scholarly journals Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Micromachines ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 774 ◽  
Author(s):  
Jie Cheng ◽  
Yang Liu ◽  
Yang Zhao ◽  
Lina Zhang ◽  
Lingqian Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Human Peripheral Blood ◽  
Microfluidic Devices ◽  
Detection Sensitivity ◽  
Cell Capture ◽  
Primary Tumors ◽  
Downstream Analysis

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

scholarly journals Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2723
Author(s):  
Yu-Ping Yang ◽  
Teresa M. Giret ◽  
Richard J. Cote
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ex Vivo ◽  
Detection Sensitivity ◽  
Clinical Utilization ◽  
Diagnosis And Prognosis ◽  
Early Cancer Diagnosis ◽  
Potential Marker ◽  
Potential Applications ◽  
Downstream Analysis

Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their associated cells (e.g., immune cells and stromal cells) in the circulation. In this review, we briefly summarize existing CTC isolation technologies and specifically focus on advances in downstream analysis of CTCs and their potential applications in precision medicine. We also discuss the current challenges and future opportunities in their clinical utilization.

scholarly journals Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 192
Author(s):  
Leonie Konczalla ◽  
Anna Wöstemeier ◽  
Marius Kemper ◽  
Karl-Frederik Karstens ◽  
Jakob Izbicki ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Application ◽  
Liquid Biopsy ◽  
Cancer Diagnostics ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
New Therapeutic Approaches ◽  
Tumor Dissemination

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

Highly Sensitive Electrochemical Biosensor for Circulating Tumor Cells Detection via Dual-Aptamer Capture and Rolling Circle Amplification Strategy

2019 ◽  
Vol 15 (7) ◽  
pp. 1568-1577 ◽  
Author(s):  
Yang Wang ◽  
Kai Chang ◽  
Cheng Yang ◽  
Shujing Li ◽  
Lixin Wang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Electrochemical Biosensor ◽  
Rolling Circle Amplification ◽  
K562 Cells ◽  
Detection Sensitivity ◽  
Experimental Conditions ◽  
Simple Method ◽  
Rolling Circle

A fast and simple strategy for early detection of circulating tumor cells (CTCs) is urgently required because of cancer metastasis. In this work, we assembled an electrochemical biosensor by two aptamers that could form hairpin and specifically recognize K562 cells. The thiolated capture aptamer was fixed on the gold electrode surface. The detection aptamer was linked with a primer at 3 end which could trigger rolling circle amplification to prolong the sequence of aptamer. The dual-aptamer model was fabricated to improve the capture specificity and efficiency for K562 cells. The rolling circle amplification improved the detection sensitivity by inhibiting electron transfer of [Fe(CN)6]3–/4– which could be measured by differential pulse voltammetry. The detection limit of 25 cells mL–1 and linear ranges of 1 × 10 2 to 1 × 105 cells mL–1 were obtained under optimal experimental conditions. Our work exhibited a label-free and simple method for detecting CTCs using cell-specific aptasensor, showing an expected possibility for further CTCs-related study and clinical applications of this novel method.

scholarly journals Multifunctional Gold Nano-Cytosensor With Quick Capture, Electrochemical Detection, and Non-Invasive Release of Circulating Tumor Cells for Early Cancer Treatment

2021 ◽  
Vol 9 ◽  
Author(s):  
Rui Zhang ◽  
Qiannan You ◽  
Mingming Cheng ◽  
Mingfeng Ge ◽  
Qian Mei ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Electrochemical Impedance ◽  
Limit Of Detection ◽  
Treatment Options ◽  
Metastatic Tumor ◽  
Quantitative Detection ◽  
Cell Capture ◽  
Primary Tumors ◽  
Relative Standard

