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Epigenetic resistance

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https://www.readbyqxmd.com/read/28439030/epithelial-ezh2-serves-as-an-epigenetic-determinant-in-experimental-colitis-by-inhibiting-tnf%C3%AE-mediated-inflammation-and-apoptosis
#1
Yongfeng Liu, Junjie Peng, Tongyu Sun, Ni Li, Le Zhang, Jiale Ren, Huairui Yuan, Shan Kan, Qiang Pan, Xiang Li, Yufeng Ding, Min Jiang, Xiaoji Cong, Minjia Tan, Yushui Ma, Da Fu, Sanjun Cai, Yichuan Xiao, Xiaoming Wang, Jun Qin
Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the mechanism through which epigenetic regulation modulates intestinal epithelial integrity remains largely undefined. Here we show that EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. In accordance with reduced EZH2 expression in patients, the inactivation of EZH2 in IECs sensitizes mice to DSS- and TNBS-induced experimental colitis...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28433423/prefrontal-cortex-expression-of-chromatin-modifier-genes-in-male-wsp-and-wsr-mice-changes-across-ethanol-dependence-withdrawal-and-abstinence
#2
Joel G Hashimoto, David P Gavin, Kristine M Wiren, John C Crabbe, Marina Guizzetti
Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines...
March 14, 2017: Alcohol
https://www.readbyqxmd.com/read/28432280/small-molecules-targeting-histone-demethylase-genes-kdms-inhibit-growth-of-temozolomide-resistant-glioblastoma-cells
#3
Barbara Banelli, Antonio Daga, Alessandra Forlani, Giorgio Allemanni, Daniela Marubbi, Maria Pia Pistillo, Aldo Profumo, Massimo Romani
In glioblastoma several histone demethylase genes (KDM) are overexpressed compared to normal brain tissue and the development of Temozolomide (TMZ) resistance is accompanied by the transient further increased expression of KDM5A and other KDMs following a mechanism that we defined as "epigenetic resilience". We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on glioblastoma cells and found that both molecules are more effective against TMZ-resistant rather than native cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430163/long-non-coding-rnas-key-regulators-of-epithelial-mesenchymal-transition-tumour-drug-resistance-and-cancer-stem-cells
#4
REVIEW
Richard Heery, Stephen P Finn, Sinead Cuffe, Steven G Gray
Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure...
April 21, 2017: Cancers
https://www.readbyqxmd.com/read/28429280/synergistic-anti-cancer-effects-of-epigenetic-drugs-on-medulloblastoma-cells
#5
Juan Yuan, Núria Llamas Luceño, Bjoern Sander, Monika M Golas
PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain...
April 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28428964/micrornas-mediated-regulation-of-skeletal-muscle-glut4-expression-and-translocation-in-insulin-resistance
#6
REVIEW
João Victor Esteves, Francisco Javier Enguita, Ubiratan Fabres Machado
The solute carrier family 2 facilitated glucose transporter member 4 (GLUT4) plays a key role in the insulin-induced glucose uptake by muscle and adipose tissues. In prediabetes and diabetes, GLUT4 expression/translocation has been detected as reduced, participating in mechanisms that impair glycemic control. Recently, a class of short endogenous noncoding RNAs named microRNAs (miRNAs) has been increasingly described as involved in the posttranscriptional epigenetic regulation of gene expression. The present review focuses on miRNAs potentially involved in the expression of GLUT4 expression, and proteins related to GLUT4 and translocation in skeletal muscle, seeking to correlate them with insulin resistance and diabetes...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28427171/evaluation-of-intracavitary-administration-of-curcumin-for-the-treatment-of-sarcomatoid-mesothelioma
#7
Daniel L Pouliquen, Béatrice Nawrocki-Raby, Joëlle Nader, Stéphanie Blandin, Myriam Robard, Philippe Birembaut, Marc Grégoire
A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration.The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#8
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28424732/evidence-for-loss-in-identity-de-differentiation-and-trans-differentiation-of-islet-%C3%AE-cells-in-type-2-diabetes
#9
REVIEW
Chad S Hunter, Roland W Stein
The two main types of diabetes mellitus have distinct etiologies, yet a similar outcome: loss of islet β-cell function that is solely responsible for the secretion of the insulin hormone to reduce elevated plasma glucose toward euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by autoimmune-mediated β-cell death leading to insulin-dependence, whereas type 2 diabetes (T2D) has hallmarks of peripheral insulin resistance, β-cell dysfunction, and cell death. However, a growing body of evidence suggests that, especially during T2D, key components of β-cell failure involves: (1) loss of cell identity, specifically proteins associated with mature cell function (e...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28423456/progesterone-resistance-in-endometriosis-origins-consequences-and-interventions
#10
Bansari G Patel, Martin Rudnicki, Jie Yu, Yimin Shu, Robert N Taylor
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis...
