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https://www.readbyqxmd.com/read/27904700/detection-of-gene-copy-number-alterations-in-dcis-and-invasive-breast-cancer-by-qm-fish
#1
Aifeng Pan, Yawei Zhou, Kun Mu, Yansong Liu, Feifei Sun, Peng Li, Li Li
The exact roles of copy number alteration (CNA) in initiation, progression and immunotherapy of breast cancer and the genomic alterations behind progression from ductal carcinoma in situ (DCIS) to invasive carcinoma remain unknown. Quantitative multi-gene fluorescence in situ hybridization (QM-FISH) opens a possibility of large scale genomic analysis of specific deletions and amplifications with high-resolution at one cell level. We detected CNAs of 30 genes using QM-FISH and analyzed their association with clinicopathological parameters and patients' outcomes in 66 breast cancers with synchronous invasive carcinoma and DCIS...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902380/antimicrobial-resistance-profiling-and-molecular-typing-of-methicillin-resistant-staphylococcus-aureus-mrsa-isolated-from-a-malaysian-teaching-hospital
#2
Ainihayati Noordin, Hassriana Fazzila Sapri, Nurul Azirah Mohamad Sani, Shih Kei Leong, Xin-Ee Tan, Toh Leong Tan, Noraziah Mohamad Zin, Hui-Min Neoh, Salasawati Hussin
The annual prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Malaysia has been estimated to be at 30-40% of all S. aureus infections. Nevertheless, data on the antimicrobial resistance and genetic diversity of Malaysian MRSAs remain few. In 2009, we collected 318 MRSA strains from various wards of our teaching hospital located in Kuala Lumpur, the capital city of Malaysia, and performed antimicrobial susceptibility testing on the strains. The strains were then molecularly characterized via SCCmec and virulence gene (cna, sea, seb, sec, sed, see, seg, seh, sei, eta, etb, PVL and TSST-1) typing; a subset of 49 strains isolated from the Intensive Care Unit (ICU) were also typed using Pulsed-Field Gel Electrophoresis (PFGE)...
November 7, 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27896739/integrating-heterogeneous-datasets-for-cancer-module-identification
#3
A K M Azad
The availability of multiple heterogeneous high-throughput datasets provides an enabling resource for cancer systems biology. Types of data include: Gene expression (GE), copy number aberration (CNA), miRNA expression, methylation, and protein-protein Interactions (PPI). One important problem that can potentially be solved using such data is to determine which of the possible pair-wise interactions among genes contributes to a range of cancer-related events, from tumorigenesis to metastasis. It has been shown by various studies that applying integrated knowledge from multi-omics datasets elucidates such complex phenomena with higher statistical significance than using a single type of dataset individually...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27886717/rubioseq-a-multiplatform-application-that-executes-parallelized-pipelines-to-analyse-next-generation-sequencing-data
#4
Miriam Rubio-Camarillo, Hugo López-Fernández, Gonzalo Gómez-López, Ángel Carro, José María Fernández, Coral Fustero Torre, Florentino Fdez-Riverola, Daniel Glez-Peña
BACKGROUND AND OBJECTIVE: To facilitate routine analysis and to improve the reproducibility of the results, next-generation sequencing (NGS) analysis requires intuitive, efficient and integrated data processing pipelines. METHODS: We have selected well-established software to construct a suite of automated and parallelized workflows to analyse NGS data for DNA-seq (single-nucleotide variants (SNVs) and indels), CNA-seq, bisulfite-seq and ChIP-seq experiments. RESULTS: Here, we present RUbioSeq+, an updated and extended version of RUbioSeq, a multiplatform application that incorporates a suite of automated and parallelized workflows to analyse NGS data...
January 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/27873319/lung-neuroendocrine-tumours-deep-sequencing-of-the-four-who-histotypes-reveals-chromatin-remodelling-genes-as-major-players-and-a-prognostic-role-for-tert-rb1-men1-and-kmt2d
#5
Michele Simbolo, Andrea Mafficini, Katarzyna O Sikora, Matteo Fassan, Stefano Barbi, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Federica Grillo, Caterina Vicentini, Roberto Ferrara, Sara Pilotto, Federico Davini, Giuseppe Pelosi, Rita T Lawlor, Marco Chilosi, Giampaolo Tortora, Emilio Bria, Gabriella Fontanini, Marco Volante, Aldo Scarpa
Next-generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours (LNET) comprising the 4 WHO classification categories: 53 typical carcinoid (TC), 35 atypical carcinoid (AC), 27 large cell neuroendocrine carcinoma (LCNEC), and 33 small cell lung carcinoma (SCLC). A discovery screen was conducted on 46 samples using whole-exome sequencing and high-coverage targeted sequencing of 418 genes. Eighty-eight recurrently mutated genes from both the discovery screen and current literature were verified in the 46 cases of the discovery screen and validated on additional 102 LNET by targeted NGS, and their prevalence was evaluated on the whole series...
