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通过喷洒靶向二肽基肽酶-IV的酶激活荧光探针检测食管胃交界早期腺癌

Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV.

作者信息

Yamamoto Keiko, Ohnishi Shunsuke, Mizushima Takeshi, Kodaira Junichi, Ono Masayoshi, Hatanaka Yutaka, Hatanaka Kanako C, Kuriki Yugo, Kamiya Mako, Ehira Nobuyuki, Shinada Keisuke, Takahashi Hiroaki, Shimizu Yuichi, Urano Yasuteru, Sakamoto Naoya

机构信息

Division of Endoscopy, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, 060-8648, Japan.

Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, 060-8638, Japan.

出版信息

BMC Cancer. 2020 Jan 28;20(1):64. doi: 10.1186/s12885-020-6537-9.

Abstract

BACKGROUND

It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD).

METHODS

Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV.

RESULTS

Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV.

CONCLUSIONS

Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

摘要

背景

使用传统内镜或图像增强内镜检测和诊断早期食管胃交界部(EGJ)腺癌仍然很困难。一种谷氨酰脯氨酰羟甲基罗丹明绿(EP-HMRG)荧光探针已被开发出来,该探针在二肽基肽酶(DPP)-IV特异性序列裂解后可被酶激活而发出荧光,据报道可用于检测头颈部和食管的鳞状细胞癌;然而,缺乏通过荧光分子成像检测EGJ腺癌的研究。因此,我们通过应用EP-HMRG并使用内镜黏膜下剥离术(ESD)切除的临床样本,研究了早期EGJ腺癌的可视化情况。

方法

对21例经ESD切除的临床样本进行EP-HMRG荧光成像,并前瞻性测量肿瘤和非肿瘤感兴趣区域的荧光强度。还进行了免疫组织化学检测以确定DPP-IV的表达。

结果

临床样本的荧光成像显示,应用EP-HMRG后几分钟内肿瘤病变即可可视化,敏感性、特异性和准确性分别为85.7%、85.7%和85.7%。然而,伴有肠化生背景的肿瘤没有足够的背景对比率,因为完全肠化生也表达DPP-IV。免疫组织化学测量显示,所有荧光肿瘤病变均表达DPP-IV。

结论

EP-HMRG荧光成像可用于检测无肠化生背景的早期EGJ腺癌病变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138f/6988364/538d10c921a6/12885_2020_6537_Fig1_HTML.jpg

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