Circulating tumor cells (CTCs) are metastatic tumor cells that shed into the blood from solid primary tumors, and their existence significantly increases the risk of metastasis and recurrence. The timely discovery and detection of CTCs are of considerable importance for the early diagnosis and treatment of metastasis. However, the low number of CTCs hinders their detection. In the present study, an ultrasensitive electrochemical cytosensor for specific capture, quantitative detection, and noninvasive release of EpCAM-positive tumor cells was developed. The biosensor was manufactured using gold nanoparticles (AuNPs) to modify the electrode. Three types of AuNPs with controllable sizes and conjugated with a targeting molecule of monoclonal anti-EpCAM antibody were used in this study. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) of the cytosensors were performed to evaluate the cell capture efficiency and performance. The captured 4T1 cells by the AuNPs hindered electron transport efficiency, resulting in increased EIS responses. The cell capture response recorded using EIS or DPV indicated that the optimal AuNPs size should be 17 nm. The cell capture response changed linearly with the concentration range from 8.0 × 10 to 1 × 107 cells/mL, and the limit of detection was 50 cells/mL. After these measurements, glycine-HCl (Gly-HCl) was used as an antibody eluent to destroy the binding between antigen and antibody to release the captured tumor cells without compromising their viability for further clinical research. This protocol realizes rapid detection of CTCs with good stability, acceptable assay precision, significant fabrication reproducibility with a relative standard deviation of 2.09%, and good recovery of cells. Our results indicate that the proposed biosensor is promising for the early monitoring of CTCs and may help customize personalized treatment options.

scholarly journals The biology and clinical potential of circulating tumor cells

2019 ◽  
Vol 53 (2) ◽  
pp. 131-147 ◽  
Author(s):  
Taja Lozar ◽  
Klara Gersak ◽  
Maja Cemazar ◽  
Cvetka Grasic Kuhar ◽  
Tanja Jesenko
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Clinical Utility ◽  
Cancer Metastasis ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Biological Properties ◽  
Great Promise ◽  
Blood Draw

Abstract Background Tumor cells can shed from the tumor, enter the circulation and travel to distant organs, where they can seed metastases. These cells are called circulating tumor cells (CTCs). The ability of CTCs to populate distant tissues and organs has led us to believe they are the primary cause of cancer metastasis. The biological properties and interaction of CTCs with other cell types during intravasation, circulation in the bloodstream, extravasation and colonization are multifaceted and include changes of CTC phenotypes that are regulated by many signaling molecules, including cytokines and chemokines. Considering a sample is readily accessible by a simple blood draw, monitoring CTC levels in the blood has exceptional implications in oncology field. A method called the liquid biopsy allows the extraction of not only CTC, but also CTC products, such as cell free DNA (cfDNA), cell free RNA (cfRNA), microRNA (miRNA) and exosomes. Conclusions The clinical utility of CTCs and their products is increasing with advances in liquid biopsy technology. Clinical applications of liquid biopsy to detect CTCs and their products are numerous and could be used for screening of the presence of the cancer in the general population, as well as for prognostic and predictive biomarkers in cancer patients. With the development of better CTC isolation technologies and clinical testing in large prospective trials, increasing clinical utility of CTCs can be expected. The understanding of their biology and interactions with other cell types, particularly with those of the immune system and the rise of immunotherapy also hold great promise for novel therapeutic possibilities.

scholarly journals ctcRbase: the gene expression database of circulating tumor cells and microemboli

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Lei Zhao ◽  
Xiaohong Wu ◽  
Tong Li ◽  
Jian Luo ◽  
Dong Dong
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Circulating Tumor Cell ◽  
Gene Signature ◽  
Primary Tumors ◽  
A Genome ◽  
Experimental Validations ◽  
Transcriptomic Changes

Abstract Circulating tumor cells/microemboli (CTCs/CTMs) are malignant cells that depart from cancerous lesions and shed into the bloodstream. Analysis of CTCs can allow the investigation of tumor cell biomarker expression from a non-invasive liquid biopsy. To date, high-throughput technologies have become a powerful tool to provide a genome-wide view of transcriptomic changes associated with CTCs/CTMs. These data provided us much information to understand the tumor heterogeneity, and the underlying molecular mechanism of tumor metastases. Unfortunately, these data have been deposited into various repositories, and a uniform resource for the cancer metastasis is still unavailable. To this end, we integrated previously published transcriptome datasets of CTCs/CTMs and constructed a web-accessible database. The first release of ctcRbase contains 526 CTCs/CTM samples across seven cancer types. The expression of 14 631 mRNAs and 3642 long non-coding RNAs of CTCs/CTMs were included. Experimental validations from the published literature are also included. Since CTCs/CTMs are considered to be precursors of metastases, ctcRbase also collected the expression data of primary tumors and metastases, which allows user to discover a unique ‘circulating tumor cell gene signature’ that is distinct from primary tumor and metastases. An easy-to-use database was constructed to query and browse CTCs/CTMs genes. ctcRbase can be freely accessible at http://www.origin-gene.cn/database/ctcRbase/.

