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Oral Naftopidil Suppresses Human Renal-Cell Carcinoma by Inducing G1 Cell-Cycle Arrest in Tumor and Vascular Endothelial Cells
http://hdl.handle.net/10076/00020028
http://hdl.handle.net/10076/00020028ea3de5fe-427b-420a-82ad-aee9957aa0fd
| 名前 / ファイル | ライセンス | アクション |
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2013DM019 (929.9 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2021-12-09 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Oral Naftopidil Suppresses Human Renal-Cell Carcinoma by Inducing G1 Cell-Cycle Arrest in Tumor and Vascular Endothelial Cells | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
岩本, 陽一
× 岩本, 陽一
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, several targeting agents are being investigated. However, the efficacy of current regimens is generally insufficient for their toxicity and poor overall response rates. We have recently reported that naftopidil exerts growth-inhibitory effects on human prostate cancer cells. In this study, we investigated the biochemical mechanisms by which naftopidil produces growth-inhibitory and antiangiogenic effects on RCC. We first tested the effects of naftopidil on the proliferation of ACHN and Caki-2 RCC cells. Next, we set up a model simulating the tumor microenvironment, in which ACHN cells were grafted onto the renal capsule of mice. We then tested the effects of naftopidil on human umbilical vein endothelial cells’ cell proliferation and Matrigel plug vascularization. Finally, to establish the antitumor activity of naftopidil on RCC, we tested the antitumor effects of naftopidil on excised tumor specimens from 20 patients with RCC that were grafted beneath the renal capsule of mice. Naftopidil showed similar in vitro growth-inhibitory effects on all cell lines. Fluorescence-activated cell sorting analysis revealed an increase in G1 cell-cycle arrest in all naftopidil-treated cell lines. In vivo tumorigenic studies showed a significant reduction of ACHN tumor weight, Ki-67 index, and microvessel density (MVD) in naftopidil-treated mice. Naftopidil attenuated neovascularization in an in vivo Matrigel plug assay. Studies in mouse xenograft models also showed a significant MVD reduction in naftopidil-treated excised human RCC. The growth-inhibitory effects of naftopidil suggest it may be a novel anticancer agent and a potential preventive option for RCC. | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 本文/Departments of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Mie, Japan | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 8p | |||||||||||
| 書誌情報 |
発行日 2014-03-25 |
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| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.1158/1940-6207.CAPR-13-0095 | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 三重大学 | |||||||||||
| 出版者（ヨミ） | ||||||||||||
| ミエダイガク | ||||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 14101 | |||||||||||
| 学位授与機関名 | 三重大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2014-03-25 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲医学第1653号 | |||||||||||
| ノート | ||||||||||||
| 資源タイプ（三重大） | ||||||||||||
| Doctoral Dissertation / 博士論文 | ||||||||||||
