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BMC Cancer. 2012; 12: 346.
Published online Aug 9, 2012. doi:  10.1186/1471-2407-12-346
PMCID: PMC3495032
Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study
Hiroaki Ito,corresponding author1 Haruhiro Inoue,1 Norimasa Sando,1 Satoshi Kimura,2 Keigo Gohda,3 Jun Sato,3 Katsuhiro Murakami,3 Shun Ito,3 Noriko Odaka,1 Hitoshi Satodate,1 and Shin-ei Kudo1
1Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasakichuo, Tsuzuki-ku, Yokohama 224-8503, Japan
2Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, 35-1 Chigasakichuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
3Central Research Laboratories, Sysmex Corporation, 4-4-4 Takatsukadai, Nishi-ku, Kobe, 651-2271, Japan
corresponding authorCorresponding author.
Hiroaki Ito: h.ito/at/med.showa-u.ac.jp; Haruhiro Inoue: haru.inoue/at/med.showa-u.ac.jp; Norimasa Sando: sandsand/at/mac.com; Satoshi Kimura: sdkimura/at/med.showa-u.ac.jp; Keigo Gohda: Gohda.Keigo/at/sysmex.co.jp; Jun Sato: Sato.Jun/at/sysmex.co.jp; Katsuhiro Murakami: Murakami.Katsuhiro/at/sysmex.co.jp; Shun Ito: Ito.Shun/at/sysmex.co.jp; Noriko Odaka: noriko1213/at/med.showa-u.ac.jp; Hitoshi Satodate: hitoshi-satodate/at/nifty.com; Shin-ei Kudo: kudos/at/med.showa-u.ac.jp
Received March 1, 2012; Accepted August 2, 2012.
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.
Methods
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 μm; 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 0–4 and those with ≥5 GFP-positive CTCs in the stage I–IV disease group and stage II–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 registration
University Hospital Medical Information Network in Japan, UMIN000002018.
Keywords: Circulating tumour cells, Gastric cancer, Telomerase
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