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 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 Paper-Based MicroRNA Expression Profiling from Plasma and Circulating Tumor Cells

2017 ◽  
Vol 63 (3) ◽  
pp. 731-741 ◽  
Author(s):  
Sai Mun Leong ◽  
Karen Mei-Ling Tan ◽  
Hui Wen Chua ◽  
Mo-Chao Huang ◽  
Wai Chye Cheong ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Molecular Characterization ◽  
Circulating Tumor Cells ◽  
Mirna Expression ◽  
Biological Samples ◽  
Expression Profiles ◽  
Patient Specific ◽  
Great Promise ◽  
Specific Information ◽  
Blood Draw

Abstract BACKGROUND Molecular characterization of circulating tumor cells (CTCs) holds great promise for monitoring metastatic progression and characterizing metastatic disease. However, leukocyte and red blood cell contamination of routinely isolated CTCs makes CTC-specific molecular characterization extremely challenging. METHODS Here we report the use of a paper-based medium for efficient extraction of microRNAs (miRNAs) from limited amounts of biological samples such as rare CTCs harvested from cancer patient blood. Specifically, we devised a workflow involving the use of Flinders Technology Associates (FTA)® Elute Card with a digital PCR-inspired “partitioning” method to extract and purify miRNAs from plasma and CTCs. RESULTS We demonstrated the sensitivity of this method to detect miRNA expression from as few as 3 cancer cells spiked into human blood. Using this method, background miRNA expression was excluded from contaminating blood cells, and CTC-specific miRNA expression profiles were derived from breast and colorectal cancer patients. Plasma separated out during purification of CTCs could likewise be processed using the same paper-based method for miRNA detection, thereby maximizing the amount of patient-specific information that can be derived from a single blood draw. CONCLUSIONS Overall, this paper-based extraction method enables an efficient, cost-effective workflow for maximized recovery of small RNAs from limited biological samples for downstream molecular analyses.

scholarly journals Association of Soluble B7-H4 and Circulating Tumor Cells in Blood of Advanced Epithelial Ovarian Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Pawel Mach ◽  
Rainer Kimmig ◽  
Sabine Kasimir-Bauer ◽  
Paul Buderath
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Survival Data ◽  
Liquid Biopsy ◽  
Therapy Response ◽  
Predictive Biomarkers ◽  
Prognostic Biomarkers ◽  
Immune Checkpoints

IntroductionEpithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy worldwide. Reliable predictive biomarkers are urgently needed to estimate the risk of relapse and to improve treatment management. Soluble immune-checkpoints in EOC are promising molecules serving as prognostic biomarkers accessible via liquid biopsy. We thus, aimed at elucidating the role of sB7-H4 in EOC.Material and MethodsWe analyzed soluble serum B7-H4 (sB7-H4) using ELISA and circulating tumor cells (CTCs) in blood applying the AdnaTest OvarianCancer in 85 patients suffering from advanced EOC. Findings were correlated with clinical parameters as well as survival data.ResultssB7-H4 was detectable in 14.1% patients, CTCs in 32.9% patients and simultaneous presence of CTCs and sB7-H4 was found in 7% patients, respectively. Although no association between sB7-H4 and CTC could be documented, each of them served as independent predictive factors for overall survival (OS).ConclusionsB7-H4 and CTCs are independent prognostic biomarkers for impaired survival in EOC. As they are easily accessible via liquid biopsy, they may be of potential benefit for the prediction of therapy response and survival for EOC patients.

Detection, manipulation and post processing of circulating tumor cells using optical techniques

2015 ◽  
Vol 29 (Supplement 1) ◽  
pp. 1530010 ◽  
Author(s):  
Somayyeh Bakhtiaridoost ◽  
Hamidreza Habibiyan ◽  
Hassan Ghafoorifard
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Blood Stream ◽  
Optical Methods ◽  
Great Promise ◽  
Post Processing ◽  
Optical Techniques ◽  
Secondary Tumors ◽  
Recent Developments

