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Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study
Authors:Hiroaki Ito  Haruhiro Inoue  Norimasa Sando  Satoshi Kimura  Keigo Gohda  Jun Sato  Katsuhiro Murakami  Shun Ito  Noriko Odaka  Hitoshi Satodate  Shin-Ei Kudo
Abstract:ABSTRACT: BACKGROUND: The identification of circulating tumour cells (CTCs) in peripheral blood is a useful approach to estimate prognosis, monitor disease progression, and measure treatment effects in various malignancies. However, clinical relevance of CTCs is controversial. We attempted to detect viable CTCs in the peripheral blood of gastric cancer patients using a telomerase-specific viral agent. We took a 7.5-ml blood sample from 65 treatment-negative gastric cancer patients before surgery and 10 healthy volunteers. We detected viable CTCs in the blood samples after incubating them with a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene (OBP-401). GFP-positive CTCs were defined as having a diameter of at least 7.735 mum; this threshold was determined by receiver operating characteristic curve analysis. GFP-positive cells were counted under a fluorescence microscope. RESULTS: There was a significant difference in overall survival among the patients with 0EN DASH]4 and those with GREATER-THAN OR EQUAL TO]5 GFP-positive CTCs in the stage IEN DASH]IV disease group and stage IIEN DASH]IV advanced disease group. The number of GFP-positive CTCs was not related to cancer stage. Among the pathological findings, the number of GFP-positive CTCs was only significantly related to venous invasion, although there were trends towards more GFP-positive CTCs with disease progression (tumour depth, lymph node metastasis, distant metastasis, lymphatic invasion, and histological type). CONCLUSIONS: There was a significant relationship between the number of GFP-positive CTCs and overall survival in the patients with gastric cancer. The detection of CTCs using OBP-401 may be useful for prognostic evaluation.Trial registrationUniversity Hospital Medical Information Network in Japan, UMIN000002018.
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