Magnetic separation of acoustically focused cancer cells from blood for magnetographic templating and analysis

AbstractCancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

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A nanostructured microfluidic device for plasmonic-assisted electrochemical detection of hydrogen peroxide released from cancer cells

Nanoscale ◽

10.1039/d0nr07608b ◽

2021 ◽

Author(s):

Carolina del Real Mata ◽

Roozbeh Siavash Moakhar ◽

Sayed Iman Isaac Hosseini ◽

Mahsa Jalali ◽

Sara Mahshid

Keyword(s):

Hydrogen Peroxide ◽

Cancer Cells ◽

Real Time ◽

Electrochemical Detection ◽

Microfluidic Device ◽

Cancer Biomarker ◽

Cancer Diagnostics ◽

Liquid Biopsies ◽

Non Invasive

Non-invasive liquid biopsies offer hope for a rapid, risk-free, real-time glimpse into cancer diagnostics. Recently, hydrogen peroxide (H2O2) is identified as a cancer biomarker due to continued release from cancer...

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Selective identification of somatic mutations in pancreatic cancer cells through a combination of next-generation sequencing of plasma DNA using molecular barcodes and a bioinformatic variant filter

PLoS ONE ◽

10.1371/journal.pone.0192611 ◽

2018 ◽

Vol 13 (2) ◽

pp. e0192611 ◽

Cited By ~ 6

Author(s):

Yoji Kukita ◽

Kazuyoshi Ohkawa ◽

Ryoji Takada ◽

Hiroyuki Uehara ◽

Kazuhiro Katayama ◽

...

Keyword(s):

Pancreatic Cancer ◽

Next Generation Sequencing ◽

Cancer Cells ◽

Somatic Mutations ◽

Next Generation ◽

Plasma Dna ◽

Pancreatic Cancer Cells ◽

Generation Sequencing ◽

Molecular Barcodes

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Circulating Tumor Cells: Diagnostic and Therapeutic Applications

Annual Review of Biomedical Engineering ◽

10.1146/annurev-bioeng-062117-120947 ◽

2018 ◽

Vol 20 (1) ◽

pp. 329-352 ◽

Cited By ~ 27

Author(s):

Eric Lin ◽

Thong Cao ◽

Sunitha Nagrath ◽

Michael R. King

Keyword(s):

Cancer Cells ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Poor Prognosis ◽

Experimental Therapeutics ◽

Next Generation ◽

Therapeutic Applications

Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.

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Detection of Cell Types Contributing to Cancer From Circulating, Cell-Free Methylated DNA

Frontiers in Genetics ◽

10.3389/fgene.2021.671057 ◽

2021 ◽

Vol 12 ◽

Author(s):

Megan E. Barefoot ◽

Netanel Loyfer ◽

Amber J. Kiliti ◽

A. Patrick McDeed ◽

Tommy Kaplan ◽

...

Keyword(s):

Cancer Cells ◽

Cell Types ◽

Circulating Tumor Dna ◽

Cancer Diagnostics ◽

Tissue Homeostasis ◽

Specific Cell ◽

Cell Type ◽

Liquid Biopsies ◽

Methylated Dna ◽

Cell Type Specific

Detection of cellular changes in tissue biopsies has been the basis for cancer diagnostics. However, tissue biopsies are invasive and limited by inaccuracies due to sampling locations, restricted sampling frequency, and poor representation of tissue heterogeneity. Liquid biopsies are emerging as a complementary approach to traditional tissue biopsies to detect dynamic changes in specific cell populations. Cell-free DNA (cfDNA) fragments released into the circulation from dying cells can be traced back to the tissues and cell types they originated from using DNA methylation, an epigenetic regulatory mechanism that is highly cell-type specific. Decoding changes in the cellular origins of cfDNA over time can reveal altered host tissue homeostasis due to local cancer invasion and metastatic spread to distant organs as well as treatment responses. In addition to host-derived cfDNA, changes in cancer cells can be detected from cell-free, circulating tumor DNA (ctDNA) by monitoring DNA mutations carried by cancer cells. Here, we will discuss computational approaches to identify and validate robust biomarkers of changed tissue homeostasis using cell-free, methylated DNA in the circulation. We highlight studies performing genome-wide profiling of cfDNA methylation and those that combine genetic and epigenetic markers to further identify cell-type specific signatures. Finally, we discuss opportunities and current limitations of these approaches for implementation in clinical oncology.

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Next-generation sequencing reveals alternative L-DOPA decarboxylase (DDC) splice variants bearing novel exons, in human hepatocellular and lung cancer cells

Gene ◽

10.1016/j.gene.2020.145262 ◽

2021 ◽

Vol 768 ◽

pp. 145262 ◽

Cited By ~ 2

Author(s):

Maria Papatsirou ◽

Panagiotis G. Adamopoulos ◽

Pinelopi I. Artemaki ◽

Vasiliki P. Georganti ◽

Andreas Scorilas ◽

...

Keyword(s):

Lung Cancer ◽

Next Generation Sequencing ◽

Cancer Cells ◽

Splice Variants ◽

Lung Cancer Cells ◽

Dopa Decarboxylase ◽

Next Generation ◽

Generation Sequencing

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Next-generation sequencing for tumor mutation quantification using liquid biopsies

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0745 ◽

2020 ◽

Vol 58 (2) ◽

pp. 306-313 ◽

Cited By ~ 1

Author(s):

Mariano Provencio ◽

Clara Pérez-Barrios ◽

Miguel Barquin ◽

Virginia Calvo ◽

Fabio Franco ◽

...

Keyword(s):

Lung Cancer ◽

Next Generation Sequencing ◽

Correlation Coefficient ◽

Resistance Mutation ◽

Response To Treatment ◽

Clinical Samples ◽

Next Generation ◽

Liquid Biopsies ◽

Nsclc Patients ◽

Generation Sequencing

AbstractBackgroundNon-small cell lung cancer (NSCLC) patients benefit from targeted therapies both in first- and second-line treatment. Nevertheless, molecular profiling of lung cancer tumors after first disease progression is seldom performed. The analysis of circulating tumor DNA (ctDNA) enables not only non-invasive biomarker testing but also monitoring tumor response to treatment. Digital PCR (dPCR), although a robust approach, only enables the analysis of a limited number of mutations. Next-generation sequencing (NGS), on the other hand, enables the analysis of significantly greater numbers of mutations.MethodsA total of 54 circulating free DNA (cfDNA) samples from 52 NSCLC patients and two healthy donors were analyzed by NGS using the Oncomine™ Lung cfDNA Assay kit and dPCR.ResultsLin’s concordance correlation coefficient and Pearson’s correlation coefficient between mutant allele frequencies (MAFs) assessed by NGS and dPCR revealed a positive and linear relationship between the two data sets (ρc = 0.986; 95% confidence interval [CI] = 0.975–0.991; r = 0.987; p < 0.0001, respectively), indicating an excellent concordance between both measurements. Similarly, the agreement between NGS and dPCR for the detection of the resistance mutation p.T790M was almost perfect (K = 0.81; 95% CI = 0.62–0.99), with an excellent correlation in terms of MAFs (ρc = 0.991; 95% CI = 0.981–0.992 and Pearson’s r = 0.998; p < 0.0001). Importantly, cfDNA sequencing was successful using as low as 10 ng cfDNA input.ConclusionsMAFs assessed by NGS were highly correlated with MAFs assessed by dPCR, demonstrating that NGS is a robust technique for ctDNA quantification using clinical samples, thereby allowing for dynamic genomic surveillance in the era of precision medicine.

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