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Cell free tumour DNA

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https://www.readbyqxmd.com/read/28723472/human-prostate-tissue-derived-extracellular-matrix-as-a-model-of-prostate-microenvironment
#1
Walter Cazzaniga, Manuela Nebuloni, Erika Longhi, Irene Locatelli, Raffaele Allevi, Roberta Lucianò, Gelsomina Senatore, Eugenio Ventimiglia, Vito Cucchiara, Luca Genovese, Francesco Montorsi, Massimo Alfano, Andrea Salonia, Ilaria Cavarretta
BACKGROUND: Clinical experience highlights the wide heterogeneity of primary prostate cancer (PPCa), even when potentially related to the same grade and stage. Currently available prediction tools and biomarkers do not always allow for early recognition of PPCa aggressive phenotype, sometimes making it impossible to distinguish among men harbouring indolent tumours or life-threatening disease. OBJECTIVE: To establish a novel ex vivo/in vitro model suitable to estimate the invasive phenotype of PPCa cells (PPCaC)...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28710679/new-phage-display-isolated-heptapeptide-recognizing-the-regulatory-carboxy-terminal-domain-of-human-tumour-protein-p53
#2
Sihem Ben Abid, Mouna Sahnoun, Ines Yacoubi-Hadj Amor, Salma Abdelmoula-Souissi, Hajer Hassairi, Raja Mokdad-Gargouri, Ali Gargouri
The transcription factor tumor protein p53 (P53) controls a variety of genes most involved in cell cycle and is at the origin of apoptosis when DNA is irreparably damaged. We planned to select novel tumor protein p53-interacting peptides through the screening of hepta-peptide phage-display libraries. For this aim, human tumor suppressor protein p53 was expressed in Escherichia coli as Glutathione S-transferase fusion and purified by affinity chromatography. The phage library was then screened on this immobilized protein target...
July 14, 2017: Protein Journal
https://www.readbyqxmd.com/read/28692984/a-study-of-cell-free-dna-fragmentation-pattern-and-its-application-in-dna-sample-type-classification
#3
Shifu Chen, Ming Liu, Xiaoni Zhang, Renwen Long, Yixing Wang, Yue Han, Shiwei Zhang, Mingyan Xu, Jia Gu
Plasma cell-free DNA (cfDNA) has certain fragmentation patterns, which can bring non-random base content curves of the sequencing data's beginning cycles. We studied the patterns and found that we could determine whether a sample is cfDNA or not by just looking into the first 10 cycles of its base content curves. We analysed 3189 FastQ files, including 1442 cfDNA, 1234 genomic DNA, 507 FFPE tumour DNA and 6 urinary cfDNA. By deep analysing these data, we find the patterns are stable enough to distinguish cfDNA from other kinds of DNA samples...
July 4, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28683468/correlation-between-circulating-mutant-dna-and-metabolic-tumour-burden-in-advanced-non-small-cell-lung-cancer-patients
#4
Anne Winther-Larsen, Christina Demuth, Joan Fledelius, Anne Tranberg Madsen, Karin Hjorthaug, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival. METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28647685/irtks-is-correlated-with-progression-and-survival-time-of-patients-with-gastric-cancer
#5
Li-Yu Huang, Xuefei Wang, Xiao-Fang Cui, He Li, Junjie Zhao, Chong-Chao Wu, Lingqiang Min, Zhicheng Zhou, Lixin Wan, Yu-Ping Wang, Chao Zhang, Wei-Qiang Gao, Yihong Sun, Ze-Guang Han
BACKGROUND AND OBJECTIVES: IRTKS functions as a novel regulator of tumour suppressor p53; however, the role of IRTKS in pathogenesis of gastric cancer is unclear. DESIGN: We used immunohistochemistry to detect IRTKS levels in 527 human gastric cancer specimens. We generated both IRTKS-deficient and p53-deficient mice to observe survival time of these mice and to isolate mouse embryonic fibroblasts (MEFs) for evaluating in vivo tumorigenicity. Co-immunoprecipitation was used to study the interaction among p53, MDM2 and IRTKS, as well as the ubiquitination of p53...
