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https://www.readbyqxmd.com/read/29932737/improving-single-nucleotide-polymorphism-based-fetal-fraction-estimation-of-maternal-plasma-circulating-cell-free-dna-using-bayesian-hierarchical-models
#1
Nicholas B Larson, Chen Wang, Jie Na, Ross A Rowsey, William Edward Highsmith, Nicole L Hoppman, Jean-Pierre Kocher, Eric W Klee
The recent advances in next-generation sequencing (NGS) technologies have enabled the development of effective high-throughput noninvasive prenatal screening (NIPS) assays for fetal genetic abnormalities using maternal circulating cell-free DNA (ccfDNA). An important NIPS quality assurance is quantifying the fetal proportion of the sampled ccfDNA. For methods using allelic read count ratios from targeted sequencing of single-nucleotide polymorphisms (SNPs), systematic biases and errors may reduce accuracy and diminish assay performance...
June 22, 2018: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/29931616/identification-of-mir-379-mir-656-c14mc-cluster-downregulation-and-associated-epigenetic-and-transcription-regulatory-mechanism-in-oligodendrogliomas
#2
Anupam Kumar, Subhashree Nayak, Pankaj Pathak, Suvendu Purkait, Prit Benny Malgulawar, Mehar Chand Sharma, Vaishali Suri, Arijit Mukhopadhyay, Ashish Suri, Chitra Sarkar
INTRODUCTION: Although role of individual microRNAs (miRNAs) in the pathogenesis of gliomas has been well studied, their role as a clustered remains unexplored in gliomas. METHODS: In this study, we performed the expression analysis of miR-379/miR-656 miRNA-cluster (C14MC) in oligodendrogliomas (ODGs) and also investigated the mechanism underlying modulation of this cluster. RESULTS: We identified significant downregulation of majority of the miRNAs from this cluster in ODGs...
June 21, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29931312/circulating-tumor-dna-assays-in-clinical-cancer-research
#3
Miguel R Ossandon, Lokesh Agrawal, Eric J Bernhard, Barbara A Conley, Sumana M Dey, Rao L Divi, Ping Guan, Tracy G Lively, Tawnya C McKee, Brian S Sorg, James V Tricoli
The importance of circulating free DNA (cfDNA) in cancer clinical research was recognized in 1994 when a mutated RAS gene fragment was detected in a patient's blood sample. Up to 1% of the total circulating DNA in patients with cancer is circulating tumor DNA (ctDNA) that originates from tumor cells. As ctDNA is rapidly cleared from the blood stream and can be obtained by minimally invasive methods, it can be used as a dynamic cancer biomarker for cancer early detection, diagnosis, and treatment monitoring...
June 20, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29930723/dna-damage-predicts-prognosis-and-treatment-response-in-colorectal-liver-metastases-superior-to-immunogenic-cell-death-and-t-cells
#4
Johannes Laengle, Judith Stift, Agnes Bilecz, Brigitte Wolf, Andrea Beer, Balazs Hegedus, Stefan Stremitzer, Patrick Starlinger, Dietmar Tamandl, Dietmar Pils, Michael Bergmann
Preclinical models indicate that DNA damage induces type I interferon (IFN), which is crucial for the induction of an anti-tumor immune response. In human cancers, however, the association between DNA damage and an immunogenic cell death (ICD), including the release and sensing of danger signals, the subsequent ER stress response and a functional IFN system, is less clear. Methods: Neoadjuvant-treated colorectal liver metastases (CLM) patients, undergoing liver resection in with a curative intent, were retrospectively enrolled in this study (n=33)...
2018: Theranostics
https://www.readbyqxmd.com/read/29929941/-cell-free-fetal-dna-analysis-in-maternal-plasma-as-a-screening-test-for-trisomy-21-in-twin-pregnancies
#5
G Le Conte, A Letourneau, J Jani, P Kleinfinger, L Lohmann, J-M Costa, A Benachi
OBJECTIVES: To evaluate the performance of noninvasive prenatal testing by cell-free circulating fetal DNA in maternal blood (cfDNA) in screening for trisomies 21 in twin pregnancies. METHODS: CfDNA was performed in 492 patients with twin pregnancies without ultrasound anomalies in the first trimester as a first-line screening test or after serum screening. Data were collected prospectively and a retrospective analysis was done. CfDNA was executed by massive parallel technique...
