• An emerging method to detect metastasis is the analysis of circulating tumor cells (CTCs), which has shown promise in filling the gaps left by other diagnostic methods. (iiarjournals.org)
  • CTCs are tumor cells originating from primary sites or metastases that circulate in the patients' bloodstream and are very rarely found in healthy individuals ( 9 , 10 ) ( Figure 1 ). (iiarjournals.org)
  • Morphological-based isolation separates CTCs according to size discrepancies, using isolation by size of epithelial tumor cells (ISET) or according to density, using density-gradient separation ( 4 ). (iiarjournals.org)
  • Ensemble-decision aliquot position (eDAR) is a sensitive and high-throughput method to analyze circulating tumor cells (CTCs) from peripheral blood. (conferencedequebec.org)
  • The enumeration of circulating tumor cells (CTCs) represents an effective prognostic and predictive biomarker, which is able to monitor efficacy of adjuvant therapies, detect early development of (micro)metastases and at last, assess therapeutic responses of advanced disease earlier than traditional imaging methods. (amegroups.org)
  • In the last decade, the detection of disseminated tumor cells (DTCs) in the bone marrow and circulating tumor cells (CTCs) in the blood have demonstrated to provide useful information for the clinical management of BC by predicting treatment benefit earlier than traditional imaging methods. (amegroups.org)
  • The use of circulating tumor cells (CTCs) as a "liquid biopsy" to interrogate the molecular profile of single patients is extremely encouraging, as these cells originate from primary tumor and metastatic sites, providing a comprehensive fingerprint of a given tumor at any time during the course of the disease with a simple blood draw [ 7 ] . (oaepublish.com)
  • The detection of CTCs, or liquid biopsy, presents several advantages over traditional tissue biopsies. (wikipedia.org)
  • Moreover, since repeated tissue biopsies are invasive, costly and not always feasible, the assessment of tumor characteristics on CTCs, by a peripheral blood sample as a 'liquid biopsy', represents an attractive opportunity. (amegroups.org)
  • CTCs were captured onto a very small area (1 mm2) with a high enrichment ratio.27 Although eDAR was more sensitive than the CellSearch method in detecting CTCs from metastatic breast cancer patients 27 the original version of eDAR still has several factors that may limit its clinical application. (conferencedequebec.org)
  • To this end, technologies with the requisite sensitivity and reproducibility to detect CTCs in patients with metastatic disease have recently been developed. (wikipedia.org)
  • Although the improvements in BC detection and adjuvant treatments led to a significant decrease in BC-related deaths in the last two decades, about 30% of women initially diagnosed with early-stage cancer eventually develop metastatic disease. (amegroups.org)
  • Since CTCs are continuously released and destroyed, such CTMat accumulate and could represent an independent biomarker for the prognostication and monitoring of metastatic disease. (amegroups.org)
  • In general, CTCs are anoikis-resistant, which means that they can survive in the bloodstream without attaching to a substrate. (wikipedia.org)
  • The apoptosis and necrosis processes of CTCs cause the leakage of intracellular components in the bloodstream, such as electrolytes, cellular debris, DNA, and chromatin. (amegroups.org)
  • CTCs are present in the bloodstream at a very low concentration, thus their detection and characterization require highly sensitive and specific methods, which consist of a combination of enrichment (isolation) and detection (identification) strategies ( Table 1 ) and both steps are essential components of the identification process ( 19 ). (amegroups.org)
  • in this scenario, careful consideration must be given to the isolation approach, whereas methods that discriminate against certain subpopulations may result in the exclusion of CTCs that carry biological relevance. (oaepublish.com)
  • Apoptotic CTCs are traditional CTCs that are undergoing apoptosis (programmed cell death). (wikipedia.org)
  • Based on size separation, this device enriches CTCs from unprocessed whole bloods, and allows for on-chip culture and molecular profiling. (harvard.edu)
  • The chip performs immunomagnetic sorting and size-based cell capture, to capture target cells and then perform molecular analyses on these cells. (harvard.edu)
  • The ultimate challenge is based on the need for downstream analyses of the isolated CTCs providing cellular and molecular information at the single-cell level which may be more important than simple enumeration. (conferencedequebec.org)
  • The implementation of molecular and genomic characterization of CTCs could contribute to improve the treatment selection and thus, to move toward more personalized treatments. (amegroups.org)
  • The detection and analysis of CTCs can assist early patient prognoses and determine appropriate tailored treatments. (wikipedia.org)
  • On the other hand, CTCs are very rare, often present as only a few cells per milliliter of blood, which makes their detection challenging. (wikipedia.org)
  • Herein, we review the history and the current status of CTC detection, discuss the prognostic, predictive, and diagnostic capabilities of these technologies, and describe application of CTCs as models for the study of tumor biology. (amegroups.org)
  • The aim of this review is to describe the current state of the art on CTCs detection and clinical use, the evidence to demonstrate their clinical validity, and their potential impact for both future clinical trial design and, decision-making process in our daily practice. (amegroups.org)
