Oncotarget

Research Papers:

Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients

Shinsaku Togo _, Nobuyoshi Katagiri, Yukiko Namba, Miniwan Tulafu, Kumi Nagahama, Kotarou Kadoya, Kazuya Takamochi, Siaki Oh, Kenji Suzuki, Fuminori Sakurai, Hiroyuki Mizuguchi, Yasuo Urata and Kazuhisa Takahashi

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Oncotarget. 2017; 8:34884-34895. https://doi.org/10.18632/oncotarget.16818

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Abstract

Shinsaku Togo1,2, Nobuyoshi Katagiri3, Yukiko Namba1,2, Miniwan Tulafu1,2, Kumi Nagahama1,2, Kotarou Kadoya1,2, Kazuya Takamochi4, Siaki Oh4, Kenji Suzuki2, Fuminori Sakurai5, Hiroyuki Mizuguchi5, Yasuo Urata3, Kazuhisa Takahashi1,2

1Department of Respiratory Medicine, Juntendo University School of Medicine and Graduate School of Medicine, Tokyo, Japan

2Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan

3Oncolys BioPharma, Inc., Tokyo, Japan

4Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan

5Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

Correspondence to:

Shinsaku Togo, email: shinsaku@juntendo.ac.jp

Keywords: circulating tumor cells, EMT, telomescan, non-small cell lung cancer, EpCAM

Received: July 26, 2016     Accepted: March 24, 2017     Published: April 04, 2017

ABSTRACT

Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of non-small cell lung cancer (NSCLC) using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase-specific replication-selective adenovirus (OBP-1101), TelomeScan F35. Peripheral venous blood samples and clinicopathological data were collected from 123 NSCLC patients. The sensitivity of CTC detection was 69.1%, and for patients with stage I, II, III and IV, it was 59.6%, 40.0%, 85.7%, and 75.0%, respectively. Among the EMT-CTC samples, 46% were vimentin positive and 39.0% of non-EMT-CTC samples were EpCAM positive. Patients testing positive for EMT-CTCs at baseline had poor response to chemotherapy (P = 0.025) and decreased progression-free survival (EMT-CTC positive vs. negative: 193 ± 47 days vs. 388 ± 47. days, P = 0.040) in comparison to those testing negative. TelomeScan F35 is a highly sensitive CTC detection system and will be a useful screening tool for early diagnosis of NSCLC patients. Mesenchymal-phenotype CTCs are crucial indicators of chemotherapeutic efficacy in NSCLC patients.


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