June 18, 2018: Gynecologie, Obstetrique, Fertilite & Senologie
https://www.readbyqxmd.com/read/29929823/bronchiolitis-obliterans-syndrome-susceptibility-and-the-pulmonary-microbiome
#6
Cody Schott, S Samuel Weigt, Benjamin A Turturice, Ahmed Metwally, John Belperio, Patricia W Finn, David L Perkins
BACKGROUND: Lung transplantation outcomes remain complicated by bronchiolitis obliterans syndrome (BOS), a major cause of mortality and retransplantation for patients. A variety of factors linking inflammation and BOS have emerged, meriting further exploration of the microbiome as a source of inflammation. In this analysis, we determined features of the pulmonary microbiome associated with BOS susceptibility. METHODS: Bronchoalveolar lavage (BAL) samples were collected from 25 patients during standard of care bronchoscopies before BOS onset...
April 26, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29929010/detection-of-fetal-subchromosomal-aberration-with-cell-free-dna-screening-led-to-diagnosis-of-parental-translocation-review-of-11344-consecutive-cases-in-a-university-hospital
#7
Ye-Qing Qian, Xiao-Qing Wang, Min Chen, Yu-Qin Luo, Kai Yan, Yan-Mei Yang, Bei Liu, Li-Ya Wang, Ying-Zhi Huang, Hong-Ge Li, Hang-Yi Pan, Fan Jin, Min-Yue Dong
BACKGROUND: Fetal chromosome aberrations and sub-chromosomal copy number variations (CNVs) are not rare. There are several ways to detect duplications and deletions; cell-free DNA screening (cfDNA screening) is nowadays an accurate and safe detection method. The objective of this study is to report the feasibility of cfDNA screening as an indicator of parental balanced chromosome translocation. RESULTS: From February 2015 to March 2016, cfDNA screening was offered to 11344 pregnant women...
June 18, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29928659/liquid-biopsy-a-new-source-of-candidate-biomarkers-in-amyotrophic-lateral-sclerosis
#8
Maite Mendioroz, Leyre Martínez-Merino, Idoia Blanco-Luquin, Amaya Urdánoz, Miren Roldán, Ivonne Jericó
Noninvasive tests to diagnose and monitor the progression of neurodegenerative disorders have been a challenge for decades. The aim of this study was to explore the feasibility of applying liquid biopsy procedures to patients with a neurodegenerative disease such as amyotrophic lateral sclerosis (ALS). We isolated plasma cell-free DNA (cfDNA) in 20 ALS patients and 20 controls and used cfDNA to identify a novel differentially methylated mark in RHBDF2 gene in ALS patients compared to controls. Our findings support the notion that liquid biopsy may be applied to living patients as a source of potential epigenetic biomarkers for neurodegenerative disorders...
June 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29928206/integrated-diagnostic-model-that-incorporates-epstein-barr-virus-dna-imaging-and-nasal-endoscopy-to-stratify-primary-tumor-and-lymph-nodes-in-a-patient-with-n1-nasopharyngeal-carcinoma-multidisciplinary-management
#9
Paolo Gamba, Luigina Rota, C Abeni, Alessandra Huscher, Gabriele Saldi, Alberto Soregaroli, Elena Padolecchia, Fausto Zorzi, Mario Bignardi, Alberto Zaniboni
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, with a high metastatic potential. Epstein-Barr virus (EBV) infection plays a fundamental role, even if it is not well understood. The diagnosis of the disease in its early stage is infrequent. Imaging studies, positron emission tomography scans in addition to clinical examination, endoscopic examination, and biopsy provide information on the extent of the disease. The application of neoadjuvant chemotherapy followed by concomitant chemoradiation can improve the control of NPC...
