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Epigenetics immune response in cancer

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https://www.readbyqxmd.com/read/29774218/new-insights-of-helicobacter-pylori-host-pathogen-interactions-the-triangle-of-virulence-factors-epigenetic-modifications-and-non-coding-rnas
#1
REVIEW
Farzam Vaziri, Samira Tarashi, Abolfazl Fateh, Seyed Davar Siadat
Helicobacter pylori ( H. pylori ) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important...
May 16, 2018: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/29771197/emerging-insights-into-wnt-%C3%AE-catenin-signaling-in-head-and-neck-cancer
#2
K A Alamoud, M A Kukuruzinska
Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits...
June 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29760044/nk-cells-mediate-synergistic-antitumor-effects-of-combined-inhibition-of-hdac6-and-bet-in-a-sclc-preclinical-model
#3
Yan Liu, Yuyang Li, Shengwu Liu, Dennis O Adeegbe, Camilla L Christensen, Max M Quinn, Ruben Dries, Shiwei Han, Kevin Buczkowski, Xiaoen Wang, Ting Chen, Peng Gao, Hua Zhang, Fei Li, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Small cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications in SCLC suggest that transcriptional and epigenetic regulations play a major role in SCLC disease evolution. Here we performed a synthetic lethal screen using the BET inhibitor JQ1 and an shRNA library targeting 550 epigenetic genes in treatment-refractory SCLC xenograft models and identified HDAC6 as a synthetic lethal target in combination with JQ1...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29754176/micrornas-regulatory-messengers-inside-and-outside-cancer-cells
#4
Simone Anfossi, Xiao Fu, Rahul Nagvekar, George A Calin
MicroRNAs (miRNAs) are a class of short non-coding RNAs (ncRNAs) with typical sequence lengths of 19-25 nucleotides and extraordinary abilities to regulate gene expression. Because miRNAs regulate multiple important biological functions of the cell (proliferation, migration, invasion, apoptosis, differentiation, and drug resistance), their expression is highly controlled. Genetic and epigenetic alterations frequently found in cancer cells can cause aberrant expression of miRNAs and, consequently, of their target genes...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29732386/naturally-occurring-canine-invasive-urothelial-carcinoma-a-model-for-emerging-therapies
#5
REVIEW
Breann C Sommer, Deepika Dhawan, Timothy L Ratliff, Deborah W Knapp
The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remission, and toxicities are common. With the complexities of the therapies, and the growing list of possible drug combinations to test, highly relevant animal models are needed to assess and select the most promising approaches to carry forward into human trials...
April 26, 2018: Bladder Cancer
https://www.readbyqxmd.com/read/29729581/immune-prophets-of-lung-cancer-the-prognostic-and-predictive-landscape-of-cellular-and-molecular-immune-markers
#6
REVIEW
Ivana Catacchio, Anna Scattone, Nicola Silvestris, Anita Mangia
Lung cancer is the leading cause of cancer deaths throughout the world. The majority of patients are diagnosed with locally advanced or metastatic disease when surgery, the best curative option, is no longer feasible. Thus, the prognosis of lung cancer remains poor and heterogeneous and new biomarkers are needed. As the immune system plays a pivotal role in cancer, the study of tumor microenvironment, with regard to the immune component, may provide valuable information for a better comprehension of the pathogenesis and progression of the disease...
May 2, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29695433/krab-zfp-repressors-enforce-quiescence-of-oncogenic-human-herpesviruses
#7
Xiaofan Li, Eric M Burton, Siva Koganti, Jizu Zhi, Francis Doyle, Scott A Tenenbaum, Biljana Horn, Sumita Bhaduri-McIntosh
Cancer-causing herpesviruses infect nearly every human and persist indefinitely in B lymphocytes in a quiescent state known as latency. A hallmark of this quiescence or latency is the presence of extrachromosomal viral genomes with highly restricted expression of viral genes. Silencing of viral genes ensures both immune evasion by the virus and limited pathology to the host; yet, how multiple genes on multiple copies of viral genomes are simultaneously silenced is a mystery. In a unifying theme, we report that both cancer-causing human herpesviruses, despite having evolved independently, are silenced through the activities of two members of the KRAB-ZFP epigenetic silencing family, revealing a novel STAT3-KRAB-ZFP axis of viral latency...
