CF-DNA

BACKGROUND: Cancer-screening tests that can detect multiple cancer types, or multi-cancer early detection (MCED) tests, have emerged recently as a potential new tool in decreasing cancer morbidity and mortality. Most MCED assays are based on detecting cell-free tumor DNA (CF-DNA) in the blood. MCEDs offer the potential for screening for cancer organ sites with high mortality, both with and without recommended screening. However, their clinical utility has not been established. Before clinical utility can be established, the clinical validity of MCEDs, i...

Circulating cell-free DNA (cf-DNA) is released from dead and/or apoptotic leukocytes and due to neutrophil extracellular traps contributing to an inflammatory response. Previous clinical studies have reported that the peak concentrations and dynamic changes of cf-DNA may be used as a noninvasive biomarker of worsening kidney function as well as a guide to the management of kidney allograft rejection. We hypothesized that the pattern and dynamic changes of cf-DNA might be a plausible predictive biomarker for patients at risk of chronic kidney disease (CKD), including individuals with type 2 diabetes mellitus, heart failure, cardiovascular disease and established CKD...

A recent article analyzed paired cell-free (cf)DNA among patients with platinum-sensitive BRCA or PALB2-mutated pancreatic cancer who received maintenance olaparib. Reversion mutations were linked with worse outcomes. These types of paired correlative studies are needed to improve our understanding of drug resistance and guide future clinical trials.

BACKGROUND: Renal allograft rejection contributes to significant morbidity and graft loss. In this setting, early detection of rejection is of paramount importance, which currently relies on histopathology. A reliable non-invasive marker to predict rejection would make surveillance and decision-making easier. Donor-derived cell-free DNA (dd-Cf-DNA) has recently been reported as an emerging tool to predict rejection noninvasively. The utility of cell-free DNA in clinical practice has so far not been studied in an Indian setting...

Malignant ascites in hepatocellular carcinoma is usually a sign of advanced disease and poor prognosis and is also thought to be associated with chronic inflammation mediated by neutrophil extracellular trap (NET) networks. Although ozone, a strong oxidant, has significant antibacterial and anti-inflammatory effects, its effectiveness in treating malignant liver ascites is unclear. We first measured the levels of NETs in the peripheral blood of patients with liver cancer and healthy individuals. Next, we constructed the H22 tumor-bearing mouse model and observed the abdominal girth, body weight, survival rate, and survival time in each group; we marked the proteins associated with NETs in mouse intestinal tissues by immunofluorescence; cf-DNA and cytokines in ascites such as: tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), matrix metalloprotein 9 (MMP-9), and interferon gamma (IFN-γ) levels in ascites were measured by enzyme-linked immunosorbent assay...

PURPOSE: Erdafitinib is the only FDA-approved targeted therapy for FGFR2/3-altered metastatic urothelial cancer. We characterized the genetic landscape of FGFR-altered urothelial carcinoma and real-world clinical outcomes with erdafitinib, including on-treatment genomic evolution. EXPERIMENTAL DESIGN: Prospectively collected clinical data were integrated with institutional genomic data to define the landscape of FGFR2/3-altered urothelial carcinoma. To identify mechanisms of erdafitinib resistance, a subset of patients underwent prospective cell-free (cf) DNA assessment...

Breast cancer is the leading cause of cancer-related deaths in women worldwide. Approximately 40% of patients with hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer have activating mutations in the PIK3CA gene. We developed a highly sensitive, specific, cost-effective, and reproducible dual-drop-off droplet digital polymerase chain reaction (PCR) assay for the simultaneous detection of ten hotspots of PIK3CA mutations in plasma cell-free (cf) DNA. We first evaluated the analytical specificity, sensitivity, limit of blank, repeatability, and reproducibility of the assay, which simultaneously detects seven mutations in exon9 and three in exon20...

Lifestyle modification represents the first-line strategy for the prevention and treatment of type 2 diabetes mellitus (T2DM), which is frequently associated with obesity and characterized by defective pancreatic insulin secretion and/or insulin resistance. Exercise training is an essential component of lifestyle modification and has been shown to ameliorate insulin resistance by reducing body fat mass and by enhancing skeletal muscle mitochondrial biogenesis and insulin-independent glucose uptake. Additionally, exercising stimulates the release of exerkines such as metabolites or cytokines, but also long non-coding RNA, microRNAs, cell-free DNA (cf-DNA), and extracellular vesicles (EVs), which contribute to inter-tissue communication...

BACKGROUND: Neutrophil extracellular traps (NETs) have been found to play a role in the development of autoimmune diseases. In the past two years, studies have demonstrated a significantly increase of NETs in skin tissues during the early stages of IgAV, indicating their involvement in disease activity among children with IgAV. However, the presence of NETs in IgAV animal models has not yet been reported. The objective of this study is to investigate whether NETs are involved in the pathogenesis of IgA vasculitis (IgAV) rats...

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms...

