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Integrative genomics cancer

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https://www.readbyqxmd.com/read/29027401/identification-of-dna-methylation-associated-gene-signatures-in-endometrial-cancer-via-integrated-analysis-of-dna-methylation-and-gene-expression-systematically
#1
Chuandi Men, Hongjuan Chai, Xumin Song, Yue Li, Huawen Du, Qing Ren
OBJECTIVE: Endometrial cancer (EC) is a common gynecologic cancer worldwide. However, the pathogenesis of EC has not been epigenetically elucidated. Here, this study aims to describe the DNA methylation profile and identify favorable gene signatures highly associated with aberrant DNA methylation changes in EC. METHODS: The data regarding DNA methylation and gene expression were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially methylated CpG sites (DMCs), differentially methylated regions (DMRs), and differentially expressed genes (DEGs) were identified, and the relationship between the 2 omics was further analyzed...
November 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29027233/dysregulated-cellular-functions-and-cell-stress-pathways-provide-critical-cues-for-activating-and-targeting-natural-killer-cells-to-transformed-and-infected-cells
#2
REVIEW
David H Raulet, Assaf Marcus, Laurent Coscoy
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29021240/integrative-genome-analysis-of-somatic-p53-mutant-osteosarcomas-identifies-ets2-dependent-regulation-of-small-nucleolar-rnas-by-mutant-p53-protein
#3
Rasoul Pourebrahim, Yun Zhang, Bin Liu, Ruli Gao, Shunbin Xiong, Patrick P Lin, Mark J McArthur, Michael C Ostrowski, Guillermina Lozano
TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable somatic osteosarcoma mouse model that is initiated with either a single p53 mutation (p53R172H) or p53 loss in osteoblasts. Our study confirmed that p53 mutant mice developed osteosarcomas with increased metastasis as compared with p53-null mice...
October 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/29019020/pharmacodynamic-and-pharmacokinetic-markers-for-anti-angiogenic-cancer-therapy-implications-for-dosing-and-selection-of-patients
#4
Matteo Morotti, Prashanth Hari Dass, Adrian L Harris, Simon Lord
Angiogenesis is integral to tumour growth and invasion, and is a key target for cancer therapeutics. However, for many of the licensed indications, only a modest clinical benefit has been observed for both monoclonal antibody and small-molecule tyrosine kinase inhibitor anti-angiogenic therapy. Pre-clinical and clinical studies have attempted to evaluate circulating, imaging, genomic, pharmacokinetic, and pharmacodynamic markers that may aid both the selection of patients for treatment and define dosing. Correct dosing is likely to be critical in the context of vascular normalization to allow better delivery of concomitant anti-cancer therapy and novel imaging techniques hold much promise in the early evaluation of pharmacodynamic response to improve efficacy...
October 10, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29018224/integrative-analysis-of-genomic-and-epigenomic-regulation-of-the-transcriptome-in-liver-cancer
#5
Hyun Goo Woo, Ji-Hye Choi, Sarah Yoon, Byul A Jee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Yoon Jun Kim
Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of DNA copy numbers and DNA methylation. Transcriptomic deregulation by these aberrations plays key driver roles in heterogeneous progression of cancers. Here, we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes and the methylation-correlated expression (METcor) genes are co-regulated significantly...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018056/functional-genomics-approach-identifies-novel-signaling-regulators-of-tgf%C3%AE-ectodomain-shedding
#6
Jennifer L Wilson, Eirini Kefalogianni, Lauren Stopfer, Christina Harrison, Venkata S Sabbisetti, Ernest Fraenkel, Douglas A Lauffenburger, Andreas Herrlich
Ectodomain shedding of cell-surface precursor proteins by metalloproteases generates important cellular signaling molecules. Of importance for disease is the release of ligands that activate the epidermal growth factor receptor (EGFR), such as transforming growth factor-alpha (TGFA), which is mostly carried out by ADAM17 [a member of the A-disintegrin and metalloprotease (ADAM) domain family]. EGFR ligand shedding has been linked to many diseases, in particular cancer development, growth and metastasis, as well as resistance to cancer therapeutics...
October 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29017571/dna-damage-response-and-cancer-therapeutics-through-the-lens-of-the-fanconi-anemia-dna-repair-pathway
#7
REVIEW
Sonali Bhattacharjee, Saikat Nandi
Fanconi Anemia (FA) is a rare, inherited genomic instability disorder, caused by mutations in genes involved in the repair of interstrand DNA crosslinks (ICLs). The FA signaling network contains a unique nuclear protein complex that mediates the monoubiquitylation of the FANCD2 and FANCI heterodimer, and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. FA proteins act at different steps of ICL repair in sensing, recognition and processing of DNA lesions...
