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Integrative genomics cancer

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https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#1
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28206814/biomarkers-in-tumor-microenvironment-upregulation-of-fibroblast-activation-protein-%C3%AE-correlates-with-gastric-cancer-progression-and-poor-prognosis
#2
Mengmou Hu, Chengjia Qian, Ziwei Hu, Bojian Fei, Haibo Zhou
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recent evidence points to importance of cross talk between cancer cells and the surrounding stroma on gastric cancer progression. Tumor microenvironment biomarkers thus represent a new opportunity for diagnostics innovation. Reactive stromal fibroblasts selectively express the fibroblast activation protein alpha (FAP-α), a homodimeric integral membrane gelatinase that belongs to the serine protease family. We report here that FAP-α expression is significantly elevated in gastric cancer samples by more than fivefold (p < 0...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28205554/the-oncoppi-network-of-cancer-focused-protein-protein-interactions-to-inform-biological-insights-and-therapeutic-strategies
#3
Zenggang Li, Andrei A Ivanov, Rina Su, Valentina Gonzalez-Pecchi, Qi Qi, Songlin Liu, Philip Webber, Elizabeth McMillan, Lauren Rusnak, Cau Pham, Xiaoqian Chen, Xiulei Mo, Brian Revennaugh, Wei Zhou, Adam Marcus, Sahar Harati, Xiang Chen, Margaret A Johns, Michael A White, Carlos Moreno, Lee A D Cooper, Yuhong Du, Fadlo R Khuri, Haian Fu
As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes. PPI hubs reveal new regulatory mechanisms for cancer genes like MYC, STK11, RASSF1 and CDK4...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28205537/her2-alterations-in-muscle-invasive-bladder-cancer-patient-selection-beyond-protein-expression-for-targeted-therapy
#4
Bernhard Kiss, Alexander W Wyatt, James Douglas, Veronika Skuginna, Fan Mo, Shawn Anderson, Diana Rotzer, Achim Fleischmann, Vera Genitsch, Tetsutaro Hayashi, Maja Neuenschwander, Christine Buerki, Elai Davicioni, Colin Collins, George N Thalmann, Peter C Black, Roland Seiler
Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205536/genomic-structure-and-insertion-sites-of-helicobacter-pylori-prophages-from-various-geographical-origins
#5
Filipa F Vale, Alexandra Nunes, Mónica Oleastro, João P Gomes, Daniel A Sampaio, Raquel Rocha, Jorge M B Vítor, Lars Engstrand, Ben Pascoe, Elvire Berthenet, Samuel K Sheppard, Matthew D Hitchings, Francis Mégraud, Jamuna Vadivelu, Philippe Lehours
Helicobacter pylori genetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements of H. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found in H. pylori isolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6-33.0 Kbp, consisting of 27-39 open reading frames...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202002/viral-e6-is-overexpressed-via-high-viral-load-in-invasive-cervical-cancer-with-episomal-hpv16
#6
Die Hong, Jia Liu, Ying Hu, Xiaonan Lu, Baohua Li, Yang Li, Dongxiao Hu, Weiguo Lu, Xing Xie, Xiaodong Cheng
BACKGROUND: The integration of HR-HPV genome into host DNA is regarded as a key step for the development of cervical cancer. However, HR-HPV genome indeed exists as episome except for integrant. It may be alternative mechanisms in episome-associated carcinogenesis, although, by which HPV 16 episome induces cervical carcinogenesis is unclear now. METHODS: Ninety-three invasive cervical cancer tissues with HPV16 positive were collected. Viral physical status was calculated from comparing E2 to E6-copies and detection of viral load was made with realtime-PCR using copy numbers of E6...
February 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28199214/base-excision-repair-of-oxidative-dna-damage-from-mechanism-to-disease
#7
Amy M Whitaker, Matthew A Schaich, Mallory S Smith, Tony S Flynn, Bret D Freudenthal
Reactive oxygen species continuously assault the structure of DNA resulting in oxidation and fragmentation of the nucleobases. Both oxidative DNA damage itself and its repair mediate the progression of many prevalent human maladies. The major pathway tasked with removal of oxidative DNA damage, and hence maintaining genomic integrity, is base excision repair (BER). The aphorism that structure often dictates function has proven true, as numerous recent structural biology studies have aided in clarifying the molecular mechanisms used by key BER enzymes during the repair of damaged DNA...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28199197/childhood-cancers-and-systems-medicine
#8
William L Stone, Kathryn J Klopfenstein, M J Hajianpour, Marcela I Popescu, Cathleen M Cook, Koymangalath Krishnan
Despite major advances in treatment, pediatric cancers in the 5-16 age group remain the most common cause of disease death, and one out of eight children with cancer will not survive. Among children that do survive, some 60% suffer from late effects such as cancer recurrence and increased risk of obesity. This paper will provide a broad overview of pediatric oncology in the context of systems medicine. Systems medicine utilizes an integrative approach that relies on patient information gained from omics technology...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198679/detecting-discordance-enrichment-among-a-series-of-two-sample-genome-wide-expression-data-sets
#9
Yinglei Lai, Fanni Zhang, Tapan K Nayak, Reza Modarres, Norman H Lee, Timothy A McCaffrey
BACKGROUND: With the current microarray and RNA-seq technologies, two-sample genome-wide expression data have been widely collected in biological and medical studies. The related differential expression analysis and gene set enrichment analysis have been frequently conducted. Integrative analysis can be conducted when multiple data sets are available. In practice, discordant molecular behaviors among a series of data sets can be of biological and clinical interest. METHODS: In this study, a statistical method is proposed for detecting discordance gene set enrichment...
