scholarly journals Liquid Biopsy and Primary Brain Tumors

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5429
Author(s):  
Robert H. Eibl ◽  
Markus Schneemann
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Minimally Invasive ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Clinical Management ◽  
Tumor Patients ◽  
New Era ◽  
The Right

Two decades of “promising results” in liquid biopsy have led to both continuing disappointment and hope that the new era of minimally invasive, personalized analysis can be applied for better diagnosis, prognosis, monitoring, and therapy of cancer. Here, we briefly highlight the promises, developments, and challenges related to liquid biopsy of brain tumors, including circulating tumor cells, cell-free nucleic acids, extracellular vesicles, and miRNA; we further discuss the urgent need to establish suitable biomarkers and the right standards to improve modern clinical management of brain tumor patients with the use of liquid biopsy.

scholarly journals DIPG-60. PILOT STUDY OF CIRCULATING TUMOR CELLS IN PEDIATRIC HIGH GRADE BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii299-iii299
Author(s):  
Wafik Zaky ◽  
Long Dao ◽  
Dristhi Ragoonanan ◽  
Izhar Bath ◽  
Sofia Yi ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Disease Assessment ◽  
Liquid Biopsies ◽  
Capture Method ◽  
Pediatric Brain

Abstract BACKGROUND Despite its increasing use, circulating tumor cells (CTCs) have not been studied in pediatric brain tumors. METHODS Cell surface vimentin (CSV) is a marker for CTC detection. We developed an automated CSV-based CTC capture method for pediatric brain tumor using the Abnova Cytoquest platform. PBMCs isolated from blood samples from 52 brain tumor patients were processed to isolate CSV+ CTCs. Captured cells were then stained for CSV and CD45 and scanned to determine the number of CTCs. DIPG samples were additionally examined for H3K27M expression on CSV+ cells. Long term cancer survivors were used as a control cohort. RESULTS 86.4% of all the samples exhibited between 1–13 CSV+ CTCs, with a median of 2 CSV+ CTCs per sample. Using a value of ≥ 1 CTC as a positive result, the sensitivity and specificity of this test was 83.05% and 60.0% respectively. 19 DIPG samples were analyzed and 70% (13 samples) were positive for 1–5 CTCs. Five of these 7 positive CSV+ CTCs DIPG samples were also positive for H3K27M mutations by immunohistochemistry (71%). Mean survival in days for the CTC positive and negative DIPG samples were 114 and 211 days, respectively (p= 0.13). CONCLUSION This is the first study of CTCs in pediatric CNS tumors using an automated approach. Patients with brain tumors can exhibit CSV+ CTCs within peripheral blood. The use of specific molecular markers such as H3K27M can improve the diagnostic capability of liquid biopsies and may enable future disease assessment for personalized therapy.

scholarly journals Biomarkers and focused ultrasound: the future of liquid biopsy for brain tumor patients

2021 ◽  
Author(s):  
Jordina Rincon-Torroella ◽  
Harmon Khela ◽  
Anya Bettegowda ◽  
Chetan Bettegowda
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Liquid Biopsy ◽  
Focused Ultrasound ◽  
Modern Medicine ◽  
Detection Methods ◽  
Liquid Biopsies ◽  
Tumor Patients ◽  
Clinical Trial Registries ◽  
Increased Risk

Abstract Introduction Despite advances in modern medicine, brain tumor patients are still monitored purely by clinical evaluation and imaging. Traditionally, invasive strategies such as open or stereotactic biopsies have been used to confirm the etiology of clinical and imaging changes. Liquid biopsies can enable physicians to noninvasively analyze the evolution of a tumor and a patient’s response to specific treatments. However, as a consequence of biology and the current limitations in detection methods, no blood or cerebrospinal fluid (CSF) brain tumor-derived biomarkers are used in routine clinical practice. Enhancing the presence of tumor biomarkers in blood and CSF via brain-blood barrier (BBB) disruption with MRI-guided focused ultrasound (MRgFUS) is a very compelling strategy for future management of brain tumor patients. Methods A literature review on MRgFUS-enabled brain tumor liquid biopsy was performed using Medline/Pubmed databases and clinical trial registries. Results The therapeutic applications of MRgFUS to target brain tumors have been under intense investigation. At high-intensity, MRgFUS can ablate brain tumors and target tissues, which needs to be balanced with the increased risk for damage to surrounding normal structures. At lower-intensity and pulsed-frequency, MRgFUS may be able to disrupt the BBB transiently. Thus, while facilitating intratumoral or parenchymal access to standard or novel therapeutics, BBB disruption with MRgFUS has opened the possibility of enhanced detection of brain tumor-derived biomarkers. Conclusions In this review, we describe the concept of MRgFUS-enabled brain tumor liquid biopsy and present the available preclinical evidence, ongoing clinical trials, limitations, and future directions of this application.

