Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumorderived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNAbased prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 disease. RT-qPCR has been the primary method of diagnosis; however, the required infrastructure is lacking in many developing countries and the virus has remained a global challenge. More inexpensive and immediate test methods are required to facilitate local, regional, and national management strategies to re-open world economies. Here we have developed a SARS-CoV-2 antigen test in an inexpensive lateral flow format to generate a chromatographic result identifying the presence of the SARS-CoV-2 antigen, and thus an active infection, within a patient anterior nares swab sample. Our 15-min test requires no equipment or laboratory infrastructure to administer with a limit of detection of 2.0 × 102 TCID50/mL and 87.5% sensitivity, 100% specificity when tested against 40 known positive and 40 known negative patient samples established by a validated RT-qPCR test.
As process complexity and number of plasma processing steps increase, process-induced charging damage becomes an emerging issue in continuously scaling device manufacturing. It is important, therefore, to be able to pinpoint most of potential sources of plasma charging-induced damage. The most commonly used approach involves processing and testing of several modules of antenna-type transistors, with charge sensitive antennas defmed and exposed to plasma at various stages of processing. Subsequent analysis of damage allows determination of the processing level at which most of damage occurred.This work presents an alternative and complementary approach to assess potential sources of charging damage. This approach is based on in-line testing of gate oxide integrity of a MOS transistor structure with a charge collecting antenna. Gate oxide integrity tests performed after poly-silicon salicidation and after metal-l level are used to separate the effect of poly etch and inter-layer dielectric (ILD) deposition. It is shown that by the in-line testing of silicided poly antennas the effect of charging damage due to plasma-enhanced chemical vapor deposition (PECVD) of oxide can be unambiguously determined. The fingerprint of PECVD-induced charging is further documented by the surface charge analysis performed on oxidized silicon wafers exposed to PECVD oxide deposition.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 disease. RT-qPCR has been the primary method of diagnosis; however, the required infrastructure is lacking in many developing countries and the virus has remained a global challenge. More inexpensive and immediate test methods are required to facilitate local, regional, and national management strategies to re-open world economies. Here we have developed a SARS-CoV-2 antigen test in an inexpensive lateral flow format to generate a chromatographic result identifying the presence of the SARS-CoV-2 antigen, and thus an active infection, within a patient anterior nares swab sample. Our 15-minute test requires no equipment or laboratory infrastructure to administer with a limit of detection of 2.0 x 102 TCID50/mL and 87.5% sensitivity, 100% specificity when tested against 40 known positive and 40 known negative patient samples established by a validated RT-qPCR test.
Introduction and Objective: Non-invasive urine and blood biomarkers are commercially available to assess the risk of clinically significant prostate cancer (csPCa) and the need for a biopsy. However, these tests are limited in their specificity resulting in a significant number of men still undergoing biopsy to avoid missing a csPCa. Exosomes and other extracellular vesicles (EVs) provide a platform for blood and urine biomarkers since they are released by all types of cells and preserve molecular constituents from their cells of origin within lipid membranes. The EPI urine test from Exosome Diagnostics (ExoDx) is currently the only commercially available EV based cancer diagnostic test; it uses three well established EV RNA markers to estimate the risk of csPCa. Studies by us and others have shown that an expanded urine EV PCa marker panel would improve disease stratification if these markers could be incorporated into a clinical grade assay. Our objective in this current study is to identify and characterize the EV RNA transcripts that are enriched by using antibodies for prostate specific membrane antigen (PSMA) to capture urinary EVs that originated from PCa cells. This is the first step in the development of a next generation urinary EV test with increased specificity for csPCa within a rigorous and reproducible assay format. Methods: Urine EVs from patients with csPCa and from healthy controls were prepared using the ExoDx clinical platform. These total EV samples were then compared with EVs enriched by immunocapture either with a PSMA specific antibody or with an isotype IgG control reagent. RNA was prepared from each of these three types of urinary EV samples and analyzed using RNAseq. Results: RNAseq analysis of urinary total EVs, PSMA-antibody captured EVs and isotype IgG control captured EVs showed excellent mapping to transcriptome regions. We detected over 600 genes differentially enriched by PSMA antibody vs. isotype IgG EV capture and identified 18 genes from a candidate list of prostate biomarkers that have been assembled based on previous studies. A principal component analysis of 196 differentially expressed transcripts obtained from EVs enriched by PSMA immunocapture vs IgG controls showed excellent discrimination between prostate cancer patients and healthy controls. By using a feature selection approach to optimize for discrimination between prostate cancer patients and healthy controls we identified a novel 6-gene signature that, when derived from a PSMA capture EV dataset, shows a superior AUC for the accuracy of cancer detection (greater than 0.95) than that obtained from applying the same 6-gene signature on total EVs or on isotype IgG controls. Conclusions: EV PSMA immuno-capture provides a robust approach to expanding the panel of PCa biomarkers that can be incorporated into clinical grade PCa urine EV assays, supporting the translation of pre-clinical discovery into clinical practice. Citation Format: Sandra M. Gaston, Douglas Roberts, Sudipto Chakrabortty, Emily Mitsock, Kailey Babcock, Rikky Xing, Benjamin Spieler, Radka Stoyanova, Mark L. Gonzalgo, Chad Ryan Ritch, Bruno Nahar, Alan Pollack, Dipen J. Parekh, Seth Yu, Johan Skog, Sanoj Punnen. Development of next generation extracellular vesicle based urine tests for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3386.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.