October 10, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28994108/value-of-a-molecular-screening-program-to-support-clinical-trial-enrollment-in-asian-cancer-patients-the-integrated-molecular-analysis-of-cancer-imac-study
#8
Valerie Heong, Nicholas L Syn, Xiao Wen Lee, Nur Sabrina Sapari, Xue Qing Koh, Zul Fazreen Adam Isa, Joey Sy Lim, Diana Lim, Brendan Pang, Yee Liang Thian, Lai Kuan Ng, Andrea L Wong, Ross Andrew Soo, Wei Peng Yong, Cheng Ean Chee, Soo-Chin Lee, Boon-Cher Goh, Richie Soong, David S P Tan
The value of precision oncology initiatives in Asian contexts remains unresolved. Here we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker-driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next-generation sequencing (NGS) and routine clinicopathological assays such as immunohistochemistry, copy number analysis, and in situ hybridization tests were performed on tumor samples...
October 9, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28990284/the-oncogenic-role-of-epstein-barr-virus-encoded-micrornas-in-epstein-barr-virus-associated-gastric-carcinoma
#9
REVIEW
Jinglin Zhang, Tingting Huang, Yuhang Zhou, Alfred S L Cheng, Jun Yu, Ka Fai To, Wei Kang
Epstein-Barr virus (EBV) infection is detected in various epithelial malignancies, such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV comprises some unique molecular features and encodes viral genes and microRNAs (miRNAs) by its own DNA sequence. EBV genes are required to maintain latency and contribute to oncogenic property. miRNAs encoded by EBV have been shown to contribute to initiation and progression of EBV-related malignancies. By a number of genomic profiling studies, some EBV miRNAs were confirmed to be highly expressed in EBV-associated gastric cancer (EBVaGC) samples and cell lines...
October 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28990079/effect-of-mir%C3%A2-146a%C3%A2-5p-on-tumor-growth-in-nsclc-using-chick-chorioallantoic-membrane-assay-and-bioinformatics-investigation
#10
Wen-Ting Huang, Wei-Luan Cen, Rong-Quan He, You Xie, Yu Zhang, Ping Li, Ting-Qing Gan, Gang Chen, Xiao-Hua Hu
Our previous study demonstrated that the expression of miR‑146a‑5p was downregulated in non‑small cell lung cancer (NSCLC) tissue, which affected the progression and prognosis of patients with NSCLC. Thus, the present study was conducted to investigate the functional mechanism of miR‑146a‑5p in tumorigenesis and angiogenesis in NSCLC. Following the construction of a H460 NSCLC cell line in which miR‑146a‑5p was overexpressed via lentivirus transduction, the NSCLC chick embryo chorioallantoic membrane (CAM) model was established by transplanting miR‑146a‑5p‑overexpressing NSCLC cells into the CAM...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28990063/bioinformatics-analysis-of-gene-expression-data-for-the-identification-of-critical-genes-in-breast-invasive-carcinoma
#11
Yi Li, Yongsheng Wang
Gene expression data were analyzed in order to identify critical genes in breast invasive carcinoma (BRCA). Data from 1,073 BRCA samples and 99 normal samples were analyzed, which were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were identified using the significance analysis of microarrays method and a functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. Relevant microRNAs (miRNAs), transcription factors (TFs) and associated small molecule drugs were revealed by Fisher's exact test...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28989987/towards-a-better-cancer-precision-medicine-systems-biology-meets-immunotherapy
#12
Bhavneet Bhinder, Olivier Elemento
Systems biology approaches that embrace the complexity of cancer are starting to gain traction in the development of new anticancer therapeutic strategies. In this review we describe how genomic analyses are helping improve our understanding of response to immunotherapy, a front-runner in cancer treatment. We argue that systems-level approaches are needed to help understand the concerted impact of tumor-specific and immune-specific molecular features on clinical outcomes, predict responders and unravel the complexity of tumor ecosystems...
April 2017: Current opinion in systems biology
https://www.readbyqxmd.com/read/28987047/-epidemiology-and-risk-factors-of-hepatocellular-carcinoma
#13
REVIEW
Agnieszka Budny, Piotr Kozłowski, Marzena Kamińska, Małgorzata Jankiewicz, Agnieszka Kolak, Bożena Budny, Witold Budny, Joanna Niemunis-Sawicka, Grzegorz Szczypiór, Bartosz Kurniawka, Franciszek Burdan
Primary liver neoplasms occurs relatively rarely in Poland. The most frequently occurring type of cancer is hepatocellular carcinoma (HCC), which globally constitutes 7% of all the occurrences of cancer. The incidence increases with age and is the highest in patients around the age of 70. It also varies significantly depending on the geographic location. The main factors that cause HCC are infection of HBV and HCV, whose genome integrates into the DNA of the host, causing mutations. The other factors include excessive alcohol consumption, contact or consumption of Aspergillus toxins as well as various metabolic disorders, such as α1-antitrypsin deficiency, hemochromatosis, tyrosinemia, porphyria, von Gierke disease and in person with gene mutation p...