scholarly journals TBIO-16. AUTOMATED CELL ENRICHMENT AND DIGITAL CELL SORTING USING DIELECTROPHORETIC ARRAYS FOR ISOLATION OF CIRCULATING TUMOR CELLS IN PEDIATRIC BRAIN TUMOR PATIENTS

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i183-i183
Author(s):  
Katherine Barnett ◽  
Kaicen Zhu ◽  
Guomiao Shen ◽  
Jonathan Serrano ◽  
David Harter ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Sorting ◽  
Pediatric Brain Tumor ◽  
Tumor Patients ◽  
Cell Enrichment ◽  
Pediatric Brain

scholarly journals Genetic variants and cognitive functions in patients with brain tumors

2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Repair ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Cell Cycle Regulation ◽  
Cognitive Outcome ◽  
Cholesterol Transport ◽  
Tumor Patients ◽  
Cycle Regulation

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.

scholarly journals Molecular and Circulating Biomarkers of Brain Tumors

2021 ◽  
Vol 22 (13) ◽  
pp. 7039
Author(s):  
Wojciech Jelski ◽  
Barbara Mroczko
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Extracellular Vesicles ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Methylguanine Dna Methyltransferase ◽  
The Central Nervous System

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.

scholarly journals High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1656 ◽  
Author(s):  
Etienne Buscail ◽  
Catherine Alix-Panabières ◽  
Pascaline Quincy ◽  
Thomas Cauvin ◽  
Alexandre Chauvet ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Neoadjuvant Treatment ◽  
Digital Pcr ◽  
Portal Blood ◽  
Ductal Adenocarcinoma ◽  
Clinical Value ◽  
Liquid Biopsies

Purpose: Expediting the diagnosis of pancreatic ductal adenocarcinoma (PDAC) would benefit care management, especially for the start of treatments requiring histological evidence. This study evaluated the combined diagnostic performance of circulating biomarkers obtained by peripheral and portal blood liquid biopsy in patients with resectable PDAC. Experimental design: Liquid biopsies were performed in a prospective translational clinical trial (PANC-CTC #NCT03032913) including 22 patients with resectable PDAC and 28 noncancer controls from February to November 2017. Circulating tumor cells (CTCs) were detected using the CellSearch® method or after RosetteSep® enrichment combined with CRISPR/Cas9-improved KRAS mutant alleles quantification by droplet digital PCR. CD63 bead-coupled Glypican-1 (GPC1)-positive exosomes were quantified by flow cytometry. Results: Liquid biopsies were positive in 7/22 (32%), 13/22 (59%), and 14/22 (64%) patients with CellSearch® or RosetteSep®-based CTC detection or GPC1-positive exosomes, respectively, in peripheral and/or portal blood. Liquid biopsy performance was improved in portal blood only with CellSearch®, reaching 45% of PDAC identification (5/11) versus 10% (2/22) in peripheral blood. Importantly, combining CTC and GPC1-positive-exosome detection displayed 100% of sensitivity and 80% of specificity, with a negative predictive value of 100%. High levels of GPC1+-exosomes and/or CTC presence were significantly correlated with progression-free survival and with overall survival when CTC clusters were found. Conclusion: This study is the first to evaluate combined CTC and exosome detection to diagnose resectable pancreatic cancers. Liquid biopsy combining several biomarkers could provide a rapid, reliable, noninvasive decision-making tool in early, potentially curable pancreatic cancer. Moreover, the prognostic value could select patients eligible for neoadjuvant treatment before surgery. This exploratory study deserves further validation.

scholarly journals Essential language function of the right hemisphere in brain tumor patients

2004 ◽  
Vol 57 (1) ◽  
pp. 128-131 ◽  
Author(s):  
Alexander Thiel ◽  
Birgit Habedank ◽  
Lutz Winhuisen ◽  
Karl Herholz ◽  
Josef Kessler ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Right Hemisphere ◽  
Language Function ◽  
Tumor Patients ◽  
The Right

Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors

1994 ◽  
Vol 81 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Takao Nakagawa ◽  
Toshihiko Kubota ◽  
Masanori Kabuto ◽  
Kazufumi Sato ◽  
Hirokazu Kawano ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Matrix Metalloproteinases ◽  
Brain Tumors ◽  
Human Brain ◽  
Tumor Cells ◽  
Tumor Invasion ◽  
Gelatinolytic Activity ◽  
Normal Brain ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Human Brain Tumor

✓ The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP-9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells.

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