ID | 115325 |
Title Alternative | 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
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Author |
Okamoto, Koichi
Tokushima University
Tokushima University Educator and Researcher Directory
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Tanaka, Takahiro
Tokushima University
Tomonari, Tetsu
Tokushima University
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Nakamura, Fumika
Tokushima University
Miyamoto, Hiroshi
Tokushima University
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Muguruma, Naoki
Tokushima University
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Morita, Akinori
Tokushima University
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Keywords | hepatocellular carcinoma
miriplatin
radiation
synergistic effect
apoptosis
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Content Type |
Thesis or Dissertation
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Description | 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. |
Journal Title |
Journal of Gastroenterology
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ISSN | 09441174
14355922
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NCID | AA10988015
AA11627089
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Publisher | Springer Nature|Japanese Society of Gastroenterology
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Volume | 55
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Issue | 11
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Start Page | 1072
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End Page | 1086
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Published Date | 2020-07-14
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Remark | 内容要旨・審査要旨・論文本文の公開
本論文は, 著者Hironori Tanakaの学位論文として提出され, 学位審査・授与の対象となっている。 This is a post-peer-review, pre-copyedit version of an article published in Journal of Gastroenterology. The final authenticated version is available online at: https://doi.org/10.1007/s00535-020-01705-8 |
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3458号
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Diploma Number | 甲医第1465号
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Granted Date | 2020-09-24
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
University Hospital
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