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Cancer genomics

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https://www.readbyqxmd.com/read/28231582/radiomics-in-head-and-neck-cancer-extracting-valuable-information-from-data-beyond-recognition
#1
Kathrin Scheckenbach, Lena Colter, Martin Wagenmann
In oncology, biomarkers that describe the characteristics of a malignancy on different levels (clinical, histological, molecular) and the patient's outcome and treatment response are increasingly integrated into the clinical routine. Extensive screening tools, "omics," offer incredible opportunities and vast amounts of data. During the last years, the field of "omics" gained a new promising partner, the "radiomics." Based on radiological imaging, multiple features can be extracted and linked to clinical, genomic, and histopathological data from other sources...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28231559/prostate-cancer-heterogeneity-discovering-novel-molecular-targets-for-therapy
#2
REVIEW
Chiara Ciccarese, Francesco Massari, Roberto Iacovelli, Michelangelo Fiorentino, Rodolfo Montironi, Vincenzo Di Nunno, Francesca Giunchi, Matteo Brunelli, Giampaolo Tortora
Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies...
February 11, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#3
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231410/transcriptomic-analyses-of-rna-binding-proteins-reveal-eif3c-promotes-cell-proliferation-in-hepatocellular-carcinoma
#4
Tangjian Li, Shengli Li, Di Chen, Bing Chen, Tao Yu, Fangyu Zhao, Qifeng Wang, Ming Yao, Shenglin Huang, Zhiao Chen, Xianghuo He
RNA-binding proteins (RBPs) play fundamental roles in the RNA life cycle. The aberrant expression of RBPs is often observed in human disease, including cancer. In this study, we screened for the expression levels of 1,542 human RBPs in The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA LIHC) samples and found 92 consistently up-regulated RBP genes in HCC compared with normal samples. Additionally, we performed a Kaplan-Meier analysis and found that high expression of 15 RBP genes was associated with poor prognosis in patients with HCC...
February 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28231327/functionally-focused-algorithmic-analysis-of-high-resolution-microarray-cgh-genomic-landscapes-demonstrates-comparable-genomic-copy-number-aberrations-in-msi-and-mss-sporadic-colorectal-cancer
#5
Hamad Ali, Milad S Bitar, Ashraf Al Madhoun, Makia Marafie, Fahd Al-Mulla
Array-based comparative genomic hybridization (aCGH) emerged as a powerful technology for studying copy number variations at higher resolution in many cancers including colorectal cancer. However, the lack of standardized systematic protocols including bioinformatic algorithms to obtain and analyze genomic data resulted in significant variation in the reported copy number aberration (CNA) data. Here, we present genomic aCGH data obtained using highly stringent and functionally relevant statistical algorithms from 116 well-defined microsatellites instable (MSI) and microsatellite stable (MSS) colorectal cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28231283/rapid-evolution-of-distinct-helicobacter-pylori-subpopulations-in-the-americas
#6
Kaisa Thorell, Koji Yahara, Elvire Berthenet, Daniel J Lawson, Jane Mikhail, Ikuko Kato, Alfonso Mendez, Cosmeri Rizzato, María Mercedes Bravo, Rumiko Suzuki, Yoshio Yamaoka, Javier Torres, Samuel K Sheppard, Daniel Falush
For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28230703/omics-and-cachexia
#7
Brigitte Twelkmeyer, Nicolas Tardif, Olav Rooyackers
PURPOSE OF REVIEW: The purpose of this review is to recapture recent advances in cachexia-related diseases, mainly cancer cachexia, and treatment using genomic, transcriptomics, proteomic, and metabolomics-related techniques. RECENT FINDINGS: From recent studies in the cancer cachexia field it is clear that the tumor has a direct effect on distant organs via its secretome. The affected pathways on the other hand were largely known from earlier studies with changes in energy-related pathways (mainly lipid metabolism) and the protein degradation pathways...
