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Epigenetic resistance

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https://www.readbyqxmd.com/read/28731456/upregulation-of-tet-activity-with-ascorbic-acid-induces-epigenetic-modulation-of-lymphoma-cells
#1
N Shenoy, T Bhagat, E Nieves, M Stenson, J Lawson, G S Choudhary, T Habermann, G Nowakowski, R Singh, X Wu, A Verma, T E Witzig
The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity. We hypothesized that AA could potentially enhance TET activity in lymphoma cells to cause DNA demethylation, reactivate expression of tumor suppressor genes and enhance chemosensitivity...
July 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28729399/decitabine-priming-enhances-mucin-1-inhibition-mediated-disruption-of-redox-homeostasis-in-cutaneous-t-cell-lymphoma
#2
Salvia Jain, Abigail Washington, Rebecca Karp Leaf, Parul Bhargava, Rachael A Clark, Thomas S Kupper, Dina Stroopinsky, Athalia Pyzer, Leandra Cole, Myrna Nahas, Arie Apel, Jacalyn Rosenblatt, Jon Arnason, Donald Kufe, David Avigan
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the MUC1-C oncoprotein plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#3
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722229/a-transposon-directed-epigenetic-change-in-zmcct-underlies-quantitative-resistance-to-gibberella-stalk-rot-in-maize
#4
Chao Wang, Qin Yang, Weixiang Wang, Yipu Li, Yanling Guo, Dongfeng Zhang, Xuena Ma, Wei Song, Jiuran Zhao, Mingliang Xu
A major resistance quantitative trait locus, qRfg1, significantly enhances maize resistance to Gibberella stalk rot, a devastating disease caused by Fusarium graminearum. However, the underlying molecular mechanism remains unknown. We adopted a map-based cloning approach to identify the resistance gene at qRfg1 and examined the dynamic epigenetic changes during qRfg1-mediated maize resistance to the disease. A CCT domain-containing gene, ZmCCT, is the causal gene at the qRfg1 locus and a polymorphic CACTA-like transposable element (TE1) c...
July 19, 2017: New Phytologist
https://www.readbyqxmd.com/read/28722143/breast-cancer-stem-cells-as-last-soldiers-eluding-therapeutic-burn-a-hard-nut-to-crack
#5
REVIEW
Pritish Nilendu, Ajay Kumar, Azad Kumar, Jayanta K Pal, Nilesh Kumar Sharma
Cancer stem cells (CSCs) are found in many cancer types, including breast carcinoma. Breast cancer stem cells (BCSCs) are considered as seed of cancer formation and they are associated with metastasis and genotoxic drug resistance. Several studies highlighted the presence of BCSCs in tumor microenvironment and they are accentuated with several carcinoma events including metastasis and resistance to genotoxic drugs and they also rebound after genotoxic burn. Stemness properties of a small population of cells in carcinoma have provided clues regarding the role of tumor microenvironment in tumor pathophysiology...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28720801/mapping-and-characterization-of-g-quadruplexes-in-mycobacterium-tuberculosis-gene-promoter-regions
#6
Rosalba Perrone, Enrico Lavezzo, Erika Riello, Riccardo Manganelli, Giorgio Palù, Stefano Toppo, Roberta Provvedi, Sara N Richter
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719907/tumor-heterogeneity-in-lymphomas-a-different-breed
#7
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#8
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
July 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#9
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T-C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell cycle inhibitor CDKN2D and CDKN1B induced stem-like features...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716093/c-elegans-sup-46-an-hnrnpm-family-rna-binding-protein-that-prevents-paternally-mediated-epigenetic-sterility
#10
Wendy L Johnston, Aldis Krizus, Arun K Ramani, Wade Dunham, Ji Young Youn, Andrew G Fraser, Anne-Claude Gingras, James W Dennis
BACKGROUND: In addition to DNA, gametes contribute epigenetic information in the form of histones and non-coding RNA. Epigenetic programs often respond to stressful environmental conditions and provide a heritable history of ancestral stress that allows for adaptation and propagation of the species. In the nematode C. elegans, defective epigenetic transmission often manifests as progressive germline mortality. We previously isolated sup-46 in a screen for suppressors of the hexosamine pathway gene mutant, gna-2(qa705)...
July 17, 2017: BMC Biology
https://www.readbyqxmd.com/read/28711660/a-novel-deletion-involving-gnas-exon-1-causes-php1a-and-further-refines-the-region-required-for-normal-methylation-at-exon-a-b
#11
Monica Reyes, Anara Karaca, Murat Bastepe, Nese Ersoz Gulcelik, Harald Jüppner
GNAS exons 1-13 encode the biallelically expressed alpha-subunit of the stimulatory G protein (Gαs). Additional transcripts derived from this locus use alternative first exons that undergo parent-specific methylation, thus allowing transcription only from the non-modified allele. Pseudohypoparathyroidism type Ia (PHP1A) is characterized by Albright's Hereditary Osteodystrophy (AHO) and resistance to multiple hormones; this disorder is caused by maternal inactivating mutations involving Gαs exons. In contrast, pseudohypoparathyroidism type Ib (PHP1B) is characterized mostly by resistance to PTH and often mild TSH resistance, usually without AHO features...
July 12, 2017: Bone
https://www.readbyqxmd.com/read/28709969/role-of-epigenome-in-tumorigenesis-and-drug-resistance
#12
Qidong Hu, Gyeong Hun Baeg
The last few decades have witnessed a tremendous advancement in understanding the genetic basis of major human diseases such as cancer. Intriguingly, there is also an evergrowing body of evidence that suggest the critical role of epigenetic regulation in pathogenesis. In contrast to genetic mechanisms often associated with changes in DNA sequence, epigenetics generally refers to the regulation of gene expression featuring alterations in histone modification, DNA methylation, chromatin conformation and noncoding RNAs, with the first two categories being the best-characterized so far...