April 19, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28420882/the-role-of-the-swi-snf-chromatin-remodeling-complex-in-maintaining-the-stemness-of-glioma-initiating-cells
#11
Hiroaki Hiramatsu, Kazuyoshi Kobayashi, Kyousuke Kobayashi, Takeshi Haraguchi, Yasushi Ino, Tomoki Todo, Hideo Iba
Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419281/expression-of-the-plasmodium-falciparum-clonally-variant-clag3-genes-in-human-infections
#12
Sofía Mira-Martínez, Evi van Schuppen, Alfred Amambua-Ngwa, Emmanuel Bottieau, Muna Affara, Marjan Van Esbroeck, Erika Vlieghe, Pieter Guetens, Núria Rovira-Graells, Gloria P Gómez-Pérez, Pedro L Alonso, Umberto D'Alessandro, Anna Rosanas-Urgell, Alfred Cortés
Background.: Many genes of the malaria parasite Plasmodium falciparum show clonally variant expression regulated at the epigenetic level. These genes participate in fundamental host-parasite interactions and contribute to adaptive processes. However, little is known about their expression patterns during human infections. A peculiar case of clonally variant genes are the 2 nearly identical clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to resistance to some toxic compounds...
February 7, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28416802/rna-editing-dependent-epitranscriptome-diversity-in-cancer-stem-cells
#13
REVIEW
Qingfei Jiang, Leslie A Crews, Frida Holm, Catriona H M Jamieson
Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli...
April 18, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28415616/z-ligustilide-restores-tamoxifen-sensitivity-of-era-negative-breast-cancer-cells-by-reversing-mta1-ifi16-hdacs-complex-mediated-epigenetic-repression-of-era
#14
Hui Ma, Li Li, Guojun Dou, Chengqiang Wang, Juan Li, Hui He, Mingxia Wu, Hongyi Qi
Emerging evidence indicates epigenetic modification represses estrogen receptor α (ERα) and contributes to the resistance to tamoxifen in aggressive ERα-negative (ERα-) breast cancer. Z-ligustilide is a major compound in Radix Angelica sinensis, an herb from traditional Chinese medicine (TCM) most frequently prescribed for breast cancer. However, the role of Z-ligustilide in ERα- breast cancer and epigenetic modification remains largely unknown. Herein we showed, for the first time, that Z-ligustilide restored the growth inhibition of tamoxifen on ERα- breast cancer cells...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415063/neuron-restrictive-silencer-factor-mediated-downregulation-of-%C3%AE-opioid-receptor-contributes-to-the-reduced-morphine-analgesia-in-bone-cancer-pain
#15
Chao Zhu, Jun Tang, Tan Ding, Lei Chen, Wei Wang, Xiao-Peng Mei, Xiao-Tao He, Wen Wang, Li-Dong Zhang, Yu-Lin Dong, Zhuo-Jing Luo
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively...
