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Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells
https://kagawa-u.repo.nii.ac.jp/records/235
https://kagawa-u.repo.nii.ac.jp/records/235ba50673d-7704-426e-9fc8-fe7862ec2909
| 名前 / ファイル | ライセンス | アクション |
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本文 (1.7 MB)
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内容の要旨 (64.3 kB)
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審査の結果の要旨 (86.4 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2019-07-31 | |||||||||
| タイトル | ||||||||||
| タイトル | Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer 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 |
Ahmed, Syed Minhaj Uddin
× Ahmed, Syed Minhaj Uddin
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in a variety of tumor cells by engaging the death receptors 4 (DR4) and 5 (DR5). We investigated the effect of chemotherapeutic drugs on DR4-mediated apoptosis in human bladder cancer cells, using a human monoclonal agonistic antibody specific for DR4, mapatumumab. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Synergy was assessed by isobolographic analysis. Treatment of human bladder cancer T24 cells with mapatumumab in combination with mitomycin C, vinblastine or gemcitabine did not overcome resistance to these agents. However, treatment with mapatumumab in combination with epirubicin (EPI) had a synergistic cytotoxic effect. Synergy was also obtained in KU7 and RT112 human bladder cancer cells. A synergistic effect was also observed with mapatumumab in combination with pirarubicin. The synergy obtained in cytotoxicity with mapatumumab and EPI was also achieved in apoptosis. EPI markedly increased DR4 expression in the bladder cancer cells at both the mRNA and protein levels. Furthermore, the combination-induced cytotoxicity was significantly suppressed by the DR4:Fc chimeric protein. The combination of EPI and mapatumumab significantly activated the caspase cascade, including caspase-8, -9 and -3, which are the downstream molecules of death receptors. These findings indicate that EPI sensitizes bladder cancer cells to DR4-mediated apoptosis through induction of DR4 and activation of caspases, suggesting that the combination therapy of EPI and mapatumumab may be effective for bladder cancer therapy. |
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| 言語 | en | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士（医学） | |||||||||
| 学位授与機関 | ||||||||||
| 識別子Scheme | kakenhi | |||||||||
| 識別子 | 16201 | |||||||||
| 言語 | ja | |||||||||
| 機関名 | 香川大学 | |||||||||
| 言語 | en | |||||||||
| 機関名 | Kagawa University | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2015-03-24 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第603号 | |||||||||
| 論文ID（NAID） | ||||||||||
| 識別子タイプ | NAID | |||||||||
| 関連識別子 | 500001358799 | |||||||||
| PubMed番号 | ||||||||||
| 識別子タイプ | PMID | |||||||||
| 関連識別子 | 25483927 | |||||||||
| 関連サイト | ||||||||||
| 関連タイプ | isVersionOf | |||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.3892/or.2014.3654 | |||||||||
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| 関連タイプ | isIdenticalTo | |||||||||
| 識別子タイプ | URI | |||||||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11344363 | |||||||||
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| 出版タイプ | P | |||||||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||||||
| KEID | ||||||||||
| 27642 | ||||||||||
