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Cell-free tumor dna

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https://www.readbyqxmd.com/read/28921800/initial-testing-stage-1-of-m6620-formerly-vx-970-a-novel-atr-inhibitor-alone-and-combined-with-cisplatin-and-melphalan-by-the-pediatric-preclinical-testing-program
#1
Raushan T Kurmasheva, Dias Kurmashev, C Patrick Reynolds, Min Kang, Jianwrong Wu, Peter J Houghton, Malcolm A Smith
BACKGROUND: M6620 is a novel inhibitor of the DNA damage repair enzyme ATR, and has potentiated the activity of cisplatin and irinotecan in non-small cell lung cancer and colon cancer xenografts, respectively. PROCEDURES: M6620 was tested in vitro at concentrations ranging from 1.0 nM to 10.0 μM and at 75 nM in combination with cisplatin or melphalan. M6620 was tested against 24 solid tumor xenografts alone and in combination with cisplatin. Cisplatin was administered intraperitoneally on days 1 and 8 at a dose of 5 mg/kg...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28915616/tdp-43-hdac6-axis-promoted-tumor-progression-and-regulated-nutrient-deprivation-induced-autophagy-in-glioblastoma
#2
Tzu-Wei Lin, Ming-Teh Chen, Liang-Ting Lin, Pin-I Huang, Wen-Liang Lo, Yi-Ping Yang, Kai-Hsi Lu, Yi-Wei Chen, Shih-Hwa Chiou, Cheng-Wen Wu
Glioblastoma Multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. Surgical resection of GBM is greatly limited due to the biological significance of brain, giving rise to tumor relapse in GBM patients. Transactive response DNA binding protein-43 (TDP-43) is a DNA/RNA-binding protein known for causing neurodegenerative diseases through post-translational modification; but little is known about its involvement in cancer development. In this study, we found that nutrient deprivation in GBM cell lines elevated TDP-43 expression by a mechanism of evasion from ubiquitin-dependent proteolytic pathway, and subsequently activated the autophagy process...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912426/deconvolution-of-dna-methylation-identifies-differentially-methylated-gene-regions-on-1p36-across-breast-cancer-subtypes
#3
Alexander J Titus, Gregory P Way, Kevin C Johnson, Brock C Christensen
Breast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912355/diverse-p53-dna-binding-modes-expand-the-repertoire-of-p53-response-elements
#4
Pratik Vyas, Itai Beno, Zhiqun Xi, Yan Stein, Dmitrij Golovenko, Naama Kessler, Varda Rotter, Zippora Shakked, Tali E Haran
The tumor suppressor protein p53 acts as a transcription factor, binding sequence-specifically to defined DNA sites, thereby activating the expression of genes leading to diverse cellular outcomes. Canonical p53 response elements (REs) are made of two decameric half-sites separated by a variable number of base pairs (spacers). Fifty percent of all validated p53 REs contain spacers between 1 and 18 bp; however, their functional significance is unclear at present. Here, we show that p53 forms two different tetrameric complexes with consensus or natural REs, both with long spacers: a fully specific complex where two p53 dimers bind to two specific half-sites, and a hemispecific complex where one dimer binds to a specific half-site and the second binds to an adjacent spacer sequence...
September 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28911154/prognostic-significance-of-circulating-ret-m918t-mutated-tumor-dna-in-patients-with-advanced-medullary-thyroid-carcinoma
#5
Gilbert J Cote, Caitlin Evers, Mimi I Hu, Elizabeth G Grubbs, Michelle D Williams, Tao Hai, Dzifa Y Duose, Michal R Houston, Jacquelin H Bui, Meenakshi Mehrotra, Steven G Waguespack, Naifa L Busaidy, Maria E Cabanillas, Mouhammed Amir Habra, Rajyalakshmi Luthra, Steven I Sherman
Context: Interpretation of calcitonin measurement to predict the prognosis of medullary thyroid carcinoma (MTC) requires multiple measurements over an extended time period, making it an imperfect biomarker for evaluating prognosis or disease behavior. Single circulating cell-free DNA (cfDNA) values have been shown to be a valuable prognostic marker for several solid tumors. Objective: We tested the hypothesis that cfDNA containing the RET M918T mutation could be detected in the blood of patients with advanced MTC whose tumor harbored an M918T mutation and would be able to predict overall survival more reliably than calcitonin...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28911086/large-scale-prospective-screening-of-egfr-mutations-in-the-blood-of-advanced-nsclc-patients-to-guide-treatment-decisions