June 24, 2017: Gut
https://www.readbyqxmd.com/read/28641314/no-additional-prognostic-value-for-mre11-in-squamous-cell-carcinomas-of-the-anus-treated-with-chemo-radiotherapy
#6
Alexandra K Walker, Christiana Kartsonaki, Elena Collantes, Judith Nicholson, Duncan C Gilbert, Anne E Kiltie
BACKGROUND: The majority of anal cancers (84-95%) are driven by infection with human papillomavirus (HPV). HPV-positive tumours show significantly better responses to chemo-radiotherapy when compared with HPV-negative tumours. HPV infection is linked to alterations in DNA damage response proteins, including MRE11. MRE11 is a potential predictive biomarker for response to radiotherapy in muscle-invasive bladder cancer and may hold predictive power in other cancers. METHODS: Using a previously reported cohort, we evaluated the levels of MRE11 in anal cancer and assessed its predictive value in this disease...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28614831/liquid-biopsies-for-monitoring-temporal-genomic-heterogeneity-in-breast-and-colon-cancers
#7
Tiziana Venesio, Giulia Siravegna, Alberto Bardelli, Anna Sapino
Cancer is a spatial and temporal dynamic disease where differently evolving genetic clones are responsible for progression. In this landscape, the genomic heterogeneity of the primary tumours can be captured by deep-sequencing representative spatial samples. However, the recognition of genetic alterations responsible for tumour evolution remains a challenging task. Recently, the "liquid biopsy" was recognized as a powerful real-time approach for the molecular monitoring of this dynamic disease. The term "liquid biopsy" generally refers to the use of circulating (cell-free) tumour DNA (ctDNA) and circulating tumour cells (CTCs) as non-invasive biomarkers for the early diagnosis, prognosis, monitoring of clinical progression, and response to treatment in different types of tumours, including the highly genomic heterogeneous breast cancer...
June 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28596550/booster-immunizations-with-dna-plasmids-encoding-her-2-neu-prevent-spontaneous-mammary-cancer-in-her-2-neu-transgenic-mice-over-life-span
#8
Mauro Provinciali, Alessandra Barucca, Fiorenza Orlando, Elisa Pierpaoli
Cancer vaccines are less effective at old than at young age because of immunosenescence. Besides, in preliminary observations we showed that the immunization with HER-2/neu DNA plasmid in transgenic young mice (standard immunization, SI) delays but not abrogate spontaneous mammary tumours progressively appearing during aging. In this study we evaluated whether booster immunizations (BI) of HER-2/neu transgenic mice with HER-2/neu DNA plasmids every 6 (ECD6), 3 (ECD3), or 1.5 (ECD1.5) months after SI induce a protective immunity that could be maintained over life span...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28540249/liquid-biopsies-for-bladder-cancer
#9
EDITORIAL
Douglas G Ward, Richard T Bryan
The development of accurate urinary biomarkers for the non-invasive detection of urothelial bladder cancer (UBC) could transform patient pathways by reducing reliance on cystoscopy, and the identification of highly prognostic (or even predictive) biomarkers could better guide patient management. A number of approaches are being utilised to address these challenges in both urinary- and plasma-borne tumour DNA (tDNA), so-called "liquid biopsies". Next generation sequencing (NGS) and droplet digital PCR (ddPCR) allow detection of very low levels of such tDNA amongst a large excess of non-tumour DNA, the former permitting large mutation panels to be assessed and the latter potentially identifying ultrarare mutant alleles yet restricted for multiplexing...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28522553/glioblastoma-derived-cells-in-vitro-unveil-the-spectrum-of-drug-resistance-capabilty-comparative-study-of-tumour-chemosensitivity-in-different-culture-systems
#10
Monika Witusik-Perkowska, Magdalena Zakrzewska, Beata Sikorska, Wielislaw Papierz, Dariusz J Jaskolski, Janusz Szemraj, Pawel P Liberski
Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28504713/elevated-pttg-and-pbf-predicts-poor-patient-outcome-and-modulates-dna-damage-response-genes-in-thyroid-cancer
#11
M L Read, J C Fong, B Modasia, A Fletcher, W Imruetaicharoenchoke, R J Thompson, H Nieto, J J Reynolds, A Bacon, U Mallick, A Hackshaw, J C Watkinson, K Boelaert, A S Turnell, V E Smith, C J McCabe
The proto-oncogene PTTG and its binding partner PBF have been widely studied in multiple cancer types, particularly thyroid and colorectal, but their combined role in tumourigenesis is uncharacterised. Here, we show for the first time that together PTTG and PBF significantly modulate DNA damage response (DDR) genes, including p53 target genes, required to maintain genomic integrity in thyroid cells. Critically, DDR genes were extensively repressed in primary thyrocytes from a bitransgenic murine model (Bi-Tg) of thyroid-specific PBF and PTTG overexpression...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28492226/circulating-tumour-dna-sequence-analysis-as-an-alternative-to-multiple-myeloma-bone-marrow-aspirates
