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Epigenetic resistance

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https://www.readbyqxmd.com/read/29241213/antibiotics-induced-obesity-a-mitochondrial-perspective
#1
Melisa J Andrade, Chinchu Jayaprakash, Smitha Bhat, Nikolaos Evangelatos, Angela Brand, Kapaettu Satyamoorthy
Antibiotics are the first line of treatment against infections and have contributed immensely to reduce the morbidity and mortality rates. Recently, extensive use of antibiotics has led to alterations of the gut microbiome, predisposition to various diseases and most importantly, increase in the emergence of antibiotic-resistant bacteria, which poses a major threat to global public health. Another major issue faced worldwide due to unregulated use of antibiotics in children as well as in adults is the influence of metabolism and body weight homeostasis, leading to obesity...
December 15, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/29239299/how-does-obesity-lead-to-insulin-resistance
#2
Chan Hee J Choi, Paul Cohen
Experiments on mice show that an enzyme called DNA methyltransferase 3a is involved in insulin resistance via an epigenetic mechanism.
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29234674/microrna-in-glioblastoma-an-overview
#3
REVIEW
Barbara Banelli, Alessandra Forlani, Giorgio Allemanni, Anna Morabito, Maria Pia Pistillo, Massimo Romani
Glioblastoma is the most aggressive brain tumor and, even with the current multimodal therapy, is an invariably lethal cancer with a life expectancy that depends on the tumor subtype but, even in the most favorable cases, rarely exceeds 2 years. Epigenetic factors play an important role in gliomagenesis, are strong predictors of outcome, and are important determinants for the resistance to radio- and chemotherapy. The latest addition to the epigenetic machinery is the noncoding RNA (ncRNA), that is, RNA molecules that are not translated into a protein and that exert their function by base pairing with other nucleic acids in a reversible and nonmutational mode...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/29233643/trichostatin-a-inhibits-deacetylation-of-histone-h3-and-p53-by-sirt6
#4
Marci Wood, Stacia Rymarchyk, Song Zheng, Yana Cen
SIRT6 is an epigenetic modification enzyme that regulates gene transcription through its deacetylase activity. In addition to histone protein, SIRT6 also modify other proteins and enzymes, some of which are central players in metabolic reprogramming and aging process. Therefore, SIRT6 has emerged as a therapeutic target for the treatment of metabolic disorder and age-related diseases. Here, we report that SIRT6 deacetylates lysine 382 of p53 in short synthetic peptide sequence and in full length p53. Further studies showed that the deacetylation of H3K9Ac and p53K382Ac are insensitive to nicotinamide inhibition, but are sensitive to trichostatin A (TSA) inhibition...
December 9, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29230394/acetylome-of-acinetobacter-baumannii-sk17-reveals-a-highly-conserved-modification-of-histone-like-protein-hu
#5
Jiahn-Haur Liao, Cheng-Han Tsai, Sanjay G Patel, Jhih-Tian Yang, I-Fan Tu, Matteo Lo Cicero, Magdalena Lipka-Lloyd, Wan-Ling Wu, Wen-Jie Shen, Meng-Ru Ho, Chi-Chi Chou, Garima R Sharma, Hiroki Okanishi, Louis Y P Luk, Yu-Hsuan Tsai, Shih-Hsiung Wu
Lysine acetylation is a prevalent post-translational modification in both eukaryotes and prokaryotes. Whereas this modification is known to play pivotal roles in eukaryotes, the function and extent of this modification in prokaryotic cells remain largely unexplored. Here we report the acetylome of a pair of antibiotic-sensitive and -resistant nosocomial pathogen Acinetobacter baumannii SK17-S and SK17-R. A total of 145 lysine acetylation sites on 125 proteins was identified, and there are 23 acetylated proteins found in both strains, including histone-like protein HU which was found to be acetylated at Lys13...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29229751/suv420h2-is-an-epigenetic-regulator-of-epithelial-mesenchymal-states-in-pancreatic-cancer
#6
Manuel Viotti, Catherine Wilson, Mark McCleland, Hartmut Koeppen, Benjamin Haley, Suchit Jhunjhunwala, Christiaan Klijn, Zora Modrusan, David Arnott, Marie Classon, Jean-Philippe Stephan, Ira Mellman
Epithelial-to-mesenchymal transition is implicated in metastasis, where carcinoma cells lose sessile epithelial traits and acquire mesenchymal migratory potential. The mesenchymal state is also associated with cancer stem cells and resistance to chemotherapy. It might therefore be therapeutically beneficial to promote epithelial identity in cancer. Because large-scale cell identity shifts are often orchestrated on an epigenetic level, we screened for candidate epigenetic factors and identified the histone methyltransferase SUV420H2 (KMT5C) as favoring the mesenchymal identity in pancreatic cancer cell lines...