Diagnosis of breast cancer by using sensitive and specific biomarkers is necessary. Cell- free DNA (cf-DNA) is a candidate biomarker in various cancers. Contrasting, shorted uniformed DNA released from apoptotic non-diseased cells, DNA released from malignant cells varies in size. DNA integrity is a ratio between 247 and 115 bp. This study aimed to evaluate the diagnostic values of cf-DNA using ALU -247 and ALU- 115 and DNA integrity in peripheral blood of breast cancer patients as a noninvasive marker. Also, to determine correlations between ALU-247 and ALU-115, DNA integrity, cancer antigen (CA )15-3 and carcinoembryonic antigen (CEA) with each other in breast cancer patients and in different stages of breast cancer...

INTRODUCTION: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide. However, current methods of screening are complicated and require special skill sets. In this observational study of prospectively collected samples, we wanted to evaluate if cell-free ( cf ) DNA could be an efficient biomarker for identification of at-risk patients. METHODS: One hundred patients attending a private prenatal clinic in Canada were enrolled in their first trimester of pregnancy and a blood draw was carried out at 11 + 0 to 14 + 2 weeks' (timepoint A) and 17 + 6 to 25 + 5 weeks of gestation (timepoint B)...

OBJECTIVE: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. METHODS: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group...

Inflammatory phenomena have a direct impact on the prognosis of orthotopic liver transplantation (OLT). Neutrophil extracellular traps (NETs) contribute to OLT inflammation and hemostasis imbalance in OLT. The association between NETosis, clinical outcomes and transfusion requirements is not determined. To evaluate NETs release during OLT and the effect of NETosis ontransfusion requirements and adverse outcomes in a prospective cohort of patients submitted to OLT. We quantified citrullinated histones (cit-H3) and circulating-free-DNA (cf-DNA) in ninety-three patients submitted to OLT in three periods: pre-transplant, after graft reperfusion and before discharge...

OBJECTIVE: A rolling circle amplification (RCA) based commercial methodology using cell-free (cf)DNA to screen for common trisomies became available in 2018. Relevant publications documented high detection but with a higher than expected 1% false positive rate. Preliminary evidence suggested assay variability was an issue. A multi-center collaboration was created to explore this further and examine whether subsequent manufacturer changes were effective. METHODS: Three academic (four devices) and two commercial (two devices) laboratories provided run date, chromosome 21, 18, and 13 run-specific standard deviations, number of samples run, and reagent lot identifications...

OBJECTIVES: A combined digital droplet PCR (ddPCR)/pyrosequencing assay system was developed that demonstrated advantages applicable to multiple qualitative and quantitative molecular genetic diagnostic applications. Data for characterizing this combined approach for hematologic stem cell transplantation (HSCT) and allele quantification from graft-derived cell-free (cf) DNA in solid organ transplantation (SOT) is presented. METHODS: ddPCR and pyrosequencing assays targeting 32 SNPs/markers were established...

PURPOSE OF REVIEW: The presence of cell-free DNA (cf-DNA) in the embryo spent culture medium allows to develop a noninvasive PGT-A (niPGTA). Noninvasive PGT-A may provide a simpler, safer and less costly approach to preimplantation genetic testing of aneuploidy (PGT-A). Furthermore, niPGTA would provide wider access to embryo genetic analysis and circumvent many legal and ethical considerations. However, the concordance rate between the results obtained by PGT-A and niPGTA varies among studies and, their clinical utility has not been already demonstrated...

OBJECTIVES: To study the changes in cell free-DNA (cf-DNA), a marker of neutrophil extracellular traps (NETs), in neonates with acute respiratory distress syndrome (ARDS), and to evaluate its relationship with the severity and early diagnosis of ARDS. METHODS: The neonates diagnosed with ARDS in the Affiliated Hospital of Jiangsu University from January 2021 to June 2022 were enrolled in the prospective study. The neonates were divided into mild, moderate, and severe ARDS groups based on the oxygen index (OI) (4≤OI<8, 8≤OI<16, and OI≥16, respectively)...

Cell-free DNA (cf-DNA) is defined as DNA fragments that are released into the body fluids from apoptosis or necrosis cells, including follicular fluid (FF), which can affect the microenvironment of the oocyte associated with infertility. We aimed to investigate a relationship between apoptosis of cumulus cells (CCs) and cf-DNA levels in FF and clinical outcomes of women undergoing intracytoplasmic sperm injection (ICSI). Therefore, 82 FF samples were collected, and the corresponding CCs were isolated for ICSI procedures...

BACKGROUND: The relationship between hepatitis B surface antigen (HBsAg)-positive carrier status and liver cancer has been extensively studied. However, the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown. The epigenetic modification of DNA hydroxymethylation is critical in tumor development. Further, 5-hydroxymethylcytosine (5hmC) is an important base for DNA demethylation and epigenetic regulation. It is also involved in the assembly of chromosomes and the regulation of gene expression...