scholarly journals Circulating biomarkers in patients with glioblastoma

2019 ◽  
Vol 122 (3) ◽  
pp. 295-305 ◽  
Author(s):  
Juliana Müller Bark ◽  
Arutha Kulasinghe ◽  
Benjamin Chua ◽  
Bryan W. Day ◽  
Chamindie Punyadeera

Abstract Gliomas are the most common tumours of the central nervous system and the most aggressive form is glioblastoma (GBM). Despite advances in treatment, patient survival remains low. GBM diagnosis typically relies on imaging techniques and postoperative pathological diagnosis; however, both procedures have their inherent limitations. Imaging modalities cannot differentiate tumour progression from treatment-related changes that mimic progression, known as pseudoprogression, which might lead to misinterpretation of therapy response and delay clinical interventions. In addition to imaging limitations, tissue biopsies are invasive and most of the time cannot be performed over the course of treatment to evaluate ‘real-time’ tumour dynamics. In an attempt to address these limitations, liquid biopsies have been proposed in the field. Blood sampling is a minimally invasive procedure for a patient to endure and could provide tumoural information to guide therapy. Tumours shed tumoural content, such as circulating tumour cells, cell-free nucleic acids, proteins and extracellular vesicles, into the circulation, and these biomarkers are reported to cross the blood–brain barrier. The use of liquid biopsies is emerging in the field of GBM. In this review, we aim to summarise the current literature on circulating biomarkers, namely circulating tumour cells, circulating tumour DNA and extracellular vesicles as potential non-invasively sampled biomarkers to manage the treatment of patients with GBM.

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Shidong Jia ◽  
Winston Patrick Kuo

This editorial article summarizes the achievements and current challenges for the Journal of Circulating Biomarkers (JCB) regarding a more strategic approach to branding and attracting a high quality variety of articles. More emphasis is placed on fostering engagement with academic and industry sources operating at the cutting-edge of translational technologies applied to the field of circulating biomarkers (interface between extracellular vesicles including exosomes and microvesicles, circulating tumour cells, cell-free circulating DNA and circulating protein markers) and with those in the investment arena seeking and providing private funding for this area of research.


2021 ◽  
Vol 22 (13) ◽  
pp. 7039
Author(s):  
Wojciech Jelski ◽  
Barbara Mroczko

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations.While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.


2018 ◽  
Vol 105 (2) ◽  
pp. e110-e120 ◽  
Author(s):  
O. Nordgård ◽  
K. Tjensvoll ◽  
B. Gilje ◽  
K. Søreide

2021 ◽  
Vol 11 ◽  
Author(s):  
Juliana Müller Bark ◽  
Arutha Kulasinghe ◽  
Gunter Hartel ◽  
Paul Leo ◽  
Majid Ebrahimi Warkiani ◽  
...  

Glioblastoma (GBM) is the most common and aggressive type of tumour arising from the central nervous system. GBM remains an incurable disease despite advancement in therapies, with overall survival of approximately 15 months. Recent literature has highlighted that GBM releases tumoural content which crosses the blood-brain barrier (BBB) and is detected in patients’ blood, such as circulating tumour cells (CTCs). CTCs carry tumour information and have shown promise as prognostic and predictive biomarkers in different cancer types. Currently, there is limited data for the clinical utility of CTCs in GBM. Here, we report the use of spiral microfluidic technology to isolate CTCs from whole blood of newly diagnosed GBM patients before and after surgery, followed by characterization for GFAP, cell-surface vimentin protein expression and EGFR amplification. CTCs were found in 13 out of 20 patients (9/20 before surgery and 11/19 after surgery). Patients with CTC counts equal to 0 after surgery had a significantly longer recurrence-free survival (p=0.0370). This is the first investigation using the spiral microfluidics technology for the enrichment of CTCs from GBM patients and these results support the use of this technology to better understand the clinical value of CTCs in the management of GBM in future studies.


2020 ◽  
Vol 21 (13) ◽  
pp. 4813 ◽  
Author(s):  
Stefano Guadagni ◽  
Marco Clementi ◽  
Francesco Masedu ◽  
Giammaria Fiorentini ◽  
Donatella Sarti ◽  
...  

Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic EOC CTCs, from 10 patients, nine with stage IIIC and one with stage IV disease, in progression after systemic chemotherapy, submitted for hypoxic isolated abdominal perfusion (HAP), are both feasible and useful in predicting response to therapy. Viable metastatic EOC CTCs (>5 cells/mL for all 10 blood samples), enriched by transient culture and identified by reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence (IF), were subjected to flow cytometry-based Annexin V-PE assays for chemosensitivity to several chemotherapeutic agents and by RT-PCR for tumour gene expression profiling. Using a cut-off value of >80% cell death, CTC chemosensitivity tests were predictive of patient RECIST 1.1 responses to HAP therapy associated with 100% sensitivity, 50% specificity, 33% positive predictive, 100% negative predictive and 60% accuracy values. We propose that the methodology employed in this study is feasible and has the potential to predict response to therapy, setting the stage for a larger study.


