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Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer.

ABSTRACT: 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 (GFP)-expressing attenuated adenovirus in which the telomerase promoter regulates viral replication (TelomeScan, OBP-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; P = 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.

SUBMITTER: Watanabe M

PROVIDER: S-EPMC6172043 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer.

Watanabe Megumi M Kagawa Shunsuke S Kuwada Kazuya K Hashimoto Yuuri Y Shigeyasu Kunitoshi K Ishida Michihiro M Sakamoto Shuichi S Ito Atene A Kikuchi Satoru S Kuroda Shinji S Kishimoto Hiroyuki H Tomida Shuta S Yoshida Ryuichi R Tazawa Hiroshi H Urata Yasuo Y Fujiwara Toshiyoshi T

Cancer science 20180923 10

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 subpop ...[more]

PMID: 30076658

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Project description:Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine.

Dataset Information

Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer.

Publications

Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer.

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