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Epigenetics immune response

Man Liu, Jingying Zhou, Zhiwei Chen, Alfred Sze-Lok Cheng
The tumour microenvironment plays an instrumental role in cancer development, progression and treatment response/resistance. Accumulating evidence underscores the fundamental importance of epigenetic regulation in tumour immune evasion. Following many pioneering discoveries demonstrating malignant transformation through epigenetic anomalies ("epimutations"), there is also growing emphasis on elucidating aberrant epigenetic mechanisms that reprogramme the milieu of tumour-associated immune and stromal cells toward an immunosuppressive state...
October 22, 2016: Journal of Pathology
Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
David F Tough, Paul P Tak, Alexander Tarakhovsky, Rab K Prinjha
Immune-mediated diseases are clinically heterogeneous but they share genetic and pathogenic mechanisms. These diseases may develop from the interplay of genetic factors and environmental or lifestyle factors. Exposure to such factors, including infectious agents, is associated with coordinated changes in gene transcription owing to epigenetic alterations. A growing understanding of how epigenetic mechanisms control gene expression patterns and cell function has been aided by the development of small-molecule inhibitors that target these processes...
October 21, 2016: Nature Reviews. Drug Discovery
Walter H Moos, Carl A Pinkert, Michael H Irwin, Douglas V Faller, Krishna Kodukula, Ioannis P Glavas, Kosta Steliou
Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population...
October 20, 2016: Drug Development Research
David Olagnier, Cindy Chiang, John Hiscott
The dynamics of chromatin structure contribute to the regulation of gene transcription and in part, the changes in chromatin structure associated with gene activation/repression are a function of the state of histone acetylation. Histone deacetylases (HDACs) deacetylate histone tails leading to a more compact structure of chromatin that in turn represses gene transcription. Given the rapid activation and/or repression of gene networks following microbial infection, the role of HDACs in the epigenetic regulation of genes involved in the innate and adaptive immune responses has become an area of extensive research...
2017: Methods in Molecular Biology
Patricio Lopez-Jaramillo
Cardiovascular diseases (CVD) are major causes of death and illness worldwide. In recent decades an increased prevalence of CVD mortality has been reported in low-medium income countries, which has been associated with changes in life styles, deficiencies in health systems and the persistence of social inequities.The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and increased adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus (DM2)...
September 2016: Journal of Hypertension
Nageatte Ibrahim, Elizabeth I Buchbinder, Scott R Granter, Scott J Rodig, Anita Giobbie-Hurder, Carla Becerra, Argyro Tsiaras, Evisa Gjini, David E Fisher, F Stephen Hodi
Epigenetic alterations by histone/protein deacetylases (HDACs) are one of the many mechanisms that cancer cells use to alter gene expression and promote growth. HDAC inhibitors have proven to be effective in the treatment of specific malignancies, particularly in combination with other anticancer agents. We conducted a phase I trial of panobinostat in patients with unresectable stage III or IV melanoma. Patients were treated with oral panobinostat at a dose of 30 mg daily on Mondays, Wednesdays, and Fridays (Arm A)...
October 17, 2016: Cancer Medicine
Maria C Cenit, Pilar Codoñer-Franch, Yolanda Sanz
Gut microbiota shapes the development of the mucosal immune system and may provide protection against immune-mediated diseases. Celiac disease (CD) is a chronic inflammatory condition triggered by dietary gluten proteins, recently associated with gut microbiota alterations in cross-sectional studies comparing patients and controls. Whether or not these differences are causally related to the disease has yet to be elucidated, but evaluation of specific bacteria isolated from CD patients in experimental models suggests that they can promote an adverse response to dietary gluten, whereas other commensal bacteria can be protective...
November 2016: Journal of Clinical Gastroenterology
I-Cheng Ho, Shi-Chuen Miaw
IL-4 was first identified as a T cell-derived growth factor for B cells. Studies over the past several decades have markedly expanded our understanding of its cellular sources and function. In addition to T cells, IL-4 is produced by innate lymphocytes, such as NTK cells, and myeloid cells, such as basophils and mast cells. It is a signature cytokine of type 2 immune response but also has a nonimmune function. Its expression is tightly regulated at several levels, including signaling pathways, transcription factors, epigenetic modifications, microRNA, and long noncoding RNA...
2016: Advances in Experimental Medicine and Biology
Amanda R Dancsok, Karama Asleh-Aburaya, Torsten O Nielsen
The heterogeneity of sarcomas with regard to molecular genesis, histology, clinical characteristics, and response to treatment makes management of these rare yet diverse neoplasms particularly challenging. This review encompasses recent developments in sarcoma diagnostics and treatment, including cytotoxic, targeted, epigenetic, and immune therapy agents. In the past year, groups internationally explored the impact of adding mandatory molecular testing to histological diagnosis, reporting some changes in diagnosis and/or management; however, the impact on outcomes could not be adequately assessed...
