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epigenetics in oncology

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https://www.readbyqxmd.com/read/28080202/chemical-probes-targeting-epigenetic-proteins-applications-beyond-oncology
#1
Suzanne Ackloo, Peter J Brown, Susanne Müller
Epigenetic chemical probes are potent, cell-active, small molecule inhibitors and 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 four 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27571355/structure-of-the-epigenetic-oncogene-mmset-and-inhibition-by-n-alkyl-sinefungin-derivatives
#14
Dominic Tisi, Elisabetta Chiarparin, Emiliano Tamanini, Puja Pathuri, Joseph E Coyle, Adam Hold, Finn P Holding, Nader Amin, Agnes C L Martin, Sharna J Rich, Valerio Berdini, Jeff Yon, Paul Acklam, Rosemary Burke, Ludovic Drouin, Jenny E Harmer, Fiona Jeganathan, Rob L M van Montfort, Yvette Newbatt, Marcello Tortorici, Maura Westlake, Amy Wood, Swen Hoelder, Tom D Heightman
The members of the NSD subfamily of lysine methyl transferases are compelling oncology targets due to the recent characterization of gain-of-function mutations and translocations in several hematological cancers. To date, these proteins have proven intractable to small molecule inhibition. Here, we present initial efforts to identify inhibitors of MMSET (aka NSD2 or WHSC1) using solution phase and crystal structural methods. On the basis of 2D NMR experiments comparing NSD1 and MMSET structural mobility, we designed an MMSET construct with five point mutations in the N-terminal helix of its SET domain for crystallization experiments and elucidated the structure of the mutant MMSET SET domain at 2...
November 18, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27569753/chemical-inhibition-of-protein-methyltransferases
#15
REVIEW
Matthieu Schapira
Protein methyltransferases (PMTs) participate in the epigenetic control of cell fate and other signaling pathways that are deregulated in disease, and the first PMT inhibitors have entered clinical trials in oncology. This review discusses structural studies that recently uncovered the mode of action of compounds in the clinic, as well as challenges and opportunities in the development of PMT inhibitors. It examines inhibitors that compete with the highly polar cofactor but preserve cell penetrance, and allosteric modes of inhibition...
September 22, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27552921/systems-heterogeneity-an-integrative-way-to-understand-cancer-heterogeneity
#16
Diane Catherine Wang, Xiangdong Wang
The concept of systems heterogeneity was firstly coined and explained in the Special Issue, as a new alternative to understand the importance and complexity of heterogeneity in cancer. Systems heterogeneity can offer a full image of heterogeneity at multi-dimensional functions and multi-omics by integrating gene or protein expression, epigenetics, sequencing, phosphorylation, transcription, pathway, or interaction. The Special Issue starts with the roles of epigenetics in the initiation and development of cancer heterogeneity through the interaction between permanent genetic mutations and dynamic epigenetic alterations...
August 20, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27542004/next-generation-sequencing-in-cancer-opportunities-and-challenges-for-precision-cancer-medicine
#17
Carmela Paolillo, Eric Londin, Paolo Fortina
Over the past decade, testing the genes of patients and their specific cancer types has become standardized practice in medical oncology since somatic mutations, changes in gene expression and epigenetic modifications are all hallmarks of cancer. However, while cancer genetic assessment has been limited to single biomarkers to guide the use of therapies, improvements in nucleic acid sequencing technologies and implementation of different genome analysis tools have enabled clinicians to detect these genomic alterations and identify functional and disease-associated genomic variants...
2016: Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum
https://www.readbyqxmd.com/read/27534782/-two-approaches-to-cancer-development
#18
J Šmardová, J Koptíková
BACKGROUND: The somatic mutation theory explaining the process of carcinogenesis is generally accepted. The theory postulates that carcinogenesis begins in a first renegade cell that undergoes gradual transformation from a healthy to a fully malignant state through the accumulation of genetic and epigenetic "hits". This theory focuses specifically on mutations and genetic aberrations, and their impact on cells. It considers tumors as populations of sick cells that lose control of their own proliferation...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27519803/the-therapeutic-potential-of-epigenetic-manipulation-during-infectious-diseases
#19
Joby Cole, Paul Morris, Mark J Dickman, David H Dockrell
Epigenetic modifications are increasingly recognized as playing an important role in the pathogenesis of infectious diseases. They represent a critical mechanism regulating transcriptional profiles in the immune system that contributes to the cell-type and stimulus specificity of the transcriptional response. Recent data highlight how epigenetic changes impact macrophage functional responses and polarization, influencing the innate immune system through macrophage tolerance and training. In this review we will explore how post-translational modifications of histone tails influence immune function to specific infectious diseases...
November 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27488298/clinical-decision-making-integrating-advances-in-the-molecular-understanding-of-spine-tumors
#20
C Rory Goodwin, Nancy Abu-Bonsrah, Mark H Bilsky, Jeremy J Reynolds, Laurence D Rhines, Ilya Laufer, Alexander C Disch, Arpad Bozsodi, Shreyaskumar R Patel, Ziya L Gokaslan, Daniel M Sciubba, Chetan Bettegowda
STUDY DESIGN: Literature review. OBJECTIVE: To describe advancements in molecular techniques, biomarkers, technology, and targeted therapeutics and the potential these modalities hold to predict treatment paradigms, clinical outcomes, and/or survival in patients diagnosed with primary spinal column tumors. SUMMARY OF BACKGROUND DATA: Advances in molecular technologies and techniques have influenced the prevention, diagnosis, and overall management of patients diagnosed with cancer...
October 15, 2016: Spine
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