Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma

• 資料種別: 博士論文
• ISSN: 0944-1174
• タイトル: Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma
• 巻次・部編番号: 55 11
• 著者・編者: Tanaka, Hironori; Okamoto, Koichi; Sato, Yasushi; Tanaka, Takahiro; Tomonari, Tetsu; Nakamura, Fumika; Fujino, Yasuteru; Mitsui, Yasuhiro; Miyamoto, Hiroshi; Muguruma, Naoki; Morita, Akinori; Ikushima, Hitoshi; Takayama, Tetsuji
• 著者標目: Tanaka, Hironori; Okamoto, Koichi; Sato, Yasushi; Tanaka, Takahiro; Tomonari, Tetsu; Nakamura, Fumika; Fujino, Yasuteru; Mitsui, Yasuhiro; Miyamoto, Hiroshi; Muguruma, Naoki; Morita, Akinori; Ikushima, Hitoshi; Takayama, Tetsuji
• 出版事項: Springer Nature|Japanese Society of Gastroenterology
• 出版年月日等: 2020-07-14
• 出版年（W3CDTF）: 2020-07-14
• 並列タイトル等: ミリプラチン及び放射線はPUMAを介したアポトーシスにより肝細胞癌に相乗効果を示す; Chemoradiotherapy with miriplatin
• タイトル（掲載誌）: Journal of Gastroenterology
• 授与機関名: 徳島大学
• 授与年月日: 2020-09-24
• 授与年月日（W3CDTF）: 2020-09-24
• 報告番号: 甲第3458号
• 学位: 博士（医学）
• 博論授与番号: 甲第3458号
• 本文の言語コード: eng
• 件名標目: hepatocellular carcinoma; miriplatin; radiation; synergistic effect; apoptosis
• 対象利用者: 一般
• 一般注記: Background: The prognosis for patients with unresectable advanced hepatocellular carcinoma (HCC) is poor. Miriplatin is a hydrophobic platinum compound that has a long retention time in lesions after transarterial chemoembolization (TACE). We investigated anti-tumor activity of miriplatin combined with irradiation on HCC cells, and its underlying mechanism of apoptosis. We also analyzed the effectiveness of miriplatin-TACE and radiotherapy for locally advanced HCC.Methods: Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of miriplatin) and radiation, and synergy was evaluated using a combination index (CI). Apoptosis-related proteins and cell cycles were analyzed by western blotting and flowcytometry. We retrospectively analyzed treatment outcomes in 10 unresectable HCC patients with vascular/bile duct invasion treated with miriplatin-TACE and radiotherapy.Results: DPC or X-ray irradiation decreased cell viability dose-dependently. DPC plus irradiation decreased cell viability synergistically in both cell lines (CI<1 respectively). Cleaved PARP expression was induced much more strongly by DPC plus irradiation than by each treatment alone. Expression of p53 up-regulated modulator of apoptosis (PUMA) was significantly induced by the combination, and knockdown of PUMA with siRNA significantly decreased apoptosis in both cell lines. DPC plus irradiation caused sub-G1, G2/M, and S phase cell arrest in those cells. The combination of miriplatin-TACE and radiotherapy showed a high response rate for patients with locally advanced HCC despite small number of patients.Conclusions: Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC.
• DOI: info:doi/10.1007/s00535-020-01705-8; https://doi.org/info:doi/10.1007/s00535-020-01705-8
• 国立国会図書館永続的識別子: info:ndljp/pid/11710908; https://dl.ndl.go.jp/pid/11710908
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2021-08-09T17:15:52+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/115325
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp