A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia
- Fudan University, China
- Zhongshan Hospital, Fudan University, China
- Shanghai Jiao Tong University School of Medicine, China
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supplementary files. Source data files have been provided.
Article and author information
Author details
Mieradilijiang Abudupataer
Funding
National Key Research and Development Program of China (2018YFC1005002)
- Weijia Zhang
National Natural Science Foundation of China (82070482,81772007,21734003,51927805)
- Weijia Zhang
Shanghai Municipal Education Commission (2017-01-07-00-07-E00027)
- Weijia Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal model procedures were conducted in accordance with the protocols approved by the Department of Laboratory Animal Science, Fudan University (202012023S).
Human subjects: Written informed consent and consent to publish were obtained from all patients before participation. All procedures were conducted in accordance with the protocols approved by the Ethics Committee of the Institutes of Biomedical Sciences, Fudan University (2020-014).
Copyright
© 2021, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia
eLife 10:e70471.
https://doi.org/10.7554/eLife.70471
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