November 22, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27869802/molecular-analysis-of-circulating-tumor-cells-identifies-distinct-copy-number-profiles-in-patients-with-chemosensitive-and-chemorefractory-small-cell-lung-cancer
#6
Louise Carter, Dominic G Rothwell, Barbara Mesquita, Christopher Smowton, Hui Sun Leong, Fabiola Fernandez-Gutierrez, Yaoyong Li, Deborah J Burt, Jenny Antonello, Christopher J Morrow, Cassandra L Hodgkinson, Karen Morris, Lynsey Priest, Mathew Carter, Crispin Miller, Andrew Hughes, Fiona Blackhall, Caroline Dive, Ged Brady
In most patients with small-cell lung cancer (SCLC)-a metastatic, aggressive disease-the condition is initially chemosensitive but then relapses with acquired chemoresistance. In a minority of patients, however, relapse occurs within 3 months of initial treatment; in these cases, disease is defined as chemorefractory. The molecular mechanisms that differentiate chemosensitive from chemorefractory disease are currently unknown. To identify genetic features that distinguish chemosensitive from chemorefractory disease, we examined copy-number aberrations (CNAs) in circulating tumor cells (CTCs) from pretreatment SCLC blood samples...
November 21, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27863505/a-genomic-case-study-of-desmoplastic-small-round-cell-tumor-comprehensive-analysis-reveals-insights-into-potential-therapeutic-targets-and-development-of-a-monitoring-tool-for-a-rare-and-aggressive-disease
#7
Elisa Napolitano Ferreira, Bruna Durães Figueiredo Barros, Jorge Estefano de Souza, Renan Valieris Almeida, Giovana Tardin Torrezan, Sheila Garcia, Ana Cristina Victorino Krepischi, Celso Abdon Lopes de Mello, Isabela Werneck da Cunha, Clóvis Antonio Lopes Pinto, Fernando Augusto Soares, Emmanuel Dias-Neto, Ademar Lopes, Sandro José de Souza, Dirce Maria Carraro
BACKGROUND: Genome-wide profiling of rare tumors is crucial for improvement of diagnosis, treatment, and, consequently, achieving better outcomes. Desmoplastic small round cell tumor (DSRCT) is a rare type of sarcoma arising from mesenchymal cells of abdominal peritoneum that usually develops in male adolescents and young adults. A specific translocation, t(11;22)(p13;q12), resulting in EWS and WT1 gene fusion is the only recurrent molecular hallmark and no other genetic factor has been associated to this aggressive tumor...
November 18, 2016: Human Genomics
https://www.readbyqxmd.com/read/27856756/global-analysis-of-somatic-structural-genomic-alterations-and-their-impact-on-gene-expression-in-diverse-human-cancers
#8
Babak Alaei-Mahabadi, Joydeep Bhadury, Joakim W Karlsson, Jonas A Nilsson, Erik Larsson
Tumor genomes are mosaics of somatic structural variants (SVs) that may contribute to the activation of oncogenes or inactivation of tumor suppressors, for example, by altering gene copy number amplitude. However, there are multiple other ways in which SVs can modulate transcription, but the general impact of such events on tumor transcriptional output has not been systematically determined. Here we use whole-genome sequencing data to map SVs across 600 tumors and 18 cancers, and investigate the relationship between SVs, copy number alterations (CNAs), and mRNA expression...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27852697/chromosomal-instability-in-cell-free-dna-as-a-highly-specific-biomarker-for-detection-of-ovarian-cancer-in-women-with-adnexal-masses
#9
Adriaan Vanderstichele, Pieter Busschaert, Dominiek Smeets, Chiara Landolfo, Els Van Nieuwenhuysen, Karin Leunen, Patrick Neven, Frederic Amant, Sven Mahner, Elena Ioana Braicu, Robert Zeilinger, An Coosemans, Dirk Timmerman, Diether Lambrechts, Ignace Vergote
PURPOSE: Chromosomal instability is a hallmark of ovarian cancer. Here, we explore copy number alteration (CNA) profiling in cell-free DNA as a potential biomarker to detect malignancy in patients presenting with an adnexal mass. EXPERIMENTAL DESIGN: We prospectively enrolled 68 patients with an adnexal mass, of which 57 were diagnosed with invasive or borderline carcinoma and 11 with benign disease. Cell-free DNA was extracted from plasma and analyzed by low-coverage whole-genome sequencing...
