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The FGF1/CPP-C chimera protein protects against intestinal adverse effects of C-ion radiotherapy without exacerbating pancreatic carcinoma
https://repo.qst.go.jp/records/49223
https://repo.qst.go.jp/records/49223c09d30e8-55e6-4926-a93c-80ac940a649c
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-10-30 | |||||
タイトル | ||||||
タイトル | The FGF1/CPP-C chimera protein protects against intestinal adverse effects of C-ion radiotherapy without exacerbating pancreatic carcinoma | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
川野, 光子
× 川野, 光子× 三浦, 太一× 藤田, 真由美× 小池, 幸子× 今留, 香織× 石川, 敦子× 安田, 武嗣× 今村, 亨× 今井, 高志× 中山, 文明× Kawano, Mitsuko× Miura, Taichi× Fujita, Mayumi× Koike, Sachiko× Imadome, Kaori× Ishikawa, Atsuko× Yasuda, Takeshi× Imamura, Toru× Imai, Takashi× Nakayama, Fumiaki |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background and purpose: Carbon ion (C-ion) beams are concentrated to irradiate pancreatic carcinoma in the upper abdomen; however, this radiotherapy potentially causes adverse reactions in the gastrointestinal tract. FGF1 is a candidate radioprotector for radiation-induced intestinal damage, but may promote the malignancy of pancreatic cancer. An FGF1/CPP-C chimeric protein was created to enhance the intracellular signaling mode of FGF1 instead of FGFR signaling. The present study investigated the effects of FGF1/CPP-C on the intestinal adverse reactions of C-ion radiotherapy as well as its influence on the malignancy of pancreatic cancer. Materials and methods: FGF1/CPP-C was administered intraperitoneally to BALB/c mice without heparin 12 h before total body irradiation (TBI) with low-LET C-ion (17 keV/lm) at 6–8 Gy. Several radioprotective effects were examined in the jejunum. The invasion and migration of the human pancreatic carcinoma cell lines MIAPaCa-2 and PANC-1 were assessed using Boyden chambers after cultures with FGF1/CPP-C. Results: The FGF1/CPP-C treatment promoted crypt survival after C-ion irradiation at 7–8 Gy significantly more than the FGF1 treatment. FGF1/CPP-C also inhibited C-ion radiotherapy-induced apoptosis and reduced cH2AX foci in crypt cells more than FGF1. However, FGF1/CPP-C inhibited the downstream signaling pathways of FGFRs and suppressed the activation of cell-cycle regulatory molecules in the intestine until 4 h after TBI. Furthermore, IEC6 cells were arrested in G2M after cultures with FGF1/CPP-C or FGF1, suggesting that DNA repair after irradiation is promoted by FGF1/CPP-C-induced G2M arrest. In contrast, FGF1/CPP-C appeared to be internalized into MIAPaCa-2 and PANC-1 cells more efficiently than FGF1. Therefore, FGF1/CPP-C reduced the in vitro proliferation, invasion, and migration of MIAPaCa-2 and PANC-1 cells significantly more than FGF1 through the cellular internalization of FGF1. Conclusion: These results suggest that the intracellular signaling mode of FGF1/CPP-C attenuates the intestinal adverse effects of C-ion radiotherapy without enhancing the malignancy of pancreatic carcinoma. |
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書誌情報 |
Clinical and Translational Radiation Oncology 巻 14, p. 8-16, 発行日 2019-01 |
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出版者 | ||||||
出版者 | ELSEVIER | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2405-6308 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.ctro.2018.10.004 | |||||
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識別子タイプ | URI | |||||
関連識別子 | https://www.sciencedirect.com/science/article/pii/S2405630818300715?via%3Dihub |