January 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28197908/the-molecular-interface-between-the-sumo-and-ubiquitin-systems
#10
Jeff L Staudinger
The SUMO conjugation system regulates key cellular processes including cell growth, division, mitochondrial dynamics, and the maintenance of genome stability in eukaryotic cells. The ubiquitin conjugation system regulates the stability of a myriad of vital cellular proteins in a signal-dependent manner by targeting them for destruction via the proteasome-mediated degradation pathway. Recent research efforts have unveiled an evolutionarily conserved and fundamental molecular interface between the SUMO and ubiquitin systems...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28197536/proteomics-reveals-a-new-dna-repair-factor-involved-in-dna-damage-signaling
#11
Markus Räschle
Stalling of the DNA replication machinery activates the ATR checkpoint kinase, which coordinates the cellular responses to replication stress. New studies identify a novel ATR activator, ETAA1, which is indispensable for the maintenance of genome integrity. Dysregulation of ETAA1 may contribute to the development of pancreatic cancer.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28196964/fancd2-binds-human-papillomavirus-genomes-and-associates-with-a-distinct-set-of-dna-repair-proteins-to-regulate-viral-replication
#12
Chelsey C Spriggs, Laimonis A Laimins
The life cycle of human papillomavirus (HPV) is dependent on the differentiation state of its host cell. HPV genomes are maintained as low-copy episomes in basal epithelial cells and amplified to thousands of copies per cell in differentiated layers. Replication of high-risk HPVs requires the activation of the ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) DNA repair pathways. The Fanconi anemia (FA) pathway is a part of the DNA damage response and mediates cross talk between the ATM and ATR pathways...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28196074/clinical-applicability-and-cost-of-a-46-gene-panel-for-genomic-analysis-of-solid-tumours-retrospective-validation-and-prospective-audit-in-the-uk-national-health-service
#13
Angela Hamblin, Sarah Wordsworth, Jilles M Fermont, Suzanne Page, Kulvinder Kaur, Carme Camps, Pamela Kaisaki, Avinash Gupta, Denis Talbot, Mark Middleton, Shirley Henderson, Anthony Cutts, Dimitrios V Vavoulis, Nick Housby, Ian Tomlinson, Jenny C Taylor, Anna Schuh
BACKGROUND: Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28194491/-merkel-cell-carcinoma-cutaneous-manifestation-of-a-highly-malignant-pre-pro-b%C3%A2-cell-neoplasia-novel-concept-about-the-cellular-origin-of-merkel-cell-carcinoma
#14
REVIEW
C M Sauer, E Chteinberg, D Rennspiess, A K Kurz, A Zur Hausen
Merkel cell carcinoma (MCC) is a relatively rare but highly malignant non-melanoma skin cancer of the elderly and immunosuppressed patients. The discovery of the Merkel cell polyomavirus (MCPyV) in 2008 significantly impacted the understanding of the etiopathogenesis of MCC. MCPyV is clonally integrated into the MCC genome and approximately 80% of MCC are MCPyV-positive. Recent results of clinical trials using blockade of the PD-1 immune modulatory pathway are promising for the future treatment of MCC. Despite this major progress of the past few years, the cellular origin of MCC still remains obscure...
February 13, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28192596/integrating-next-generation-sequencing-into-pediatric-oncology-practice-an-assessment-of-physician-confidence-and-understanding-of-clinical-genomics
#15
Liza-Marie Johnson, Jessica M Valdez, Emily A Quinn, April D Sykes, Rose B McGee, Regina Nuccio, Stacy J Hines-Dowell, Justin N Baker, Chimene Kesserwan, Kim E Nichols, Belinda N Mandrell
BACKGROUND: The incorporation of genomic testing to identify targetable somatic alterations and predisposing germline mutations into the clinical setting is becoming increasingly more common. Despite its potential usefulness, to the authors' knowledge physician confidence with regard to understanding and applying genomic testing remains unclear, particularly within the realm of pediatric oncology. METHODS: Before initiating an institutional feasibility study regarding the integration of clinical genomic testing, the authors surveyed pediatric oncologists regarding their confidence around understanding of genomic testing, perceived usefulness of test results, preferences around the disclosure of germline test results, and possible risks and benefits of testing...