May 2017: Pain
https://www.readbyqxmd.com/read/28412359/potentiation-of-docetaxel-sensitivity-by-mir-638-via-regulation-of-stard10-pathway-in-human-breast-cancer-cells
#16
Ge Zhao, Ying Li, Ting Wang
Acquired resistance to classical chemotherapeutics such as docetaxel (DTX) remains a critical challenge in breast cancer (BCa) treatment. Epigenetic modification by microRNAs (miRNAs) has been shown to play a crucial role in cancer drug resistance. Previous study, using human drug-resistant BCa tissues, has identified miR-638 as one of the most down-regulated miRNAs, but its exact roles and underlying mechanisms during the pathogenesis of chemoresistance remain to be determined. In the current study, we found that miR-638 expression was significantly down-regulated in clinical DTX-resistant BCa tissues compared to that in DTX-sensitive BCa tissues...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28410117/racial-disparities-disruptive-genes-in-prostate-carcinogenesis
#17
Savita Singh, Alexis Plaga, Girish C Shukla
Population specific studies in prostate cancer (PCa) reveal a unique heterogeneous etiology. Various factors, such as genetics, environment and dietary regimen seems to determine disease progression, therapeutic resistance and rate of mortality. Enormous disparity documented in disease incidences, aggressiveness and mortality in PCa among AAs (African Americans) and CAs (Caucasian Americans) is attributed to the variations in genetics, epigenetics and their association with metabolism. Scientific and clinical evidences have revealed the influence of variations in Androgen Receptor (AR), RNAse L, macrophage scavenger receptor 1 (MRS1), androgen metabolism by cytochrome P450 3A4, differential regulation of microRNAs, epigenetic alterations and diet in racial disparity in PCa incidences and mortality...
June 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28407579/plga-peg-nano-delivery-system-for-epigenetic-therapy
#18
Asia Naz, Yi Cui, Christopher J Collins, David H Thompson, Joseph Irudayaraj
Efficient delivery of cytidine analogues such as Azacitidine (AZA) into solid tumors constitutes a primary challenge in epigenetic therapies. We developed a di-block nano-vector based on poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) for stabilization of the conjugated AZA under physiological conditions. With equimolar drug content, our nano-conjugate could elicit a better anti-proliferative effect over free drug in breast cancer both in vitro and in vivo, through reactivation of p21 and BRCA1 to restrict cell proliferation...
April 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28403792/nanocarriers-in-improving-chemotherapy-of-multidrug-resistant-tumors-key-developments-and-perspective
#19
Dimitry A Chistiakov, Veronika A Myasoedova, Alexander N Orekhov, Yuri V Bobryshev
The multidrug resistance (MDR) of tumor cells significantly reduces the efficiency of traditional anticancer therapy. Tumor MDR is complex and involves several mechanisms such as decreased drug uptake, increased drug efflux, enhanced drug exocytosis, increased drug detoxification and inactivation by drug-metabolizing enzymes, altered drug targets due to genetic and epigenetic modifications, altered DNA repair, and impaired apoptotic pathways. Implementation of nanoparticles can markedly improve drug delivery through increased stability in the plasma, prolonged half-life, enhanced specificity of transfer, and advanced drug accumulation and retention in the tumor cells...
April 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28403629/methylation-of-slfn11-is-a-marker-of-poor-prognosis-and-cisplatin-resistance-in-colorectal-cancer
#20
Tao He, Meiying Zhang, Ruipan Zheng, Shufang Zheng, Enqiang Linghu, James G Herman, Mingzhou Guo
AIM: The expression of human SLFN11 was reported to sensitize cancer cells to DNA damaging agents. This study is to explore the epigenetic change and the function of SLFN11 in human colorectal cancer (CRC). MATERIALS & METHODS: Six CRC cell lines and 128 primary CRC samples were used. RESULTS: SLFN11 was methylated in 55.47% (71/128) of primary CRC. The expression of SLFN11 was regulated by promoter region methylation. Methylation of SLFN11 was significantly associated with age, poor 5-year overall survival and 5-year relapse-free survival (all p < 0...
April 13, 2017: Epigenomics
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