February 21, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28229366/mining-cancer-transcriptomes-bioinformatic-tools-and-the-remaining-challenges
#8
Thomas Milan, Brian T Wilhelm
The development of next-generation sequencing technologies has had a profound impact on the field of cancer genomics. With the enormous quantities of data being generated from tumor samples, researchers have had to rapidly adapt tools or develop new ones to analyse the raw data to maximize its value. While much of this effort has been focused on improving specific algorithms to get faster and more precise results, the accessibility of the final data for the research community remains a significant problem. Large amounts of data exist but are not easily available to researchers who lack the resources and experience to download and reanalyze them...
February 22, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28229117/dna-methylation-data-for-identification-of-epigenetic-targets-of-resveratrol-in-triple-negative-breast-cancer-cells
#9
Rubiceli Medina-Aguilar, Carlos Pérez-Plasencia, Patricio Gariglio, Laurence A Marchat, Ali Flores-Pérez, César López-Camarillo, Jaime García Mena
Previous studies revealed that some bioactive food components have anti-cancer effects. However epigenetic effects of dietary compound resveratrol are largely unknown in breast cancer cells (M.A. Dawson, T. Kouzarides, 2012) [1]. Here we provide novel data and comparisons of DNA methylation status of promoter gene regions in response to resveratrol treatment at 24 h and 48 h versus untreated MDA-MB-231 breast cancer cells. DNA methylation changes were measured using Array-PRIMES method (aPRIMES) followed by whole-genome hybridization using human DNA methylation promoter microarray NimbleGen HG18 Refseq Promoter 3×720 K array...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28228534/topbp1-dpb11-plays-a-conserved-role-in-homologous-recombination-dna-repair-through-the-coordinated-recruitment-of-53bp1-rad9
#10
Yi Liu, José Renato Cussiol, Diego Dibitetto, Jennie Rae Sims, Shyam Twayana, Robert Samuel Weiss, Raimundo Freire, Federica Marini, Achille Pellicioli, Marcus Bustamante Smolka
Genome maintenance and cancer suppression require homologous recombination (HR) DNA repair. In yeast and mammals, the scaffold protein TOPBP1(Dpb11) has been implicated in HR, although its precise function and mechanism of action remain elusive. In this study, we show that yeast Dpb11 plays an antagonistic role in recombination control through regulated protein interactions. Dpb11 mediates opposing roles in DNA end resection by coordinating both the stabilization and exclusion of Rad9 from DNA lesions. The Mec1 kinase promotes the pro-resection function of Dpb11 by mediating its interaction with the Slx4 scaffold...
February 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#11
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#12
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28226421/opening-plenary-speaker-human-genomics-precision-medicine-and-advancing-human-health
#13
Eric D Green
Starting with the launch of the Human Genome Project in 1990, the past quarter-century has brought spectacular achievements in genomics that dramatically empower the study of human biology and disease. The human genomics enterprise is now in the midst of an important transition, as the growing foundation of genomic knowledge is being used by researchers and clinicians to tackle increasingly complex problems in biomedicine. Of particular prominence is the use of revolutionary new DNA sequencing technologies for generating prodigious amounts of DNA sequence data to elucidate the complexities of genome structure, function, and evolution, as well as to unravel the genomic bases of rare and common diseases...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225791/characterization-of-long-noncoding-rna-and-messenger-rna-signatures-in-melanoma-tumorigenesis-and-metastasis
#14
Siqi Wang, Wenliang Fan, Bing Wan, Mengqi Tu, Feng Jin, Fang Liu, Haibo Xu, Ping Han
The incidence of melanoma, the most aggressive and life-threatening form of skin cancer, has significantly risen over recent decades. Therefore, it is essential to identify the mechanisms that underlie melanoma tumorigenesis and metastasis and to explore novel and effective melanoma treatment strategies. Accumulating evidence s uggests that aberrantly expressed long noncoding RNAs (lncRNAs) have vital functions in multiple cancers. However, lncRNA functions in melanoma tumorigenesis and metastasis remain unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28225755/intragenic-dna-methylation-prevents-spurious-transcription-initiation
#15
Francesco Neri, Stefania Rapelli, Anna Krepelova, Danny Incarnato, Caterina Parlato, Giulia Basile, Mara Maldotti, Francesca Anselmi, Salvatore Oliviero
In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28225080/dna-g-quadruplexes-in-the-human-genome-detection-functions-and-therapeutic-potential
#16
REVIEW
Robert Hänsel-Hertsch, Marco Di Antonio, Shankar Balasubramanian
Single-stranded guanine-rich DNA sequences can fold into four-stranded DNA structures called G-quadruplexes (G4s) that arise from the self-stacking of two or more guanine quartets. There has been considerable recent progress in the detection and mapping of G4 structures in the human genome and in biologically relevant contexts. These advancements, many of which align with predictions made previously in computational studies, provide important new insights into the functions of G4 structures in, for example, the regulation of transcription and genome stability, and uncover their potential relevance for cancer therapy...
