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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.\nMethods: 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.\nResults: 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.\nConclusion: 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.", "subitem_description_type": "Abstract"}]}, "item_8_publisher_8": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "IVYSPRING"}]}, "item_8_relation_14": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "10.7150/thno.30353", "subitem_relation_type_select": "DOI"}}]}, "item_8_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1838-7640", "subitem_source_identifier_type": "ISSN"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "metadata only access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_14cb"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "大島, 康宏"}], "nameIdentifiers": [{"nameIdentifier": "872905", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "河野, 暢明"}], "nameIdentifiers": [{"nameIdentifier": "872906", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "横田, 裕一郎"}], "nameIdentifiers": [{"nameIdentifier": "872907", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "渡辺, 茂樹"}], "nameIdentifiers": [{"nameIdentifier": "872908", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "佐々木, 一郎"}], "nameIdentifiers": [{"nameIdentifier": "872909", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "石岡, 典子"}], "nameIdentifiers": [{"nameIdentifier": "872910", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "坂下, 哲哉"}], "nameIdentifiers": [{"nameIdentifier": "872911", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "荒川, 和晴"}], "nameIdentifiers": [{"nameIdentifier": "872912", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Oshima, Yasuhiro", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "872913", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yokota, Yuuichiro", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "872914", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Watanabe, Shigeki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "872915", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sasaki, Ichiro", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "872916", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ishioka, Noriko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "872917", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sakashita, Tetsuya", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "872918", "nameIdentifierScheme": "WEKO"}]}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Anti-tumor effects and potential therapeutic response biomarkers in alpha-emitting meta-At-211-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Anti-tumor effects and potential therapeutic response biomarkers in alpha-emitting meta-At-211-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing"}]}, "item_type_id": "8", "owner": "1", "path": ["1"], "permalink_uri": "https://repo.qst.go.jp/records/73849", "pubdate": {"attribute_name": "公開日", "attribute_value": "2019-02-27"}, "publish_date": "2019-02-27", "publish_status": "0", "recid": "73849", "relation": {}, "relation_version_is_last": true, "title": ["Anti-tumor effects and potential therapeutic response biomarkers in alpha-emitting meta-At-211-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing"], "weko_shared_id": -1}
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) | |||||
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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 |