#12
Olena Kis, Rayan Kaedbey, Signy Chow, Arnavaz Danesh, Mark Dowar, Tiantian Li, Zhihua Li, Jessica Liu, Mark Mansour, Esther Masih-Khan, Tong Zhang, Scott V Bratman, Amit M Oza, Suzanne Kamel-Reid, Suzanne Trudel, Trevor J Pugh
The requirement for bone-marrow aspirates for genomic profiling of multiple myeloma poses an obstacle to enrolment and retention of patients in clinical trials. We evaluated whether circulating cell-free DNA (cfDNA) analysis is comparable to molecular profiling of myeloma using bone-marrow tumour cells. We report here a hybrid-capture-based Liquid Biopsy Sequencing (LB-Seq) method used to sequence all protein-coding exons of KRAS, NRAS, BRAF, EGFR and PIK3CA in 64 cfDNA specimens from 53 myeloma patients to >20,000 × median coverage...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28487489/apelin-a-putative-novel-predictive-biomarker-for-bevacizumab-response-in-colorectal-cancer
#13
Linda Zuurbier, Arman Rahman, Martijn Cordes, Jennifer Scheick, Tse J Wong, François Rustenburg, Jesu Christopher Joseph, Peter Dynoodt, Rory Casey, Paul Drillenburg, Michael Gerhards, Ana Barat, Rut Klinger, Bozena Fender, Darran P O'Connor, Johannes Betge, Matthias P Ebert, Timo Gaiser, Jochen H M Prehn, Arjan W Griffioen, Nicole C T van Grieken, Bauke Ylstra, Annette T Byrne, Laurens G van der Flier, William M Gallagher, Ruben Postel
Bevacizumab (bvz) is currently employed as an anti-angiogenic therapy across several cancer indications. Bvz response heterogeneity has been well documented, with only 10-15% of colorectal cancer (CRC) patients benefitting in general. For other patients, clinical efficacy is limited and side effects are significant. This reinforces the need for a robust predictive biomarker of response. To identify such a biomarker, we performed a DNA microarray-based transcriptional profiling screen with primary endothelial cells (ECs) isolated from normal and tumour colon tissues...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442757/comparison-of-circulating-tumour-cells-and-circulating-cell-free-epstein-barr-virus-dna-in-patients-with-nasopharyngeal-carcinoma-undergoing-radiotherapy
#14
Jess Honganh Vo, Wen Long Nei, Min Hu, Wai Min Phyo, Fuqiang Wang, Kam Weng Fong, Terence Tan, Yoke Lim Soong, Shie Lee Cheah, Kiattisa Sommat, Huiyu Low, Belinda Ling, Johnson Ng, Wan Loo Tan, Kian Sing Chan, Lynette Oon, Jackie Y Ying, Min-Han Tan
Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used in clinical settings as a circulating biomarker in nasopharyngeal carcinoma (NPC), but there has been no comparison with circulating tumour cells (CTCs). Our study aims to compare the performance of CTC enumeration against EBV cfDNA quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples from 46 NPC patients at baseline and one month after radiotherapy with or without concurrent chemotherapy were analysed...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28430577/synthetic-lethal-interaction-between-the-tumour-suppressor-stag2-and-its-paralog-stag1
#15
Lorena Benedetti, Matteo Cereda, LeeAnn Monteverde, Nikita Desai, Francesca D Ciccarelli
Cohesin is a multi-protein complex that tethers sister chromatids during mitosis and mediates DNA repair, genome compartmentalisation and regulation of gene expression. Cohesin subunits frequently acquire cancer loss-of-function alterations and act as tumour suppressors in several tumour types. This has led to increased interest in cohesin as potential target in anti-cancer therapy. Here we show that the loss-of-function of STAG2, a core component of cohesin and an emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells on its paralog STAG1...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387924/high-number-of-kinome-mutations-in-non-small-cell-lung-cancer-is-associated-with-reduced-immune-response-and-poor-relapse-free-survival
#16
Å Helland, O T Brustugun, S Nakken, A R Halvorsen, T Dønnem, R Bremnes, L T Busund, J Sun, S Lorenz, S K Solberg, L H Jørgensen, D Vodak, O Myklebost, E Hovig, L A Meza-Zepeda
Lung cancer is the leading cause of cancer related death, and the past years' improved insight into underlying molecular events has significantly improved outcome for specific subsets of patients. In particular, several new therapies that target protein kinases have been implemented, and many more are becoming available. We have investigated lung cancer specimens for somatic mutations in a targeted panel of 612 human genes, the majority being protein kinases. The somatic mutation profiles were correlated to profiles of immune cell infiltration as well as relapse-free survival...
