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

• Material Type: 博士論文
• ISSN: 0944-1174
• Title: Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma
• Volume: 55 11
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: Springer Nature|Japanese Society of Gastroenterology
• Publication Date: 2020-07-14
• Publication Date (W3CDTF): 2020-07-14
• Alternative Title: 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
• Periodical title: Journal of Gastroenterology
• Degree grantor/type: 徳島大学
• Date Granted: 2020-09-24
• Date Granted (W3CDTF): 2020-09-24
• Dissertation Number: 甲第3458号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3458号
• Text Language Code: eng
• Subject Heading: hepatocellular carcinoma; miriplatin; radiation; synergistic effect; apoptosis
• Target Audience: 一般
• Note (General): 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
• Persistent ID (NDL): info:ndljp/pid/11710908; https://dl.ndl.go.jp/pid/11710908
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• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-08-09T17:15:52+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/115325
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