February 22, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28225043/prevention-of-tumorigenesis-in-mice-by-exercise-is-dependent-on-strain-background-and-timing-relative-to-carcinogen-exposure
#17
Scott A Kelly, Liyang Zhao, Kuo-Chen Jung, Kunjie Hua, David W Threadgill, Yunjung Kim, Fernando Pardo Manuel de Villena, Daniel Pomp
Among cancer diagnoses, colorectal cancer (CRC) is prevalent, with a lifetime risk of developing CRC being approximately 5%. Population variation surrounding the mean risk of developing CRCs has been associated with both inter-individual differences in genomic architecture and environmental exposures. Decreased risk of CRC has been associated with physical activity, but protective responses are variable. Here, we utilized a series of experiments to examine the effects of genetic background (strain), voluntary exercise (wheel running), and their interaction on azoxymethane (AOM)-induced intestinal tumor number and size in mice...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224650/androgen-receptor-splice-variants-are-not-substrates-of-nonsense-mediated-decay
#18
Atinuke S Ajiboye, David Esopi, Srinivasan Yegnasubramanian, Samuel R Denmeade
BACKGROUND: Androgen receptor (AR) splice variants have been clinically associated with progressive cancer, castration-resistance, and resistance to AR antagonists and androgen synthesis inhibitors. AR variants can be generated by genomic alterations and alternative splicing, and their expression is androgen-regulated. There has been a suggestion that AR variants bearing premature termination codons and coding for truncated proteins should be regulated by the nonsense-mediated decay (NMD) mRNA surveillance pathway, suggesting that either the NMD pathway is dysfunctional in variant-expressing cell lines or that variants are somehow able to evade degradation by NMD...
February 22, 2017: Prostate
https://www.readbyqxmd.com/read/28224495/hidden-markov-models-in-bioinformatics-snv-inference-from-next-generation-sequence
#19
Jiawen Bian, Xiaobo Zhou
The rapid development of next generation sequencing (NGS) technology provides a novel avenue for genomic exploration and research. Hidden Markov models (HMMs) have wide applications in pattern recognition as well as Bioinformatics such as transcription factor binding sites and cis-regulatory modules detection. An application of HMM is introduced in this chapter with the in-deep developing of NGS. Single nucleotide variants (SNVs) inferred from NGS are expected to reveal gene mutations in cancer. However, NGS has lower sequence coverage and poor SNV detection capability in the regulatory regions of the genome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28224383/oncologist-and-organizational-factors-associated-with-variation-in-breast-cancer-multigene-testing
#20
Tracy A Lieu, G Thomas Ray, Stephanie R Prausnitz, Laurel A Habel, Stacey Alexeeff, Yan Li, Scott D Ramsey, Charles E Phelps, Neetu Chawla, Suzanne C O'Neill, Jeanne S Mandelblatt
PURPOSE: Multigene testing for breast cancer recurrence risk became available in 2007, yet many eligible patients remain untested. This study evaluated variation in testing rates, and oncologist and organizational factors associated with variation, in a setting without financial influences on testing. METHODS: We conducted a retrospective cohort study using electronic data and oncologist surveys within Kaiser Permanente Northern California, a large integrated health care system...
February 21, 2017: Breast Cancer Research and Treatment
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