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https://www.readbyqxmd.com/read/29783088/evaluation-of-genotoxicity-and-mutagenic-effects-of-vector-dna-nanocomplexes-in-transfected-mesenchymal-stem-cells-by-flow-cytometry
#1
Alireza Nomani, Xuguang Chen, Arash Hatefi
In recent years, there has been a great deal of interest in ex-vivo genetic modification of mesenchymal stem cells (MSCs) to meet various biomedical needs. Considering the self-renewal potential of MSCs, it is critically important to ensure that transfection vectors (gene carriers) do not induce genotoxicity because they could theoretically turn a single stem cell into a cancer-initiating cell. Unfortunately, there is currently no reliable, unbiased, and quantitative method to measure genotoxicity (micronuclei formation) of gene carriers directly in transfected MSCs...
May 18, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29782924/emerging-biomarkers-for-immune-checkpoint-inhibition-in-lung-cancer
#2
REVIEW
George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker...
May 18, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29782246/precision-medicine-and-radiogenomics-in-breast-cancer-new-approaches-toward-diagnosis-and-treatment
#3
Katja Pinker, Joanne Chin, Amy N Melsaether, Elizabeth A Morris, Linda Moy
Precision medicine is medicine optimized to the genotypic and phenotypic characteristics of an individual and, when present, his or her disease. It has a host of targets, including genes and their transcripts, proteins, and metabolites. Studying precision medicine involves a systems biology approach that integrates mathematical modeling and biology genomics, transcriptomics, proteomics, and metabolomics. Moreover, precision medicine must consider not only the relatively static genetic codes of individuals, but also the dynamic and heterogeneous genetic codes of cancers...
June 2018: Radiology
https://www.readbyqxmd.com/read/29781548/multi-omics-in-high-grade-serous-ovarian-cancer-biomarkers-from-genome-to-the-immunome
#4
Cole Clifford, Natasha Vitkin, Sarah Nersesian, Gillian Reid-Schachter, Julie-Ann Francis, Madhuri Koti
Epithelial ovarian cancer (EOC) is a lethal gynaecological disease that imposes significant burden on health care and patient quality of life. High-grade serous carcinoma of the ovary (HGSC) is the most prevalent histological type of EOC. A vast majority of HGSC cases are diagnosed at late stages of the disease, limiting the opportunity for clinical intervention and resulting in a 10-year survival rate of <20%. Recent innovations in high-throughput molecular analysis of patient-derived specimens may address these clinical challenges by providing an enhanced understanding of the molecular aetiology of ovarian cancer, in addition to offering several opportunities for rational biomarker and targeted therapy discovery...
May 21, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29781033/microarray-analysis-of-circular-rna-expression-profiles-associated-with-gemcitabine-resistance-in-pancreatic-cancer-cells
#5
Chao Xu, Yue Yu, Fei Ding
Pancreatic cancer (PC) is one of the most malignant tumors of the digestive system due to its rapid progression, metastasis and resistance to chemotherapy. Gemcitabine (GEM) chemotherapy is the first‑choice treatment for advanced PC. However, the effect of GEM‑based chemotherapy on PC is limited due to the development of chemoresistance, and the molecular mechanisms underlying this resistance have yet to be investigated. Circular RNAs (circRNAs), which can function as microRNA sponges, have been found to be involved in the development of several types of cancer...
May 17, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29780774/optimization-to-detect-tp53-mutations-in-circulating-cell-free-tumor-dna-from-patients-with-serous-epithelial-ovarian-cancer
#6
Yu Ran Park, Yong-Man Kim, Shin Wha Lee, Ha Young Lee, Gun Eui Lee, Jong-Eun Lee, Young-Tak Kim
Objective: Circulating cell-free tumor DNA (cfDNA) is the DNA released by apoptotic and necrotic cells of the primary tumor into the blood during the period of tumor development. The cfDNA reflects the genetic and epigenetic alterations of the original tumor. TP53 mutations are a defining feature of high-grade serous ovarian carcinoma. We optimized the methods for detecting TP53 mutations in cfDNA from blood samples. We confirmed the correlation of TP53 mutation in primary ovarian cancer tissue and it in cfDNA using digital polymerase chain reaction (dPCR)...
