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Anti-tumor effects and potential therapeutic response biomarkers in alpha-emitting meta-At-211-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing
https://repo.qst.go.jp/records/73849
https://repo.qst.go.jp/records/738493821dcdd-dc10-4a5a-8dc2-f8c45b035cd8
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-02-27 | |||||
| タイトル | ||||||
| タイトル | Anti-tumor effects and potential therapeutic response biomarkers in alpha-emitting meta-At-211-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
大島, 康宏
× 大島, 康宏× 河野, 暢明× 横田, 裕一郎× 渡辺, 茂樹× 佐々木, 一郎× 石岡, 典子× 坂下, 哲哉× 荒川, 和晴× Oshima, Yasuhiro× Yokota, Yuuichiro× Watanabe, Shigeki× Sasaki, Ichiro× Ishioka, Noriko× Sakashita, Tetsuya |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Targeted α-particle therapy is a promising option for patients with malignant pheochromocytoma. Recent observations regarding meta-211At-astato-benzylguanidine (211At-MABG) in a pheochromocytoma mouse model showed a strong anti-tumor effect, though the molecular mechanism remains elusive. Here, we present the first comprehensive RNA-sequencing (RNA-seq) data for pheochromocytoma cells based on in vitro 211At-MABG administration experiments. Key genes and pathways in the tumor α-particle radiation response are also examined to obtain potential response biomarkers. Methods: We evaluated genome-wide transcriptional alterations in the rat pheochromocytoma cell line PC12 at 3, 6, and 12 h after 211At-MABG treatment; a control experiment using 60Co γ-ray irradiation was carried out to highlight 211At-MABG-specific gene expression. For comparisons, 10% and 80% iso-survival doses (0.8 and 0.1 kBq/mL for 211At-MABG and 10 and 1 Gy for 60Co γ-rays) were used. Results: Enrichment analysis of differentially expressed genes (DEGs) and analysis of the gene expression profiles of cell cycle checkpoints revealed similar modes of cell death via the p53-p21 signaling pathway after 211At-MABG treatment and γ-ray irradiation. The top list of ranked DEGs demonstrated the expression of key genes on the decrease in the survival following 211At-MABG exposure, and four potential genes (Mien1, Otub1, Vdac1 and Vegfa genes) of 211At-MABG therapy. Western blot analysis indicated increased expression of TSPO in 211At-MABG-treated cells, suggesting its potential as a PET imaging probe. Conclusion: Comprehensive RNA-seq revealed contrasting cellular responses to γ-ray and α-particle therapy, leading to the identification of four potential candidate genes that may serve as molecular imaging and 211At-MABG therapy targets. |
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| 書誌情報 |
Theranostics 巻 9, 号 6, 発行日 2019-03 |
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| 出版者 | ||||||
| 出版者 | IVYSPRING | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1838-7640 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.7150/thno.30353 | |||||
