scholarly journals A pilot study to establish non-invasive biomarkers for higher-grade meningioma

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv6-iv6
Author(s):  
Daniele Baiz ◽  
Caterina Negroni ◽  
Emanuela Ercolano ◽  
Claire L Adams ◽  
Kathreena M Kurian ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Regulation Of Gene Expression ◽  
Diagnostic Tools ◽  
Malignant Tumours ◽  
Liquid Biopsies ◽  
Benign Meningioma ◽  
Non Invasive ◽  
Serum Exosomes

Abstract Introduction Meningioma brain tumours are the most common primary tumour in adults. Despite surgery and/or radiation therapy, meningioma may recur. The 5-year recurrence rate in benign meningioma is estimated in about 10% while much greater in atypical and malignant tumours. MicroRNAs (miRNAs) represent a large class of small RNAs driving regulation of gene expression and playing a role in tumour progression and therefore proposed as diagnostic tools. Moreover, miRNAs can be released from tumour cells into the blood stream via exosomes, showing potential to be used as liquid biopsies. Methods Identification of novel circulating biomarkers was conducted by performing an unbiased Cancer MicroRNA qPCR Array, followed by bioinformatics analysis. In parallel, we conducted a biased in silico analysis of the miRNAs targeting Cyclin D1 and E1, recently proposed as immunohistochemical meningioma biomarkers. Validation studies performed using TaqMan® reagents. Results Stringent unbiased (p<0.01) miRNA profiling followed by validation in ex vivo samples revealed that the miR-9-1 is upregulated in higher-grade meningioma tissues and serum exosomes, controlled by the EGFR/AP-1 axis and correlated with lower levels of E-Cadherin, a proposed biomarker for malignant meningioma. On the contrary, biased analysis, followed by validation in vitro and ex vivo, showed that the miR-497~195 cluster is downregulated in higher-grade meningioma tissues and serum exosomes, correlating with the overexpression of GATA-4, a novel meningioma tissue biomarker. Conclusion Our data demonstrated that both miR-497~195 and miR-9-1 show potential to become promising non-invasive biomarkers for higher-grade meningioma, reflecting their expression status in tissues. (DB and CN contributed equally).

scholarly journals Endothelial function as a marker of pre-clinical atherosclerosis: assessment techniques and clinical implications

2015 ◽  
Vol 80 (3) ◽  
Author(s):  
Donatella Ruggiero ◽  
Stefania Paolillo ◽  
Giuseppe Della Ratta ◽  
Antonio Mariniello ◽  
Tiziana Formisano ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Ex Vivo ◽  
Clinical Indication ◽  
Diagnostic Tools ◽  
Special Focus ◽  
Peripheral Arteries ◽  
Doppler Flowmetry ◽  
Non Invasive

Endothelium plays a key role in maintenance of vascular homeostasis. Cardiovascular risk factors promote development of endothelial dysfunction, characterized by increased vasoconstriction and by procoagulant/pro-inflammatory endothelial activities. In coronary artery, endothelium-dependent dilation improves blood flow, while the occurrence of endothelial dysfunction reduces myocardial perfusion, so new methods have been developed for assessment of endothelial function in coronary and peripheral arteries. The quantitative angiography with intracoronary infusion of acetylcholine remains the “gold standard” to assess the endothelium-dependent vasodilatation. The use of this technique is restricted to patients who have a clinical indication for coronary angiography, so new imaging methods have been considered for noninvasive diagnosis of coronary microvascular disease, such as magnetic resonance imaging phase contrast and positron emission tomography. The advent of new techniques has facilitated testing of endothelial dysfunction in peripheral arteries with non-invasive methods. This review presents available invivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic tools include local vasodilatation by venous occlusion plethysmography and assessment of flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, laser Doppler flowmetry. The possibility to detect endothelial dysfunction as an early marker of atherosclerosis makes these instruments useful for early stratification of patients at risk for cardiovascular events. Aim of this review is to summarize the characteristics of non-invasive assessment of endothelial function in order to optimize cardiovascular risk management.

scholarly journals Epigenetic Biomarkers of Renal Cell Carcinoma for Liquid Biopsy Tests

2021 ◽  
Vol 22 (16) ◽  
pp. 8846
Author(s):  
Raimonda Kubiliute ◽  
Sonata Jarmalaite
Keyword(s):  
Dna Methylation ◽  
Liquid Biopsy ◽  
Renal Cell ◽  
Morphological Changes ◽  
Diagnostic Tools ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Epigenetic Biomarkers ◽  
Treatment Changes

