title: Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study.
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.
  
  
  BACKGROUND
  University Hospital Medical Information Network in Japan, UMIN000002018.
authors.affiliation: Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasakichuo, Tsuzuki-ku, Yokohama 224-8503, Japan. h.ito@med.showa-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Inoue
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sando
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Keigo
authors.initials: K
authors.lastname: Gohda
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Shun
authors.initials: S
authors.lastname: Ito
authors.forename: Noriko
authors.initials: N
authors.lastname: Odaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Satodate
authors.forename: Shin-ei
authors.initials: SE
authors.lastname: Kudo
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D013274:Stomach Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology / Q000821:virology; D019098:Telomerase / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D019098:Telomerase