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epigenetics in oncology

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https://www.readbyqxmd.com/read/28271563/gastric-cancer-managment-kinases-as-a-target-therapy
#1
Batoul Farran, Susanne Müller, Raquel C Montenegro
The molecular diagnostics revolution has reshaped the practice of oncology by facilitating the identification of genetic, epigenetic and proteomic modifications correlated with cancer, thus delineating 'oncomaps' for various cancer types. These advances have enhanced our understanding of gastric cancer, one of the most fatal diseases worldwide, and culminated in the approval of novel molecular therapies such as trastuzumab. Gastric tumours display recurrent aberrations in key kinase oncogenes such as Her2, EGFR, PI3K, mTOR or c-Met, suggesting that these receptors are amenable to inhibition using specific drug agents...
March 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#2
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28229117/dna-methylation-data-for-identification-of-epigenetic-targets-of-resveratrol-in-triple-negative-breast-cancer-cells
#3
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/28212714/droplet-based-digital-pcr-application-in-cancer-research
#4
G Perkins, H Lu, F Garlan, V Taly
The efficient characterization of genetic and epigenetic alterations in oncology, virology, or prenatal diagnostics requires highly sensitive and specific high-throughput approaches. Nevertheless, with the use of conventional methods, sensitivity and specificity were largely limited. By partitioning individual target molecules within distinct compartments, digital PCR (dPCR) could overcome these limitations and detect very rare sequences with unprecedented precision and sensitivity. In dPCR, the sample is diluted such that each individual partition will contain no more than one target sequence...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28187790/retinoic-acid-and-tgf-%C3%AE-signalling-cooperate-to-overcome-mycn-induced-retinoid-resistance
#5
David J Duffy, Aleksandar Krstic, Melinda Halasz, Thomas Schwarzl, Anja Konietzny, Kristiina Iljin, Desmond G Higgins, Walter Kolch
BACKGROUND: Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance...
February 10, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28149883/focusing-the-management-of-rectal-cancer
#6
COMMENT
Rachel Dbeis, Neil J Smart, Ian R Daniels
Rectal cancer treatment has undergone major changes over the last 15 years with a focus on individualized care based around MRI assessment of the relationship of the tumour to the mesorectal fascia, improved surgical techniques and targeted use of pre-operative oncological therapies in patients with locally advanced disease. The recognition that some tumours responded completely to pre-operative chemoradiotherapy, and the selective use of a non-operative policy has led to a quest to further identify those patients and their tumour in whom this approach could be used, irrespective of MRI stage...
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28105334/chronic-kidney-disease-in-children-and-the-role-of-epigenetics-future-therapeutic-trajectories
#7
Samuel N Uwaezuoke, Henrietta U Okafor, Vivian N Muoneke, Odutola I Odetunde, Chioma L Odimegwu
Global differences in the observed causes of chronic kidney disease (CKD) in children are well documented and are attributed to dissimilarities in clime, race, hereditary, and ancestry. Thus, familial clustering and disparities in CKD prevalence rates across ethnic and racial groups indicate that the progression of renal disease has a strong genetic component. Mammalian studies have demonstrated a feasible nexus between nutrition and non-genetic exposure (around the time of conception and in epigenetic changes) in the expression of major genes identified in renal organogenesis...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28080202/chemical-probes-targeting-epigenetic-proteins-applications-beyond-oncology
#8
Suzanne Ackloo, Peter J Brown, Susanne Müller
Epigenetic chemical probes are potent, cell-active, small molecule inhibitors or antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about 4 thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro...
January 12, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28074387/epigenetic-sampling-effects-nephrectomy-modifies-the-clear-cell-renal-cell-cancer-methylome
#9
Christophe Van Neste, Alexander Laird, Fiach O'Mahony, Wim Van Criekinge, Dieter Deforce, Filip Van Nieuwerburgh, Thomas Powles, David J Harrison, Grant D Stewart, Tim De Meyer
PURPOSE: Currently, it is unclear to what extent sampling procedures affect the epigenome. Here, this phenomenon was evaluated by studying the impact of artery ligation on DNA methylation in clear cell renal cancer. METHODS: DNA methylation profiles between vascularised tumour biopsy samples and devascularised nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort...