2019 ◽  
Vol 7 (43) ◽  
pp. 6670-6704 ◽  
Author(s):  
Narshone Soda ◽  
Bernd H. A. Rehm ◽  
Prashant Sonar ◽  
Nam-Trung Nguyen ◽  
Muhammad J. A. Shiddiky

In this review, we have summarised the biogenesis, biological significance, isolation and detection technologies of four widely known circulating biomarkers namely circulating tumour cells, circulating tumor specific DNA, microRNA, and exosomes.


2018 ◽  
Vol 122 (1) ◽  
pp. 152-159 ◽  
Author(s):  
Giorgio I. Russo ◽  
Simone Bier ◽  
Jörg Hennenlotter ◽  
Gunthild Beger ◽  
Lucretia Pavlenco ◽  
...  

2014 ◽  
Vol 8 (9-10) ◽  
pp. 715 ◽  
Author(s):  
Vladimir Bobek ◽  
Martin Cegan ◽  
Katarina Kolostova

Introduction: Results of clinical trials have demonstrated that circulating tumour cells (CTCs) are frequently detected in patients with urothelial tumours. The monitoring of CTCs has the potential to improve therapeutic management at an early stage and also to identify patients with increased risk of tumour progression or recurrence before the onset of clinically detected metastasis. In this study, we report a new effectively simplified methodology for a separation and in vitro culturing of viable CTCs from peripheral blood.Method: We include patients diagnosed with 3 types of urothelial tumours (prostate cancer, urinary bladder cancer, and kidney cancer). A size-based separation method for viable CTC - enrichment from unclothed peripheral blood has been introduced (MetaCell, Ostrava, Czech Republic). The enriched CTCs fraction was cultured directly on the separation membrane, or transferred from the membrane and cultured on any plastic surface or a microscopic slide.Results: We report a successful application of a CTCs isolation procedure in patients with urothelial cancers. The CTCs captured on the membrane are enriched with a remarkable proliferation potential. This has enabled us to set up in vitro cell cultures from the viable CTCs unaffected by any fixation buffers, antibodies or lysing solutions. Next, the CTCs were cultured in vitro for a minimum of 10 to 14 days to enable further downstream analysis (e.g., immunohistochemistry).Conclusion: We demonstrated an efficient CTCs capture platform, based on a cell size separation principle. Furthermore, we report an ability to culture the enriched cells – a critical requirement for post-isolation cellular analysis.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 852 ◽  
Author(s):  
Etienne Buscail ◽  
Charlotte Maulat ◽  
Fabrice Muscari ◽  
Laurence Chiche ◽  
Pierre Cordelier ◽  
...  

Pancreatic cancer is a public health problem because of its increasing incidence, the absence of early diagnostic tools, and its aggressiveness. Despite recent progress in chemotherapy, the 5-year survival rate remains below 5%. Liquid biopsies are of particular interest from a clinical point of view because they are non-invasive biomarkers released by primary tumours and metastases, remotely reflecting disease burden. Pilot studies have been conducted in pancreatic cancer patients evaluating the detection of circulating tumour cells, cell-free circulating tumour DNA, exosomes, and tumour-educated platelets. There is heterogeneity between the methods used to isolate circulating tumour elements as well as the targets used for their identification. Performances for the diagnosis of pancreatic cancer vary depending of the technique but also the stage of the disease: 30–50% of resectable tumours are positive and 50–100% are positive in locally advanced and/or metastatic cases. A significant prognostic value is demonstrated in 50–70% of clinical studies, irrespective of the type of liquid biopsy. Large prospective studies of homogeneous cohorts of patients are lacking. One way to improve diagnostic and prognostic performances would be to use a combined technological approach for the detection of circulating tumour cells, exosomes, and DNA.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Niki Christou ◽  
Jeremy Meyer ◽  
Sotirios Popeskou ◽  
Valentin David ◽  
Christian Toso ◽  
...  

Despite many advances in the diagnosis and treatment of colorectal cancer (CRC), its incidence and mortality rates continue to make an impact worldwide and in some countries rates are mounting. Over the past decade, liquid biopsies have been the object of fundamental and clinical research with regard to the different steps of CRC patient care such as screening, diagnosis, prognosis, follow-up, and therapeutic response. They are attractive because they are considered to encompass both the cellular and molecular heterogeneity of tumours. They are easily accessible and can be applied to large-scale settings despite the cost. However, liquid biopsies face drawbacks in detection regardless of whether we are testing for circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), or miRNA. This review highlights the different advantages and disadvantages of each type of blood-based biopsy and underlines which specific one may be the most useful and informative for each step of CRC patient care.


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