November 14, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27846907/copy-number-analysis-by-low-coverage-whole-genome-sequencing-using-ultra-low-input-dna-from-formalin-fixed-paraffin-embedded-tumor-tissue
#10
Tanjina Kader, David L Goode, Stephen Q Wong, Jacquie Connaughton, Simone M Rowley, Lisa Devereux, David Byrne, Stephen B Fox, Gisela Mir Arnau, Richard W Tothill, Ian G Campbell, Kylie L Gorringe
Unlocking clinically translatable genomic information, including copy number alterations (CNA), from formalin-fixed paraffin-embedded (FFPE) tissue is challenging due to low yields and degraded DNA. We describe a robust, cost-effective low-coverage whole genome sequencing (LC WGS) method for CNA detection using 5 ng of FFPE-derived DNA. CN profiles using 100 ng or 5 ng input DNA were highly concordant and comparable with molecular inversion probe (MIP) array profiles. LC WGS improved CN profiles of samples that performed poorly using MIP arrays...
November 15, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27845595/cna-loaded-plga-nanoparticles-improve-humoral-response-against-s-aureus-mediated-infections-in-a-mouse-model-subcutaneous-vs-nasal-administration-strategy
#11
I Genta, C Colonna, B Conti, P Caliceti, S Salmaso, P Speziale, G Pietrocola, E Chiesa, T Modena, R Dorati
The aim of this work was the assessment of the "in vivo" immune response of a poly(lactide-co-glycolide) based nanoparticulate adjuvant for a sub-unit vaccine, namely a purified recombinant collagen binding bacterial adhesion fragment (CNA19), against S. aureus-mediated infections. "In vivo" immunogenicity studies were performed on mice: immunization protocols encompassed subcutaneous and intranasal administration of CNA19 formulated as nanoparticles (NPs) and furthermore CNA19 loaded NPs formulated in a set-up thermosetting chitosan-β-glycerolphosphate (chitosan-β-GP) solution for intranasal route in order to extend antigen exposure to nasal mucosa...
November 15, 2016: Journal of Microencapsulation
https://www.readbyqxmd.com/read/27831464/a-network-of-epigenetic-modifiers-and-dna-repair-genes-controls-tissue-specific-copy-number-alteration-preference
#12
Dina Cramer, Luis Serrano, Martin H Schaefer
Copy number alterations (CNAs) in cancer patients show a large variability in their number, length and position, but the sources of this variability are not known. CNA number and length are linked to patient survival, suggesting clinical relevance. We have identified genes that tend to be mutated in samples that have few or many CNAs, which we term CONIM genes (COpy Number Instability Modulators). CONIM proteins cluster into a densely connected subnetwork of physical interactions and many of them are epigenetic modifiers...
November 10, 2016: ELife
https://www.readbyqxmd.com/read/27798635/platform-independent-genome-wide-pattern-of-dna-copy-number-alterations-predicting-astrocytoma-survival-and-response-to-treatment-revealed-by-the-gsvd-formulated-as-a-comparative-spectral-decomposition
#13
Katherine A Aiello, Orly Alter
We use the generalized singular value decomposition (GSVD), formulated as a comparative spectral decomposition, to model patient-matched grades III and II, i.e., lower-grade astrocytoma (LGA) brain tumor and normal DNA copy-number profiles. A genome-wide tumor-exclusive pattern of DNA copy-number alterations (CNAs) is revealed, encompassed in that previously uncovered in glioblastoma (GBM), i.e., grade IV astrocytoma, where GBM-specific CNAs encode for enhanced opportunities for transformation and proliferation via growth and developmental signaling pathways in GBM relative to LGA...
2016: PloS One
https://www.readbyqxmd.com/read/27798063/diversity-of-species-and-antimicrobial-resistance-determinants-of-staphylococci-in-superficial-waters-in-spain
#14
Paula Gómez, Cristina Casado, Yolanda Sáenz, Laura Ruiz-Ripa, Vanesa Estepa, Myriam Zarazaga, Carmen Torres
The objectives were to determine the presence and diversity of staphylococcal species in surface waters in La Rioja region (Spain), and to characterize recovered isolates. Staphylococci were detected in 42 of 47 evaluable samples, and 72 isolates were obtained, of which 13 were coagulase-positive (CoPS) and 59 were coagulase-negative (CoNS). Twelve CoPS were identified as S. aureus and typed as follows (number of strains): t002/t502/ST5 (four), t10668/ST425 (one), t10712//ST1643 (one), t843/ST130 (one), t10855/ST2461 (one), t3369/ST2657 (one), t1166/ST133 (one), t8083/ST2049 (one) and t045/ST2460 (one); and one as S...
