title: Detection and preliminary evaluation of circulating tumor cells in the peripheral blood of patients with eight types of cancer using a telomerase-specific adenovirus.
abstract: We developed a detection method for circulating tumor cells (CTCs) using the telomerase-specific adenovirus OBP-401. This recombinant virus has a telomerase promoter at the 5'-end of the viral genome and GFP at the 3'-end. To date, CTC enumeration using OBP-401 has shown prognostic impact for gastric and small cell lung cancer patients. In the present study, peripheral blood samples from patients with eight types of cancer, including some cancers previously untested with OBP-401 (i.e., esophagus, pancreas, and prostate cancers) were subjected to this method in order to evaluate its versatility. It was recently discovered that some white blood cells (WBCs) false-positively react with OBP-401. Although anti-CD45 antibodies can absorb these adverse cells from peripheral blood, the simplicity of the OBP-401 method would be diminished by the introduction of antibody treatment. Therefore, we evaluated another approach to minimize the false positivity of WBCs. Seven anti-CD antibodies were employed to stain the species of WBCs that false-positively reacted with OBP-401. We revealed that the false-positively reacted WBCs were monocytes in the peripheral blood of both healthy subjects and cancer patients. Based on a size distribution analysis of the GFP-positive monocytes, the size criterion for CTCs using OBP-401 was defined to be a cellular diameter>8.4 µm. In total, 43% of 86 cancer patients examined in the present study were CTC-positive using this definition. CTCs were enumerated from peripheral blood samples collected from patients with each of the eight types of cancer; the detectability of CTCs for esophagus, pancreas and prostate cancers by the OBP-401 method was confirmed for the first time in the present study. However, no clear correlation between CTC positivity and the clinical characteristics of patients with any type of cancer was observed because of the small number of patients with each type of cancer. An additional clinical study will be conducted to confirm the clinical meaning of CTCs enumerated by OBP-401.
authors.affiliation: Central Research Laboratories, Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Yabusaki
authors.affiliation: Central Research Laboratories, Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.affiliation: Division of Colorectal and Pelvic Surgery, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kohyama
authors.affiliation: Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nobuoka
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Central Research Laboratories, Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Central Research Laboratories, Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Gohda
authors.affiliation: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Okegawa
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takamatsu
authors.affiliation: Division of Colorectal and Pelvic Surgery, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D003955:Diagnostic Tests, Routine / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D019098:Telomerase
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D011993:Recombinant Fusion Proteins; D019098:Telomerase