ID | 112373 |
Author |
Muguruma, Naoki
Tokushima University
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Okamoto, Koichi
Tokushima University
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Sannomiya, Katsutaka
Tokushima University
Fujimoto, Shota
Tokushima University
Miyamoto, Hiroshi
Tokushima University
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Shimada, Mitsuo
Tokushima University
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Horino, Yoko
Olympus Corporation
Matsumoto, Shinya
Olympus Corporation
Hanaoka, Kenjiro
The University of Tokyo
Nagano, Tetsuo
The University of Tokyo
Shibutani, Makoto
Tokyo University of Agriculture and Technology
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Content Type |
Journal Article
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Description | Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.
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Journal Title |
Scientific Reports
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ISSN | 20452322
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Publisher | Springer Nature
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Volume | 7
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Start Page | 6536
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Published Date | 2017-07-26
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Remark | Supplementary information : srep_7_6536_s1.pdf
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Rights | © The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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language |
eng
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TextVersion |
Publisher
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departments |
Medical Sciences
University Hospital
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