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https://www.readbyqxmd.com/read/29053005/rbcs-homeostatically-bind-mtdna-through-tlr9-to-maintain-quiescence-and-prevent-lung-injury
#1
Meghan J Hotz, Danielle Qing, Michael G S Shashaty, Peggy Zhang, Hilary Faust, Neal Sondheimer, Stefano Rivella, G Scott Worthen, Nilam S Mangalmurti
RATIONALE: Potentially hazardous CpG-containing cell-free mitochondrial DNA (cf-mtDNA) is routinely released into the circulation and is associated with morbidity and mortality in critically ill patients. How the body avoids inappropriate innate immune activation by cf-mtDNA remains unknown. Because red blood cells (RBCs) modulate innate immune responses by scavenging chemokines, we hypothesized that RBCs may attenuate CpG-induced lung inflammation through direct scavenging of CpG-containing DNA...
October 20, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29050948/detection-of-malaria-parasites-after-treatment-in-travelers-a-12-months-longitudinal-study-and-statistical-modelling-analysis
#2
Manijeh Vafa Homann, S Noushin Emami, Victor Yman, Christine Stenström, Klara Sondén, Hanna Ramström, Mattias Karlsson, Muhammad Asghar, Anna Färnert
The rapid clearance of malaria parasite DNA from circulation has widely been accepted as a fact without being systemically investigated. We assessed the persistence of parasite DNA in travelers treated for Plasmodium falciparum malaria in a malaria-free area. Venous blood was collected at the time of admission and prospectively up to one year. DNA and RNA were extracted and analyzed using species-specific and gametocyte-specific real-time PCR as well as merozoite surface protein 2 (msp2)-PCR. In 31 successfully treated individuals, asexual parasites were seen by microscopy until two days after treatment, whereas parasite DNA was detected by msp2- and species-specific PCR up to days 31 and 42, respectively...
October 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29049454/association-of-mitochondrial-dna-copy-number-with-cardiovascular-disease
#3
Foram N Ashar, Yiyi Zhang, Ryan J Longchamps, John Lane, Anna Moes, Megan L Grove, Josyf C Mychaleckyj, Kent D Taylor, Josef Coresh, Jerome I Rotter, Eric Boerwinkle, Nathan Pankratz, Eliseo Guallar, Dan E Arking
Importance: Mitochondrial dysfunction is a core component of the aging process and may play a key role in atherosclerotic cardiovascular disease. Mitochondrial DNA copy number (mtDNA-CN), which represents the number of mitochondria per cell and number of mitochondrial genomes per mitochondrion, is an indirect biomarker of mitochondrial function. Objective: To determine whether mtDNA-CN, measured in an easily accessible tissue (buffy coat/circulating leukocytes), can improve risk classification for cardiovascular disease (CVD) and help guide initiation of statin therapy for primary prevention of CVD...
October 11, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/29045530/tracking-evolution-of-aromatase-inhibitor-resistance-with-circulating-tumour-dna-analysis-in-metastatic-breast-cancer
#4
Charlotte Fribbens, Isaac Garcia Murillas, Matthew Beaney, Sarah Hrebien, Ben O'Leary, Lucy Kilburn, Karen Howarth, Michael Epstein, Emma Green, Nitzan Rosenfeld, Alistair Ring, Stephen Johnston, Nicholas Turner
Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Patients and Methods: 83 patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study...
October 4, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29038235/rare-tumor-clinic-the-university-of-california-san-diego-moores-cancer-center-experience-with-a-precision-therapy-approach
#5
Shumei Kato, Kellie Kurasaki, Sadakatsu Ikeda, Razelle Kurzrock
BACKGROUND: Patients with rare tumors may lack approved treatments and clinical trial access. Although each rare tumor is uncommon, cumulatively they account for approximately 25% of cancers. We recently initiated a Rare Tumor Clinic that emphasized a precision medicine strategy. MATERIALS AND METHODS: We investigated the first 40 patients presenting at the Rare Tumor Clinic. Next-generation sequencing (NGS) of tissue and plasma-derived, circulating-tumor DNA (ctDNA), and protein markers were assessed...
October 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29035458/concordance-of-mutation-detection-in-circulating-tumor-dna-in-early-clinical-trials-using-different-blood-collection-protocols
#6
Lise B Ahlborn, Mette Madsen, Lars Jonson, Finn C Nielsen, Ulrik Lassen, Christina W Yde, Morten Mau-Sorensen
BACKGROUND: Small fragments of tumor DNA can be found in the circulation of cancer patients, providing a noninvasive access to tumor material (liquid biopsy). Analysis of circulating tumor DNA (ctDNA) has been used for diagnosis, treatment decisions, and detection of therapy resistance, including in patients with tumors inaccessible for biopsy, making ctDNA an important alternative source of tumor material. Immediate separation of plasma is widely used in standard isolation of cell-free DNA to ensure high quality plasma DNA...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29034235/coagulofibrinolytic-changes-in-patients-with-post-cardiac-arrest-syndrome
#7
REVIEW
Takeshi Wada
Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which consists of four syndromes including systemic ischemia/reperfusion responses and post-cardiac arrest brain injury. The major pathophysiologies underlying systemic ischemia/reperfusion responses are systemic inflammatory response syndrome and increased coagulation, leading to disseminated intravascular coagulation (DIC), which clinically manifests as obstruction of microcirculation and multiple organ dysfunction...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29027583/changes-in-circulating-cell-free-dna-and-nucleosomes-in-patients-with-exacerbated-psoriasis
#8
Martin Beranek, Zdenek Fiala, Jan Kremlacek, Ctirad Andrys, Jan Krejsek, Kvetoslava Hamakova, Marcela Chmelarova, Vladimir Palicka, Lenka Borska
Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects. The study included 28 patients with exacerbated psoriasis vulgaris and 22 controls. The clinical and laboratory investigations included the determination of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-α, CRP, and IL-6...
