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| 題名: | Novel multi-drugs incorporating hybrid-structured nanofibers enhance alkylating agent activity in malignant gliomas. |
| 作者: | 曾元昀
Shih-Jung Liu, Shun-Tai Yang, Shu-Mei Chen, Yin-Chen Huang, Wei-Hwa Lee, Jui Ho, Yin-Chun Chen, Yuan-Yun Tseng |
| 貢獻者: | 醫學系外科學科 |
| 日期: | 2019-09 |
| 上傳時間: | 2025-04-02 16:45:00 (UTC+8) |
| 摘要: | Abstract
Background: Malignant gliomas (MGs) are highly chemotherapy-resistant. Temozolomide (TMZ) and carmustine (BiCNU) are alkylating agents clinically used for treating MGs. However, their effectiveness is restrained by overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in tumors. O6-benzylguanine (O6-BG) is a nonreversible inhibitor of MGMT, it promotes the cytotoxicity of alkylating chemotherapy. The authors have developed a hybrid-structured nanofibrous membrane (HSNM) that sequentially delivers high concentrations of O6-BG, BiCNU, and TMZ in an attempt to provide an alternative to the current therapeutic options for MGs.
Methods: The HSNMs were implanted onto the cerebral surface of pathogen-free rats following surgical craniectomy, while the in vivo release behaviors of O6-BG, TMZ, and BiCNU from the HSNMs were explored. Subsequently, the HSNMs were surgically implanted onto the brain surface of two types of tumor-bearing rats. The survival rate, tumor volume, malignancy of tumor, and apoptotic cell death were evaluated and compared with other treatment regimens.
Results: The biodegradable HSNMs sequentially and sustainably delivered high concentrations of O6-BG, BiCNU, and TMZ for more than 14 weeks. The tumor-bearing rats treated with HSNMs demonstrated therapeutic advantages in terms of retarded and restricted tumor growth, prolonged survival time, and attenuated malignancy.
Conclusion: The results demonstrated that O6-BG potentiates the effects of interstitially transported BiCNU and TMZ. Therefore, O6-BG may be required for alkylating agents to offer maximum therapeutic benefits for the treatment of MGMT-expressing tumors. In addition, the HSNM-supported chemoprotective gene therapy enhanced chemotherapy tolerance and efficacy. It can, therefore, potentially provide an improved therapeutic alternative for MGs. |
| 關聯: | Ther Adv Med Oncol. 2019 Sep 26; 11: 1758835919875555 |
| 描述: | 【109-1 升等】臺北醫學大學教師升等專門著作
職別：專任
送審等級：教授
著作送審 |
| 資料類型: | article |
| 顯示於類別: | [教師升等送審著作] 109
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