Detection of circulating epithelial cells after surgery for benign bereast disease

Crisan, Domnita; RUARK, D; Decker, David A.; Drevon, Ann M.; DICARLO, R

doi:10.1016/s1084-8592(00)00008-4

Cited by 3 publications

(3 citation statements)

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“…The MCF-7 cell line, used as a model for CTC selection and enumeration via the integrated HTMSU, is a breast cancer cell line that possesses an overexpressed membrane antigen termed the epithelial cell adhesion molecule, EpCAM. – MCF-7 cells are typically 15−30 μm in diameter (mean = 24 μm) and have been closely associated with micrometastatic breast cancer . EpCAM occurs at a frequency of 5.1 × 10 5 molecules per cell .…”

Section: Resultsmentioning

confidence: 99%

Highly Efficient Circulating Tumor Cell Isolation from Whole Blood and Label-Free Enumeration Using Polymer-Based Microfluidics with an Integrated Conductivity Sensor

et al. 2008

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A novel microfluidic device that can selectively and specifically isolate exceedingly small numbers of circulating tumor cells (CTCs) through a monoclonal antibody (mAB) mediated process by sampling large input volumes (≥1 mL) of whole blood directly in short time periods (<37 min) was demonstrated. The CTCs were concentrated into small volumes (190 nL), and the number of cells captured was read without labeling using an integrated conductivity sensor following release from the capture surface. The microfluidic device contained a series (51) of high-aspect ratio microchannels (35 μm width × 150 μm depth) that were replicated in poly(methyl methacrylate), PMMA, from a metal mold master. The microchannel walls were covalently decorated with mABs directed against breast cancer cells overexpressing the epithelial cell adhesion molecule (EpCAM). This microfluidic device could accept inputs of whole blood, and its CTC capture efficiency was made highly quantitative (>97%) by designing capture channels with the appropriate widths and heights. The isolated CTCs were readily released from the mAB capturing surface using trypsin. The released CTCs were then enumerated on-device using a novel, label-free solution conductivity route capable of detecting single tumor cells traveling through the detection electrodes. The conductivity readout provided near 100% detection efficiency and exquisite specificity for CTCs due to scaling factors and the nonoptimal electrical properties of potential interferences (erythrocytes or leukocytes). The simplicity in manufacturing the device and its ease of operation make it attractive for clinical applications requiring one-time use operation.

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Section: Resultsmentioning

confidence: 99%

Highly Efficient Circulating Tumor Cell Isolation from Whole Blood and Label-Free Enumeration Using Polymer-Based Microfluidics with an Integrated Conductivity Sensor

et al. 2008

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“…Generally, for positive enrichment methods, one type of antigen, the epithelial surface tumor marker (EpCAM), is targeted and typically results in a high-purity separation depending on the antigen. With this method, only CTCs originating in epithelial tumor (breast, colon, prostate, and lung) scans are captured [82], but in recent studies, nonmalignant epithelial cells with the same antigen characteristics have been found in patients with benign colon [82], pancreatic [83], and breast [84, 85] diseases. Nonmalignant tumor cells that have similar characteristics as epithelial CTCs may result in false-positive results; thus, it is also important to consider epithelial-to-mesenchymal transition (EMT) and stem cell markers.…”

Section: Technologies For Ctc Enrichment From Whole Blood Samplesmentioning

confidence: 99%

Technologies for circulating tumor cell separation from whole blood

Bankó

Lee

Nagygyörgy³

et al. 2019

J Hematol Oncol

265

180

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The importance of early cancer diagnosis and improved cancer therapy has been clear for years and has initiated worldwide research towards new possibilities in the care strategy of patients with cancer using technological innovations. One of the key research fields involves the separation and detection of circulating tumor cells (CTC) because of their suggested important role in early cancer diagnosis and prognosis, namely, providing easy access by a liquid biopsy from blood to identify metastatic cells before clinically detectable metastasis occurs and to study the molecular and genetic profile of these metastatic cells. Provided the opportunity to further progress the development of technology for treating cancer, several CTC technologies have been proposed in recent years by various research groups and companies. Despite their potential role in cancer healthcare, CTC methods are currently mainly used for research purposes, and only a few methods have been accepted for clinical application because of the difficulties caused by CTC heterogeneity, CTC separation from the blood, and a lack of thorough clinical validation. Therefore, the standardization and clinical application of various developed CTC technologies remain important subsequent necessary steps. Because of their suggested future clinical benefits, we focus on describing technologies using whole blood samples without any pretreatment and discuss their advantages, use, and significance. Technologies using whole blood samples utilize size-based, immunoaffinity-based, and density-based methods or combinations of these methods as well as positive and negative enrichment during separation. Although current CTC technologies have not been truly implemented yet, they possess high potential as future clinical diagnostic techniques for the individualized therapy of patients with cancer. Thus, a detailed discussion of the clinical suitability of these new advanced technologies could help prepare clinicians for the future and can be a foundation for technologies that would be used to eliminate CTCs in vivo.

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“…For example, previous researches have used commercial antibodies specific to epithelial antigens for isolation of CTCs, thus enriching the benign epithelial cells and CTCs in the blood indiscriminately and giving false-positive results591011. Several papers have found epithelial cells in the blood of subjects without malignancy, such as the patients with benign inflammatory colon disease11, benign bowel disease28, or epithelial proliferative disease2930, and the subjects after the surgery of benign breast cancer31. These epithelial normal cells were detectable with current CTC assays, indicating the need for further characterization of the cells.…”

Section: Resultsmentioning

confidence: 99%

DNA methylation as a potential diagnosis indicator for rapid discrimination of rare cancer cells and normal cells

Zhao

Yang

et al. 2015

Sci Rep

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The global DNA methylation degree may be a ubiquitous and early biomarker to distinguish cancer cells from benign cells. However, its usefulness in clinical diagnosis was scarcely demonstrated, because the cancer cells isolated from patients were usually very rare. Even if 10 mL of peripheral blood was sampled from a patient, only tens of cancer cells could be isolated. So a method to quantify DNA methylation from small number of cells was needed to apply DNA methylation in clinical environment. In this study, we found that normal breast cell line MCF10A and breast cancer cell line MCF7 cells present significantly different percentage of genomic 5-methylcytosine (p < 0.02, n = 8), it could be a potential indicator for rapid discrimination of rare cancer cells from normal cells. However, conventional mass spectrometry needs usually ~106 cells to quantify DNA methylation degree, which was too large to be applied in clinical diagnosis. Here we developed a fast mass spectrometry-based method capable of analyzing the DNA methylation degree from only ~100 human cells. Our method could reveal the different DNA methylation degree between MCF10A and MCF7 cells in less than two hours, having the potential to provide reliable information for clinical application.

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Detection of circulating epithelial cells after surgery for benign bereast disease

Abstract: This finding shows that benign epithelial cells can be mobilized during breast surgery; this effect of surgical manipulation warrants caution in the interpretation of RT-PCR positivity for cytokeratin mRNA in the peripheral blood of patients undergoing surgery for breast cancer.

Cited by 3 publications

References 0 publications

Highly Efficient Circulating Tumor Cell Isolation from Whole Blood and Label-Free Enumeration Using Polymer-Based Microfluidics with an Integrated Conductivity Sensor

Highly Efficient Circulating Tumor Cell Isolation from Whole Blood and Label-Free Enumeration Using Polymer-Based Microfluidics with an Integrated Conductivity Sensor

Technologies for circulating tumor cell separation from whole blood

DNA methylation as a potential diagnosis indicator for rapid discrimination of rare cancer cells and normal cells

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