April 25, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29680223/dysregulation-of-micrornas-in-autoimmune-diseases-pathogenesis-biomarkers-and-potential-therapeutic-targets
#8
Hai Long, Xin Wang, Yongjian Chen, Ling Wang, Ming Zhao, Qianjin Lu
MicroRNAs (miRNAs) are small, single-stranded, endogenous non-coding RNAs that repress the expression of target genes via post-transcriptional mechanisms. Due to their broad regulatory effects, the precisely regulated, spatial-specific and temporal-specific expression of miRNAs is fundamentally important to various biological processes including the immune homeostasis and normal function of both innate and adaptive immune response. Aberrance of miRNAs is implicated in the development of various human diseases, especially cancers...
April 19, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29669262/dna-mismatch-repair-in-cancer
#9
REVIEW
Marina Baretti, Dung T Le
Microsatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide substitution, as consequence of DNA mismatch repair (MMR) deficiency. MSI secondary to germline mutation in DNA MMR proteins is the molecular fingerprint of Lynch syndrome (LS), while epigenetic inactivation of these genes is more commonly found in sporadic MSI tumors. MSI occurs at different frequencies across malignancies, although original methods to assess MSI or MMR deficiency have been developed mostly in LS related cancers...
April 15, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29666625/dying-to-be-noticed-epigenetic-regulation-of-immunogenic-cell-death-for-cancer-immunotherapy
#10
REVIEW
Brianne Cruickshank, Michael Giacomantonio, Paola Marcato, Sherri McFarland, Jonathan Pol, Shashi Gujar
Immunogenic cell death (ICD) activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various "hallmarks" of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29666300/a-pan-cancer-landscape-of-interactions-between-solid-tumors-and-infiltrating-immune-cell-populations
#11
David Tamborero, Carlota Rubio-Perez, Ferran Muiños, Radhakrishnan Sabarinathan, Josep Maria Piulats, Aura Muntasell, Rodrigo Dienstmann, Nuria Lopez-Bigas, Abel Gonzalez-Perez
PURPOSE: Throughout their development tumors are challenged by the immune system and they acquire features to evade its surveillance. A systematic view of these traits which sheds light on how tumors respond to immunotherapies is still lacking. EXPERIMENTAL DESIGN: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immune-phenotypes...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29664561/the-function-and-dysfunction-of-memory-cd8-t-cells-in-tumor-immunity
#12
REVIEW
James L Reading, Felipe Gálvez-Cancino, Charles Swanton, Alvaro Lladser, Karl S Peggs, Sergio A Quezada
The generation and maintenance of CD8+ T cell memory is crucial to long-term host survival, yet the basic tenets of CD8+ T cell immunity are still being established. Recent work has led to the discovery of tissue-resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8+ T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de-repress the anti-tumor response...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29625385/targeting-macrophage-immunometabolism-dawn-in-the-darkness-of-sepsis
#13
REVIEW
V Kumar
Sepsis is known since the time (470 BC) of great Greek physician, Hippocrates. Advancement in modern medicine and establishment of separate branches of medical science dealing with sepsis research have improved its outcome. However, mortality associated with sepsis still remains higher (25-30%) that further increases to 40-50% in the presence of septic shock. For example, sepsis-associated deaths account more in comparison to deaths-associated with myocardial-infarction and certain cancers (i.e. breast and colorectal cancer)...
May 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29603746/mbd2-enables-tumourigenesis-within-the-intestine-while-preventing-tumour-promoting-inflammation
#14
Stephanie May, Heather Owen, Toby J Phesse, Kirsty R Greenow, Gareth-Rhys Jones, Adam Blackwood, Peter C Cook, Christopher Towers, Awen M Gallimore, Geraint T Williams, Michael Stürzl, Nathalie Britzen-Laurent, Owen J Sansom, Andrew S MacDonald, Adrian P Bird, Alan R Clarke, Lee Parry
Epigenetic regulation plays a key role in the link between inflammation and cancer. Here we examine Mbd2, which mediates epigenetic transcriptional silencing by binding to methylated DNA. In separate studies the Mbd2-/- mouse has been shown to be (1) resistant to intestinal tumourigenesis and (2) have an enhanced inflammatory/immune response; observations that are inconsistent with the links between inflammation and cancer. To clarify its role in tumourigenesis and inflammation, we used constitutive and conditional models of Mbd2 deletion to explore its epithelial and non-epithelial roles in the intestine...
March 30, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29601548/roles-of-nf-%C3%AE%C2%BAb-signaling-in-the-regulation-of-mirnas-impacting-on-inflammation-in-cancer
#15
REVIEW
Georgios S Markopoulos, Eugenia Roupakia, Maria Tokamani, Georgia Alabasi, Raphael Sandaltzopoulos, Kenneth B Marcu, Evangelos Kolettas
The NF-κB family of transcription factors regulate the expression of genes encoding proteins and microRNAs (miRNA, miR) precursors that may either positively or negatively regulate a variety of biological processes such as cell cycle progression, cell survival, and cell differentiation. The NF-κB-miRNA transcriptional regulatory network has been implicated in the regulation of proinflammatory, immune, and stress-like responses. Gene regulation by miRNAs has emerged as an additional epigenetic mechanism at the post-transcriptional level...