  • CTCs that originate from carcinomas (cancers of epithelial origin, which are the most prevalent) can be classified according to the expression of epithelial markers, as well as their size and whether they are apoptotic. (wikipedia.org)
  • Cytokeratin-negative CTCs are characterised by the lack of EpCAM or cytokeratins, which may indicate an undifferentiated phenotype (circulating cancer stem cells) or the acquisition of a mesenchymal phenotype (known as epithelial-mesenchymal transition or EMT). (wikipedia.org)
  • For example, one study involving prostate cancer showed an eight-fold longer mean survival rate for patients with only single CTCs versus those with CTC clusters, while other studies have shown similar correlations for colon cancer. (wikipedia.org)
  • These analyses have been successfully performed by researchers investigating various cancer biomarkers including the human epidermal growth factor receptor 2 (HER-2) in breast cancer 11 epidermal growth factor receptor (EGFR) in lung cancer 12 and TMPRSS2-ERG in prostate cancer.13 Enrichment ratio and purity of the captured CTCs are crucial to the downstream analyses because they will determine the throughput and accuracy of these measurements. (conferencedequebec.org)
  • Small CTCs have been implicated in progressive disease and differentiation into small cell carcinomas, which often require a different therapeutic course. (wikipedia.org)
  • Additionally, a deeper understanding of the metastatic cascade in breast cancer will be critical for developing therapeutic interventions to combat breast cancer metastasis. (iiarjournals.org)
  • CTCs are recognized as playing important roles in the metastasis of carcinomas ( 11 , 12 ) and their analysis enables the prediction of metastatic relapse and progression ( 11 ). (iiarjournals.org)
  • Measuring the ratio of traditional CTC to apoptotic CTCs-from baseline to therapy-provides clues to treatment efficacy in targeting and killing cancer cells. (wikipedia.org)
  • CTC clusters are two or more individual CTCs bound together. (wikipedia.org)
  • Imaging quality of the isolated CTCs is also important if downstream analyses are performed Z-DEVD-FMK on the same device that captures CTCs because many bioassays may be performed based on detailed labeling and imaging studies of individual CTCs. (conferencedequebec.org)
  • CTCs can extravasate and become seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. (wikipedia.org)
  • Importantly, small CTCs have cancer-specific biomarkers that identify them as CTCs. (wikipedia.org)
  • These clusters have cancer-specific biomarkers that identify them as CTCs. (wikipedia.org)
  • A multimodal combination of circulating tumor DNAs (ctDNAs), CTCs, proteomics, and CTC-derived xenografts (CDXs) to create computational models useful in diagnosis, prognostication, and predictiveness to treatment is likely the future of tailoring individualized cancer care. (amegroups.org)
  • Some of the innovative technologies developed to date are shown below. (harvard.edu)
  • Small CTCs are cytokeratin-positive and CD45-negative, but with sizes and shapes similar to white blood cells. (wikipedia.org)
  • The CTC cluster may contain traditional, small or CK- CTCs. (wikipedia.org)
  • Immunological techniques, which are the most widely used methods, employ immunomagnetic isolation ( 4 ). (iiarjournals.org)
  • After isolation, the source and genetic make-up of CTCs are characterized using nucleic acid-based methods, such as quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), or cytometric-based methods, such as flow cytometry and enzyme-linked immunospot assay technology ( 4 ). (iiarjournals.org)
  • Generally, CTCs are firstly isolated and enriched through either morphological or immunological techniques ( 4 ). (iiarjournals.org)
  • Cytokeratin-negative CTCs are characterised by the lack of EpCAM or cytokeratins, which may indicate an undifferentiated phenotype (circulating cancer stem cells) or the acquisition of a mesenchymal phenotype (known as epithelial-mesenchymal transition or EMT). (wikipedia.org)
  • However, the isolation of CTCs for molecular analysis is challenging due to their extreme rarity and phenotypic heterogeneity, which hinders the transformation of CTCs into traditional clinical applications. (oaepublish.com)
  • therefore, a number of different enrichment and isolation methods have been developed ( 2 ). (iiarjournals.org)
  • Although many methods have been developed to isolate CTCs, there are only two basic approaches to isolate CTCs: a) isolation methods based on detection of specific surface markers of the CTCs (and/or white blood cells), also called "label-dependent systems/methods" and b) methods independent of specific markers, based on physical or biological properties of the CTCs, "label-independent systems/methods" ( 2 ). (iiarjournals.org)
  • The term "label-dependent methods" comprises all CTC isolation methods, which identify CTCs according to the presence or absence of specific markers. (iiarjournals.org)
  • CTCs must express the specific markers tracked by the particular isolation method. (iiarjournals.org)
  • CTCs were identified and counted using microfluidic isolation and immunofluorescent staining of CD45, HE4, and epithelial and mesenchymal (E&M) markers (epithelial cell adhesion molecule, cytokeratins, and vimentin). (oncotarget.com)
  • Isolation of rare cells (1 CTC in 10 8 leucocytes) presents considerable technological challenges requiring a robust analytical technique and a number of different approaches have been developed based on the physical and biological properties of CTC [ 1 , 13 ]. (biomedcentral.com)