January 10, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28056336/the-clinical-role-of-circulating-free-tumor-dna-in-gastrointestinal-malignancy
#10
REVIEW
Jessica A Howell, Shahid A Khan, Susanne Knapp, Mark R Thursz, Rohini Sharma
Circulating cell-free DNA (cfDNA) is DNA released from necrotic or apoptotic cells into the bloodstream. While both healthy cells and cancer cells release cfDNA, tumors are associated with higher levels of tumor-derived circulating cell-free DNA (ctDNA) detectable in blood. Absolute levels of ctDNA and its genetic mutations and epigenetic changes show promise as potentially useful biomarkers of tumor biology, progression, and response to therapy. Moreover, studies have demonstrated the discriminative accuracy of ctDNA levels for diagnosis of gastrointestinal cancer compared with benign inflammatory diseases...
December 22, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28031556/advances-in-the-molecular-genetics-of-gliomas-implications-for-classification-and-therapy
#11
REVIEW
Guido Reifenberger, Hans-Georg Wirsching, Christiane B Knobbe-Thomsen, Michael Weller
Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible...
December 29, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28019723/therapeutical-potential-of-deregulated-lysine-methyltransferase-smyd3-as-a-safe-target-for-novel-anticancer-agents
#12
Gurukumari Rajajeyabalachandran, Swetha Kumar, Thanabal Murugesan, Shanthi Ekambaram, Ramya Padmavathy, Sooriya Kumar Jegatheesan, Ramesh Mullangi, Sriram Rajagopal
SET and MYND domain containing-3 (SMYD3) is a member of the lysine methyltransferase family of proteins, and plays an important role in the methylation of various histone and non-histone targets. Proper functioning of SMYD3 is very important for the target molecules to determine their different roles in chromatin remodeling, signal transduction and cell cycle control. Due to the abnormal expression of SMYD3 in tumors, it is projected as a prognostic marker in various solid cancers. Areas covered: Here we elaborate on the general information, structure and the pathological role of SMYD3 protein...
December 26, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28018344/adjunct-strategies-for-tuberculosis-vaccines-modulating-key-immune-cell-regulatory-mechanisms-to-potentiate-vaccination
#13
REVIEW
Lakshmi Jayashankar, Richard Hafner
Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette-Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28008934/driver-gene-classification-reveals-a-substantial-overrepresentation-of-tumor-suppressors-among-very-large-chromatin-regulating-proteins
#14
Zeev Waks, Omer Weissbrod, Boaz Carmeli, Raquel Norel, Filippo Utro, Yaara Goldschmidt
Compiling a comprehensive list of cancer driver genes is imperative for oncology diagnostics and drug development. While driver genes are typically discovered by analysis of tumor genomes, infrequently mutated driver genes often evade detection due to limited sample sizes. Here, we address sample size limitations by integrating tumor genomics data with a wide spectrum of gene-specific properties to search for rare drivers, functionally classify them, and detect features characteristic of driver genes. We show that our approach, CAnceR geNe similarity-based Annotator and Finder (CARNAF), enables detection of potentially novel drivers that eluded over a dozen pan-cancer/multi-tumor type studies...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27930094/cancer-stem-cell-hypothesis-for-therapeutic-innovation-in-clinical-oncology-taking-the-root-out-not-chopping-the-leaf
#15
Kevin Dzobo, Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Lamech M Mwapagha, Nasir Al-Awwad, Collet Dandara, M Iqbal Parker
Clinical oncology is in need of therapeutic innovation. New hypotheses and concepts for translation of basic research to novel diagnostics and therapeutics are called for. In this context, the cancer stem cell (CSC) hypothesis rests on the premise that tumors comprise tumor cells and a subset of tumor-initiating cells, CSCs, in a quiescent state characterized by slow cell cycling and expression of specific stem cell surface markers with the capability to maintain a tumor in vivo. The CSCs have unlimited self-renewal abilities and propagate tumors through division into asymmetric daughter cells...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27927793/tumour-biomarkers-homeostasis-as-a-novel-prognostic-indicator
#16
REVIEW
Michela Falco, Giuseppe Palma, Domenica Rea, Davide De Biase, Stefania Scala, Massimiliano D'Aiuto, Gaetano Facchini, Sisto Perdonà, Antonio Barbieri, Claudio Arra
The term 'personalized medicine' refers to a medical procedure that consists in the grouping of patients based on their predicted individual response to therapy or risk of disease. In oncologic patients, a 'tailored' therapeutic approach may potentially improve their survival and well-being by not only reducing the tumour, but also enhancing therapeutic response and minimizing the adverse effects. Diagnostic tests are often used to select appropriate and optimal therapies that rely both on patient genome and other molecular/cellular analysis...
