Change in number and size of circulating tumor cells with high telomerase activity during treatment of patients with gastric cancer

Ito,Hiroaki; Yamaguchi,Noriko; Onimaru,Manabu; Kimura,Satoshi; Ohmori,Tohru; Ishikawa,Fumihiro; Sato,Jun; Ito,Shun; Inoue,Haruhiro

doi:10.3892/ol.2016.5239

Change in number and size of circulating tumor cells with high telomerase activity during treatment of patients with gastric cancer

Authors:
- Hiroaki Ito
- Noriko Yamaguchi
- Manabu Onimaru
- Satoshi Kimura
- Tohru Ohmori
- Fumihiro Ishikawa
- Jun Sato
- Shun Ito
- Haruhiro Inoue
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Affiliations: Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135‑8577, Japan, Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224‑8503, Japan, Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224‑8503, Japan, Institute of Molecular Oncology, Showa University School of Medicine, Tokyo 142‑8555, Japan, Department of Cancer Cell Biology, Showa University School of Pharmacy, Tokyo 142‑8555, Japan, Central Research Laboratories, Sysmex Corporation, Kobe, Hyōgo 651‑2271, Japan
Published online on: October 11, 2016 https://doi.org/10.3892/ol.2016.5239
Pages: 4720-4726

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Abstract

Detection of circulating tumor cells (CTCs) in peripheral blood is useful for estimating the prognosis of patients with cancer. We previously reported the detection of CTCs by OBP‑401, a telomerase‑specific, replication‑selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. We demonstrated that the number of large (L)‑GFP+ cells (≥7.735 µm in diameter) in peripheral blood samples correlated significantly with the prognosis of treatment-naïve gastric cancer patients, whereas the number of small (S)‑GFP+ cells (<7.735 µm in diameter) did not. In the present study, we studied the change in the number of GFP+ cells during treatment, and analyzed the association between the number of GFP+ cells in blood samples and the outcome of patients. Peripheral blood samples were obtained from 37 gastric patients prior and subsequent to surgery (three samples per time point). Upon infection of blood cells with OBP‑401, GFP+ cells of different sizes were counted and measured. The association between the number of GFP+ cells and surgical outcome was determined by statistical analysis. The median follow‑up period after surgery was 39 months. Although the difference was not significant, patients with ≥6 L‑GFP+ cells in preoperative blood samples had a lower relapse‑free survival rate than patients with 0‑5 L‑GFP+ cells. There was no significant correlation between the number of L‑GFP+ cells in postoperative blood samples and the prognosis of patients receiving adjuvant therapy. Although the difference was not significant, the number of S‑GFP+ cells in samples from patients who had received postoperative chemotherapy was higher than in those who had not. The number of L‑GFP+ cells was not significantly correlated with the relapse‑free survival rate in gastric cancer patients who underwent surgery. The number of S‑GFP+ cells was relatively high in samples from patients who had received postoperative chemotherapy.

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