu S;Takata R;Ashikawa K;Hosono N;Kamatani N;Fujioka T;Ogawa O;Kubo M;Nakamura Y;Nakagawa H.;篠原信雄
• 通讯作者: 篠原信雄

Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma.

S-1 在细胞因子难治性转移性肾细胞癌患者中的多中心 II 期试验。

• 发表时间: 2010
• 期刊: J Clin Oncol 28
• 作者: Naito S;Eto M;Shinohara N;Tomita Y;Fujisawa M;Namiki M;Nishikido M;Usami M;Tsukamoto T;Akaza H
• 通讯作者: Akaza H

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

癌组织血管内皮细胞从基因表达异常到染色体异常

• 发表时间: 2009
• 作者: 樋田京子;秋野文臣;樋田泰浩
• 通讯作者: 樋田泰浩