December 2016: Open Biology
https://www.readbyqxmd.com/read/27796306/structural-basis-of-checkpoint-blockade-by-monoclonal-antibodies-in-cancer-immunotherapy
#17
Ju Yeon Lee, Hyun Tae Lee, Woori Shin, Jongseok Chae, Jaemo Choi, Sung Hyun Kim, Heejin Lim, Tae Won Heo, Kyeong Young Park, Yeon Ji Lee, Seong Eon Ryu, Ji Young Son, Jee Un Lee, Yong-Seok Heo
Cancer cells express tumour-specific antigens derived via genetic and epigenetic alterations, which may be targeted by T-cell-mediated immune responses. However, cancer cells can avoid immune surveillance by suppressing immunity through activation of specific inhibitory signalling pathways, referred to as immune checkpoints. In recent years, the blockade of checkpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies has enabled the development of breakthrough therapies in oncology, and four therapeutic antibodies targeting these checkpoint molecules have been approved by the FDA for the treatment of several types of cancer...
October 31, 2016: Nature Communications
https://www.readbyqxmd.com/read/27779677/-corrigendum-genetic-and-epigenetic-alterations-are-involved-in-the-regulation-of-tpm1-in-cholangiocarcinoma
#18
Wei Yang, Xiaoyuan Wang, Wei Zheng, Kedong Li, Haofeng Liu, Yueming Sun
Following the publication of this article, an interested reader drew to our attention anomalies associated with the data shown in Fig. 2, which presented the mRNA and protein expression levels of tropomyosin 1 (TPM1) in HuCCT1 cells. Essentially, the control bands for α-tubulin had been duplicated across from Fig. 2A to Fig. 2B, and from Fig. 2D to Fig. 2E [the experiments showing treatment of the cells with (A) manumycin A, (B) U0126, (D) 5-aza-2-deoxycytidine (DAC) and (E) trichostatin A (TSA)], respectively...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27721934/novel-concepts-in-radiation-induced-cardiovascular-disease
#19
REVIEW
Jason R Cuomo, Gyanendra K Sharma, Preston D Conger, Neal L Weintraub
Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future...
September 26, 2016: World Journal of Cardiology
https://www.readbyqxmd.com/read/27607592/cancer-therapies-in-hiv-cure-research
#20
Thomas A Rasmussen, Jenny L Anderson, Fiona Wightman, Sharon R Lewin
PURPOSE OF REVIEW: This article provides an overview of anticancer therapies in various stages of clinical development as potential interventions to target HIV persistence. RECENT FINDINGS: Epigenetic drugs developed for cancer have been investigated in vitro, ex vivo and in clinical trials as interventions aimed at reversing HIV latency and depleting the amount of virus that persists on antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV expression in patients on antiretroviral therapy but did not reduce the frequency of infected cells...
January 2017: Current Opinion in HIV and AIDS
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