Renal cell carcinomas (RCC) account for 2–3% of the global cancer burden and are characterized by the highest mortality rate among all genitourinary cancers. However, excluding conventional imagining approaches, there are no reliable diagnostic and prognostic tools available for clinical use at present. Liquid biopsies, such as urine, serum, and plasma, contain a significant amount of tumor-derived nucleic acids, which may serve as non-invasive biomarkers that are particularly useful for early cancer detection, follow-up, and personalization of treatment. Changes in epigenetic phenomena, such as DNA methylation level, expression of microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), are observed early during cancer development and are easily detectable in biofluids when morphological changes are still undetermined by conventional diagnostic tools. Here, we reviewed recent advances made in the development of liquid biopsy-derived DNA methylation-, miRNAs- and lncRNAs-based biomarkers for RCC, with an emphasis on the performance characteristics. In the last two decades, a mass of circulating epigenetic biomarkers of RCC were suggested, however, most of the studies done thus far analyzed biomarkers selected from the literature, used relatively miniature, local, and heterogeneous cohorts, and suffered from a lack of sufficient validations. In summary, for improved translation into the clinical setting, there is considerable demand for the validation of the existing pool of RCC biomarkers and the discovery of novel ones with better performance and clinical utility.

scholarly journals Liquid Biopsy: A Family of Possible Diagnostic Tools

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1391
Author(s):  
Battistelli Michela
Keyword(s):  
Liquid Biopsy ◽  
Maternal Plasma ◽  
Diagnostic Tools ◽  
Invasive Technique ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Pathological Conditions ◽  
Different Types ◽  
Functional Involvement ◽  
Invasive Evaluation

Liquid biopsies could be considered an excellent diagnostic tool, in different physiological or pathological conditions. The possibility of using liquid biopsies for non-invasive clinical purposes is quite an old idea: indeed many years ago it was already being used in the field of non-invasive prenatal tests (NIPT) for autosomal fetal aneuploidy evaluation. In 1997 Lo et al. had identified fetal DNA in maternal plasma and serum, showing that about 10–15% of cfDNA in maternal plasma is derived from the placenta, and biologic fluid represents an important and non-invasive technique to evaluate state diseases and possible therapies. Nowadays, several body fluids, such as blood, urine, saliva and other patient samples, could be used as liquid biopsy for clinical non-invasive evaluation. These fluids contain numerous and various biomarkers and could be used for the evaluation of pathological and non-pathological conditions. In this review we will analyze the different types of liquid biopsy, their potential role in clinical diagnosis and the functional involvement of extracellular vesicles in these fluids as carriers.

scholarly journals Raman spectroscopic analysis of skin as a diagnostic tool for Human African Trypanosomiasis

2021 ◽  
Vol 17 (11) ◽  
pp. e1010060
Author(s):  
Alexandre Girard ◽  
Anneli Cooper ◽  
Samuel Mabbott ◽  
Barbara Bradley ◽  
Steven Asiala ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Trypanosoma Brucei ◽  
Diagnostic Tool ◽  
Human African Trypanosomiasis ◽  
Ex Vivo ◽  
Principal Component ◽  
Medical Diagnostics ◽  
Diagnostic Tools ◽  
African Trypanosomiasis ◽  
Non Invasive

Human African Trypanosomiasis (HAT) has been responsible for several deadly epidemics throughout the 20th century, but a renewed commitment to disease control has significantly reduced new cases and motivated a target for the elimination of Trypanosoma brucei gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests to detect Trypanosoma brucei infection by interrogating the skin are therefore needed. Recent advances have improved the cost, sensitivity and portability of Raman spectroscopy technology for non-invasive medical diagnostics, making it an attractive tool for gambiense-HAT detection. The aim of this work was to assess and develop a new non-invasive diagnostic method for T. brucei through Raman spectroscopy of the skin. Infections were performed in an established murine disease model using the animal-infective Trypanosoma brucei brucei subspecies. The skin of infected and matched control mice was scrutinized ex vivo using a confocal Raman microscope with 532 nm excitation and in situ at 785 nm excitation with a portable field-compatible instrument. Spectral evaluation and Principal Component Analysis confirmed discrimination of T. brucei-infected from uninfected tissue, and a characterisation of biochemical changes in lipids and proteins in parasite-infected skin indicated by prominent Raman peak intensities was performed. This study is the first to demonstrate the application of Raman spectroscopy for the detection of T. brucei by targeting the skin of the host. The technique has significant potential to discriminate between infected and non-infected tissue and could represent a unique, non-invasive diagnostic tool in the goal for elimination of gambiense-HAT as well as for Animal African Trypanosomiasis (AAT).

scholarly journals Circulating miRNAs Related to Epithelial–Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis

2021 ◽  
Vol 43 (2) ◽  
pp. 900-916
Author(s):  
Anna Zubrzycka ◽  
Monika Migdalska-Sęk ◽  
Sławomir Jędrzejczyk ◽  
Ewa Brzeziańska-Lasota
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Diagnostic Tools ◽  
Endometrial Stromal Cells ◽  
Disease Etiology ◽  
Diagnostic Biomarkers ◽  
Mesenchymal Transition ◽  
Non Invasive

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial–mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.