May 2018: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/29780747/precision-medicine-in-hormone-receptor-positive-breast-cancer
#7
REVIEW
Azadeh Nasrazadani, Roby A Thomas, Steffi Oesterreich, Adrian V Lee
In recent decades, breast cancer has become largely manageable due to successes with hormone receptor targeting. Hormone receptor-positive tumors have favorable outcomes in comparison to estrogen receptor (ESR1, ER)/progesterone receptor-negative tumors given the targetable nature of these tumors, as well as their inherently less aggressive character. Nonetheless, treatment resistance is frequently encountered due to a variety of mechanisms, including ESR1 mutations and loss of ER expression. A new era of precision medicine utilizes a range of methodologies to allow real-time analysis of individual genomic signatures in metastases and liquid biopsies with the goal of finding clinically actionable targets...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29780635/liquid-biopsy-for-lung-cancer-early-detection
#8
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Alessandro D'Aveni, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Chiara Lazzari, Giuseppe Altavilla, Rafael Rosell
Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients...
April 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29780391/concepts-collide-genomic-immune-and-microbial-influences-on-the-tumor-microenvironment-and-response-to-cancer-therapy
#9
REVIEW
Miles C Andrews, Alexandre Reuben, Vancheswaran Gopalakrishnan, Jennifer A Wargo
Cancer research has seen unprecedented advances over the past several years, with tremendous insights gained into mechanisms of response and resistance to cancer therapy. Central to this has been our understanding of crosstalk between the tumor and the microenvironment, with the recognition that complex interactions exist between tumor cells, stromal cells, overall host immunity, and the environment surrounding the host. This is perhaps best exemplified in cancer immunotherapy, where numerous studies across cancer types have illuminated our understanding of the genomic and immune factors that shape responses to therapy...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29780284/up-regulation-of-ctd-2547g23-4-in-hepatocellular-carcinoma-tissues-and-its-prospective-molecular-regulatory-mechanism-a-novel-qrt-pcr-and-bioinformatics-analysis-study
#10
Dong-Yue Wen, Peng Lin, Hai-Wei Liang, Xia Yang, Hai-Yuan Li, Yun He, Hong Yang, Gang Chen
Background: Dysregulated expression of long non-coding RNAs (lncRNAs) has been reported in the pathogenesis and progression of multiple cancers, including hepatocellular carcinoma (HCC). LncRNA CTD-2547G23.4 is a novel lncRNA, and its role in HCC is still unknown. Here, we aimed to clarify the expression pattern and clinical value of CTD-2547G23.4 and to investigate the prospective regulatory mechanism via bioinformatics analysis in HCC. Methods: To identify differentially expressed lncRNAs in HCC, we downloaded RNA-Seq data for HCC and adjacent non-tumour tissues via The Cancer Genome Atlas (TCGA)...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29779986/photodynamic-therapy-corrects-abnormal-cancer-associated-gene-expression-observed-in-actinic-keratosis-lesions-and-induces-a-remodeling-effect-in-photodamaged-skin
#11
Florence Joly, Sophie Deret, Bastien Gamboa, Corinne Menigot, Paul Fogel, Carine Mounier, Pascale Reiniche, Farzaneh Sidou, Jérome Aubert, John Lear, Anthony A Fryer, Francesca Zolezzi, Johannes J Voegel
BACKGROUND: Actinic keratoses (AK) are proliferations of neoplastic keratinocytes in the epidermis resulting from cumulative exposure to ultraviolet radiation (UVR), which are liable to transform into squamous cell carcinoma (SCC). Organ Transplant Recipients (OTR) have an increased risk of developing SCC as a consequence of long-term immunosuppressive therapy. The aim of this study was to determine the molecular signature of AKs from OTR prior to treatment with methyl aminolevulinate-photodynamic therapy (MAL-PDT), and to assess what impact the treatment has on promoting remodeling of the photo-damaged skin...
