1. Biochemistry and Chemical Biology
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A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia

  1. Hui Huang
  2. Youpei Lin
  3. Wenrui Ma
  4. Jiannan Liu
  5. Jing Han
  6. Xiaoyi Hu
  7. Meilin Tang
  8. Shiqiang Yan
  9. Mieradilijiang Abudupataer
  10. Chenping Zhang
  11. Qiang Gao
  12. Weijia Zhang  Is a corresponding author
  1. Fudan University, China
  2. Zhongshan Hospital, Fudan University, China
  3. Shanghai Jiao Tong University School of Medicine, China
Research Article
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Cite this article as: eLife 2021;10:e70471 doi: 10.7554/eLife.70471

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

  1. Hui Huang

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Youpei Lin

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Wenrui Ma

    Zhongshan Hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Jiannan Liu

    Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Jing Han

    Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Xiaoyi Hu

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Meilin Tang

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Shiqiang Yan

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Mieradilijiang Abudupataer

    Zhongshan Hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5421-9820
  10. Chenping Zhang

    Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Qiang Gao

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Weijia Zhang

    Fudan University, Shanghai, China
    For correspondence
    weijiazhang@fudan.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6928-0416

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).

Reviewing Editor

  1. Caigang Liu, Shengjing Hospital of China Medical University, China

Publication history

  1. Received: May 18, 2021
  2. Accepted: October 8, 2021
  3. Accepted Manuscript published: October 11, 2021 (version 1)

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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