October 13, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28993799/genetic-characterization-of-brain-metastases-in-the-era-of-targeted-therapy
#9
REVIEW
Catherine H Han, Priscilla K Brastianos
In the current era of molecularly targeted therapies and precision medicine, choice of cancer treatment has been increasingly tailored according to the molecular or genomic characterization of the cancer the individual has. Previously, the clinical observation of inadequate control of brain metastases was widely attributed to a lack of central nervous system (CNS) penetration of the anticancer drugs. However, more recent data have suggested that there are genetic explanations for such observations. Genomic analyses of brain metastases and matching primary tumor and other extracranial metastases have revealed that brain metastases can harbor potentially actionable driver mutations that are unique to them...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28990755/tunable-and-linker-free-nanogaps-in-core-shell-plasmonic-nanorods-for-selective-and-quantitative-detection-of-circulating-tumor-cells-by-sers
#10
Yang Zhang, Peng Yang, Madathumpady Abubaker Habeeb Muhammed, Shahad K Alsaiari, Basem Moosa, Abdulaziz Almalik, Anjli Kumar, Emilie Ringe, Niveen M Khashab
Controlling the size, number, and shape of nanogaps in plasmonic nanostructures is of significant importance for the development of novel quantum plasmonic devices and quantitative sensing techniques such as surface-enhanced Raman scattering (SERS). Here, we introduce a new synthetic method based on coordination interactions and galvanic replacement to prepare core-shell plasmonic nanorods with tunable enclosed nanogaps. Decorating Au nanorods with Raman reporters that strongly coordinate Ag(+) ions (e.g., 4-mercaptopyridine) afforded uniform nucleation sites to form a sacrificial Ag shell...
October 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28982739/discovery-of-methylated-circulating-dna-biomarkers-for-comprehensive-non-invasive-monitoring-of-treatment-response-in-metastatic-colorectal-cancer
#11
Ludovic Barault, Alessio Amatu, Giulia Siravegna, Agostino Ponzetti, Sebastian Moran, Andrea Cassingena, Benedetta Mussolin, Chiara Falcomatà, Alexandra M Binder, Carmen Cristiano, Daniele Oddo, Simonetta Guarrera, Carlotta Cancelliere, Sara Bustreo, Katia Bencardino, Sean Maden, Alice Vanzati, Patrizia Zavattari, Giuseppe Matullo, Mauro Truini, William M Grady, Patrizia Racca, Karin B Michels, Salvatore Siena, Manel Esteller, Alberto Bardelli, Andrea Sartore-Bianchi, Federica Di Nicolantonio
OBJECTIVE: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC)...
October 5, 2017: Gut
https://www.readbyqxmd.com/read/28982650/incidental-detection-of-maternal-neoplasia-in-noninvasive-prenatal-testing
#12
Nilesh G Dharajiya, Daniel S Grosu, Daniel H Farkas, Ron M McCullough, Eyad Almasri, Youting Sun, Sung K Kim, Taylor J Jensen, Juan-Sebastian Saldivar, Eric J Topol, Dirk van den Boom, Mathias Ehrich
BACKGROUND: Noninvasive prenatal testing (NIPT) uses cell-free DNA (cfDNA)(5) as an analyte to detect copy-number alterations in the fetal genome. Because maternal and fetal cfDNA contributions are comingled, changes in the maternal genome can manifest as abnormal NIPT results. Circulating tumor DNA (ctDNA) present in cases of maternal neoplasia has the potential to distort the NIPT readout to a degree that prevents interpretation, resulting in a nonreportable test result for fetal aneuploidy...