May 17, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29779563/association-of-polygenic-risk-scores-for-multiple-cancers-in-a-phenome-wide-study-results-from-the-michigan-genomics-initiative
#12
Lars G Fritsche, Stephen B Gruber, Zhenke Wu, Ellen M Schmidt, Matthew Zawistowski, Stephanie E Moser, Victoria M Blanc, Chad M Brummett, Sachin Kheterpal, Gonçalo R Abecasis, Bhramar Mukherjee
Health systems are stewards of patient electronic health record (EHR) data with extraordinarily rich depth and breadth, reflecting thousands of diagnoses and exposures. Measures of genomic variation integrated with EHRs offer a potential strategy to accurately stratify patients for risk profiling and discover new relationships between diagnoses and genomes. The objective of this study was to evaluate whether polygenic risk scores (PRS) for common cancers are associated with multiple phenotypes in a phenome-wide association study (PheWAS) conducted in 28,260 unrelated, genotyped patients of recent European ancestry who consented to participate in the Michigan Genomics Initiative, a longitudinal biorepository effort within Michigan Medicine...
May 17, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29779155/prioritising-risk-factors-for-type-2-diabetes-causal-inference-through-genetic-approaches
#13
REVIEW
Laura B L Wittemans, Luca A Lotta, Claudia Langenberg
PURPOSE OF THE REVIEW: Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology. Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D. RECENT FINDINGS: Genetic discoveries have led to the identification of novel potential aetiological factors of T2D, including the protective role of peripheral fat storage capacity and specific metabolic pathways, such as the branched-chain amino acid breakdown...
May 19, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29779017/-xpg-rs17655-g-c-polymorphism-associated-with-cancer-risk-evidence-from-60-studies
#14
Jie Zhao, Shanshan Chen, Haixia Zhou, Ting Zhang, Yang Liu, Jing He, Jinhong Zhu, Jichen Ruan
Xeroderma pigmentosum group G (XPG), a key component in nucleotide excision repair pathway, functions to cut DNA lesions during DNA repair. Genetic variations that alter DNA repair gene expression or function may decrease DNA repair ability and impair genome integrity, thereby predisposing to cancer. The association between XPG rs17655 G>C polymorphism and cancer risk has been investigated extensively, but the results remain contradictory. To get a more accurate conclusion, we performed a comprehensive meta-analysis of 60 case-control studies, involving 27,098 cancer cases and 30,535 healthy controls...
May 20, 2018: Aging
https://www.readbyqxmd.com/read/29778876/genome-sequence-analysis-of-a-novel-bacillus-thuringiensis-strain-blb406-active-against-aedes-aegypti-larvae-a-novel-potential-bioinsecticide
#15
Raida Zribi Zghal, Kais Ghedira, Jihen Elleuch, Marwa Kharrat, Slim Tounsi
BLB406 is a novel isolate of Bacillus thuringiensis with a larvicidal activity against Aedes aegypti larvae. It displays original plasmidic and crystal protein patterns. The present work reported molecular and bioinformatic analyses for the genome sequence of BLB406 using MiSeq Illumina next-generation sequencing technology. The reads were assembled by Velvet tool. Using RAST program and PGAAP the genome of BLB406 strain was shown to contain 6297 genes corresponding to 5924 protein coding sequences. The BLB406 genome investigation with BtToxin_scanner program shows that this strain has an original and different combination of toxins compared to the published ones: five cry genes (cry11, cry22, cry2, cry60, cry64) and two distinct vegetative insecticidal vip4 genes...
May 17, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29778836/interrogation-of-mammalian-protein-complex-structure-function-and-membership-using-genome-scale-fitness-screens
#16
Joshua Pan, Robin M Meyers, Brittany C Michel, Nazar Mashtalir, Ann E Sizemore, Jonathan N Wells, Seth H Cassel, Francisca Vazquez, Barbara A Weir, William C Hahn, Joseph A Marsh, Aviad Tsherniak, Cigall Kadoch
Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex...
