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Models and Technologies

A Combinatory Strategy for Detection of Live CTCs Using Microfiltration and a New Telomerase-Selective Adenovirus

Yanchun Ma, Sijie Hao, Shuwen Wang, Yuanjun Zhao, Bora Lim, Ming Lei, David J. Spector, Wafik S. El-Deiry, Si-yang Zheng and Jiyue Zhu
Yanchun Ma
College of Life Science, Northwest A&F University, Taicheng Road, Yangling, Shaanxi, China.Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
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Sijie Hao
Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
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Shuwen Wang
Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington.
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Yuanjun Zhao
Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
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Bora Lim
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington.
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Ming Lei
College of Life Science, Northwest A&F University, Taicheng Road, Yangling, Shaanxi, China.
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David J. Spector
Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, Pennsylvania.
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Wafik S. El-Deiry
Division of Hematology-Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
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Si-yang Zheng
Micro & Nano Integrated Biosystem Laboratory, Department of Biomedical Engineering and Materials Research Institute, Pennsylvania State University, University Park, Pennsylvania.
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Jiyue Zhu
Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington.
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  • For correspondence: jiyue.zhu@wsu.edu
DOI: 10.1158/1535-7163.MCT-14-0693
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Abstract

Circulating tumor cells (CTC) have become an important biomarker for early cancer diagnosis, prognosis, and treatment monitoring. Recently, a replication-competent recombinant adenovirus driven by a human telomerase gene (hTERT) promoter was shown to detect live CTCs in blood samples of patients with cancer. Here, we report a new class of adenoviruses containing regulatory elements that repress the hTERT gene in normal cells. Compared with the virus with only the hTERT core promoter, the new viruses showed better selectivity for replication in cancer cells than in normal cells. In particular, Ad5GTSe, containing three extra copies of a repressor element, displayed a superior tropism for cancer cells among leukocytes and was thus selected for CTC detection in blood samples. To further improve the efficiency and specificity of CTC identification, we tested a combinatory strategy of microfiltration enrichment using flexible micro spring arrays and Ad5GTSe imaging. Our experiments showed that this method efficiently detected both cancer cells spiked into healthy blood and potential CTCs in blood samples of patients with breast and pancreatic cancer, demonstrating its potential as a highly sensitive and reliable system for detection and capture of CTCs of different tumor types. Mol Cancer Ther; 14(3); 1–9. ©2015 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Received August 19, 2014.
  • Revision received December 15, 2014.
  • Accepted December 29, 2014.
  • ©2015 American Association for Cancer Research.
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Published OnlineFirst February 20, 2015
doi: 10.1158/1535-7163.MCT-14-0693

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A Combinatory Strategy for Detection of Live CTCs Using Microfiltration and a New Telomerase-Selective Adenovirus
Yanchun Ma, Sijie Hao, Shuwen Wang, Yuanjun Zhao, Bora Lim, Ming Lei, David J. Spector, Wafik S. El-Deiry, Si-yang Zheng and Jiyue Zhu
Mol Cancer Ther February 20 2015 DOI: 10.1158/1535-7163.MCT-14-0693

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A Combinatory Strategy for Detection of Live CTCs Using Microfiltration and a New Telomerase-Selective Adenovirus
Yanchun Ma, Sijie Hao, Shuwen Wang, Yuanjun Zhao, Bora Lim, Ming Lei, David J. Spector, Wafik S. El-Deiry, Si-yang Zheng and Jiyue Zhu
Mol Cancer Ther February 20 2015 DOI: 10.1158/1535-7163.MCT-14-0693
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Molecular Cancer Therapeutics
eISSN: 1538-8514
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