May 2018: Case Reports in Oncology
https://www.readbyqxmd.com/read/29927686/loci-specific-differences-in-blood-dna-methylation-in-hbv-negative-populations-at-risk-for-hepatocellular-carcinoma-development
#10
Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Jay Qiu, Lucinda Kurzava, Hannah Buvala, Adam Ruhayel, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M Flanagan, Barbara Stefanska
Late onset of clinical symptoms in hepatocellular carcinoma (HCC) results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable tools that would distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed. We used the Illumina HumanMethylation450 BeadChip microarray to test whether white blood cell DNA, an easily accessible source of DNA, exhibits site-specific changes in DNA methylation in blood of diagnosed HCC patients (post-diagnostic, 24 cases, 24 controls) and in prospectively collected blood specimens of HCC patients who were cancer-free at blood collection (pre-diagnostic, 21 cases, 21 controls)...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29927243/cyclometalated-ruthenium-ii-complexes-derived-from-%C3%AE-oligothiophenes-as-highly-selective-cytotoxic-or-photocytotoxic-agents
#11
Goutam Ghosh, Katsuya L Colón, Anderson Fuller, Tariq Sainuddin, Evan Bradner, Julia McCain, Susan M A Monro, Huimin Yin, Marc W Hetu, Colin G Cameron, Sherri A McFarland
The photophysical and photobiological properties of a new class of cyclometalated ruthenium(II) compounds incorporating π-extended benzo[ h]imidazo[4,5- f]quinoline (IBQ) cyclometalating ligands (C^N) bearing thienyl rings ( n = 1-4, compounds 1-4) were investigated. Their octanol-water partition coefficients (log Po/w ) were positive and increased with n. Their absorption and emission energies were red-shifted substantially compared to the analogous Ru(II) diimine (N^N) complexes. They displayed C^N-based intraligand (IL) fluorescence and triplet excited-state absorption that shifted to longer wavelengths with increasing n and N^N-based metal-to-ligand charge transfer (MLCT) phosphorescence that was independent of n...
June 21, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29926512/potentially-effective-method-for-fetal-gender-determination-by-non-invasive-prenatal-testing-for-x-linked-disease
#12
Yoshiteru Noda, Takema Kato, Asuka Kato, Haruki Nishizawa, Jun Miyazaki, Mayuko Ito, Sumire Terasawa, Takao Sekiya, Takuma Fujii, Hiroki Kurahashi
Examination of maternal plasma cell free DNA (cfDNA) for noninvasive prenatal testing for fetal trisomy is a highly effective method for pregnant women at high risk. This can be also applied to fetal gender determination in female carriers of severe X-linked disease. PCR analysis is a relatively simpler and less expensive method of detecting Y chromosome-specific repeats (Y-specific PCR; YSP), but is limited by the risk of false-negative results. To address this, we have developed a combined strategy incorporating YSP and an estimation of the fetal DNA fraction...
June 21, 2018: Congenital Anomalies
https://www.readbyqxmd.com/read/29925947/nuclear-arp2-3-drives-dna-break-clustering-for-homology-directed-repair
#13
Benjamin R Schrank, Tomas Aparicio, Yinyin Li, Wakam Chang, Brian T Chait, Gregg G Gundersen, Max E Gottesman, Jean Gautier
DNA double-strand breaks repaired by non-homologous end joining display limited DNA end-processing and chromosomal mobility. By contrast, double-strand breaks undergoing homology-directed repair exhibit extensive processing and enhanced motion. The molecular basis of this movement is unknown. Here, using Xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, WASP, and the actin-nucleating ARP2/3 complex are recruited to damaged chromatin undergoing homology-directed repair. We demonstrate that nuclear actin polymerization is required for the migration of a subset of double-strand breaks into discrete sub-nuclear clusters...
June 20, 2018: Nature
https://www.readbyqxmd.com/read/29925834/urinary-cell-free-dna-is-a-versatile-analyte-for-monitoring-infections-of-the-urinary-tract
#14
Philip Burnham, Darshana Dadhania, Michael Heyang, Fanny Chen, Lars F Westblade, Manikkam Suthanthiran, John Richard Lee, Iwijn De Vlaminck
Urinary tract infections are one of the most common infections in humans. Here we tested the utility of urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics in bacterial and viral urinary tract infections. We isolated cfDNA from 141 urine samples from a cohort of 82 kidney transplant recipients and performed next-generation sequencing. We found that urinary cfDNA is highly informative about bacterial and viral composition of the microbiome, antimicrobial susceptibility, bacterial growth dynamics, kidney allograft injury, and host response to infection...