  • The system consists of two major instrumental components: the AutoPrep station for the fully-automated immunomagnetic isolation of cells from whole blood and an Analyser for the semi-automated identification of CTC based on 4-channel fluorescence microscopy [ 14 ]. (biomedcentral.com)
  • To this end, technologies with the requisite sensitivity and reproducibility to detect CTCs in patients with metastatic disease have recently been developed. (wikipedia.org)
  • In addition, they often express a variety of markers which vary from patient to patient, which makes it difficult to develop techniques with high sensitivity and specificity. (wikipedia.org)
  • In order to achieve clinically significant CTC detection, devices utilizing novel microfluidics and nanotechnology have been developed to achieve high sensitivity and specificity capture of CTCs. (oaepublish.com)
  • Importantly, small CTCs have cancer-specific biomarkers that identify them as CTCs. (wikipedia.org)
  • These clusters have cancer-specific biomarkers that identify them as CTCs. (wikipedia.org)
  • CTC analysis has a variety of clinical applications, including real-time non-invasive monitoring of CTCs as biomarkers for new cancer therapies as well as identifying new potential therapeutic targets that directly inhibit cancer metastasis. (oaepublish.com)
  • Upon reaching a suitable niche, the CTCs undergo mesenchymal-epithelial transition (MET), subsequently reacquiring the stem cell properties and reactivating proliferative capability to colonize at metastatic sites [ 2 ] . (oaepublish.com)
  • Although the potential applications of CTC analysis appear to be very promising, due to the rarity (one CTC per billion hematologic cells) and heterogeneity (e.g., differences in morphology and gene expression) of CTCs in the blood of cancer patients, there are few commercially available techniques for clinical use. (oaepublish.com)
  • Current methods commonly use EpCAM to capture CTCs, but this results in a loss of information on other CTC subsets (EpCAM-negative cells) due to the heterogeneity of CTCs. (bvsalud.org)
  • Here, we report a novel microfluidic device that integrates the capture and release of heterogeneous CTCs directly from whole blood. (bvsalud.org)
  • The CTCs enrichment methods as well as their potential clinical use in lung cancer is introduced below. (iiarjournals.org)
  • It has been shown that the CTC population has a continuum of phenotypes, from strictly epithelial CTCs, hybrid CTCs to mesenchymal CTCs ( 7 ), due to their ability to undergo epithelial-to-mesenchymal transition ( 2 ). (iiarjournals.org)
  • In this review, we discuss these newly developed devices for CTC capture and molecular characterization for early diagnosis and determining ideal treatment regimen to better manage these cancers clinically. (oaepublish.com)
  • CTCs that originate from carcinomas (cancers of epithelial origin, which are the most prevalent) can be classified according to the expression of epithelial markers, as well as their size and whether they are apoptotic. (wikipedia.org)
  • CTCs can extravasate and become seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. (wikipedia.org)
  • CTCs, detached from the primary tumor or metastases and shed in patient's bloodstream, represent a relatively easily obtainable sample of cancer tissue. (iiarjournals.org)
  • Small CTCs are cytokeratin-positive and CD45-negative, but with sizes and shapes similar to white blood cells. (wikipedia.org)
  • Measuring the ratio of traditional CTC to apoptotic CTCs-from baseline to therapy-provides clues to treatment efficacy in targeting and killing cancer cells. (wikipedia.org)
  • In addition, the potential prognostic values of CTCs as treatment guidelines and that ultimately contribute to realize personalized treatment are also discussed. (oaepublish.com)
  • [ 2 ] In addition, CTCs have been found in blood during early stages of tumorigenesis. (medscape.com)
  • A spiral chip was designed for the separation of differently sized cells, and larger CTCs were effectively separated from smaller blood cells with a 98% recovery rate. (bvsalud.org)
  • Additionally, systems including both heart and cancer tissue have been developed to investigate tissue-tissue interactions' effect on cardiac tissue response to cancer drugs. (bvsalud.org)
  • For example, one study involving prostate cancer showed an eight-fold longer mean survival rate for patients with only single CTCs versus those with CTC clusters, while other studies have shown similar correlations for colon cancer. (wikipedia.org)
  • CTCs can be used in cancer diagnosis or screening, real-time long-term disease monitoring and even therapy guidance. (iiarjournals.org)
  • Small CTCs have been implicated in progressive disease and differentiation into small cell carcinomas, which often require a different therapeutic course. (wikipedia.org)
  • Apoptotic CTCs are traditional CTCs that are undergoing apoptosis (programmed cell death). (wikipedia.org)
  • The CTC cluster may contain traditional, small or CK- CTCs. (wikipedia.org)
  • In this regard, heart-on-chip (HOC) systems have been developed as a more efficient and cost-effective solution than traditional methods, such as 2D cell culture and animal models. (bvsalud.org)
  • The core idea of this article rests in dividing µPADs according to their type into two groups: A) instrumentation-free µPADs for resource-limited scenarios or developing countries and B) instrumentation-based µPADs as futuristic POC devices for e-diagnostics mainly aimed at developed countries. (bvsalud.org)
  • CTCs were first detected in cancer patient in 1869 by Australian physician named Thomas Ashworth. (oaepublish.com)