Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1

Abstract 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 so...

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Autores principales:	Naoki Muguruma, Koichi Okamoto, Tadahiko Nakagawa, Katsutaka Sannomiya, Shota Fujimoto, Yasuhiro Mitsui, Tetsuo Kimura, Hiroshi Miyamoto, Jun Higashijima, Mitsuo Shimada, Yoko Horino, Shinya Matsumoto, Kenjiro Hanaoka, Tetsuo Nagano, Makoto Shibutani, Tetsuji Takayama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2635b899c8674201a9f1d849f452cd8d
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spelling	oai:doaj.org-article:2635b899c8674201a9f1d849f452cd8d2021-12-02T11:50:55ZMolecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-110.1038/s41598-017-06857-x2045-2322https://doaj.org/article/2635b899c8674201a9f1d849f452cd8d2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06857-xhttps://doaj.org/toc/2045-2322Abstract 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.Naoki MugurumaKoichi OkamotoTadahiko NakagawaKatsutaka SannomiyaShota FujimotoYasuhiro MitsuiTetsuo KimuraHiroshi MiyamotoJun HigashijimaMitsuo ShimadaYoko HorinoShinya MatsumotoKenjiro HanaokaTetsuo NaganoMakoto ShibutaniTetsuji TakayamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naoki Muguruma Koichi Okamoto Tadahiko Nakagawa Katsutaka Sannomiya Shota Fujimoto Yasuhiro Mitsui Tetsuo Kimura Hiroshi Miyamoto Jun Higashijima Mitsuo Shimada Yoko Horino Shinya Matsumoto Kenjiro Hanaoka Tetsuo Nagano Makoto Shibutani Tetsuji Takayama Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1
description	Abstract 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.
format	article
author	Naoki Muguruma Koichi Okamoto Tadahiko Nakagawa Katsutaka Sannomiya Shota Fujimoto Yasuhiro Mitsui Tetsuo Kimura Hiroshi Miyamoto Jun Higashijima Mitsuo Shimada Yoko Horino Shinya Matsumoto Kenjiro Hanaoka Tetsuo Nagano Makoto Shibutani Tetsuji Takayama
author_facet	Naoki Muguruma Koichi Okamoto Tadahiko Nakagawa Katsutaka Sannomiya Shota Fujimoto Yasuhiro Mitsui Tetsuo Kimura Hiroshi Miyamoto Jun Higashijima Mitsuo Shimada Yoko Horino Shinya Matsumoto Kenjiro Hanaoka Tetsuo Nagano Makoto Shibutani Tetsuji Takayama
author_sort	Naoki Muguruma
title	Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1
title_short	Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1
title_full	Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1
title_fullStr	Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1
title_full_unstemmed	Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1
title_sort	molecular imaging of aberrant crypt foci in the human colon targeting glutathione s-transferase p1-1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2635b899c8674201a9f1d849f452cd8d
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Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1

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