著者・編者Bureta, Costansia Anselim
学位博士(医学)
Doctor of Philosophy in Medical Science
一般注記博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
The treatment of glioblastoma is a critical health issue, owing to its resistance to chemotherapy. The current standard of treatment is surgical resection, followed by adjuvant radiotherapy and temozolomide treatment. Long‑term local treatment of glioblastoma is rarely achieved and the majority of the patients undergo relapse. Resistance to temozolomide emerges from numerous signalling pathways that are altered in glioblastoma, including the Hedgehog signalling pathway. Hence, further research is required to identify effective treatment modalities. We investigated the effect of vismodegib, arsenic trioxide and temozolomide on glioblastoma in vitro and in vivo to apply our findings to the clinical setting. WST‑1 assay revealed that glioblastoma proliferation was inhibited following treatment with these drugs either in single or in combination; this synergistic effect was confirmed by CalcuSyn software. Western blot analysis revealed an increase in the expression of cleaved caspase‑3 and γH2AX. Furthermore, there was marked inhibition and decreased tumour growth in mice that received combination therapy, unlike those that received single agent or vehicle treatment. Our results revealed that the combination of arsenic trioxide/vismodegib and temozolomide may be an attractive therapeutic method for the treatment of glioblastoma.
Costansia Bureta, Yoshinobu Saitoh, Hiroto Tokumoto, Hiromi Sasaki, Shingo Maeda, Satoshi Nagano, Setsuro Komiya, Noboru Taniguchi, Takao Setoguchi
Synergistic effect of arsenic trioxide, vismodegib and temozolomide on glioblastoma
Oncology Reports 2019 41(6) 3404-3412
https://doi.org/10.3892/or.2019.7100
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）