Circulating tumor cells: not all detected cells are bad and not all bad cells are detected.

The University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
Journal of Clinical Oncology (Impact Factor: 17.88). 03/2011; 29(12):1508-11. DOI: 10.1200/JCO.2010.34.0026
Source: PubMed
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    ABSTRACT: The present study evaluated the presence and clinical relevance of a cluster of differentiation (CD)26(+)/CD326(-) subset of circulating tumor cells (CTCs) in pre- and post-operative blood samples of colorectal cancer patients, who had undergone curative or palliative intervention, in order to find a novel prognostic factor for patient management and follow-up. In total, 80 colorectal cancer patients, along with 25 healthy volunteers were included. The easily transferable methodology of flow cytometry, along with multiparametric antibody staining were used to selectively evaluate CD26(+)/CD326(-) CTCs in the peripheral blood samples of colorectal cancer patients. The multiparametric selection allowed any enrichment methods to be avoided thus rendering the whole procedure suitable for clinical routine. The presence of CD26(+)/CD326(-) cells was higher in advanced Dukes' stages and was significantly associated with poor survival and high recurrence rates. Relapsing and non-surviving patients showed the highest number of CD26(+)/CD326(-) CTCs. High pre-operative levels of CD26(+)/CD326(-) CTCs correctly predicted tumor relapse in 44.4% of the cases, while 69% of post-operative CD26(+)/CD326(-) CTC-positive patients experienced cancer recurrence, with a test accuracy of 88.8%. By contrast, post-operative CD26(+)/CD326(-) CTC-negative patients showed an increase in the three-year progression-free survival rate of 86%, along with a reduced risk of tumor relapse of >90%. In conclusion, CD26(+)/CD326(-) CTCs are an independent prognostic factor for tumor recurrence rate in multivariate analysis, suggesting that their evaluation could be an additional factor for colorectal cancer recurrence risk evaluation in patient management.
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    ABSTRACT: An electrochemical Lab-on-a-Disc (eLoaD) platform for the automated quantification of ovarian cancer cells (SKOV3) from whole blood is reported. This centrifugal microfluidic system combines complex sample handling, i.e., blood separation and cancer cell extraction from plasma, with specific capture and sensitive detection using label-free electrochemical impedance. Flow control is facilitated using rotationally actuated valving strategies including siphoning, capillary and centrifugo-pneumatic dissolvable-film (DF) valves. For the detection systems, the thiol-containing amino acid, l-Cysteine, was self-assembled onto smooth gold electrodes and functionalized with anti-EpCAM. By adjusting the concentration of buffer electrolyte, the thickness of the electrical double layer was extended so the interfacial electric field interacts with the bound cells. Significant impedance changes were recorded at 117.2Hz and 46.5Hz upon cell capture. Applying AC amplitude of 50mV at 117.2Hz and open circuit potential, a minimum of 214capturedcells/mm(2) and 87% capture efficiency could be recorded. The eLoaD platform can perform five different assays in parallel with linear dynamic range between 16,400 and (2.6±0.0003)×10(6)cancercells/mL of blood, i.e. covering nearly three orders of magnitude. Using the electrode area of 15.3mm(2) and an SKOV3 cell radius of 5µm, the lower detection limit is equivalent to a fractional surface coverage of approximately 2%, thus making eLoaD a highly sensitive and efficient prognostic tool that can be developed for clinical settings where ease of handling and minimal sample preparation are paramount. Copyright © 2014 Elsevier B.V. All rights reserved.
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    ABSTRACT: Tumors metastasis is responsible for 1 in 4 deaths in USA. Though it is well documented in last two decades that CTCs in blood can be used as a biomarker for metastatic cancer, there are enormous challenges till now to capture and identify CTC with sufficient sensitivity and specificity. Due to heterogeneous expression of CTC markers, it is now well understood that a single CTC marker is insufficient to capture all CTCs from the blood. Driven by the need, current manuscript reports for the first time highly efficient capture and accurate identification of multiple types of CTCs from infected blood using aptamer modified porous graphene oxide membranes. Reported results demonstrate that dye modified S6, A9 and YJ-1 aptamers attached 20-40 microns porous garphene oxide membranes are capable of capturing multiple types of tumor cells (SKBR3 breast cancer cells, LNCaP prostate cancer cells and SW-948 colon cancer cells) selectively and simultaneously from infected blood. Our result shows that capture efficiency of graphene oxide membranes is about 95% for multiple types of tumor cells, for each tumor concentration of 10 cells/mL are present in blood sample. Selectivity of our assay for capturing targeted tumor cells has been demonstrated using membranes without antibody. Blood infected by different cells also has been used to demonstrate targeted tumor cells capturing ability by aptamer conjugated membrane. Our reported data also demonstrate that accurate analysis of captured multiple types CTCs can be performed using multicolor fluorescence imaging. Aptamer attached membranes reported here has good potential.
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