scholarly journals Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1111
Author(s):  
Jerry Xiao ◽  
Paula R. Pohlmann ◽  
Claudine Isaacs ◽  
Benjamin A. Weinberg ◽  
Aiwu R. He ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Single Cells ◽  
Circulatory System ◽  
Clinical Importance ◽  
Progression Free Survival ◽  
Primary Tumors ◽  
Isolation Techniques

Circulating tumor cells (CTCs) are single cells or clusters of cells within the circulatory system of a cancer patient. While most CTCs will perish, a small proportion will proceed to colonize the metastatic niche. The clinical importance of CTCs was reaffirmed by the 2008 FDA approval of CellSearch®, a platform that could extract EpCAM-positive, CD45-negative cells from whole blood samples. Many further studies have demonstrated the presence of CTCs to stratify patients based on overall and progression-free survival, among other clinical indices. Given their unique role in metastasis, CTCs could also offer a glimpse into the genetic drivers of metastasis. Investigation of CTCs has already led to groundbreaking discoveries such as receptor switching between primary tumors and metastatic nodules in breast cancer, which could greatly affect disease management, as well as CTC-immune cell interactions that enhance colonization. In this review, we will highlight the growing variety of isolation techniques for investigating CTCs. Next, we will provide clinically relevant context for CTCs, discussing key clinical trials involving CTCs. Finally, we will provide insight into the future of CTC studies and some questions that CTCs are primed to answer.

scholarly journals Detection and clinical significance of circulating tumor cells in colorectal cancer

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Miao Jiang ◽  
Shuiling Jin ◽  
Jinming Han ◽  
Tong Li ◽  
Jianxiang Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Histopathological Examination ◽  
Peripheral Circulation ◽  
Future Research ◽  
Dynamic Changes ◽  
Primary Tumors ◽  
Invasive Method

AbstractHistopathological examination (biopsy) is the “gold standard” for the diagnosis of colorectal cancer (CRC). However, biopsy is an invasive method, and due to the temporal and spatial heterogeneity of the tumor, a single biopsy cannot reveal the comprehensive biological characteristics and dynamic changes of the tumor. Therefore, there is a need for new biomarkers to improve CRC diagnosis and to monitor and treat CRC patients. Numerous studies have shown that “liquid biopsy” is a promising minimally invasive method for early CRC detection. A liquid biopsy mainly samples circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA (miRNA) and extracellular vesicles (EVs). CTCs are malignant cells that are shed from the primary tumors and/or metastases into the peripheral circulation. CTCs carry information on both primary tumors and metastases that can reflect dynamic changes in tumors in a timely manner. As a promising biomarker, CTCs can be used for early disease detection, treatment response and disease progression evaluation, disease mechanism elucidation, and therapeutic target identification for drug development. This review will discuss currently available technologies for plasma CTC isolation and detection, their utility in the management of CRC patients and future research directions.

scholarly journals Lymph-Circulating Tumor Cells show distinct properties to Blood-Circulating Tumor Cells and constitute extraordinary efficient metastatic precursors

2018 ◽  
Author(s):  
Sulma I Mohammed ◽  
Odalys Torres Luquis ◽  
El Wood Walls ◽  
Frank Lloyd
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Expression Profiles ◽  
Parental Cell ◽  
Breast Cancer Metastasis ◽  
Primary Tumors ◽  
Gene And Protein Expression ◽  
Protein Expression Profiles

The molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known. We developed an innovative technique that enables the collection of lymph and lymph-circulating tumor cells (LCTCs) en route to the SLN in immunocompetent animal model of breast cancer metastasis. We found that LCTCs and blood circulating tumor cells (BCTCs) as exited the primary tumor shared similar gene and protein expression profiles that were distinct from those of primary tumors and lymph node metastases (LNMs) despite their common parental cell origin. LCTCs but not BCTC exist in clusters, display a hybrid epithelial/mesenchymal phenotype and cancer stem cell-like properties and constitute extraordinarily efficient metastatic precursors. These results demonstrate that tumor cell metastasizing through the lymphatic are different from those spread by the blood circulation. The contribution of these cells to overall peripheral blood CTC is important in cancer therapy. Whether these two types of cells occur in cancer patients remain to be determined.

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