May 14, 2018: Cell Systems
https://www.readbyqxmd.com/read/29778426/germline-cytoskeletal-and-extra-cellular-matrix-related-single-nucleotide-variations-associated-with-distinct-cancer-survival-rates
#17
Shayan Falasiri, Tasnif Rahman, Yaping N Tu, Timothy J Fawcett, George Blanck
BACKGROUND: Human mutagenesis has a large stochastic component. Thus, large coding regions, especially cytoskeletal and extra-cellular matrix protein (CECMP) coding regions are particularly vulnerable to mutations. Recent results have verified a high level of somatic mutations in the CECMP coding regions in the cancer genome atlas (TCGA), and a relatively common occurrence of germline, deleterious mutations in the TCGA breast cancer dataset. METHODS: The objective of this study was to determine the correlations of CECMP coding region, germline nucleotide variations with both overall survival (OS) and disease-free survival (DFS)...
May 17, 2018: Gene
https://www.readbyqxmd.com/read/29777908/breast-cancer-in-the-gcc-countries-a-focus-on-brca1-2-and-non-brca1-2-genes
#18
REVIEW
Sumaya Rahman, Hatem Zayed
The GCC is an economic alliance of six Arab countries, including Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates (UAE). The rate of endogamous marriage among the GCC countries is approaching 100%, with very high consanguineous marriage rates. Although breast cancer is on the rise in the GCC countries, there are dearth of studies reporting on the genetic epidemiology of breast cancer. In this study, we investigated the frequency of BRCA1/2 and non-BRCA1/2 mutations in breast cancer patients in the GCC countries...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777785/psmd2-regulates-breast-cancer-cell-proliferation-and-cell-cycle-progression-by-modulating-p21-and-p27-proteasomal-degradation
#19
Yunhai Li, Jing Huang, Beilei Zeng, Dejuan Yang, Jiazheng Sun, Xuedong Yin, Mengqi Lu, Zhu Qiu, Weiyan Peng, Tingxiu Xiang, Hongzhong Li, Guosheng Ren
Alterations in the ubiquitin-proteasome system (UPS) and UPS-associated proteins have been implicated in the development of many human malignancies. In this study, we investigated the expression profiles of 797 UPS-related genes using HiSeq data from The Cancer Genome Atlas and identified that PSMD2 was markedly upregulated in breast cancer. High PSMD2 expression was significantly correlated with poor prognosis. Gene set enrichment analysis revealed that transcriptome signatures involving proliferation, cell cycle, and apoptosis were critically enriched in specimens with elevated PSMD2...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777112/micrornas-as-potential-therapeutics-to-enhance-chemosensitivity-in-advanced-prostate-cancer
#20
Hui-Ming Lin, Iva Nikolic, Jessica Yang, Lesley Castillo, Niantao Deng, Chia-Ling Chan, Nicole K Yeung, Eoin Dodson, Benjamin Elsworth, Calan Spielman, Brian Y Lee, Zoe Boyer, Kaylene J Simpson, Roger J Daly, Lisa G Horvath, Alexander Swarbrick
Docetaxel and cabazitaxel are taxane chemotherapy treatments for metastatic castration-resistant prostate cancer (CRPC). However, therapeutic resistance remains a major issue. MicroRNAs are short non-coding RNAs that can silence multiple genes, regulating several signalling pathways simultaneously. Therefore, synthetic microRNAs may have therapeutic potential in CRPC by regulating genes involved in taxane response and minimise compensatory mechanisms that cause taxane resistance. To identify microRNAs that can improve the efficacy of taxanes in CRPC, we performed a genome-wide screen of 1280 microRNAs in the CRPC cell lines PC3 and DU145 in combination with docetaxel or cabazitaxel treatment...
May 18, 2018: Scientific Reports
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