Isolation by Size of Epithelial Tumor Cells

Vona, Giovanna; Sabile, Abdelmajid; Louha, Malek; Sitruk, Véronique; Romana, Serge; Schütze, Karin; Capron, Frédérique; Franco, Dominique; Pazzagli, Mario; Vekemans, Michel; Lacour, Bernard; Bréchot, Christian; Paterlini‐Bréchot, Patrizia

doi:10.1016/s0002-9440(10)64706-2

Cited by 957 publications

(535 citation statements)

References 16 publications

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“…As EpCAM and cytokeratin are not expressed in a fair proportion of CTCs, this method has had to be continuously improved. Isolation by size of epithelial tumor cells (ISET) allows highly sensitive enrichment, morphological identification, and enumeration of CTCs (Vona et al, 2000). In one study based on the ISET method, CTCs were found in 18 of 29 patients (62.0%) with primary invasive melanoma and in five out of eight patients (62.5%) with metastatic melanoma (De Giorgi et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Sun

Liang

Wang

et al. 2018

Journal Cellular Physiology

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Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4′,6‐diamidino‐2‐phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45‐/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2–5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7–7.3, p < 0.001) were both associated with shorter disease‐free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2–6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8–8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Sun

Liang

Wang

et al. 2018

Journal Cellular Physiology

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“…8) On the other hand, it has been reported that non-adherent abnormal CTCs can be detected based on the expression of tumor antigens and biophysical deformities. 9,[11][12][13][14][15][16][17][18] The positive expression of CTC protein markers such as cytokeratin -8, -18 and -19, CD44 and the epithelial cell adhesion molecule (EpCAM) is often found in a CTC. 10) To date, the CellSearch system (Veridex, LLC, USA), which is based on immunostaining for CKs + , CD45 -and nucleus + , is the only device that is currently approved by the Food and Drug Administration for CTC detection,.…”

Section: Introductionmentioning

confidence: 99%

Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-Recognition PC Software

Shashni

Ariyasu

Takeda

et al. 2018

Biological & Pharmaceutical Bulletin

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SummaryDetection of anomalous cells such as cancer cells from normal blood cells has the potential to contribute greatly to cancer diagnosis and therapy. Conventional methods for the detection of cancer cells are usually tedious and cumbersome. Herein, we report on the use of a particle size analyzer for the convenient size-based differentiation of cancer cells from normal cells. Measurements made using a particle size analyzer revealed that size parameters for cancer cells are significantly greater (e.g., inner diameter and width) than the corresponding values for normal cells (white blood cells (WBC), lymphocytes and splenocytes), with no significant difference in shape parameters (e.g., circularity and convexity). The inner diameter of many cancer cell lines is greater than 10 μm, in contrast to normal cells. For the detection of WBC having similar size to that of cancer cells, we developed a PC software "Cancer Cell Finder" that differentiates them from cancer cells based on brightness inflection points on a cell surface. Furthermore, the aforementioned method was validated for cancer cell/clusters detection in spiked mouse blood samples (a B16 melanoma mouse xenograft model) and circulating tumor cell cluster-like particles in the cat and dog (diagnosed with cancer) blood samples. These results provide insights into the possible applicability of the use of a particle size analyzer in conjunction with PC software for the convenient detection of cancer cells in experimental and clinical samples for theranostics.

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“…9,10 CTCs are rare cells present in the blood in numbers as low as one CTC per 10 6 -10 7 leukocytes, which makes their capture and detection very challenging. The techniques currently used for CTC capture include immunomagnetic separation, 6,8 membrane filters, 11,12 and micro-electro-mechanical system (MEMS) chips. 13,14 All of these techniques are subject to limitations.…”

mentioning

confidence: 99%

ApoStream™, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood

et al. 2012

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Isolation and enumeration of circulating tumor cells (CTCs) are used to monitor metastatic disease progression and guide cancer therapy. However, currently available technologies are limited to cells expressing specific cell surface markers, such as epithelial cell adhesion molecule (EpCAM) or have limited specificity because they are based on cell size alone. We developed a device, ApoStream TM that overcomes these limitations by exploiting differences in the biophysical characteristics between cancer cells and normal, healthy blood cells to capture CTCs using dielectrophoretic technology in a microfluidic flow chamber. Further, the system overcomes throughput limitations by operating in continuous mode for efficient isolation and enrichment of CTCs from blood. The performance of the device was optimized using a design of experiment approach for key operating parameters such as frequency, voltage and flow rates, and buffer formulations. Cell spiking studies were conducted using SKOV3 or MDA-MB-231 cell lines that have a high and low expression level of EpCAM, respectively, to demonstrate linearity and precision of recovery independent of EpCAM receptor levels. The average recovery of SKOV3 and MDA-MB-231 cancer cells spiked into approximately 12 Â 10 6 peripheral blood mononuclear cells obtained from 7.5 ml normal human donor blood was 75.4% 6 3.1% (n ¼ 12) and 71.2% 6 1.6% (n ¼ 6), respectively. The intra-day and inter-day precision coefficients of variation of the device were both less than 3%. Linear regression analysis yielded a correlation coefficient (R

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Isolation by Size of Epithelial Tumor Cells

Cited by 957 publications

References 16 publications

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-Recognition PC Software

ApoStream™, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood

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