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Greene B.T.,BioCytics Inc | Greene B.T.,Carolina BioOncology Institute PLLC | Hughes A.D.,Cornell University | King M.R.,Cornell University
Frontiers in Oncology | Year: 2012

Circulating tumor cells (CTCs) are believed to be responsible for the development of metastatic disease. Over the last several years there has been a great interest in understanding the biology of CTCs to understand metastasis, as well as for the development of companion diagnostics to predict patient response to anti-cancer targeted therapies. Understanding CTC biology requires innovative technologies for the isolation of these rare cells. Here we review several methods for the detection, capture, and analysis of CTCs and also provide insight on improvements for CTC capture amenable to cellular therapy applications. © 2012 Greene, Hughes and King. Source

Hughes A.D.,Cornell University | Mattison J.,Cornell University | Powderly J.D.,BioCytics Inc | Powderly J.D.,Carolina BioOncology Institute PLLC | And 3 more authors.
Journal of Visualized Experiments | Year: 2012

Circulating tumor cells (CTC) are cells that disseminate from a primary tumor throughout the circulatory system and that can ultimately form secondary tumors at distant sites. CTC count can be used to follow disease progression based on the correlation between CTC concentration in blood and disease severity 1. As a treatment tool, CTC could be studied in the laboratory to develop personalized therapies. To this end, CTC isolation must cause no cellular damage, and contamination by other cell types, particularly leukocytes, must be avoided as much as possible 2. Many of the current techniques, including the sole FDA-approved device for CTC enumeration, destroy CTC as part of the isolation process (for more information see Ref. 2). A microfluidic device to capture viable CTC is described, consisting of a surface functionalized with E-selectin glycoprotein in addition to antibodies against epithelial markers 3. To enhance device performance a nanoparticle coating was applied consisting of halloysite nanotubes, an aluminosilicate nanoparticle harvested from clay 4. The E-selectin molecules provide a means to capture fast moving CTC that are pumped through the device, lending an advantage over alternative microfluidic devices wherein longer processing times are necessary to provide target cells with sufficient time to interact with a surface. The antibodies to epithelial targets provide CTC-specificity to the device, as well as provide a readily adjustable parameter to tune isolation. Finally, the halloysite nanotube coating allows significantly enhanced isolation compared to other techniques by helping to capture fast moving cells, providing increased surface area for protein adsorption, and repelling contaminating leukocytes 3,4. This device is produced by a straightforward technique using off-the-shelf materials, and has been successfully used to capture cancer cells from the blood of metastatic cancer patients. Captured cells are maintained for up to 15 days in culture following isolation, and these samples typically consist of >50% viable primary cancer cells from each patient. This device has been used to capture viable CTC from both diluted whole blood and buffy coat samples. Ultimately, we present a technique with functionality in a clinical setting to develop personalized cancer therapies. © 2012 Creative Commons Attribution-NonCommercial License. Source

Hughes A.D.,Cornell University | Mattison J.,Cornell University | Western L.T.,Cornell University | Powderly J.D.,BioCytics Inc | And 4 more authors.
Clinical Chemistry | Year: 2012

BACKGROUND: Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage. METHODS: We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer. RESULTS: Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20-704 viable CTCs per 3.75-mL sample, achieving purities of 18%-80% CTCs. The nanotubecoated surface significantly improved capture purities (P < 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading. CONCLUSIONS: The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies. © 2012 American Association for Clinical Chemistry. Source

Hughes A.D.,Cornell University | Marshall J.R.,Cornell University | Keller E.,BioCytics Inc | Keller E.,Carolina BioOncology Institute PLLC | And 5 more authors.
Cancer Letters | Year: 2014

Personalized medicine holds great promise for cancer treatment, with the potential to address challenges associated with drug sensitivity and interpatient variability. Circulating tumor cells (CTC) can be useful for screening cancer drugs as they may reflect the severity and heterogeneity of primary tumors. Here we present a platform for rapidly evaluating individualized drug susceptibility. Treatment efficacy is evaluated directly in blood, employing a relevant environment for drug administration, and assessed by comparison of CTC counts in treated and control samples. Multiple drugs at varying concentrations are evaluated simultaneously to predict an appropriate therapy for individual patients. © 2013 The Authors. Source

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