A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia.
A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia.
复制标题
通过细胞质粘度和缺氧成像来评估切除肿瘤边缘的预筛选策略
DOI：
10.7554/elife.70471
复制
发表时间：
2021-10-11
期刊：
影响因子：
7.7
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Huang H;Lin Y;Ma W;Liu J;Han J;Hu X;Tang M;Yan S;Abudupataer M;Zhang C;Gao Q;Zhang W
为了确保肿瘤完全切除，冷冻切片分析是术中对切除的肿瘤边缘进行病理评估的最常见程序。然而，在一次手术中，可能会有多个活检组织被送去检查，但由于复杂的准备方案和耗时的病理分析，只有少数活检组织被制成冷冻切片，这可能会增加忽视肿瘤累及的风险。在这里，我们提出了一种基于荧光的预筛选策略，允许高通量，方便，快速的大体评估切除的肿瘤边缘。开发了双重可激活的阳离子荧光分子转子，以通过响应于缺氧诱导的硝基还原酶（生化标志物）和细胞质粘度（生物物理标志物）（癌细胞的两个特征）的升高而发射两种不同的荧光信号来特异性地照射活肿瘤细胞的细胞质。通过与苏木精和伊红染色比较，在小鼠和人的多种组织标本中评价荧光分子转子检测肿瘤细胞的能力。重要的是，荧光分子转子在区分肺癌和肝癌与正常组织方面实现了100%的特异性，允许预先筛选无肿瘤的手术切缘并促进临床决策。总之，这种类型的荧光分子转子和所提出的策略可以作为一种新的选择，以方便术中评估切除的肿瘤边缘。
To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells’ cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100 % specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.