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Cell-free tumor dna

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https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#1
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29138500/circulating-androgen-receptor-combined-with-18f-fluorocholine-pet-ct-metabolic-activity-and-outcome-to-androgen-receptor-signalling-directed-therapies-in-castration-resistant-prostate-cancer
#2
V Conteduca, E Scarpi, P Caroli, S Salvi, C Lolli, S L Burgio, C Menna, G Schepisi, S Testoni, G Gurioli, G Paganelli, V Casadio, F Matteucci, U De Giorgi
The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137355/a-pilot-study-evaluating-concordance-between-blood-based-and-patient-matched-tumor-molecular-testing-within-pancreatic-cancer-patients-participating-in-the-know-your-tumor-kyt-initiative
#3
Michael J Pishvaian, R Joseph Bender, Lynn M Matrisian, Lola Rahib, Andrew Hendifar, William A Hoos, Sam Mikhail, Vincent Chung, Vincent Picozzi, Craig Heartwell, Kimberly Mason, Katelyn Varieur, Metasebia Aberra, Subha Madhavan, Emanuel Petricoin, Jonathan R Brody
Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRB-approved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136733/-exploratory-study-of-circulating-tumor-dna-detection-in-early-breast-cancer-an-analysis-of-75-next-generation-sequencing-results
#4
B Zhou, L Xin, L Xu, Y H Liu, M M Zhang, R L Jing, X Y Liang, S B Cao
Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29133142/dedifferentiated-endometrial-carcinomas-with-neuroendocrine-features-a-clinicopathologic-immunohistochemical-and-molecular-genetic-study
#5
Iñigo Espinosa, Antonio De Leo, Emanuela D'Angelo, Juan M Rosa-Rosa, Marina Corominas, Alan Gonzalez, José Palacios, Jaime Prat
Undifferentiated endometrial carcinoma is an aggressive type of uterine cancer which is occasionally associated with a low-grade endometrioid carcinoma component. This combination is referred to as "dedifferentiated endometrioid endometrial carcinoma." Neuroendocrine expression may occur in undifferentiated endometrial carcinoma but its significance in dedifferentiated endometrial carcinomas is unknown. To gain insight into the pathogenesis of these tumors we have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, b-catenin, SMARCB1, synaptophysin, chromogranin A, and CD56) and mutational status (PTEN, KRAS, PIK3CA, TP53 and POLE) of 4 dedifferentiated endometrial carcinomas with strong and diffuse neuroendocrine expression...
November 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/29132396/circulating-cell-free-dna-and-circulating-tumor-cells-the-liquid-biopsies-in-ovarian-cancer
#6
REVIEW
Xianliang Cheng, Lei Zhang, Yajuan Chen, Chen Qing
Limited understanding of ovarian cancer (OC) genome portrait has hindered the therapeutic advances. The serial monitoring of tumor genotypes is becoming increasingly attainable with circulating cell-free DNA (cf-DNA) and circulating tumor cells (CTCs) emerging as "liquid biopsies". They represent non-invasive biomarkers and are viable, as they can be isolated from human plasma, serum and other body fluids. Molecular characterization of circulating tumor DNA (ct-DNA) and CTCs offer unique potentials to better understand the biology of metastasis and resistance to therapies...
November 13, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29130947/application-of-digital-pcr-in-detecting-human-diseases-associated-gene-mutation
#7
Yu Tong, Shizhen Shen, Hui Jiang, Zhi Chen
Gene mutation has been considered a research hotspot, and the rapid development of biomedicine has enabled significant advances in the evaluation of gene mutations. The advent of digital polymerase chain reaction (dPCR) elevates the detection of gene mutations to unprecedented levels of precision, especially in cancer-associated genes. dPCR has been utilized in the detection of tumor markers in cell-free DNA (cfDNA) samples from patients with different types of cancer in samples such as plasma, cerebrospinal fluid, urine and sputum, which confers significant value for dPCR in both clinical applications and basic research...