July 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28335889/human-papillomavirus-as-prognostic-marker-with-rising-prevalence-in-neck-squamous-cell-carcinoma-of-unknown-primary-a-retrospective-multicentre-study
#17
Lea Schroeder, Paolo Boscolo-Rizzo, Elisa Dal Cin, Salvatore Romeo, Lorena Baboci, Gerhard Dyckhoff, Jochen Hess, Carlota Lucena-Porcel, Anne Byl, Nikolaus Becker, Laia Alemany, Xavier Castellsagué, Miquel Quer, Xavier León, Manuel Wiesenfarth, Michael Pawlita, Dana Holzinger
Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers for HPV transformation in NSCCUP could allow focussing on the oropharynx in primary tumour search and could be of value for choice and extent of treatment...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28334731/characterisation-of-cct271850-a-selective-oral-and-potent-mps1-inhibitor-used-to-directly-measure-in-vivo-mps1-inhibition-vs-therapeutic-efficacy
#18
Amir Faisal, Grace W Y Mak, Mark D Gurden, Cristina P R Xavier, Simon J Anderhub, Paolo Innocenti, Isaac M Westwood, Sébastien Naud, Angela Hayes, Gary Box, Melanie R Valenti, Alexis K De Haven Brandon, Lisa O'Fee, Jessica Schmitt, Hannah L Woodward, Rosemary Burke, Rob L M vanMontfort, Julian Blagg, Florence I Raynaud, Suzanne A Eccles, Swen Hoelder, Spiros Linardopoulos
BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28306358/the-genetics-of-gastroesophageal-adenocarcinoma-and-the-use-of-circulating-cell-free-dna-for-disease-detection-and-monitoring
#19
REVIEW
Mark R Openshaw, Catherine J Richards, David S Guttery, Jacqueline A Shaw, Anne L Thomas
Gastroesophageal adenocarcinoma (GOA) is a frequently occurring cancer worldwide with a poor clinical outcome. Adenocarcinomas of the esophagus and gastroesophageal junction have shown a recent increase in frequency, therefore there is need to increase our understanding of GOA in order to improve our ability to detect, monitor and treat the disease. Areas covered: The authors discuss the current classification of GOA in the context of recent changes in incidence. The authors also discuss developments in the understanding of disease biology and recent discoveries from whole genome and whole exome sequencing, and studies in immunotherapy...
May 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28298070/pulmonary-injury-associated-with-radiation-therapy-assessment-complications-and-therapeutic-targets
#20
REVIEW
Rasmi Rajan Radha, Guruvayoorappan Chandrasekharan
Pulmonary injury is more common in patients undergoing radiation therapy for lungs and other thoracic malignancies. Recently with the use of most-advanced technologies powerful doses of radiation can be delivered directly to tumor site with exquisite precision. The awareness of technical and clinical parameters that influence the chance of radiation induced lung injury is important to guide patient selection and toxicity minimization strategies. At the cellular level, radiation activates free radical production, leading to DNA damage, apoptosis, cell cycle changes, and reduced cell survival...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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