March 30, 2018: Biomedicines
https://www.readbyqxmd.com/read/29588320/urinary-bladder-cancer-tregs-suppress-mmp2-and-potentially-regulate-invasiveness
#16
Malin E Winerdal, David Krantz, Ciputra A Hartana, Ali A Zirakzadeh, Ludvig Linton, Emma A Bergman, Robert Rosenblatt, Janos Vasko, Farhood Alamdari, Johan Hansson, Benny Holmström, Markus Johansson, Max Winerdal, Per Marits, Amir Sherif, Ola Winqvist
Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This discrepancy has partly been attributed to the shear misidentification of Tregs, but also to the inflammatory profile of the tumor. Our aim was to determine whether tumor-infiltrating Forkhead box P3+ (FOXP3+ ) cells confer a stable Treg phenotype and to investigate putative beneficial Treg functions, focusing on tumor-promoting inflammatory pathways in UBC...
March 27, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29581297/inhibition-of-enhancer-of-zeste-homolog-2-ezh2-induces-natural-killer-cell-mediated-eradication-of-hepatocellular-carcinoma-cells
#17
Suresh Bugide, Michael R Green, Narendra Wajapeyee
Natural killer (NK) cell-mediated tumor cell eradication could inhibit tumor initiation and progression. However, the factors that regulate NK cell-mediated cancer cell eradication remain unclear. We determined that hepatocellular carcinoma (HCC) cells exhibit transcriptional down-regulation of NK group 2D (NKG2D) ligands and are largely resistant to NK cell-mediated eradication. Because the down-regulation of NKG2D ligands occurred at the transcriptional level, we tested 32 chemical inhibitors of epigenetic regulators for their ability to re-express NKG2D ligands and enhance HCC cell eradication by NK cells and found that Enhancer of zeste homolog 2 (EZH2) was a transcriptional repressor of NKG2D ligands...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29562193/combination-cancer-therapy-with-immune-checkpoint-blockade-mechanisms-and-strategies
#18
REVIEW
Shetal A Patel, Andy J Minn
The success of immune checkpoint blockade in patients with a wide variety of malignancies has changed the treatment paradigm in oncology. However, combination therapies with immune checkpoint blockade will be needed to overcome resistance and broaden the clinical utility of immunotherapy. Here we discuss a framework for rationally designing combination therapy strategies based on enhancing major discriminatory functions of the immune system that are corrupted by cancer-namely, antigenicity, adjuvanticity, and homeostatic feedback inhibition...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29559981/gene-profiling-in-patients-with-systemic-sclerosis-reveals-the-presence-of-oncogenic-gene-signatures
#19
Marzia Dolcino, Andrea Pelosi, Piera Filomena Fiore, Giuseppe Patuzzo, Elisa Tinazzi, Claudio Lunardi, Antonio Puccetti
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by three pathogenetic hallmarks: vasculopathy, dysregulation of the immune system, and fibrosis. A particular feature of SSc is the increased frequency of some types of malignancies, namely breast, lung, and hematological malignancies. Moreover, SSc may also be a paraneoplastic disease, again indicating a strong link between cancer and scleroderma. The reason of this association is still unknown; therefore, we aimed at investigating whether particular genetic or epigenetic factors may play a role in promoting cancer development in patients with SSc and whether some features are shared by the two conditions...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29556023/demethylator-phenotypes-in-acute-myeloid-leukemia
#20
Andrew D Kelly, Jozef Madzo, Priyanka Madireddi, Patricia Kropf, Charly R Good, Jaroslav Jelinek, Jean-Pierre J Issa
Acute myeloid leukemia (AML) often harbors mutations in epigenetic regulators, and also has frequent DNA hypermethylation, including the presence of CpG island methylator phenotypes (CIMPs). Although global hypomethylation is well known in cancer, the question of whether distinct demethylator phenotypes (DMPs) exist remains unanswered. Using Illumina 450k arrays for 194 patients from The Cancer Genome Atlas, we identified two distinct DMPs by hierarchical clustering: DMP.1 and DMP.2. DMP.1 cases harbored mutations in NPM1 (94%), FLT3 (71%) and DNMT3A (61%)...
March 7, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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