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Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases
http://hdl.handle.net/10271/0002000103
http://hdl.handle.net/10271/0002000103343d3b50-1e5a-4988-8315-5d8ad1138d5b
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
DT_926ronbun.pdf (3.1 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2024-03-11 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases | |||||||||||
| 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 | |||||||||||
| その他のタイトル | ||||||||||||
| その他のタイトル | 肺がん脳転移モデルに対するmodified HSV-TK発現ヒト脱落乳歯歯髄幹細胞 (SHED) を用いたTK/GCV自殺遺伝子療法の有効性 | |||||||||||
| 著者 |
大石, 知也
× 大石, 知也
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| 書誌情報 |
en : Molecular Therapy - Methods & Clinical Development 巻 26, p. 253-265, 発行日 2022-09-08 |
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| 出版者 | ||||||||||||
| 出版者 | Elsevier | |||||||||||
| 言語 | en | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | (C) 2022 The Authors. | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||||||||
| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Lung cancer is one of the most common cancers, and the number of patients with intracranial metastases is increasing. Previously, we developed an enzyme prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVTK)/ganciclovir (GCV) system using various mesenchymal stem cells to induce apoptosis in malignant gliomas through bystander killing effects. Here, we describe stem cells from human exfoliated deciduous teeth (SHED) as gene vehicles of the TK/GCV system against a brain metastasis model of non-small cell lung cancer (NSCLC). We introduced the A168H mutant TK (TKA168H) into SHED to establish the therapeutic cells because of the latent toxicity of wild type. SHED expressing TKA168H (SHED-TK) exhibited chemotaxis to the conditioned medium of NSCLC and migrated toward implanted NSCLC in vivo. SHED-TK demonstrated a strong bystander effect in vitro and in vivo and completely eradicated H1299 NSCLC in the brain. SHED-TK cells implanted intratumorally followed by GCV administration significantly suppressed the growth of H1299 and improved survival time. These results indicate that the TKA168H variant is suitable for establishing therapeutic cells and that intratumoral injection of SHED-TK followed by GCV administration may be a useful strategy for therapeutic approaches. | |||||||||||
| 言語 | en | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士（医学） | |||||||||||
| 学位の区分 | ||||||||||||
| 内容記述 | dotoral | |||||||||||
| 学位の分野 | ||||||||||||
| 内容記述 | 医学系研究科 | |||||||||||
| 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 | 13802 | |||||||||||
| 学位授与機関名 | 浜松医科大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2023-03-16 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第926号 | |||||||||||
| EISSN | ||||||||||||
| 収録物識別子タイプ | EISSN | |||||||||||
| 収録物識別子 | 2329-0501 | |||||||||||
| PubMed番号 | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 35892087 | |||||||||||
| 出版社DOI | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1016/j.omtm.2022.07.001 | |||||||||||
| 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 | |||||||||||