October 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29124314/prophylactic-dna-vaccine-targeting-foxp3-regulatory-t-cells-depletes-myeloid-derived-suppressor-cells-and-improves-anti-melanoma-immune-responses-in-a-murine-model
#8
Afshin Namdar, Reza Mirzaei, Arash Memarnejadian, Roobina Boghosian, Morteza Samadi, Hamid Reza Mirzaei, Hamid Farajifard, Mehdi Zavar, Kayhan Azadmanesh, Shokrollah Elahi, Farshid Noorbakhsh, Abbas Rezaei, Jamshid Hadjati
Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumor-free conditions. In the present study, we investigated the immune modulatory effects of a prophylactic regimen of the redesigned Foxp3 vaccine in the B16F10 melanoma model...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29119276/phase-ib-ii-study-of-gemcitabine-nab-paclitaxel-and-pembrolizumab-in-metastatic-pancreatic-adenocarcinoma
#9
Glen J Weiss, Lisa Blaydorn, Julia Beck, Kirsten Bornemann-Kolatzki, Howard Urnovitz, Ekkhard Schütz, Vivek Khemka
Background A single center phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab (GNP) to evaluate the safety and efficacy in metastatic pancreatic adenocarcinoma (PDAC) was conducted (NCT02331251). Methods PDAC patients (pts) with measurable disease, biopsy proven metastasis, adequate laboratory tests, and KPS ≥ 70% received GNP until progression or toxicity. Safety monitoring, RECIST 1.1, and irRECIST assessments were conducted. Response imaging was performed prior to cycle 4, then every 3 months...
November 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29116071/-crispr-cas9-editing-based-modeling-of-hypoxia-in-renal-cancer-cells
#10
N A Zhigalova, S V Zhenilo, A V Artemov, E B Prokhortchouk
Uncontrolled growth in the cell mass of malignant tumors induces intensive angiogenesis. However, the demands of the cancer cells for nutrients and oxygen remain only partially met. Hypoxia is a process that accompanies malignant transformation and evokes changes in the DNA methylation profile in solid tumors. To a certain extent, these changes, including the hypermethylation of tumor suppressor gene promoters, are related to the decrease in the activity of Tet proteins under the conditions of oxygen and free radical deficit...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29113658/circulating-cell-free-dna-in-plasma-of-colorectal-cancer-patients-a-potential-biomarker-for-tumor-burden
#11
Jagdeep Singh Bhangu, Hossein Taghizadeh, Tamara Braunschmid, Thomas Bachleitner-Hofmann, Christine Mannhalter
BACKGROUND: Measurement of cell-free DNA (cfDNA) in plasma - the so called liquid biopsy - is a novel method for early detection of cancer. Necrotic cancer cells release various DNA fragments that can be detected in plasma or serum. The aim of our study was to investigate the concentration of circulating ALU115, LINE79 and LINE297 fragments in plasma from venous and arterial blood of colorectal cancer (CRC) patients before, during and 5 days after surgical intervention. PATIENTS AND METHODS: Thirty patients (16 female, 14 male, median age 56 years), undergoing surgery for colorectal and appendix cancer, and 17 healthy volunteers were included in this study...