#6
C Mayo-de-Las-Casas, N Jordana-Ariza, M Garzón-Ibañez, A Balada-Bel, J Bertrán-Alamillo, S Viteri-Ramírez, N Reguart, M A Muñoz-Quintana, P Lianes-Barragan, C Camps, E Jantús, J Remon-Massip, S Calabuig, D Aguiar, M L Gil, N Viñolas, A K Santos-Rodríguez, M Majem, B García-Peláez, S Villatoro, A Pérez-Rosado, J C Monasterio, E Ovalle, M J Catalán, R Campos, D Morales-Espinosa, A Martínez-Bueno, M González-Cao, X González, I Moya-Horno, A E Sosa, N Karachaliou, R Rosell, M A Molina-Vila
Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28911069/clinical-utility-of-circulating-dna-analysis-for-rapid-detection-of-actionable-mutations-to-select-metastatic-colorectal-patients-for-anti-egfr-treatment
#7
A R Thierry, S El Messaoudi, C Mollevi, J L Raoul, R Guimbaud, D Pezet, P Artru, E Assenat, C Borg, M Mathonnet, C De La Fouchardière, O Bouché, C Gavoille, C Fiess, B Auzemery, R Meddeb, E Lopez-Crapez, C Sanchez, B Pastor, M Ychou
Background: While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods: Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients)...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28905672/the-influence-of-ketogenic-therapy-on-the-5-r-s-of-radiobiology
#8
Rainer J Klement
PURPOSE: Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by inducing free radical stress in tumor cells, leading to loss of reproductive integrity. The optimal treatment strategy has to consider damage to both tumor and normal cells and is determined by five factors known as the 5 R's of radiobiology: Reoxygenation, DNA Repair, Radiosensitivity, Redistribution in the cell cycle and Repopulation. The aim of this review is (i) to present evidence that these 5 R's are strongly influenced by cellular and whole body metabolism that in turn can be modified through ketogenic therapy in form of ketogenic diets and short term fasting, and (ii) to stimulate new research into this field including some research questions deserving further study...
September 14, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28903565/liquid-biopsies-the-clinics-and-the-molecules
#9
V Kubaczková, L Sedlarikova, B Bollová, V Sandecká, M Stork, L Pour, S Sevcikova
Unlike bone marrow biopsies, liquid biopsies represent a gentler, more accessible, less painful, repeatable and more comprehensive approach to get biologically relevant information about the entire tumor but also about treatment response and level of minimal residual disease. This is all possible since peripheral blood contains not only circulating tumor cells but also many circulating molecules of nucleic acids (microRNA, cell-free DNA, long non-coding RNA etc.). Multiple myeloma is a genetically heterogeneous disease characterized by multifocal tumor deposits in the bone marrow but also focal lesions elsewhere...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903353/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#10
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903321/alu-based-cell-free-dna-a-novel-biomarker-for-screening-of-gastric-cancer
#11
Chen Qian, Shaoqing Ju, Jing Qi, Jianmei Zhao, Xianjuan Shen, Rongrong Jing, Juan Yu, Li Li, Yingjuan Shi, Lurong Zhang, Zhiwei Wang, Hui Cong
Gastric cancer (GC) is the fourth most common cancer and the second major cause of cancer-related deaths worldwide. In our previous study, a novel and sensitive method for quantifying cell-free DNA (CFD) in human blood was established and tested for its ability to predict patients with tumor. We want to investigate CFD expression in the sera of GC patients in an attempt to explore the clinical significance of CFD in improving the early screening of GC and monitoring GC progression by the branched DNA (bDNA)-based Alu assay...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902490/direct-intra-nuclear-anticancer-drug-delivery-via-polydimethylsiloxane-nanoparticles-in-vitro-and-in-vivo-xenograft-studies
#12
Gargi Mishra, Souryadeep Bhattacharyya, Vipul Bhatia, Bushra Ateeq, Ashutosh Sharma, Sri Sivakumar
Direct delivery of anticancer drugs to nuclei of tumor cells is required to enhance the therapeutic activity which can be achieved by a nuclear localization signal (NLS) or peptide-decorated nano-vehicles. However, NLS/peptide-based approaches may create certain undesirable immunological responses and the utilized synthesis processes are generally labor intensive. To this end, we report ligand-free, enhanced intra-nuclear delivery of Doxorubicin (Dox) to different cancer cells via porous polydimethylsiloxane (PDMS) nanoparticles (NPs)...