February 13, 2017: Cancer
https://www.readbyqxmd.com/read/28187513/collaboration-to-accelerate-proteogenomics-cancer-care-the-department-of-veterans-affairs-department-of-defense-and-the-national-cancer-institute-s-applied-proteogenomics-organizational-and-learning-apollo-network
#16
L D Fiore, H Rodriguez, C D Shriver
The ability to interrogate cancer at the proteogenomic level has the potential to transform oncology care from trial-and-error treatment strategies based on the anatomy and genomic profiling of tumors to one that is precisely based on the tumor's molecular profile. The next step in the evolution of precision oncology is developing proteogenomic approaches that make no exclusive assumptions a priori as to the molecular level of the patient's disease. The DoD, VA, and NCI responded to the Cancer Moonshot initiative by linking each agency's unique capabilities in clinical and basic science, computing, and high-throughput sequencing...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187443/analysis-of-the-cancer-genome-atlas-sequencing-data-reveals-novel-properties-of-the-human-papillomavirus-16-genome-in-head-and-neck-squamous-cell-carcinoma
#17
Tara J Nulton, Amy L Olex, Mikhail Dozmorov, Iain M Morgan, Brad Windle
Human papillomavirus (HPV) DNA is detected in up to 80% of oropharyngeal carcinomas (OPC) and this HPV positive disease has reached epidemic proportions. To increase our understanding of the disease, we investigated the status of the HPV16 genome in HPV-positive head and neck cancers (HNC). Raw RNA-Seq and Whole Genome Sequence data from The Cancer Genome Atlas HNC samples were analyzed to gain a full understanding of the HPV genome status for these tumors. Several remarkable and novel observations were made following this analysis...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187428/a-novel-integrative-risk-index-of-papillary-thyroid-cancer-progression-combining-genomic-alterations-and-clinical-factors
#18
Qing Cheng, Xuechan Li, Chaitanya R Acharya, Terry Hyslop, Julie Ann Sosa
Although the majority of papillary thyroid cancer (PTC) is indolent, a subset of PTC behaves aggressively despite the best available treatment. A major clinical challenge is to reliably distinguish early on between those patients who need aggressive treatment from those who do not. Using a large cohort of PTC samples obtained from The Cancer Genome Atlas (TCGA), we analyzed the association between disease progression and multiple forms of genomic data, such as transcriptome, somatic mutations, and somatic copy number alterations, and found that genes related to FOXM1 signaling pathway were significantly associated with PTC progression...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186991/c-terminal-truncated-hepatitis-b-virus-x-protein-regulates-tumorigenicity-self-renewal-and-drug-resistance-via-stat3-nanog-signaling-pathway
#19
Rachel Hiu Ha Ching, Karen Man Fong Sze, Eunice Yuen Ting Lau, Yung-Tuen Chiu, Joyce Man Fong Lee, Irene Oi Lin Ng, Terence Kin Wah Lee
Hepatitis B virus (HBV) is a major risk factor of chronic liver disease and hepatocellular carcinoma (HCC). Random integration of HBV DNA into the host genome is frequent in HCC leading to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). C-terminally truncated HBx (HBx-ΔC) has been implicated in playing a pro-oncogenic role in hepatocarcinogenesis. However, the mechanism whereby HBx-ΔC1 contributes to hepatocarcinogenesis remains unclear. In this study, we investigated the functional role of HBx-ΔC1 in regulating liver cancer stem cell (CSC) properties...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185568/identification-of-expression-patterns-in-the-progression-of-disease-stages-by-integration-of-transcriptomic-data
#20
Sara Aibar, Maria Abaigar, Francisco Jose Campos-Laborie, Jose Manuel Sánchez-Santos, Jesus M Hernandez-Rivas, Javier De Las Rivas
BACKGROUND: In the study of complex diseases using genome-wide expression data from clinical samples, a difficult case is the identification and mapping of the gene signatures associated to the stages that occur in the progression of a disease. The stages usually correspond to different subtypes or classes of the disease, and the difficulty to identify them often comes from patient heterogeneity and sample variability that can hide the biomedical relevant changes that characterize each stage, making standard differential analysis inadequate or inefficient...
November 22, 2016: BMC Bioinformatics
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