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Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma
https://kagawa-u.repo.nii.ac.jp/records/384
https://kagawa-u.repo.nii.ac.jp/records/384d58f5b34-c882-4bb9-89be-1e520d7c491b
| 名前 / ファイル | ライセンス | アクション |
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本文 (2.3 MB)
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審査の結果の要旨 (758.0 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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| 公開日 | 2019-07-17 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma | |||||||||||||
| 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 |
横倉, 繁行
× 横倉, 繁行
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Background: Human multiple myeloma (MM) is an incurable hematological malignancy for which novel therapeutic agents are needed. Calmodulin (CaM) antagonists have been reported to induce apoptosis and inhibit tumor cell invasion and metastasis in various tumor models. However, the antitumor effects of CaM antagonists on MM are poorly understood. In this study, we investigated the antitumor effects of naphthalenesulfonamide derivative selective CaM antagonists W-7 and W-13 on MM cell lines both in vitro and in vivo. | |||||||||||||
| 言語 | en | |||||||||||||
| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Methods: The proliferative ability was analyzed by the WST-8 assay. Cell cycle was evaluated by flow cytometry after staining of cells with PI. Apoptosis was quantified by flow cytometry after double-staining of cells by Annexin-V/PI. Molecular changes of cell cycle and apoptosis were determined by Western blot. Intracellular calcium levels and mitochondrial membrane potentials were determined using Fluo-4/AM dye and JC-10 dye, respectively. Moreover, we examined the in vivo anti-MM effects of CaM antagonists using a murine xenograft model of the human MM cell line. | |||||||||||||
| 言語 | en | |||||||||||||
| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Results: Treatment with W-7 and W-13 resulted in the dose-dependent inhibition of cell proliferation in various MM cell lines. W-7 and W-13 induced G1 phase cell cycle arrest by downregulating cyclins and upregulating p21cip1. In addition, W-7 and W-13 induced apoptosis via caspase activation; this occurred partly through the elevation of intracellular calcium levels and mitochondrial membrane potential depolarization and through inhibition of the STAT3 phosphorylation and subsequent downregulation of Mcl-1 protein. In tumor xenograft mouse models, tumor growth rates in CaM antagonist-treated groups were significantly reduced compared with those in the vehicle-treated groups. | |||||||||||||
| 言語 | en | |||||||||||||
| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Conclusions: Our results demonstrate that CaM antagonists induce cell cycle arrest, induce apoptosis via caspase activation, and inhibit tumor growth in a murine MM model and raise the possibility that inhibition of CaM might be a useful therapeutic strategy for the treatment of MM. | |||||||||||||
| 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 | 2016-03-24 | |||||||||||||
| 学位授与番号 | ||||||||||||||
| 学位授与番号 | 甲第630号 | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報 | Copyright © 2014, Yokokura et al.; licensee BioMed Central Ltd. | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報Resource | http://creativecommons.org/licenses/by/4.0/ | |||||||||||||
| 権利情報 | This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. | |||||||||||||
| 権利 | ||||||||||||||
| 権利情報Resource | http://creativecommons.org/publicdomain/zero/1.0/ | |||||||||||||
| 権利情報 | The Creative Commons Public Domain Dedication waiver applies to the data made available in this article, unless otherwise stated. | |||||||||||||
| 論文ID（NAID） | ||||||||||||||
| 識別子タイプ | NAID | |||||||||||||
| 関連識別子 | 500001356623 | |||||||||||||
| PubMed番号 | ||||||||||||||
| 識別子タイプ | PMID | |||||||||||||
| 関連識別子 | 25424011 | |||||||||||||
| 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/10.1186/1471-2407-14-882 | |||||||||||||
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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/11337594 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | hasVersion | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4258255/ | |||||||||||||
| 著者版フラグ | ||||||||||||||
| 出版タイプ | P | |||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Calmodulin | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Multiple myeloma | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Cell cycle | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Apoptosis | |||||||||||||
| KEID | ||||||||||||||
| 28748 | ||||||||||||||