September 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28900844/a-pilot-study-on-the-use-of-cerebrospinal-fluid-cell-free-dna-in-intramedullary-spinal-ependymoma
#13
Ian David Connolly, Yingmei Li, Wenying Pan, Eli Johnson, Linya You, Hannes Vogel, John Ratliff, Melanie Hayden Gephart
Cerebrospinal fluid (CSF) represents a promising source of cell-free DNA (cfDNA) for tumors of the central nervous system. A CSF-based liquid biopsy may obviate the need for riskier tissue biopsies and serve as a means for monitoring tumor recurrence or response to therapy. Spinal ependymomas most commonly occur in adults, and aggressive resection must be delicately balanced with the risk of injury to adjacent normal tissue. In patients with subtotal resection, recurrence commonly occurs. A CSF-based liquid biopsy matched to the patient's spinal ependymoma mutation profile has potential to be more sensitive then surveillance MRI, but the utility has not been well characterized for tumors of the spinal cord...
September 12, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28899967/circulating-cell-free-dna-for-metastatic-cervical-cancer-detection-genotyping-and-monitoring
#14
Zhigang Kang, Sanja Stevanović, Christian S Hinrichs, Liang Cao
PURPOSE: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making. PATIENTS AND METHODS: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet (dd) PCR...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28891048/identifying-actionable-variants-using-next-generation-sequencing-in-patients-with-a-historical-diagnosis-of-undifferentiated-pleomorphic-sarcoma
#15
Jeremy Lewin, Swati Garg, Beatrice Y Lau, Brendan C Dickson, Frank Traub, Nalan Gokgoz, Anthony M Griffin, Peter C Ferguson, Irene L Andrulis, Hao-Wen Sim, Suzanne Kamel-Reid, Tracy L Stockley, Lillian Siu, Jay S Wunder, Albiruni Ra Razak
There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological re-evaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons)...
September 10, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28890826/mutational-burden-on-circulating-cell-free-tumor-dna-testing-as-a-surrogate-marker-of-mismatch-repair-deficiency-or-microsatellite-instability-in-patients-with-colorectal-cancers
#16
Pashtoon Murtaza Kasi
No abstract text is available yet for this article.
August 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28889390/dna-methylation-analysis-from-body-fluids
#17
Dimo Dietrich
Circulating cell-free DNA (ccfDNA) can be found in various body fluids, i.e., blood (serum and plasma), urine, pleural effusions, and ascites. While ccfDNA predominantly originates from physiological processes, a fraction might be related to pathological events, e.g., cancer. Aberrant DNA methylation, which is considered a hallmark of cancer, can be assessed accurately in ccfDNA. Consequently, DNA methylation testing in body fluids represents a powerful diagnostic tool in the clinical management of malignant diseases...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28884371/egfr-t790m-mutation-testing-of-non-small-cell-lung-cancer-tissue-and-blood-samples-artificially-spiked-with-circulating-cell-free-tumor-dna-results-of-a-round-robin-trial
#18
Jana Fassunke, Michaela Angelika Ihle, Dido Lenze, Annika Lehmann, Michael Hummel, Claudia Vollbrecht, Roland Penzel, Anna-Lena Volckmar, Albrecht Stenzinger, Volker Endris, Andreas Jung, Ulrich Lehmann, Silke Zeugner, Gustavo Baretton, Hans Kreipe, Peter Schirmacher, Thomas Kirchner, Manfred Dietel, Reinhard Büttner, Sabine Merkelbach-Bruse
The European Commision (EC) recently approved osimertinib for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR T790M mutations. Besides tissue-based testing, blood samples containing cell-free circulating tumor DNA (ctDNA) can be used to interrogate T790M status. Herein, we describe the conditions and results of a round robin trial (RRT) for T790M mutation testing in NSCLC tissue specimens and peripheral blood samples spiked with cell line DNA mimicking tumor-derived ctDNA...
September 8, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28882678/rna-interference-mediated-knockdown-of-sirt1-and-or-sirt2-in-melanoma-identification-of-downstream-targets-by-large-scale-proteomics-analysis
#19
Melissa J Wilking-Busch, Mary A Ndiaye, Xiaoqi Liu, Nihal Ahmad
Melanoma is the most notorious and fatal of all skin cancers and the existing treatment options have not been proven to effectively manage this neoplasm, especially the metastatic disease. Sirtuin (SIRT) proteins have been shown to be differentially expressed in melanoma. We have shown that SIRTs 1 and 2 were overexpressed in melanoma and inhibition of SIRT1 imparts anti-proliferative responses in human melanoma cells. To elucidate the impact of SIRT 1 and/or 2 in melanoma, we created stable knockdowns of SIRTs 1, 2, and their combination using shRNA mediated RNA interference in A375 human melanoma cells...
September 4, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28881671/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#20
Liyong Zhang, Yan Wang, Mohammad H Rashid, Min Liu, Kartik Angara, Nahid F Mivechi, Nita J Maihle, Ali S Arbab, Lan Ko
Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 (PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198(+) pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models...
August 1, 2017: Oncotarget
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