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https://www.readbyqxmd.com/read/28918032/microrna-31-regulates-chemosensitivity-in-malignant-pleural-mesothelioma
#1
Hannah L Moody, Michael J Lind, Stephen G Maher
Malignant pleural mesothelioma (MPM) is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31) is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917518/genome-stability-of-programmed-stem-cell-products
#2
REVIEW
Ulrich Martin
Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives...
September 13, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28917257/exploiting-molecular-genomics-in-precision-radiation-oncology-a-marriage-of-biological-and-physical-precision
#3
Janice S H Tan, Xiaotian Lin, Kevin L M Chua, Paula Y Lam, Khee-Chee Soo, Melvin L K Chua
Achieving local tumour control is paramount for cure in head and neck and prostate cancers. With the transition to precision radiotherapy (RT) techniques, survival rates have improved in the majority of these cancers, but a substantial proportion of 30-40% still relapse following primary treatment. Recent large-scale molecular profiling studies have revealed unique biological events that could explain for tumour aggression and resistance to therapies, redefining the molecular taxonomy of head and neck and prostate cancers...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28916782/predicting-clinical-outcomes-from-large-scale-cancer-genomic-profiles-with-deep-survival-models
#4
Safoora Yousefi, Fatemeh Amrollahi, Mohamed Amgad, Chengliang Dong, Joshua E Lewis, Congzheng Song, David A Gutman, Sameer H Halani, Jose Enrique Velazquez Vega, Daniel J Brat, Lee A D Cooper
Translating the vast data generated by genomic platforms into accurate predictions of clinical outcomes is a fundamental challenge in genomic medicine. Many prediction methods face limitations in learning from the high-dimensional profiles generated by these platforms, and rely on experts to hand-select a small number of features for training prediction models. In this paper, we demonstrate how deep learning and Bayesian optimization methods that have been remarkably successful in general high-dimensional prediction tasks can be adapted to the problem of predicting cancer outcomes...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916750/comprehensive-multiregional-analysis-of-molecular-heterogeneity-in-bladder-cancer
#5
Mathilde Borg Houlberg Thomsen, Iver Nordentoft, Philippe Lamy, Søren Vang, Line Reinert, Christophe Kamungu Mapendano, Søren Høyer, Torben F Ørntoft, Jørgen Bjerggaard Jensen, Lars Dyrskjøt
Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916446/cancer-derived-exosomes-as-a-delivery-platform-of-crispr-cas9-confer-cancer-cell-tropism-dependent-targeting
#6
Seung Min Kim, Yoosoo Yang, Seung Ja Oh, Yeonsun Hong, Mihue Jang
An intracellular delivery system for CRISPR/Cas9 is crucial for its application as a therapeutic genome editing technology in a broad range of diseases. Current vehicles carrying CRISPR/Cas9 limit in vivo delivery because of low tolerance and immunogenicity; thus, the in vivo delivery of genome editing remains challenging. Here, we report that cancer-derived exosomes function as natural carriers that can efficiently deliver CRISPR/Cas9 plasmids to cancer. Compared to epithelial cell-derived exosomes, cancer-derived exosomes provide potential vehicles for effective in vivo delivery via selective accumulation in ovarian cancer tumors of SKOV3 xenograft mice, most likely because of their cell tropism...
September 12, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28916367/rucaparib-maintenance-treatment-for-recurrent-ovarian-carcinoma-after-response-to-platinum-therapy-ariel3-a-randomised-double-blind-placebo-controlled-phase-3-trial
#7
Robert L Coleman, Amit M Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I Weberpals, Andrew Clamp, Giovanni Scambia, Alexandra Leary, Robert W Holloway, Margarita Amenedo Gancedo, Peter C Fong, Jeffrey C Goh, David M O'Malley, Deborah K Armstrong, Jesus Garcia-Donas, Elizabeth M Swisher, Anne Floquet, Gottfried E Konecny, Iain A McNeish, Clare L Scott, Terri Cameron, Lara Maloney, Jeff Isaacson, Sandra Goble, Caroline Grace, Thomas C Harding, Mitch Raponi, James Sun, Kevin K Lin, Heidi Giordano, Jonathan A Ledermann
BACKGROUND: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries...
September 12, 2017: Lancet
https://www.readbyqxmd.com/read/28916343/the-role-of-a-new-class-of-long-noncoding-rnas-transcribed-from-ultraconserved-regions-in-cancer
#8
REVIEW
Daniela Terracciano, Sara Terreri, Filomena de Nigris, Valerio Costa, George A Calin, Amelia Cimmino
Ultraconserved regions (UCRs) represent a relatively new class of non-coding genomic sequences highly conserved between human, rat and mouse genomes. These regions can reside within exons of protein-coding genes, despite the vast majority of them localizes within introns or intergenic regions. Several studies have undoubtedly demonstrated that most of these regions are actively transcribed in normal cells/tissues, where they contribute to regulate many cellular processes. Interestingly, these non-coding RNAs exhibit aberrant expression levels in human cancer cells and their expression profiles have been used as prognostic factors in human malignancies, as well as to unambiguously distinguish among distinct cancer types...