December 2017: Surgical Oncology
https://www.readbyqxmd.com/read/29113268/jab1-stat3-activation-loop-is-associated-with-recurrence-following-5-fluorouracil-based-adjuvant-chemotherapy-in-human-colorectal-cancer
#12
Naruji Kugimiya, Arata Nishimoto, Tohru Hosoyama, Koji Ueno, Yoshihiro Takemoto, Eijiro Harada, Tadahiko Enoki, Kimikazu Hamano
Jun activation domain-binding protein 1 (JAB1) has been shown to have multiple roles in tumorigenesis, including the degradation of tumor suppressor proteins such as p53, Smad7, Runx3 and the cyclin-dependent kinase inhibitor p27(Kip1), and the activation of oncogenic transcription factors, such as c-Jun and hypoxia-inducible factor-1α. In addition, our previous study revealed that JAB1 positively regulates signal transducer and activator of transcription 3 (STAT3) DNA-binding activity in human colon cancer cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113230/squamous-cell-transformation-and-egfr-t790m-mutation-as-acquired-resistance-mechanisms-in-a-patient-with-lung-adenocarcinoma-treated-with-a-tyrosine-kinase-inhibitor-a-case-report
#13
Rossella Bruno, Agnese Proietti, Greta Alì, Gianfranco Puppo, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
The present case report describes the infrequent coexistence of squamous cell transformation and the epidermal growth factor receptor (EGFR) T790M mutation as resistance mechanisms to first line treatment with tyrosine kinase inhibitors. The patient was a 44-year-old female, diagnosed with a primitive advanced lung adenocarcinoma with bone metastases. The tumor was positive for the EGFR exon 19 deletion, therefore the patient was treated with afatinib (40 mg/day, orally) and radiotherapy for bone lesions. After 16 months, the patient developed resistance...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112956/hiv-1-persistence-following-extremely-early-initiation-of-antiretroviral-therapy-art-during-acute-hiv-1-infection-an-observational-study
#14
Timothy J Henrich, Hiroyu Hatano, Oliver Bacon, Louise E Hogan, Rachel Rutishauser, Alison Hill, Mary F Kearney, Elizabeth M Anderson, Susan P Buchbinder, Stephanie E Cohen, Mohamed Abdel-Mohsen, Christopher W Pohlmeyer, Remi Fromentin, Rebecca Hoh, Albert Y Liu, Joseph M McCune, Jonathan Spindler, Kelly Metcalf-Pate, Kristen S Hobbs, Cassandra Thanh, Erica A Gibson, Daniel R Kuritzkes, Robert F Siliciano, Richard W Price, Douglas D Richman, Nicolas Chomont, Janet D Siliciano, John W Mellors, Steven A Yukl, Joel N Blankson, Teri Liegler, Steven G Deeks
BACKGROUND: It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29109393/scalable-whole-exome-sequencing-of-cell-free-dna-reveals-high-concordance-with-metastatic-tumors
#15
Viktor A Adalsteinsson, Gavin Ha, Samuel S Freeman, Atish D Choudhury, Daniel G Stover, Heather A Parsons, Gregory Gydush, Sarah C Reed, Denisse Rotem, Justin Rhoades, Denis Loginov, Dimitri Livitz, Daniel Rosebrock, Ignaty Leshchiner, Jaegil Kim, Chip Stewart, Mara Rosenberg, Joshua M Francis, Cheng-Zhong Zhang, Ofir Cohen, Coyin Oh, Huiming Ding, Paz Polak, Max Lloyd, Sairah Mahmud, Karla Helvie, Margaret S Merrill, Rebecca A Santiago, Edward P O'Connor, Seong H Jeong, Rachel Leeson, Rachel M Barry, Joseph F Kramkowski, Zhenwei Zhang, Laura Polacek, Jens G Lohr, Molly Schleicher, Emily Lipscomb, Andrea Saltzman, Nelly M Oliver, Lori Marini, Adrienne G Waks, Lauren C Harshman, Sara M Tolaney, Eliezer M Van Allen, Eric P Winer, Nancy U Lin, Mari Nakabayashi, Mary-Ellen Taplin, Cory M Johannessen, Levi A Garraway, Todd R Golub, Jesse S Boehm, Nikhil Wagle, Gad Getz, J Christopher Love, Matthew Meyerson
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29108273/sensitive-droplet-digital-pcr-method-for-detection-of-tert-promoter-mutations-in-cell-free-dna-from-patients-with-metastatic-melanoma
#16
Ashleigh C McEvoy, Leslie Calapre, Michelle R Pereira, Tindaro Giardina, Cleo Robinson, Muhammad A Khattak, Tarek M Meniawy, Antonia L Pritchard, Nicholas K Hayward, Benhur Amanuel, Michael Millward, Melanie Ziman, Elin S Gray