January 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/27795393/mechanical-strength-and-inhibition-of-the-staphylococcus-aureus-collagen-binding-protein-cna
#15
Philippe Herman-Bausier, Claire Valotteau, Giampiero Pietrocola, Simonetta Rindi, David Alsteens, Timothy J Foster, Pietro Speziale, Yves F Dufrêne
: The bacterial pathogen Staphylococcus aureus expresses a variety of cell surface adhesion proteins that bind to host extracellular matrix proteins. Among these, the collagen (Cn)-binding protein Cna plays important roles in bacterium-host adherence and in immune evasion. While it is well established that the A region of Cna mediates ligand binding, whether the repetitive B region has a dedicated function is not known. Here, we report the direct measurement of the mechanical strength of Cna-Cn bonds on living bacteria, and we quantify the antiadhesion activity of monoclonal antibodies (MAbs) targeting this interaction...
October 25, 2016: MBio
https://www.readbyqxmd.com/read/27783674/kinetic-controlled-tag-catcher-interactions-for-directed-covalent-protein-assembly
#16
Lee Ling Tan, Shawn S Hoon, Fong T Wong
Over the last few years, a number of different protein assembly strategies have been developed, greatly expanding the toolbox for controlling macromolecular assembly. One of the most promising developments is a rapid protein ligation approach using a short polypeptide SpyTag and its partner, SpyCatcher derived from Streptococcus pyogenes fibronectin-binding protein, FbaB. To extend this technology, we have engineered and characterized a new Tag-Catcher pair from a related fibronectin-binding protein in Streptococcus dysgalactiae...
2016: PloS One
https://www.readbyqxmd.com/read/27767176/sumoylation-independent-activation-of-calcineurin-nfat-signaling-via-sumo2-mediates-cardiomyocyte-hypertrophy
#17
Alexander Bernt, Ashraf Y Rangrez, Matthias Eden, Andreas Jungmann, Sylvia Katz, Claudia Rohr, Oliver J Müller, Hugo A Katus, Samuel T Sossalla, Tatjana Williams, Oliver Ritter, Derk Frank, Norbert Frey
The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10(7) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27761465/in-vitro-and-in-vivo-biofilm-characterization-of-methicillin-resistant-staphylococcus-aureus-from-patients-associated-with-pharyngitis-infection
#18
Shanmugaraj Gowrishankar, Arumugam Kamaladevi, Krishnaswamy Balamurugan, Shunmugiah Karutha Pandian
The present investigation was deliberately aimed at evaluating the biofilm-forming ability of 63 clinical MRSA isolates recovered from pharyngitis patients through different phenotypic assays. The molecular detection of adhesion (icaA/icaD/icaB/icaC), adhesins (fnbA/fnbB, clfA, and cna), staphylococcal accessory regulator (sarA), and α-toxin (hla) genes was done by employing polymerase chain reaction (PCR). Out of 63 isolates, 49 (77.8%) were found slime positive by the Congo red agar (CRA) method and 44 (69...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27733115/cnara-reliability-assessment-for-genomic-copy-number-profiles
#19
Ni Ai, Haoyang Cai, Caius Solovan, Michael Baudis
BACKGROUND: DNA copy number profiles from microarray and sequencing experiments sometimes contain wave artefacts which may be introduced during sample preparation and cannot be removed completely by existing preprocessing methods. Besides, large derivative log ratio spread (DLRS) of the probes correlating with poor DNA quality is sometimes observed in genome screening experiments and may lead to unreliable copy number profiles. Depending on the extent of these artefacts and the resulting misidentification of copy number alterations/variations (CNA/CNV), it may be desirable to exclude such samples from analyses or to adapt the downstream data analysis strategy accordingly...
October 12, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27729614/genomic-profiling-of-stage-ii-and-iii-colon-cancers-reveals-apc-mutations-to-be-associated-with-survival-in-stage-iii-colon-cancer-patients
#20
Evert van den Broek, Oscar Krijgsman, Daoud Sie, Marianne Tijssen, Sandra Mongera, Mark A van de Wiel, Eric J. Belt, Sjoerd H den Uil, Herman Bril, Hein B A C Stockmann, Bauke Ylstra, Beatriz Carvalho, Gerrit A Meijer, Remond J A Fijneman
Tumor profiling of DNA alterations, i.e. gene point mutations, somatic copy number aberrations (CNAs) and structural variants (SVs), improves insight into the molecular pathology of cancer and clinical outcome. Here, associations between genomic aberrations and disease recurrence in stage II and III colon cancers were investigated. A series of 114 stage II and III microsatellite stable colon cancer samples were analyzed by high-resolution array-comparative genomic hybridization (array-CGH) to detect CNAs and CNA-associated chromosomal breakpoints (SVs)...
October 6, 2016: Oncotarget
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