Journal article
Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture
Clinical cancer research, Vol.24(11), pp.2539-2547
06/01/2018
DOI: 10.1158/1078-0432.CCR-17-3078
PMCID: PMC5984698
PMID: 29545463
Abstract
Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment.
Experimental Design: Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to five time points, including before radiotherapy, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of radiotherapy. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR.
Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK+/CD45(-)/DAPI(+)) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before radiotherapy to 32 CTCs/mL at completion of radiotherapy (P = 0.001). CTCs declined throughout radiotherapy in patients with complete clinical and/or radiographic response, in contrast with an elevation in CTCs at mid or post-radiotherapy in the two patients with known pathologic residual disease.
Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared with multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment. (C) 2018 AACR.
Details
- Title: Subtitle
- Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture
- Creators
- Ja Hye Myung - University of Illinois at ChicagoMichael J. Eblan - University of North Carolina at Chapel HillJoseph M. Caster - University of North Carolina at Chapel HillSin-Jung Park - University of Illinois at ChicagoMichael J. Poellmann - University of Wisconsin–MadisonKyle Wang - University of North Carolina at Chapel HillKevin A. Tam - University of Illinois at ChicagoSeth M. Miller - University of North Carolina at Chapel HillColette Shen - University of North Carolina at Chapel HillRonald C. Chen - University of North Carolina at Chapel HillTian Zhang - Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, North Carolina.Joel E. Tepper - University of North Carolina at Chapel HillBhishamjit S. Chera - University of North Carolina at Chapel HillAndrew Z. Wang - University of North Carolina at Chapel HillSeungpyo Hong - University of Illinois at Chicago
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.24(11), pp.2539-2547
- Publisher
- Amer Assoc Cancer Research
- DOI
- 10.1158/1078-0432.CCR-17-3078
- PMID
- 29545463
- PMCID
- PMC5984698
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Number of pages
- 9
- Grant note
- 1R01CA178748; R21CA182322; U54CA198999 / NIH/NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) DMR-1409161 / National Science Foundation (NSF) R21CA182322 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01-CA182528 / National Cancer Institute (NCI)/National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) University of North Carolina Department of Radiation Oncology
- Language
- English
- Date published
- 06/01/2018
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984313095002771
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