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Screening for Synergistic Reagents With Pazopanib Against Osteosarcoma Using a Compound Library
http://hdl.handle.net/10076/0002001116
http://hdl.handle.net/10076/00020011161467df2f-dce1-4385-8903-ef72cefa5eb4
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2024DM0920.pdf (421 KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2024-12-18 | |||||||||
| タイトル | ||||||||||
| タイトル | Screening for Synergistic Reagents With Pazopanib Against Osteosarcoma Using a Compound Library | |||||||||
| 言語 | en | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Pazopanib | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | crizotinib | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | osteosarcoma | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | vascular endothelial growth factor receptor (VEGFR) | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | platelet-derived growth factor receptor (PDGF) | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | c-KIT | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | C-Met | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | ALK | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | ROS-1 | |||||||||
| 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 |
矢田, 祐基
× 矢田, 祐基
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Background/aim: Osteosarcoma (OS) is the most common malignant bone tumor. As the same agents have been in use since the mid-1970s, new therapeutic approaches are needed to improve prognosis. Pazopanib (PZP) has already demonstrated marked antitumor activity clinically and can be effective in patients with metastatic OS. We investigated the combination treatment of candidate agents with PZP and examined effects on tumor growth using an in vivo model. Materials and methods: A library of 324 compounds was used. MG63 OS cells were treated with PZP and each compound. Cell viability was measured. The antiproliferative effects of compound combination on four OS cell lines was tested. Cell signaling was evaluated by western blot analysis. In vivo antitumor testing was performed using 143B-bearing mice. Results: The screening process identified crizotinib (CRZ) as the most effective drug for combination with PZP. The combination of PZP and CRZ demonstrated effects compared to control or single therapy. Cell signal investigation showed that dual therapy down-regulated c-MYC, p-AKT, p-STAT3, p-cyclin D1 and survivin and up-regulated cleaved caspase-3 and cleaved PARP compared to control or single therapy. In vivo analysis showed dual therapy achieved synergic effects for tumor growth compared to control or single-treatment groups. No significant difference in the change in body weight was observed among groups. Conclusion: Combined use of PZP and CRZ offers synergic anti-tumor effects against OS, inducing apoptosis in vitro and in vivo by down-regulating AKT and STAT3. Our data suggest that these agents can be used for patients clinically. |
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| 言語 | en | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 本文/Department of Orthopedic Surgery, Mie University School of Medicine, Tsu, 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 2024-09-25 |
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| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | 10.21873/anticanres.16902 | |||||||||
| フォーマット | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
| 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 | 2024-09-25 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 乙医学第1103号 | |||||||||
| ノート | ||||||||||
| 資源タイプ（三重大） | ||||||||||
| Doctoral Dissertation / 博士論文 | ||||||||||
