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  1. 原著論文

Regulation of gene expression in retrovirus vectors by X-ray and proton beam radiation with artificially constructed promoters

https://repo.qst.go.jp/records/46967
https://repo.qst.go.jp/records/46967
c1eda8a2-4a63-4294-a31b-98ca960112aa
Item type 学術雑誌論文 / Journal Article(1)
公開日 2014-11-26
タイトル
タイトル Regulation of gene expression in retrovirus vectors by X-ray and proton beam radiation with artificially constructed promoters
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 Ogawa, Ryohei

× Ogawa, Ryohei

WEKO 468764

Ogawa, Ryohei

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Morii, Akihiro

× Morii, Akihiro

WEKO 468765

Morii, Akihiro

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Watanabe, Akihiko

× Watanabe, Akihiko

WEKO 468766

Watanabe, Akihiko

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Cui, Zheng-Guo

× Cui, Zheng-Guo

WEKO 468767

Cui, Zheng-Guo

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Kagiya, Go

× Kagiya, Go

WEKO 468768

Kagiya, Go

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Fukuda, Shigekazu

× Fukuda, Shigekazu

WEKO 468769

Fukuda, Shigekazu

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et.al

× et.al

WEKO 468770

et.al

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福田 茂一

× 福田 茂一

WEKO 468771

en 福田 茂一

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抄録
内容記述タイプ Abstract
内容記述 BACKGROUND:
\nWe previously obtained an X-ray responsive promoter from 11 promoters that we constructed. In the present study, we aimed to determine the efficiency of our promoter construction method. In addition, the reactivity of the promoter to X-rays in vivo is also investigated.
METHODS:
\nPromoters constructed by linking the TATA box to randomly combined binding sequences of transcription factors activated by radiation were cloned to prepare a promoter library. Combinations of promoters and various genes were stably-transfected into HeLa cells to establish recombinant cell lines, which were then exposed to X-rays or a proton beam to observe gene expression enhancement with or without anti-oxidants. Tumors of luciferase-expressing recombinant cells on mice were exposed to X-rays and promoter activation was evaluated by detecting bioluminescence. As a model for in vitro suicide gene therapy, fcy::fur-expressing recombinant cells were exposed to X-rays before incubation with 5-fluorocytosin. Cell viability was determined with WST-8.
RESULTS:
\nTwenty-five of the 62 promoters in the library enhanced luciferase activity over five-fold, 6 h after receiving 10 Gy of X-ray irradiation, suggesting the effectiveness of our method. Luciferase activity in recombinant cells was enhanced by X-rays and, to a lesser extent, by a proton beam. Anti-oxidants attenuated the enhancement, suggesting the involvement of oxidative stress. Promoters were less reactive to X-rays in tumors on mice. In our suicide gene therapy model, survival of post-irradiated cells decreased dose-dependently with 5-fluorocytosin.
CONCLUSIONS:
\nOur method was efficient in generating radiation responsive promoters. Furthermore, we have successfully shown a potential therapeutic use for one of these promoters.
書誌情報 The Journal of Gene Medicine

巻 14, 号 5, p. 316-327, 発行日 2012-05
出版者
出版者 John Wiley & Sons, Ltd.
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