Background: Currently mainly BRAF mutant circulating tumor DNA (ctDNA) is utilized to monitor patients with melanoma. TERT promoter mutations are common in various cancers and found in up to 70% of melanomas, including half of BRAF wild-type cases. Therefore, a sensitive method for detection of TERT promoter mutations would increase the number of patients that could be monitored through ctDNA analysis. Methods: A droplet digital PCR (ddPCR) assay was designed for the concurrent detection of chr5:1,295,228 C>T and chr5:1,295,250 C>T TERT promoter mutations...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107586/ru-fe-bimetallic-complexes-synthesis-characterization-cytotoxicity-and-study-of-their-interactions-with-dna-hsa-and-human-topoisomerase-ib
#17
Jessica E Takarada, Adriana P M Guedes, Rodrigo S Correa, Elisângela de P Silveira-Lacerda, Silvia Castelli, Federico Iacovelli, Victor Marcelo Deflon, Alzir Azevedo Batista, Alessandro Desideri
Three ruthenium/iron-based compounds, 1: [Ru(MIm)(bipy)(dppf)]PF6 (MIm = 2-mercapto-1-methylimidazole anion), 2: [RuCl(Im)(bipy)(dppf)]PF6 (Im = imidazole), and 3: [Ru(tzdt)(bipy)(dppf)]PF6 (tzdt = 1,3-thiazolidine-2-thione anion) (dppf = 1,1'-bis(diphenylphosphine)ferrocene and bipy = 2,2'-bipyridine), were synthesized, and characterized by elemental analyses, conductivity, UV/Vis, IR, (1)H, (13)C and (31)P{1H} NMR spectroscopies, and by electrochemical technique. The complex 3 was also characterized by single-crystal X-ray...
October 28, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29106415/evolution-and-clinical-impact-of-co-occurring-genetic-alterations-in-advanced-stage-egfr-mutant-lung-cancers
#18
Collin M Blakely, Thomas B K Watkins, Wei Wu, Beatrice Gini, Jacob J Chabon, Caroline E McCoach, Nicholas McGranahan, Gareth A Wilson, Nicolai J Birkbak, Victor R Olivas, Julia Rotow, Ashley Maynard, Victoria Wang, Matthew A Gubens, Kimberly C Banks, Richard B Lanman, Aleah F Caulin, John St John, Anibal R Cordero, Petros Giannikopoulos, Andrew D Simmons, Philip C Mack, David R Gandara, Hatim Husain, Robert C Doebele, Jonathan W Riess, Maximilian Diehn, Charles Swanton, Trever G Bivona
A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers...
November 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29106372/53bp1-and-brca1-control-pathway-choice-for-stalled-replication-restart
#19
Yixi Xu, Shaokai Ning, Zheng Wei, Ran Xu, Xinlin Xu, Mengtan Xing, Rong Guo, Dongyi Xu
The cellular pathways that restart stalled replication forks are essential for genome stability and tumor prevention. However, how many of these pathways exist in cells and how these pathways are selectively activated remain unclear. Here, we describe two major fork restart pathways, and demonstrate that their selection is governed by 53BP1 and BRCA1, which are known to control the pathway choice to repair double-strand DNA breaks (DSBs). Specifically, 53BP1 promotes a fork cleavage-free pathway, whereas BRCA1 facilitates a break-induced replication (BIR) pathway coupled with SLX-MUS complex-mediated fork cleavage...
November 6, 2017: ELife
https://www.readbyqxmd.com/read/29090099/a-signature-of-enhanced-lipid-metabolism-lipid-peroxidation-and-aldehyde-stress-in-therapy-induced-senescence
#20
Amy C Flor, Don Wolfgeher, Ding Wu, Stephen J Kron
At their proliferative limit, normal cells arrest and undergo replicative senescence, displaying large cell size, flat morphology, and senescence-associated beta-galactosidase (SA-β-Gal) activity. Normal or tumor cells exposed to genotoxic stress undergo therapy-induced senescence (TIS), displaying a similar phenotype. Senescence is considered a DNA damage response, but cellular heterogeneity has frustrated identification of senescence-specific markers and targets. To explore the senescent cell proteome, we treated tumor cells with etoposide and enriched SA-β-Gal(HI) cells by fluorescence-activated cell sorting (FACS)...
2017: Cell Death Discovery
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