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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
Author
Tanaka, Hironori Tokushima University
Nakamura, Fumika Tokushima University
Keywords
hepatocellular carcinoma
miriplatin
radiation
synergistic effect
apoptosis
Content Type
Thesis or Dissertation
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
ISSN
09441174
14355922
NCID
AA10988015
AA11627089
Publisher
Springer Nature|Japanese Society of Gastroenterology
Published Date
2020-07-14
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。
論文本文は2021-07-14以降公開予定。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
jpn
TextVersion
その他
MEXT report number
甲第3458号
Diploma Number
甲医第1465号
Granted Date
2020-09-24
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital