Integrated fluorescent cytology with nano‐biologics in peritoneally disseminated gastric cancer

  • Megumi Watanabe
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Shunsuke Kagawa
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Kazuya Kuwada
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Yuuri Hashimoto
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Kunitoshi Shigeyasu
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Michihiro Ishida
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Shuichi Sakamoto
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Atene Ito
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Satoru Kikuchi
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Shinji Kuroda
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Hiroyuki Kishimoto
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Shuta Tomida
    Translational Research Network Project Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Ryuichi Yoshida
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Hiroshi Tazawa
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
  • Yasuo Urata
    Oncolys BioPharma, Inc. Tokyo Japan
  • Toshiyoshi Fujiwara
    Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan

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<jats:p>Gastric cancer patients positive for peritoneal cytology are at increased risk of tumor recurrence, but although a certain proportion of cytology‐positive patients relapse rapidly with aggressive progression, others survive longer with conventional chemotherapies. This heterogeneity makes it difficult to stratify patients for more intensive therapy and poses a substantial challenge for the implementation of precision medicine. We developed a new approach to identify biologically malignant subpopulations in cytology‐positive gastric cancer patients, using a green fluorescent protein (<jats:styled-content style="fixed-case">GFP</jats:styled-content>)‐expressing attenuated adenovirus in which the telomerase promoter regulates viral replication (TelomeScan, <jats:styled-content style="fixed-case">OBP</jats:styled-content>‐401). The fluorescence emitted from TelomeScan‐positive cells was successfully quantified using a multi‐mode microplate reader. We then analyzed clinical peritoneal washes obtained from 68 gastric cancer patients and found that patients positive for TelomeScan had a significantly worse prognosis. In 21 cytology‐positive patients, the median survival time of those who were TelomeScan positive (235 days) was significantly shorter than that for those who were TelomeScan negative (671 days; <jats:italic>P</jats:italic> = 0.0062). This fluorescent virus‐guided cytology detects biologically malignant cancer cells from the peritoneal washes of gastric cancer patients and may thus be useful for both therapy stratification and precision medicine approaches based on genetic profiling of disseminated cells.</jats:p>

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