October 9, 2016: Oncotarget
Rob J W Arts, Mihai G Netea
The innate immune system is considered to have no immune memory. However, lately there has been as shift in paradigm. Cells of the innate immune system, and especially monocytes and macrophages, are capable of building a nonspecific memory, resulting in either better or worse responses to secondary stimulations/infections, as a result of epigenetic changes. This review gives a general overview of the at-the-moment available data.
August 2016: Microbiology Spectrum
Jun Udagawa, Kodai Hino
Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon...
2016: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Fang Zhang, Guiyou Liu, Yali Bu, Xiaofeng Ma, Junwei Hao
For the epigenetic characterization of myasthenia gravis (MG), we determined whether long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) are expressed differentially in subjects with and without MG. Compared with healthy control subjects, the MG patients had 1561 upregulated lncRNAs, 1034 downregulated lncRNAs, 921 upregulated mRNAs, and 806 downregulated mRNAs (fold change>2.0). Several GO terms including nucleic acid transcription factor activity, inflammatory response, regulation of leukocyte activation, lymphocyte proliferation and regulation of B cell proliferation were enriched in gene lists, suggesting a potential correlation with MG...
October 15, 2016: Journal of Neuroimmunology
Maximilian Stahl, Nathan Kohrman, Steven D Gore, Tae Kon Kim, Amer M Zeidan, Thomas Prebet
For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis...
October 2016: PLoS Genetics
Patrícia Oliveira, Joana Carvalho, Sara Rocha, Mafalda Azevedo, Inês Reis, Vânia Camilo, Bárbara Sousa, Sofia Valente, Joana Paredes, Raquel Almeida, David Huntsman, Carla Oliveira
Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown...
October 10, 2016: Scientific Reports
Amber Dahlin, Scott T Weiss
Aspirin-exacerbated respiratory disease (AERD) severity and its clinical phenotypes are characterized by genetic variation within pathways for arachidonic acid metabolism, inflammation, and immune responses. Epigenetic effects, including DNA methylation and histone protein modification, contribute to regulation of many genes that contribute to inflammatory states in AERD. The development of noninvasive, predictive clinical tests using data from genetic, epigenetic, pharmacogenetic, and biomarker studies will improve precision medicine efforts for AERD and asthma treatment...
November 2016: Immunology and Allergy Clinics of North America
Y H Zhang, J L Meng, Y Gao, J Y Zhang, S L Niu, X Z Yu, Y B Li, Y T Guan, B X Sun, Z H Zhao
DNA methylation is an important epigenetic modification in eukaryotes, which plays a significant role in regulating gene expression. When the host is invaded by the influenza virus, gene expression is regulated via changes in DNA methylation levels or patterns, leading to the activation or suppression of relevant signaling pathways or networks, triggering a series of immune responses against viral invasion. Here, we investigated the changes in genomic DNA methylation in the immune organs of chicken infected with H5N1 influenza virus...
September 16, 2016: Genetics and Molecular Research: GMR
Carmela Nardelli, Ilaria Granata, Laura Iaffaldano, Valeria D'Argenio, Valentina Del Monaco, Giuseppe Maria Maruotti, Luigi Del Vecchio, Pasquale Martinelli, Francesco Salvatore, Mario Rosario Guarracino, Lucia Sacchetti, Lucio Pastore
Experimental evidence indicates differences between women and men in several medical areas, including susceptibility to metabolic diseases. Sexual dimorphism could be influenced by microRNA (miRNA)-mediated regulation of gene expression, and miRNAs have also been implicated in fetal programming of obesity. Our previous finding of altered proteome in human amniotic stem cells (hA-MSCs) during obesity (Ob-) prompted us to look for gender-related differences in the miRNA regulation of gene expression in Ob-hA-MSCs that might be involved in metabolic changes...
October 5, 2016: Stem Cells and Development
David L Marks, Rachel Lo Olson, Martin E Fernandez-Zapico
Stromal cells of the tumor microenvironment have been shown to play important roles in both supporting and limiting cancer growth. The altered phenotype of tumor-associated stromal cells (fibroblasts, immune cells, endothelial cells etc.) is proposed to be mainly due to epigenetic dysregulation of gene expression; however, only limited studies have probed the roles of epigenetic mechanisms in the regulation of stromal cell function. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation and histone post-translational modification-based gene expression regulation, and miRNA-mediated translational regulation) drive aspects of stromal cell phenotype, and discuss the implications of these findings for treatment of malignancies...
October 4, 2016: Epigenomics
Karmen Stankov, Sunčica Stankov, Jasmina Katanić
BACKGROUND: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders of hematopoietic system, characterized by genetic, epigenetic or microenvironmental alterations of aging hematopoietic stem cells. Pathophysiology of MDS comprises the suppression of normal hematopoiesis and reduced myeloid progenitor cells differentiation, with the main consequence of peripheral cytopenias and increased risk to evolution in acute myeloid leukemia (AML). METHOD: This review summarizes the evolving understanding of the role of genetic and epigenetic alterations involved in pathogenesis and current and future strategies for therapeutic targeting in myelodysplastic syndromes...
October 3, 2016: Current Pharmaceutical Design
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