دورية أكاديمية
Novel multi-drugs incorporating hybrid-structured nanofibers enhance alkylating agent activity in malignant gliomas
| العنوان: | Novel multi-drugs incorporating hybrid-structured nanofibers enhance alkylating agent activity in malignant gliomas |
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| المؤلفون: | Shih-Jung Liu, Shun-Tai Yang, Shu-Mei Chen, Yin-Chen Huang, Wei-Hwa Lee, Jui Ho, Yin-Chun Chen, Yuan-Yun Tseng |
| المصدر: | Therapeutic Advances in Medical Oncology, Vol 11 (2019) |
| بيانات النشر: | SAGE Publishing, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | 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 O 6 -methylguanine-DNA methyltransferase (MGMT) in tumors. O 6 -benzylguanine (O 6 -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 O 6 -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 O 6 -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 O 6 -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 O 6 -BG potentiates the effects of interstitially transported BiCNU and TMZ. Therefore, O 6 -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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1758-8359 17588359 |
| العلاقة: | https://doaj.org/toc/1758-8359Test |
| DOI: | 10.1177/1758835919875555 |
| الوصول الحر: | https://doaj.org/article/3c56cf15b42e4fa68f3bb6c68bbb2396Test |
| رقم الانضمام: | edsdoj.3c56cf15b42e4fa68f3bb6c68bbb2396 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17588359 |
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| DOI: | 10.1177/1758835919875555 |