June 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29925683/monitoring-liver-damage-using-hepatocyte-specific-methylation-markers-in-cell-free-circulating-dna
#15
Roni Lehmann-Werman, Judith Magenheim, Joshua Moss, Daniel Neiman, Ofri Abraham, Sheina Piyanzin, Hai Zemmour, Ilana Fox, Talya Dor, Markus Grompe, Giora Landesberg, Bao-Li Loza, Abraham Shaked, Kim Olthoff, Benjamin Glaser, Ruth Shemer, Yuval Dor
Liver damage is typically inferred from serum measurements of cytoplasmic liver enzymes. DNA molecules released from dying hepatocytes are an alternative biomarker, unexplored so far, potentially allowing for quantitative assessment of liver cell death. Here we describe a method for detecting acute hepatocyte death, based on quantification of circulating, cell-free DNA (cfDNA) fragments carrying hepatocyte-specific methylation patterns. We identified 3 genomic loci that are unmethylated specifically in hepatocytes, and used bisulfite conversion, PCR, and massively parallel sequencing to quantify the concentration of hepatocyte-derived DNA in mixed samples...
June 21, 2018: JCI Insight
https://www.readbyqxmd.com/read/29925671/bacterial-reca-protein-promotes-adenoviral-recombination-during-in-vitro-infection
#16
Jeong Yoon Lee, Ji Sun Lee, Emma C Materne, Rahul Rajala, Ashrafali M Ismail, Donald Seto, David W Dyer, Jaya Rajaiya, James Chodosh
Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity...
June 27, 2018: MSphere
https://www.readbyqxmd.com/read/29925277/maternal-age-trends-support-uptake-of-non-invasive-prenatal-testing-nipt-in-the-low-risk-population
#17
Kelly M Chen, Karen White, Junaid Shabbeer, Maximilian Schmid
PURPOSE: To examine trends in patients submitting samples for cell-free DNA screening to determine whether they reflect a shift towards NIPT use in the low-risk population. METHODS: A review of demographic information was performed for all specimens submitted to the Ariosa Diagnostics clinical laboratory for the Harmony® prenatal test between January 1, 2014 and December 30, 2017. The proportions of specimens for patients under 35 years and 35 years and older were compared...
June 20, 2018: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29924986/replication-fork-reversal-during-dna-interstrand-crosslink-repair-requires-cmg-unloading
#18
Ravindra Amunugama, Smaranda Willcox, R Alex Wu, Ummi B Abdullah, Afaf H El-Sagheer, Tom Brown, Peter J McHugh, Jack D Griffith, Johannes C Walter
DNA interstrand crosslinks (ICLs) are extremely cytotoxic, but the mechanism of their repair remains incompletely understood. Using Xenopus egg extracts, we previously showed that repair of a cisplatin ICL is triggered when two replication forks converge on the lesion. After CDC45/MCM2-7/GINS (CMG) ubiquitylation and unloading by the p97 segregase, FANCI-FANCD2 promotes DNA incisions by XPF-ERCC1, leading to ICL unhooking. Here, we report that, during this cell-free ICL repair reaction, one of the two converged forks undergoes reversal...
June 19, 2018: Cell Reports
https://www.readbyqxmd.com/read/29923661/spermine-oxidase-is-up-regulated-and-promotes-tumor-growth-in-hepatocellular-carcinoma
#19
Tingting Hu, Dalong Sun, Jie Zhang, Ruyi Xue, Harry L A Janssen, Wenqing Tang, Ling Dong
AIM: The polyamine catabolic enzyme, spermine oxidase (SMOX) is up-regulated in chronic inflammatory conditions and linked to increased reactive oxygen species (ROS) and DNA damage in various forms of cancers. The present study aims to explore the expression pattern and biological function of SMOX in hepatocellular carcinoma (HCC). METHODS: We used qRT-PCR, Western blotting and immunohistochemistry to examine SMOX expression in four HCC cell lines and 120 cases of HCC clinical samples, and the clinical significance of SMOX was analyzed...
June 20, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29923368/human-electronegative-ldl-induces-mitochondrial-dysfunction-and-premature-senescence-of-vascular-cells-in-vivo
#20
Yu-Chen Wang, An-Sheng Lee, Long-Sheng Lu, Liang-Yin Ke, Wei-Yu Chen, Jian-Wen Dong, Jonathan Lu, Zhenping Chen, Chih-Sheng Chu, Hua-Chen Chan, Taha Y Kuzan, Ming-Hsien Tsai, Wen-Li Hsu, Richard A F Dixon, Tatsuya Sawamura, Kuan-Cheng Chang, Chu-Huang Chen
Dysregulation of plasma lipids is associated with age-related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low-density lipoprotein (LDL), induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg-1  day-1 ) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence-associated β-galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5-treated but not L1-treated mice...
June 19, 2018: Aging Cell
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