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Potent effect of adenoviral vector expressing short hairpin RNA targeting ribonucleotide reductase large subunit M1 on cell viability and chemotherapeutic sensitivity to gemcitabine in non-small cell lung cancer cells
https://kagawa-u.repo.nii.ac.jp/records/375
https://kagawa-u.repo.nii.ac.jp/records/37535523014-8b81-446b-b9cf-9ad4c94fd9d3
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本文 (4.1 MB)
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内容の要旨 (50.0 kB)
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審査の結果の要旨 (432.1 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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| 公開日 | 2019-07-11 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Potent effect of adenoviral vector expressing short hairpin RNA targeting ribonucleotide reductase large subunit M1 on cell viability and chemotherapeutic sensitivity to gemcitabine in non-small cell lung 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 |
徳永, 義昌
× 徳永, 義昌
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Background: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides used during DNA synthesis. It is also a cellular target for gemcitabine (GEM). Overexpression of RRM1 is reportedly associated with resistance to GEM and the poor prognosis for many types of malignant tumours. Aim of the present study is to establish gene therapy against RRM1-overexpressing tumours. | |||||||||||||
| 言語 | en | |||||||||||||
| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Method: An adenoviral vector that encoded a short hairpin siRNA targeting the RRM1 gene (Ad-shRRM1) was constructed. Two RRM1-overexpressing non-small cell lung cancer (NSCLC) lines, MAC10 and RERF-LC-MA, were used. Finally, a human tumour xenograft model in nude mice was prepared by subcutaneously implanting tumours derived from RERF-LC-MA cells. | |||||||||||||
| 言語 | en | |||||||||||||
| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Results: Ad-shRRM1 effectively downregulated RRM1 mRNA and protein in both types of NSCLC cells and significantly reduced the percentage of viable cells as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (p<0.005). Caspase 3/7 analysis revealed that transfection with Ad-RRM1 increased the percentage of apoptotic cells in culture containing either type of RRM1-overexpressing cell (p<0.001). Treatment with Ad-shRRM1 exerted a potent antitumour effect against the RRM1-overexpressing RERF-LC-MA xenografts (p<0.05). Furthermore, Ad-shRRM1-mediated inhibition of RRM1 specifically increased sensitivity to gemcitabine of each type of RRM1-overexpressing tumour cell. Combination treatment with Ad-shRRM1 and GEM exerted significantly greater inhibition on cell proliferation than Ad-shRRM1 or GEM treatment alone. | |||||||||||||
| 言語 | en | |||||||||||||
| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Conclusion: RRM1 appeared to be a promising target for gene therapy, and Ad-shRRM1 had strong antitumour effects, specifically anti-proliferative and pro-apoptotic effects, against NSCLC cells that overexpressed RRM1. Combination therapy with Ad-shRRM1 and GEM may become a new treatment option for patients with NSCLC. | |||||||||||||
| 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621号 | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報 | Copyright © 2015 Elsevier Ltd. All rights reserved. | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | ja | |||||||||||||
| 権利情報 | この博士論文の本文については、次のエルゼビアの著作権ポリシーの規定により公開しています。「博士論文の場合は、エンバーゴ期間に関係なく機関リポジトリに出版社版を公開することができます。」 | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報 | The text of this doctoral dissertation is published according to the following Elsevier copyright policy. "In the case of doctoral dissertations, publishers can be published in institutional repositories regardless of the Embargo period." | |||||||||||||
| 論文ID（NAID） | ||||||||||||||
| 識別子タイプ | NAID | |||||||||||||
| 関連識別子 | 500001356491 | |||||||||||||
| PubMed番号 | ||||||||||||||
| 識別子タイプ | PMID | |||||||||||||
| 関連識別子 | 26254808 | |||||||||||||
| 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/10.1016/j.ejca.2015.05.013 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11337525 | |||||||||||||
| 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 | RRM1 | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | shRNA | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Adenovirus | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Gene therapy | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Gemcitabine | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Chemotherapeutic sensitivity | |||||||||||||
| KEID | ||||||||||||||
| 28739 | ||||||||||||||