December 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29229600/genomic-and-epigenomic-signatures-in-ovarian-cancer-associated-with-re-sensitization-to-platinum-drugs
#7
Fang Fang, Horacio Cardenas, Hao Huang, Guanglong Jiang, Susan M Perkins, Chi Zhang, Harold N Keer, Yunlong Liu, Kenneth P Nephew, Daniela Matei
DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer (OC). In this study, we elucidated an epigenetic signature associated with platinum drug re-sensitization that may offer utility in predicting the outcomes of patients who are co-administered a DNA methyltransferase inhibitror. The OC specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant OC who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard of care chemotherapy regimen selected by the treating physician...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29225137/valproic-acid-a-histone-deacetylase-inhibitor-induces-apoptosis-in-breast-cancer-stem-cells
#8
Nazlıhan Aztopal, Merve Erkisa, Elif Erturk, Engin Ulukaya, Asuman Hatice Tokullugil, Ferda Ari
Cancer stem-like cells (CSCs) are a cell subpopulation that can reinitiate tumors, resist chemotherapy, give rise to metastases and lead to disease relapse because of an acquired resistance to apoptosis. Especially, epigenetic alterations play a crucial role in the regulation of stemness and also have been implicated in the development of drug resistance. Hence, in the present study, we examined the cytotoxic and apoptotic activity of valproic acid (VPA) as an inhibitor of histone deacetylases (HDACs) against breast CSCs (BCSCs)...
December 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29222300/emerging-options-in-multiple-myeloma-targeted-immune-and-epigenetic-therapies
#9
REVIEW
Shaji Kumar
Considerable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221571/micrornas-milk-s-epigenetic-regulators
#10
REVIEW
Bodo C Melnik, Gerd Schmitz
Our perception of milk has changed from a "simple food" to a highly sophisticated maternal-neonatal nutrient and communication system orchestrating early programming of the infant. Milk miRNAs delivered by exosomes and milk fat globules derived from mammary gland epithelial cells play a key role in this process. Exosomes resist the harsh intestinal environment, are taken up by intestinal cells via endocytosis, and reach the systemic circulation of the milk recipient. The most abundant miRNA found in exosomes and milk fat globules of human and cow's milk, miRNA-148a, attenuates the expression of DNA methyltransferase 1, which is critically involved in epigenetic regulation...
August 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29221178/cytotoxic-stress-induces-transfer-of-mitochondria-associated-human-endogenous-retroviral-rna-and-proteins-between-cancer-cells
#11
David Díaz-Carballo, Jacqueline Klein, Ali H Acikelli, Camilla Wilk, Sahitya Saka, Holger Jastrow, Gunther Wennemuth, Phillip Dammann, Urs Giger-Pabst, Veria Khosrawipour, Joachim Rassow, Mikalai Nienen, Dirk Strumberg
About 8 % of the human genome consists of human endogenous retroviruses (HERVs), which are relicts of ancient exogenous retroviral infections incurred during evolution. Although the majority of HERVs have functional gene defects or epigenetic modifications, many of them are still able to produce retroviral proteins that have been proposed to be involved in cellular transformation and cancer development. We found that, in chemo-resistant U87RETO glioblastoma cells, cytotoxic stress induced by etoposide promotes accumulation and large-scale fission of mitochondria, associated with the detection of HERV-WE1 (syncytin-1) and HERV-FRD1 (syncytin-2) in these organelles...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218097/histone-deacetylase-inhibitor-nabut-suppresses-cell-proliferation-and-induces-apoptosis-by-targeting-p21-in-multiple-myeloma
#12
Ruosi Yao, Danyang Han, Xiaoyang Sun, Chunling Fu, Qingyun Wu, Yao Yao, Hujun Li, Zhenyu Li, Kailin Xu
Multiple myeloma (MM) is an extremely serious hematological malignancy that remains incurable due to chemotherapy resistance. Epigenetic regulation is closely associated with progression of MM. Histone deacetylase inhibitor NaBut functions in various physiologic processes, including inflammation and differentiation. Its' possible roles in MM progression have not been explored. In this report, NaBut decreased survival of several human MM cell lines in a dose- and time-dependent manner. NaBut could also lead to cell cycle arrest at the G2/M phase in a dose-dependent manner...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29216878/adaptive-phenotype-drives-resistance-to-androgen-deprivation-therapy-in-prostate-cancer
#13
Nicoletta Ferrari, Ilaria Granata, Matteo Capaia, Marina Piccirillo, Mario Rosario Guarracino, Roberta Venè, Antonella Brizzolara, Andrea Petretto, Elvira Inglese, Martina Morini, Simonetta Astigiano, Adriana Agnese Amaro, Francesco Boccardo, Cecilia Balbi, Paola Barboro
BACKGROUND: Prostate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges. METHODS: Western blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP...