A NOVEL EXTENSIVE EX-VIVO OCT DATABASE FROM MURINE MODELS OF COLORECTAL CANCER

2021 ◽  
Vol 108 (Supplement_3) ◽  
Author(s):  
J Bote ◽  
J F Ortega-Morán ◽  
C L Saratxaga ◽  
B Pagador ◽  
A Picón ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Machine Learning ◽  
Structural Information ◽  
Ex Vivo ◽  
Ground Truth ◽  
Colon Polyps ◽  
Learning Methods ◽  
Non Invasive ◽  
Machine Learning Methods ◽  
In Situ Methods

Abstract INTRODUCTION New non-invasive technologies for improving early diagnosis of colorectal cancer (CRC) are demanded by clinicians. Optical Coherence Tomography (OCT) provides sub-surface structural information and offers diagnosis capabilities of colon polyps, further improved by machine learning methods. Databases of OCT images are necessary to facilitate algorithms development and testing. MATERIALS AND METHODS A database has been acquired from rat colonic samples with a Thorlabs OCT system with 930nm centre wavelength that provides 1.2KHz A-scan rate, 7μm axial resolution in air, 4μm lateral resolution, 1.7mm imaging depth in air, 6mm x 6mm FOV, and 107dB sensitivity. The colon from anaesthetised animals has been excised and samples have been extracted and preserved for ex-vivo analysis with the OCT equipment. RESULTS This database consists of OCT 3D volumes (C-scans) and 2D images (B-scans) of murine samples from: 1) healthy tissue, for ground-truth comparison (18 samples; 66 C-scans; 17,478 B-scans); 2) hyperplastic polyps, obtained from an induced colorectal hyperplastic murine model (47 samples; 153 C-scans; 42,450 B-scans); 3) neoplastic polyps (adenomatous and adenocarcinomatous), obtained from clinically validated Pirc F344/NTac-Apcam1137 rat model (232 samples; 564 C-scans; 158,557 B-scans); and 4) unknown tissue (polyp adjacent, presumably healthy) (98 samples; 157 C-scans; 42,070 B-scans). CONCLUSIONS A novel extensive ex-vivo OCT database of murine CRC model has been obtained and will be openly published for the research community. It can be used for classification/segmentation machine learning methods, for correlation between OCT features and histopathological structures, and for developing new non-invasive in-situ methods of diagnosis of colorectal cancer.

scholarly journals Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1132
Author(s):  
Emel Rothzerg ◽  
Xuan Dung Ho ◽  
Jiake Xu ◽  
David Wood ◽  
Aare Märtson ◽  
...  
Keyword(s):  
Tumour Progression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Osteosarcoma Cell ◽  
Osteoblast Cell Line ◽  
Antisense Lncrnas ◽  
Non Coding Rnas ◽  
Polymerase Chain ◽  
Multiple Levels

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.

scholarly journals Immunomagnetic sequential ultrafiltration (iSUF) platform for enrichment and purification of extracellular vesicles from biofluids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingjing Zhang ◽  
Luong T. H. Nguyen ◽  
Richard Hickey ◽  
Nicole Walters ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Culture Media ◽  
Metastatic Breast ◽  
Clinical Samples ◽  
Clinical Use ◽  
Immunomagnetic Beads ◽  
Liquid Biopsies ◽  
Cell Culture Media ◽  
Non Invasive ◽  
Healthy Donors

AbstractExtracellular vesicles (EVs) derived from tumor cells have the potential to provide a much-needed source of non-invasive molecular biomarkers for liquid biopsies. However, current methods for EV isolation have limited specificity towards tumor-derived EVs that limit their clinical use. Here, we present an approach called immunomagnetic sequential ultrafiltration (iSUF) that consists of sequential stages of purification and enrichment of EVs in approximately 2 h. In iSUF, EVs present in different volumes of biofluids (0.5–100 mL) can be significantly enriched (up to 1000 times), with up to 99% removal of contaminating proteins (e.g., albumin). The EV recovery rate by iSUF for cell culture media (CCM), serum, and urine corresponded to 98.0% ± 3.6%, 96.0% ± 2.0% and 94.0% ± 1.9%, respectively (p > 0.05). The final step of iSUF enables the separation of tumor-specific EVs by incorporating immunomagnetic beads to target EV subpopulations. Serum from a cohort of clinical samples from metastatic breast cancer (BC) patients and healthy donors were processed by the iSUF platform and the isolated EVs from patients showed significantly higher expression levels of BC biomarkers (i.e., HER2, CD24, and miR21).

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