並列タイトル等抗がん剤α-SQAPはマウス悪性胸膜中皮腫モデルにおいて放射線感受性を増強する
タイトル(掲載誌)Journal of Radiation Research
授与機関名Nagasaki University (長崎大学)
一般注記Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1377号 学位授与年月日:令和3年12月1日
Author: Eiko Inamasu, Tomoshi Tsuchiya, Motohiro Yamauchi, Kodai Nishi, Katsuya Matsuda, Fumio Sugawara, Kengo Sakaguchi, Ryoichi Mori, Keitaro Matsumoto, Takuro Miyazaki, Go Hatachi, Ryoichiro Doi, Hironosuke Watanabe, Koichi Tomoshige, Naoki Matsuda, Yoshikazu Higami, Isao Shimokawa, Masahiro Nakashima, Takeshi Nagayasu
Citation: Journal of Radiation Research, 63(1), pp. 19–29; 2022
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-12-01)
一次資料へのリンクURLhttps://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27102&item_no=1&attribute_id=70&file_no=1 (fulltext)
著作権情報© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
関連情報http://hdl.handle.net/10069/00041138
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)