September 29, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28985359/parp1-controls-klf4-mediated-telomerase-expression-in-stem-cells-and-cancer-cells
#14
Meng-Hsun Hsieh, Yi-Ting Chen, You-Tzung Chen, Yi-Hsuan Lee, Jean Lu, Chung-Liang Chien, Hsin-Fu Chen, Hong-Nerng Ho, Chia-Jung Yu, Zhao-Qi Wang, Shu-Chun Teng
Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) and implicated in controlling genome integrity, cancer formation and stemness. Previous studies identified that Krüppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression and contributes to the maintenance of self-renewal in ESCs. However, little is known about how KLF4 regulates TERT expression. Here, we discover poly(ADP-ribose) polymerase 1 (PARP1) as a novel KLF4-interacting partner. Knockdown of PARP1 reduces TERT expression and telomerase activity not only in cancer cells, but also in human and mouse ESCs...
August 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28984675/feasibility-of-prostate-paxgene-fixation-for-molecular-research-and-diagnostic-surgical-pathology-comparison-of-matched-fresh-frozen-ffpe-and-pfpe-tissues
#15
Gunilla Högnäs, Kati Kivinummi, Heini M L Kallio, Reija Hieta, Pekka Ruusuvuori, Antti Koskenalho, Juha Kesseli, Teuvo L J Tammela, Jarno Riikonen, Joanna Ilvesaro, Saara Kares, Pasi P Hirvikoski, Marita Laurila, Tuomas Mirtti, Matti Nykter, Paula M Kujala, Tapio Visakorpi, Teemu Tolonen, G Steven Bova
Advances in prostate cancer biology and diagnostics are dependent upon high-fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin-embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied...
October 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28984195/md-miner-a-network-based-approach-for-personalized-drug-repositioning
#16
Haoyang Wu, Elise Miller, Denethi Wijegunawardana, Kelly Regan, Philip R O Payne, Fuhai Li
BACKGROUND: Due to advances in next generation sequencing technologies and corresponding reductions in cost, it is now attainable to investigate genome-wide gene expression and variants at a patient-level, so as to better understand and anticipate heterogeneous responses to therapy. Consequently, it is feasible to inform personalized drug treatment decisions using personal genomics data. However, these efforts are limited due to a lack of reliable computational approaches for predicting effective drugs for individual patients...
October 3, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28983581/bioinformatics-analysis-of-fibroblasts-exposed-to-tgf%C3%A2-%C3%AE-at-the-early-proliferation-phase-of-wound-repair
#17
Bobin Mi, Guohui Liu, Wu Zhou, Huijuan Lv, Kun Zha, Yi Liu, Qipeng Wu, Jing Liu
The aim of the current study was to identify gene signatures during the early proliferation stage of wound repair and the effect of TGF‑β on fibroblasts and reveal their potential mechanisms. The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co‑expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool...
September 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28982688/deep-learning-based-multi-omics-integration-robustly-predicts-survival-in-liver-cancer
#18
Kumardeep Chaudhary, Olivier B Poirion, Liangqun Lu, Lana X Garmire
Identifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill in this gap, we present a deep learning (DL) based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We build the DL based, survival-sensitive model on 360 HCC patients' data using RNA-seq, miRNA-seq and methylation data from TCGA, which predicts prognosis as good as an alternative model where genomics and clinical data are both considered...
October 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28982488/twenty-first-century-precision-medicine-in-oncology-genomic-profiling-in-patients-with-cancer
#19
REVIEW
Mitesh J Borad, Patricia M LoRusso
The advent of next-generation sequencing has accelerated the implementation of genomic profiling in the care and management of patients with cancer. Initial efforts have focused on target identification in patients with advanced cancer. Prognostication, resistance detection, disease monitoring, and early detection efforts are also underway. This review highlights some of the challenges in this evolving space. This includes choosing between gene-panel and comprehensive approaches, DNA and transcriptome data integration, reduction of false-positive variants, addressing tumor heterogeneity, establishment of workflows to address unsolicited findings, and data sharing and privacy concerns...
October 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28978832/clinical-sequencing-in-leukemia-with-the-assistance-of-artificial-intelligence
#20
Arinobu Tojo
Next generation sequencing (NGS) of cancer genomes is now becoming a prerequisite for accurate diagnosis and proper treatment in clinical oncology. Because the genomic regions for NGS expand from a certain set of genes to the whole exome or whole genome, the resulting sequence data becomes incredibly enormous and makes it quite laborious to translate the genomic data into medicine, so-called annotation and curation. We organized a clinical sequencing team and established a bidirectional (bed-to-bench and bench-to-bed) system to integrate clinical and genomic data for hematological malignancies...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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