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(64)Cu-ATSM therapy targets regions with activated DNA repair and enrichment of CD133(+) cells in an HT-29 tumor model: Sensitization with a nucleic acid antimetabolite.
https://repo.qst.go.jp/records/47585
https://repo.qst.go.jp/records/47585fbd99f3b-5fcc-4ab6-8d63-4674896ef442
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2016-11-17 | |||||
タイトル | ||||||
タイトル | (64)Cu-ATSM therapy targets regions with activated DNA repair and enrichment of CD133(+) cells in an HT-29 tumor model: Sensitization with a nucleic acid antimetabolite. | |||||
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 |
Yoshii, Yukie
× Yoshii, Yukie× Furukawa, Takako× Matsumoto, Hiroki× Yoshimoto, Mitsuyoshi× Kiyono, Yasushi× Zhang, Ming-Rong× Fujibayashi, Yasuhisa× Saga, Tsuneo× 吉井 幸恵× 張 明栄× 藤林 康久 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | (64)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) is a potential theranostic agent targeting the over-reduced state under hypoxia within tumors. Recent clinical Cu-ATSM positron emission tomography studies have revealed a correlation between uptake and poor prognosis; however, the reason is unclear. Here, using a human colon carcinoma HT-29 model, we demonstrated that the intratumoral (64)Cu-ATSM high-uptake regions exhibited malignant characteristics, such as upregulated DNA repair and elevated %CD133(+) cancer stem-like cells. Based on this evidence, we developed a strategy to enhance the efficacy of (64)Cu-ATSM internal radiotherapy (IRT) by inhibiting DNA repair with a nucleic acid (NA) antimetabolite. The results of the analyses showed upregulation of pathways related to DNA repair along with NA incorporation (bromodeoxyuridine uptake) and elevation of %CD133(+) cells in (64)Cu-ATSM high-uptake regions. In an in vivo(64)Cu-ATSM treatment study, co-administration of an NA antimetabolite and (64)Cu-ATSM synergistically inhibited tumor growth, with little toxicity, and effectively reduced %CD133(+) cells. (64)Cu-ATSM therapy targeted malignant tumor regions with activated DNA repair and high concentrations of CD133(+) cells in the HT-29 model. NA antimetabolite co-administration can be an effective approach to enhance the therapeutic effect of (64)Cu-ATSM IRT. | |||||
書誌情報 |
Cancer letters 巻 376, 号 1, p. 74-82, 発行日 2016-06 |
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出版者 | ||||||
出版者 | Elsevier Science Ireland | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0304-3835 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 26996296 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.canlet.2016.03.020 |