Circulating tumor cells (CTCs) are malignant cells that are derived from a solid tumor in the metastasis stage and are shed into the blood stream. These cells hold great promise to be used as liquid biopsy that is less aggressive than traditional biopsy. Recently, detection and enumeration of these cells has received ever-increasing attention from researchers as a way of early detection of cancer metastasis, determining the effectiveness of treatment and studying the mechanism of formation of secondary tumors. CTCs are found in blood at low concentration, which is a major limitation of isolation and detection of these cells. Over the last few years, multifarious research studies have been conducted on accurate isolation and detection and post processing of CTCs. Among all the proposed systems, microfluidic systems seem to be more attractive for researchers due to their numerous advantages. On the other hand, recent developments in optical methods have made the possibility of cellular studies at single-cell level. Thus, accuracy and efficiency of separation, detection and manipulation of CTCs can be improved using optical techniques. In this review, we describe optical methods that have been used for CTC detection, manipulation and post processing.

scholarly journals Fast and Label-Free Isolation of Circulating Tumor Cells from Blood: From a Research Microfluidic Platform to an Automated Fluidic Instrument, VTX-1 Liquid Biopsy System

2018 ◽  
Vol 23 (1) ◽  
pp. 16-29 ◽  
Author(s):  
Clementine A. Lemaire ◽  
Sean Z. Liu ◽  
Charles L. Wilkerson ◽  
Vishnu C. Ramani ◽  
Nasim A. Barzanian ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Blood Cells ◽  
Liquid Biopsy ◽  
White Blood Cells ◽  
Automated System ◽  
Cell Recovery ◽  
Blood Draw ◽  
Multiple Tumor

Tumor tissue biopsies are invasive, costly, and collect a limited cell population not completely reflective of patient cancer cell diversity. Circulating tumor cells (CTCs) can be isolated from a simple blood draw and may be representative of the diverse biology from multiple tumor sites. The VTX-1 Liquid Biopsy System was designed to automate the isolation of clinically relevant CTC populations, making the CTCs available for easy analysis. We present here the transition from a cutting-edge microfluidic innovation in the lab to a commercial, automated system for isolating CTCs directly from whole blood. As the technology evolved into a commercial system, flexible polydimethylsiloxane microfluidic chips were replaced by rigid poly(methyl methacrylate) chips for a 2.2-fold increase in cell recovery. Automating the fluidic processing with the VTX-1 further improved cancer cell recovery by nearly 1.4-fold, with a 2.8-fold decrease in contaminating white blood cells and overall improved reproducibility. Two isolation protocols were optimized that favor either the cancer cell recovery (up to 71.6% recovery) or sample purity (≤100 white blood cells/mL). The VTX-1’s performance was further tested with three different spiked breast or lung cancer cell lines, with 69.0% to 79.5% cell recovery. Finally, several cancer research applications are presented using the commercial VTX-1 system.

Cell free DNA as an evolving liquid biopsy biomarker for initial diagnosis and therapeutic nursing in Cancer- An evolving aspect in Medical Biotechnology

2020 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Nuclear Dna ◽  
Fragment Size ◽  
Body Fluids ◽  
Response To Therapy ◽  
Significant Information ◽  
Cell Free Dna ◽  
Free Dna

: Cell-free DNA (cfDNA) is present in numerous body fluids in addition to initiates generally from blood cells. It is undoubtedly the utmost promising tool among all components of liquid biopsy. Liquid biopsy is a specialized method investigating the nonsolid biological tissue by revealing of circulating cells, cell free DNA etc. that enter body fluids. Since, cancer cells disengage from compact tumors circulate in peripheral blood, evaluating blood of cancer patients holds the opportunities for capture and molecular level analysis of various tumor-derived constituents. Cell free DNA samples can deliver a significant perceptions into oncology, for instance tumor heterogeneity, instantaneous tumor development, response to therapy and treatment, comprising immunotherapy and mechanisms of cancer metastasis. Malignant growth at any phase can outhouse tumor cells in addition to fragments of neoplasticity causing DNA into circulatory system giving noble sign of mutation in the tumor at sampling time. Liquid biopsy distinguishes diverse blood based evolving biomarkers comprising circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cfDNA, circulating RNA (cfRNA) and exosomes. Cell free DNA are little DNA fragments found circulating in plasma or serum, just as other fluids present in our body. Cell free DNA involves primarily double stranded nuclear DNA and mitochondrial DNA, present both on a surface level and in the lumen of vesicles. The probable origins of the tumor-inferred portion of cfDNA are apoptosis or tumor necrosis, lysis of CTCs or release of DNA from the tumor cells into circulation. The evolution of innovations, refinement and improvement in therapeutics for determination of cfDNA fragment size and its distribution provide significant information related with pathological conditions of the cell, thus emerging as promising indicator for clinical output in medical biotechnology.

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