July 11, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28706528/molecular-mechanisms-behind-the-physiological-resistance-to-intense-transient-warming-in-an-iconic-marine-plant
#13
Lazaro Marín-Guirao, Laura Entrambasaguas, Emanuela Dattolo, Juan M Ruiz, Gabriele Procaccini
The endemic Mediterranean seagrass Posidonia oceanica is highly threatened by the increased frequency and intensity of heatwaves. Meadows of the species offer a unique opportunity to unravel mechanisms marine plants activate to cope transient warming, since their wide depth distribution impose divergent heat-tolerance. Understanding these mechanisms is imperative for their conservation. Shallow and deep genotypes within the same population were exposed to a simulated heatwave in mesocosms, to analyze their transcriptomic and photo-physiological responses during and after the exposure...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28704968/epigenetic-modifications-and-head-and-neck-cancer-implications-for-tumor-progression-and-resistance-to-therapy
#14
REVIEW
Rogerio M Castilho, Cristiane H Squarize, Luciana O Almeida
Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28700951/diabetic-retinopathy-metabolic-memory-and-epigenetic-modifications
#15
Renu A Kowluru
Retinopathy, a sight-threatening disease, remains one of the most feared complications of diabetes. Although hyperglycemia is the main initiator progression of diabetic retinopathy continues even after re-institution of normal glycemic control in diabetic patients, and the deleterious effects of prior hyperglycemic insult depend on the duration and the severity of this insult, suggesting a 'metabolic memory' phenomenon. Metabolic memory phenomenon is successfully duplicated in the experimental models of diabetic retinopathy...
July 9, 2017: Vision Research
https://www.readbyqxmd.com/read/28698948/pirna-3878-targets-p450-cpcyp307b1-to-regulate-pyrethroid-resistance-in-culex-pipiens-pallens
#16
Wenyun Ye, Xianmiao Liu, Juxin Guo, Xueli Sun, Yan Sun, Bo Shen, Dan Zhou, Changliang Zhu
Piwi-interacting RNAs (piRNAs) are a novel class of noncoding single-strand RNAs. They play an important role in the germ cell maintenance, brain development, epigenetic regulation of cancer, and antiviral function. However, little is known about the relationship between the piRNAs and insecticide resistance in mosquitoes. In this study, we reported that piRNA-3878 was related with pyrethroid resistance in Culex pipiens pallens. The expression level of piRNA-3878 was lower in both laboratory and field-collected deltamethrin-resistant (DR) strains...
July 11, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28697338/hdac-inhibitors-finally-open-up-chromatin-accessibility-signatures-of-ctcl
#17
Christopher J Ott, Catherine J Wu
In this issue of Cancer Cell, Qu et al. describe the chromatin accessibility profiles of cutaneous T cell lymphoma, with dynamic assessments of response and resistance to histone deacetylase inhibitor therapy. Their "personal regulome" analysis framework reveals chromatin features that may be predictive of clinical response to epigenetic therapy.
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28696296/multiplexed-rnai-therapy-against-brain-tumor-initiating-cells-via-lipopolymeric-nanoparticle-infusion-delays-glioblastoma-progression
#18
Dou Yu, Omar F Khan, Mario L Suvà, Biqin Dong, Wojciech K Panek, Ting Xiao, Meijing Wu, Yu Han, Atique U Ahmed, Irina V Balyasnikova, Hao F Zhang, Cheng Sun, Robert Langer, Daniel G Anderson, Maciej S Lesniak
Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28695331/vorinostat-and-mithramycin-a-in-combination-therapy-as-an-interesting-strategy-for-the-treatment-of-s%C3%A3-zary-t-lymphoma-a-transcriptomic-approach
#19
R Ragheb, G Venton, R Chelbi, N Bonnet, T Le Treut, V Ivanov, C Mercier, P Poulin, N Beaufils, J Gabert, P Suchon, P Rihet, B Loriod, B Kahn-Perlès, Régis T Costello
SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and Drug Administration (FDA) for treating advanced refractory cutaneous T cell lymphomas. As SAHA alters the expression of many genes under control of the Sp1 transcription factor, we examined the effect of its association with the FDA-approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive inhibitor of Sp1 binding to DNA. Sézary syndrome (SS) cells, expanded ex vivo from peripheral blood mononuclear cells of 4 patients, were tested for their sensitivity to the drugs regarding cytotoxicity and differential responsive gene expression...
July 10, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28694783/mpa-modulates-tight-junctions-permeability-via-midkine-pi3k-pathway-in-caco-2-cells-a-possible-mechanism-of-leak-flux-diarrhea-in-organ-transplanted-patients
#20
Niamat Khan, Lutz Binder, D V Krishna Pantakani, Abdul R Asif
Mycophenolic acid (MPA) is prescribed to prevent allograft rejection in organ transplanted patients. However, its use is sporadically linked to leak flux diarrhea and other gastrointestinal (GI) disturbances in around 75% of patients through yet unknown mechanisms. Recently, we identified Midkine as a modulator of tight junctions (TJs) permeability in MPA treated Caco-2 monolayer. In the present study, we investigated the possible involvement of Midkine dependent PI3K pathway in alteration of TJs under MPA treatment...
2017: Frontiers in Physiology
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