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Anti-tumor effects of [At-211]-MABG treatment in PC12 pheochromocytoma cells and cell death via p53-p21 signaling pathway

https://repo.qst.go.jp/records/77532
https://repo.qst.go.jp/records/77532
f822f942-bfba-4294-8a77-8f09b4d7feea
Item type 会議発表用資料 / Presentation(1)
公開日 2019-09-10
タイトル
タイトル Anti-tumor effects of [At-211]-MABG treatment in PC12 pheochromocytoma cells and cell death via p53-p21 signaling pathway
言語
言語 jpn
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_c94f
資源タイプ conference object
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 坂下, 哲哉

× 坂下, 哲哉

WEKO 804570

坂下, 哲哉

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大島, 康宏

× 大島, 康宏

WEKO 804571

大島, 康宏

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河野, 暢明

× 河野, 暢明

WEKO 804572

河野, 暢明

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横田, 裕一郎

× 横田, 裕一郎

WEKO 804573

横田, 裕一郎

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渡辺, 茂樹

× 渡辺, 茂樹

WEKO 804574

渡辺, 茂樹

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佐々木, 一郎

× 佐々木, 一郎

WEKO 804575

佐々木, 一郎

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石岡, 典子

× 石岡, 典子

WEKO 804576

石岡, 典子

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荒川, 和晴

× 荒川, 和晴

WEKO 804577

荒川, 和晴

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Sakashita, Tetsuya

× Sakashita, Tetsuya

WEKO 804578

en Sakashita, Tetsuya

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Oshima, Yasuhiro

× Oshima, Yasuhiro

WEKO 804579

en Oshima, Yasuhiro

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Yokota, Yuuichiro

× Yokota, Yuuichiro

WEKO 804580

en Yokota, Yuuichiro

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Watanabe, Shigeki

× Watanabe, Shigeki

WEKO 804581

en Watanabe, Shigeki

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Sasaki, Ichiro

× Sasaki, Ichiro

WEKO 804582

en Sasaki, Ichiro

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Ishioka, Noriko

× Ishioka, Noriko

WEKO 804583

en Ishioka, Noriko

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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 of α-emitting meta-[At-211]-astato-benzylguanidine ([At-211]-MABG) in a pheochromocytoma mouse model showed a strong anti-tumor effect [1], though the molecular mechanism remained elusive. Here, we show the comprehensive RNA-sequencing (RNA-seq) data for rat pheochromocytoma cell line PC12 cells based on in vitro [At-211]-MABG administration experiments. Enrichment analysis of differentially expressed genes (DEGs) and analysis of the gene expression profiles of cell cycle checkpoints revealed the mode of cell death via the p53-p21 signaling pathway after [At-211]-MABG treatment. Only p53-targeted genes were ranked among representative DEGs for decreased survival at all time points. Also, we estimated the low fluence rate of α-particles in in vitro [At-211]-MABG administration, approximately “one α-particle emission per one cell in one hour” for 10% survival. Long-lasting p53-induced signaling may break the wall of the “low fluence rate” in PC12 tumor cell death to exert anti-tumor effects. We recently published these findings on RNA-seq of in vitro PC12 transcriptome, suggesting that p53-p21 signaling pathway was an important cell death mechanism in anti-tumor effect of [At-211]-MABG [2].

References:
[1] Y. Ohshima et al., Eur J Nucl Med Mol Imaging, 2018.
[2] Y. Ohshima et al., Theranostics, 2019
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 日本放射線影響学会第62回大会
発表年月日
日付 2019-11-15
日付タイプ Issued
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