December 8, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29212856/tamoxifen-resistance-in-breast-cancer-is-regulated-by-the-ezh2-er%C3%AE-greb1-transcriptional-axis
#14
Yanming Wu, Zhao Zhang, Mauro E Cenciarini, Cecilia J Proietti, Matias F Amasino, Tao Hong, Mei Yang, Yiji Liao, Huai-Chin Chiang, Virginia Kaklamani, Rinath Jeselsohn, Ratna K Vadlamudi, Tim H-M Huang, Rong Li, Carmine De Angelis, Xiaoyong Fu, Patricia V Elizalde, Rachel Schiff, Myles Brown, Kexin Xu
Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents...
December 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#15
Fintan Geoghegan, Robert J Buckland, Eric T Rogers, Karima Khalifa, Emma B O'Connor, Mary F Rooney, Parviz Behnam-Motlagh, Torbjörn K Nilsson, Kjell Grankvist, Richard K Porter
Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209639/enhancer-remodeling-regulates-epigenetic-adaptation-and-resistance-to-mek1-2-inhibition-in-triple-negative-breast-cancer
#16
Samantha M Bevill, Jon S Zawistowski, Gary L Johnson
Kinase inhibitors targeting the mitogen/extracellular signal-regulated kinase kinase (MEK)- extracellular signal related kinase (ERK) signaling pathway have limited durability in inhibiting growth of triple-negative breast cancer. We defined genome wide enhancer remodeling following MEK inhibition capable of driving adaptive gene transcription. Targeting positive elongation factor (P-TEFb) transcriptional regulatory complex members can block enhancer remodeling making the response to MEK-ERK inhibition durable...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29209432/epigenetic-modifications-of-the-vgf-gene-in-human-non-small-cell-lung-cancer-tissues-pave-the-way-towards-enhanced-expression
#17
Sebastian Marwitz, Lena Heinbockel, Swetlana Scheufele, Dörte Nitschkowski, Christian Kugler, Sven Perner, Martin Reck, Ole Ammerpohl, Torsten Goldmann
Hwang et al. recently showed that VGF substantially contributes to the resistance of human lung cancer cells towards epidermal growth factor receptor kinase inhibitors. This was further linked to enhanced epithelial-mesenchymal transition. Here, we demonstrate that VGF is epigenetically modified in non-small cell lung cancer tissues compared to corresponding tumor-free lung tissues from the same donors by using methylome bead chip analyses. These epigenetic modifications trigger an increased transcription of the VGF gene within the tumors, which then leads to an increased expression of the protein, facilitating epithelial-mesenchymal transition, and the resistance to kinase inhibitors...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29206844/restoration-of-the-prolyl-hydroxylase-domain-protein-3-oxygen-sensing-mechanism-is-responsible-for-regulation-of-hif2%C3%AE-expression-and-induction-of-sensitivity-of-myeloma-cells-to-hypoxia-mediated-apoptosis
#18
Gilberto Gastelum, Aleksandra Poteshkina, Mysore Veena, Edgar Artiga, Geraldine Weckstein, Patrick Frost
Multiple myeloma (MM) is an incurable disease of malignant plasma B-cells that infiltrate the bone marrow (BM), resulting in bone destruction, anemia, renal impairment and infections. Physiologically, the BM microenvironment is hypoxic and this promotes MM progression and contributes to resistance to chemotherapy. Since aberrant hypoxic responses may result in the selection of more aggressive tumor phenotypes, we hypothesized that targeting the hypoxia-inducible factor (HIF) pathways will be an effective anti-MM therapeutic strategy...
2017: PloS One
https://www.readbyqxmd.com/read/29206651/novel-therapeutic-strategies-and-targets-in-advanced-uveal-melanoma
#19
Vivian Chua, Andrew E Aplin
PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. RECENT FINDINGS: Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1)...
December 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29203141/interacting-cancer-machineries-cell-signaling-lipid-metabolism-and-epigenetics
#20
REVIEW
Thomas W Grunt
Cancer-specific perturbations of signaling, metabolism, and epigenetics can be a cause and/or consequence of malignant transformation. Evidence indicates that these regulatory systems interact with each other to form highly flexible and robust cybernetic networks that promote malignant growth and confer treatment resistance. Deciphering these plexuses using holistic approaches known from systems biology can be instructive for the future design of novel anticancer strategies. In this review, I discuss novel findings elucidating the multiple molecular interdependence among cancer-specific signaling, cell metabolism, and epigenetics to provide an insightful understanding of how major cancer machineries interact with each other during cancer development and progression, and how this knowledge may be used for future co-targeting strategies...
December 1, 2017: Trends in Endocrinology and Metabolism: TEM
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