Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus.
Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus.
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DOI：
10.1007/s00259-021-05582-y
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发表时间：
2022-05
影响因子：
9.1
通讯作者：
Quante, Michael
中科院分区：
文献类型：
--
作者：
Fang, Hsin-Yu;Stangl, Stefan;Marcazzan, Sabrina;Carvalho, Marcos J. Braz;Baumeister, Theresa;Anand, Akanksha;Strangmann, Julia;Huspenina, Julia Slotta;Wang, Timothy C.;Schmid, Roland M.;Feith, Marcus;Friess, Helmut;Ntziachristos, Vasilis;Multhoff, Gabriele;Gorpas, Dimitris;Quante, Michael
关键词：
几十年来，食管癌（EAC）的发病率一直在增加，但治疗方法没有显著改善。Barrett食管（BE）是EAC最确定的危险因素，但由于高清晰度白光内窥镜的低灵敏度和特异性，目前的随机活检监测不能预测大多数BE患者的癌症进展。在这里，我们在引导荧光分子内镜活检中评估了膜结合的高特异性hsp70特异性造影剂肿瘤穿透肽（Hsp70-TPP）。通过免疫组化检测，Hsp70在患者样本（n = 12）和转基因（L2-IL1b） BE小鼠模型的高度发育不良病变中与非发育不良BE相比，在发育不良和EAC中显著过表达。在延时显微镜下，Hsp70-TPP被人类BE发育不良患者来源的类器官迅速吸收和内化。BE小鼠模型的柔性荧光内窥镜可以特异性检测Hsp70-TPP-Cy5.5, Hsp70-TPP-Cy5.5与异型增生程度密切相关，但与BE无关。将Hsp70-TPP-Cy5.5体外应用于新鲜切除的整个人EAC标本，显示出高（bbbb4）的肿瘤与背景比，并特异性检测到以前未检测到的肿瘤浸润。综上所述，这些发现表明使用荧光标记的TPP肽进行hsp70靶向成像可以改善BE患者的肿瘤监测。在线版本包含补充材料，可在10.1007/s00259-021-05582-y获得。
The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett’s esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized by human BE dysplastic patient–derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients. The online version contains supplementary material available at 10.1007/s00259-021-05582-y.
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影响因子：
50.3
作者：
Quante M;Bhagat G;Abrams JA;Marache F;Good P;Lee MD;Lee Y;Friedman R;Asfaha S;Dubeykovskaya Z;Mahmood U;Figueiredo JL;Kitajewski J;Shawber C;Lightdale CJ;Rustgi AK;Wang TC
通讯作者：
Wang TC
影响因子：
29.4
作者：
Muench, Natasha Stephens;Fang, Hsin-Yu;Quante, Michael
通讯作者：
Quante, Michael
影响因子：
3.5
作者：
Glatz, Juergen;Varga, Julia;Ntziachristos, Vasilis
通讯作者：
Ntziachristos, Vasilis
影响因子：
--
作者：
Lee, Michelle H;Buterbaugh, Kristin;Anandasabapathy, Sharmila
通讯作者：
Anandasabapathy, Sharmila
影响因子：
6.4
作者：
MULTHOFF, G;BOTZLER, C;ISSELS, RD
通讯作者：
ISSELS, RD