Fluorescence endoscopic detection of murine colitis-associated colon cancer by topically applied enzymatically rapid-activatable probe.
Fluorescence endoscopic detection of murine colitis-associated colon cancer by topically applied enzymatically rapid-activatable probe.
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DOI：
10.1136/gutjnl-2011-301795
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发表时间：
2013-08
期刊：
影响因子：
24.5
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Mitsunaga M;Kosaka N;Choyke PL;Young MR;Dextras CR;Saud SM;Colburn NH;Sakabe M;Nagano T;Asanuma D;Urano Y;Kobayashi H
由于长期结肠炎相关的异常粘膜模式，筛查结肠镜以监测早期结肠炎相关结肠癌（CAC）是困难的。本研究的目的是开发一种快速荧光检测方法，用于结肠镜检查期间，利用局部应用的酶激活探针（gGlu-HMRG）提高CAC的检测，该探针在γ-谷氨酰转肽酶（GGT）（一种与癌症相关的酶）存在下发出荧光。用荧光显微镜和流式细胞仪检测结肠癌细胞系中GGT的表达。使用CAC的小鼠模型（氧化偶氮甲烷/葡聚糖硫酸钠），在局部给予gGlu-HMRG之前和之后，用白色光和荧光结肠镜检查小鼠。GGT的表达，虽然可变，但在人结肠癌细胞中高于正常人结肠细胞。在小鼠中使用荧光结肠镜检查，局部给药后5分钟检测到gGlu-HMRG荧光病变，荧光持续至少30分钟。荧光引导活检显示所有荧光病变包含癌症或异型增生（n=16），而12个非荧光病变中有3个包含低度异型增生，其他病变不包含肿瘤组织学。显微镜下的炎性浸润也有不同的荧光，但通常比癌症的信号低得多（约10倍）。重复荧光内窥镜检查允许监测单个肿瘤。这些结果表明，gGlu-HMRG可以改善CAC的内窥镜检测，具有比传统白色光结肠镜更高的目标与背景比。这可能对长期结肠炎患者有益，他们必须接受重复的结肠镜检查。
Screening colonoscopy to monitor for early colitis-associated colon cancer (CAC) is difficult due to the aberrant mucosal patterns associated with longstanding colitis. The aim of this study was to develop a rapid fluorescent detection method for use during colonoscopy for improving the detection of CAC utilising a topically applied enzymatically activatable probe (gGlu-HMRG) which fluoresces in the presence of γ-glutamyltranspeptidase (GGT), an enzyme associated with cancer. Expression of GGT in colon cell lines was examined with fluorescence microscopy and flow cytometry. A mouse model (azoxymethane/dextran sulphate sodium) of CAC was used and mice were examined with white light and fluorescence colonoscopy before and after topical gGlu-HMRG administration. Expression of GGT, although variable, was higher in human colon cancer cells than normal human colon cells. Using fluorescence colonoscopy in mice, gGlu-HMRG fluorescent lesions were detected 5 min after topical administration and fluorescence persisted for at least 30 min. Fluorescence guided biopsy revealed all fluorescent lesions that contained cancer or dysplasia (n=16), whereas three out of 12 non-fluorescent lesions contained low grade dysplasia and others did not contain neoplastic histology. Microscopic inflammatory infiltration also had variable fluorescence but in general was much lower (∼10-fold) in signal than cancer. Repeat fluorescence endoscopy allowed individual tumours to be monitored. These results suggest that gGlu-HMRG can improve endoscopic detection of CAC with a higher target to background ratio than conventional white light colonoscopy. This could be of benefit to patients with long-standing colitis who must undergo repeated screening colonoscopies.
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影响因子：
24.5
作者：
Lutgens, M. W. M. D.;Vleggaar, F. P.;Samsom, M.
通讯作者：
Samsom, M.
影响因子：
5.8
作者：
Pompella, A;De Tata, V;Zunino, F
通讯作者：
Zunino, F
影响因子：
4.8
作者：
Bremer, C;Tung, CH;Weissleder, R
通讯作者：
Weissleder, R
影响因子：
4.7
作者：
Kosaka, Nobuyuki;Ogawa, Mikako;Kobayashi, Hisataka
通讯作者：
Kobayashi, Hisataka
DOI：
10.1158/1940-6207.capr-10-0334
发表时间：
2011-05
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Mitsunaga M;Kosaka N;Kines RC;Roberts JN;Lowy DR;Schiller JT;Ishihara Y;Hasegawa A;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H