September 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28915902/development-and-clinical-application-of-radiomics-in-lung-cancer
#9
REVIEW
Bojiang Chen, Rui Zhang, Yuncui Gan, Lan Yang, Weimin Li
Since the discovery of X-rays at the end of the 19(th) century, medical imageology has progressed for 100 years, and medical imaging has become an important auxiliary tool for clinical diagnosis. With the launch of the human genome project (HGP) and the development of various high-throughput detection techniques, disease exploration in the post-genome era has extended beyond investigations of structural changes to in-depth analyses of molecular abnormalities in tissues, organs and cells, on the basis of gene expression and epigenetics...
September 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28915899/association-between-polymorphisms-of-tas2r16-and-susceptibility-to-colorectal-cancer
#10
Jonathan Barontini, Marco Antinucci, Sergio Tofanelli, Maurizio Cammalleri, Massimo Dal Monte, Federica Gemignani, Pavel Vodicka, Roberto Marangoni, Ludmila Vodickova, Juozas Kupcinskas, Veronika Vymetalkova, Asta Forsti, Federico Canzian, Angelika Stein, Victor Moreno, Nicola Mastrodonato, Francesca Tavano, Anna Panza, Roberto Barale, Stefano Landi, Daniele Campa
BACKGROUND: Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin...
September 15, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28915719/genomic-analysis-of-exceptional-responder-to-regorafenib-in-treatment-refractory-metastatic-rectal-cancer-a-case-report-and-review-of-the-literature
#11
Krittiya Korphaisarn, Jonathan M Loree, Van Nguyen, Ryanne Coulson, Vijaykumar Holla, Beate C Litzenburger, Ken Chen, Gordon B Mills, Dipen M Maru, Funda Meric-Bernstan, Kenna R Mills Shaw, Scott Kopetz
We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915716/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#12
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915707/augmented-expression-of-polo-like-kinase-1-indicates-poor-clinical-outcome-for-breast-patients-a-systematic-review-and-meta-analysis
#13
REVIEW
Yunfeng Zhang, Zhibin Wu, Dapeng Liu, Meng Wang, Guodong Xiao, Peili Wang, Xin Sun, Hong Ren, Shou-Ching Tang, Ning Du
Polo-like kinases 1 (PLK1), a key regulator of mitosis, plays an essential role in maintaining genomic stability. Up-regulation of PLK1 was found in tumorigenesis and tumor progression of diverse cancers. However, the clinicopathological and prognostic implications of PLK1 in breast cancer (BC) have yet to be unveiled. Therefore, using PubMed, Web of Science, Embase, and Chinese databases, we conducted a meta-analysis to define the potential clinical value of PLK1 in BC. Eleven eligible articles with 2481 patients enrolled were included in the present meta-analysis, of which eight studies reported on the relationship between PLK1 expression and clinicopathological features, and nine studies provided survival data in BC patients...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915706/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#14
REVIEW
Lian Liu, Jia-Zhi Liao, Xing-Xing He, Pei-Yuan Li
Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell's components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915699/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#15
REVIEW
Chinthalapally V Rao, Sanya Pal, Altaf Mohammed, Mudassir Farooqui, Mark P Doescher, Adam S Asch, Hiroshi Y Yamada
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#16
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915574/comparative-study-of-whole-genome-amplification-and-next-generation-sequencing-performance-of-single-cancer-cells
#17
Anna Babayan, Malik Alawi, Michael Gormley, Volkmar Müller, Harriet Wikman, Ryan P McMullin, Denis A Smirnov, Weimin Li, Maria Geffken, Klaus Pantel, Simon A Joosse
BACKGROUND: Whole genome amplification (WGA) is required for single cell genotyping. Effectiveness of currently available WGA technologies in combination with next generation sequencing (NGS) and material preservation is still elusive. RESULTS: In respect to the accuracy of SNP/mutation, indel, and copy number aberrations (CNA) calling, the HiSeq2000 platform outperformed IonProton in all aspects. Furthermore, more accurate SNP/mutation and indel calling was demonstrated using single tumor cells obtained from EDTA-collected blood in respect to CellSave-preserved blood, whereas CNA analysis in our study was not detectably affected by fixation...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915562/detecting-the-genetic-link-between-alzheimer-s-disease-and-obesity-using-bioinformatics-analysis-of-gwas-data
#18
Qi-Shuai Zhuang, Hao Zheng, Xiao-Dan Gu, Liang Shen, Hong-Fang Ji
Alzheimer's disease (AD) represents the major form of dementia in the elderly. In recent years, accumulating evidence indicate that obesity may act as a risk factor for AD, while the genetic link between the two conditions remains unclear. This bioinformatics analysis aimed to detect the genetic link between AD and obesity on single nucleotide polymorphisms (SNPs), gene, and pathway levels based on genome-wide association studies data. A total of 31 SNPs were found to be shared by AD and obesity, which were linked to 7 genes...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#19
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915241/the-relative-contribution-of-dna-methylation-and-genetic-variants-on-protein-biomarkers-for-human-diseases
#20
Muhammad Ahsan, Weronica E Ek, Mathias Rask-Andersen, Torgny Karlsson, Allan Lind-Thomsen, Stefan Enroth, Ulf Gyllensten, Åsa Johansson
Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs...
September 15, 2017: PLoS Genetics
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