October 5, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28978093/molecular-characterization-of-circulating-colorectal-tumor-cells-defines-genetic-signatures-for-individualized-cancer-care
#13
Say Li Kong, Xingliang Liu, Nur-Afidah Mohamed Suhaimi, Kenneth Jia Hao Koh, Min Hu, Daniel Yoke San Lee, Igor Cima, Wai Min Phyo, Esther Xing Wei Lee, Joyce A Tai, Yu Miin Foong, Jess Honganh Vo, Poh Koon Koh, Tong Zhang, Jackie Y Ying, Bing Lim, Min-Han Tan, Axel M Hillmer
Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978004/detection-of-esr1-mutations-in-circulating-cell-free-dna-from-patients-with-metastatic-breast-cancer-treated-with-palbociclib-and-letrozole
#14
Rekha Gyanchandani, Karthik J Kota, Amruth R Jonnalagadda, Tanya Minteer, Beth A Knapick, Steffi Oesterreich, Adam M Brufsky, Adrian V Lee, Shannon L Puhalla
ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28973495/identification-of-mutations-in-cell-free-circulating-tumor-dna-in-adrenocortical-carcinoma-a-case-series
#15
Sara G Creemers, Esther Korpershoek, Peggy N Atmodimedjo, Winand N M Dinjens, Peter M van Koetsveld, Richard A Feelders, Leo J Hofland
Context: The disease course of adrenocortical carcinoma (ACC) patients is heterogeneous. A marker for prognosis and treatment response would facilitate choices on diagnosis and therapy. In other cancer types, circulating cell-free tumor DNA (ctDNA) predicted tumor dynamics. Case descriptions: This pilot study included six patients. Next-generation sequencing (NGS) showed mutations in 3 ACCs. From these patients, blood was drawn before (1-2 weeks) and after surgery, from which cell-free circulating DNA (cfDNA) was isolated...
June 30, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28972084/hypermutated-circulating-tumor-dna-correlation-with-response-to-checkpoint-inhibitor-based-immunotherapy
#16
Yulian Khagi, Aaron M Goodman, Gregory A Daniels, Sandip P Patel, Assuntina G Sacco, James M Randall, Lyudmila A Bazhenova, Razelle Kurzrock
Purpose: Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.Experimental Design: We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations...
October 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28968167/gefitinib-plus-chemotherapy-versus-chemotherapy-in-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-resistant-to-first-line-gefitinib-impress-overall-survival-and-biomarker-analyses
#17
Tony S K Mok, Sang-We Kim, Yi-Long Wu, Kazuhiko Nakagawa, Jin-Ji Yang, Myung-Ju Ahn, Jie Wang, James Chih-Hsin Yang, You Lu, Shinji Atagi, Santiago Ponce, Xiaojin Shi, Yuri Rukazenkov, Vincent Haddad, Kenneth S Thress, Jean-Charles Soria
Purpose The Iressa Mutation-Positive Multicentre Treatment Beyond ProgRESsion Study (IMPRESS) compared the continuation of gefitinib plus chemotherapy with placebo plus chemotherapy in patients with epidermal growth factor receptor ( EGFR) mutation-positive advanced non-small-cell lung cancer with progression (Response Evaluation Criteria in Solid Tumors 1.1) after first-line gefitinib. Primary results indicated no difference between treatments in terms of progression-free survival (PFS). The current analysis presents final, mature, overall survival (OS) data, together with exploratory analyses that examined whether specific biomarkers, including T790M mutation status, were able to differentiate a relative treatment effect...
October 2, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28958829/monitoring-treatment-response-and-metastatic-relapse-in-advanced-bladder-cancer-by-liquid-biopsy-analysis
#18
Karin Birkenkamp-Demtröder, Emil Christensen, Iver Nordentoft, Michael Knudsen, Ann Taber, Søren Høyer, Philippe Lamy, Mads Agerbæk, Jørgen Bjerggaard Jensen, Lars Dyrskjøt
Of the patients undergoing radical cystectomy, 20-80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes...
September 25, 2017: European Urology
https://www.readbyqxmd.com/read/28958406/clinical-utility-of-emerging-liquid-biomarkers-in-advanced-prostate-cancer
#19
REVIEW
Gillian Vandekerkhove, Kim N Chi, Alexander W Wyatt
The therapeutic landscape of advanced prostate cancer (PCa) has rapidly expanded in recent years. Despite significant improvements in patient overall survival, it remains challenging to determine the optimal therapy and sequence of therapies for individual patients. The development of molecular biomarkers will be key for patient stratification, and for monitoring response and resistance to therapy. In this context, minimally-invasive blood-based "liquid" biopsies are attractive as a practical surrogate for solid tumor tissue, providing a window into metastatic disease...
August 25, 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28954786/a-phase-1-dose-escalation-study-of-oral-asp8273-in-patients-with-non-small-cell-lung-cancers-with-epidermal-growth-factor-receptor-mutations
#20
Helena Yu, Alexander I Spira, Leora Horn, Jared Weiss, Howard West, Giuseppe Giaccone, Tracey L Evans, Ronan J Kelly, Bhardwai B Desai, Andrew Krivoshik, Diarmuid Moran, Srinivasu Poondru, Fei Jie, Kouji Aoyama, Anne Keating, Geoffrey R Oxnard
PURPOSE: Acquired EGFR T790M mutations are the most frequently identified resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant lung cancers. ASP8273 is a third-generation EGFR TKI with antitumor activity in preclinical models of EGFR-mutant lung cancer that targets mutant EGFR, including EGFR T790M. EXPERIMENTAL DESIGN: In this multi-cohort, phase 1 study (NCT02113813), escalating doses of ASP8273 (25-500mg) were administered once daily to non-small cell lung cancer (NSCLC) patients with disease progression after prior treatment with an EGFR TKI...
September 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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