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Epigenetic resistance

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https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#1
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28213404/hydrogen-sulfide-alleviates-hypertensive-kidney-dysfunction-through-an-epigenetic-mechanism
#2
Gregory Weber, Sathnur Pushpakumar, Utpal Sen
Hypertension is a major risk factor for chronic kidney disease (CKD) and renal inflammation is an integral part in this pathology. Hydrogen sulfide (H2S) has been shown to mitigate renal damage through reduction in blood pressure and reactive oxygen species; however, the exact mechanisms are not clear. While several studies have underlined the role of epigenetics in renal inflammation and dysfunction, the mechanisms through which epigenetic regulators play role in hypertension are not well defined. In this study, we sought to identify if microRNAs are dysregulated in response to angiotensin-II (Ang-II) induced hypertension in the kidney and whether H2S donor, GYY 4137, could reverse the microRNA alteration and kidney function...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28210913/dietary-and-commercialized-fructose-sweet-or-sour
#3
REVIEW
Aslihan Yerlikaya, Tuncay Dagel, Christopher King, Masanari Kubawara, Miguel A Lanaspa, Ana Andres-Hernando, Adrian Covic, Jacek Manitius, Alan A Sag, Mehmet Kanbay
Metabolic syndrome and diabetes are main health problems of modern life in the twenty-first century. Alarming ratios of global prevalence lead to conduct more and more researches about etiological factors and pathogenesis. Disease mechanism is elementary for advancing more efficient and practicable treatment methods. Concurrent increase in both fructose consumption with Western diet and metabolic syndrome has revealed fructose hypothesis that suggests fructose as one of etiological factor of metabolic syndrome (insulin resistance, central obesity, hypertension, etc...
February 16, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#4
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28203090/exploring-targeted-therapy-of-osteosarcoma-using-proteomics-data
#5
Parunya Chaiyawat, Jongkolnee Settakorn, Apiruk Sangsin, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Aungsumalee Soongkhaw, Dumnoensun Pruksakorn
Despite multimodal therapeutic treatments of osteosarcoma (OS), some patients develop resistance to currently available regimens and eventually end up with recurrent or metastatic outcomes. Many attempts have been made to discover effective drugs for improving outcome; however, due to the heterogeneity of the disease, new therapeutic options have not yet been identified. This study aims to explore potential targeted therapy related to protein profiles of OS. In this review of proteomics studies, we extracted data on differentially expressed proteins (DEPs) from archived literature in PubMed and our in-house repository...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28191457/the-copper-transport-associated-protein-ctr4-can-form-prion-like-epigenetic-determinants-in-schizosaccharomyces-pombe
#6
Theodora Sideri, Yoko Yashiroda, David A Ellis, María Rodríguez-López, Minoru Yoshida, Mick F Tuite, Jürg Bähler
Prions are protein-based infectious entities associated with fatal brain diseases in animals, but also modify a range of host-cell phenotypes in the budding yeast, Saccharomyces cerevisiae. Many questions remain about the evolution and biology of prions. Although several functionally distinct prion-forming proteins exist in S. cerevisiae, [HET-s] of Podospora anserina is the only other known fungal prion. Here we investigated prion-like, protein-based epigenetic transmission in the fission yeast Schizosaccharomyces pombe...
January 2017: Microbial Cell
https://www.readbyqxmd.com/read/28191013/quercetin-and-quercetin-rich-red-onion-extract-alter-pgc-1%C3%AE-promoter-methylation-and-splice-variant-expression
#7
Prasad P Devarshi, Aarin D Jones, Erin M Taylor, Barbara Stefanska, Tara M Henagan
Pgc-1α and its various isoforms may play a role in determining skeletal muscle mitochondrial adaptations in response to diet. 8 wks of dietary supplementation with the flavonoid quercetin (Q) or red onion extract (ROE) in a high fat diet (HFD) ameliorates HFD-induced obesity and insulin resistance in C57BL/J mice while upregulating Pgc-1α and increasing skeletal muscle mitochondrial number and function. Here, mice were fed a low fat (LF), high fat (HF), high fat plus quercetin (HF + Q), or high fat plus red onion extract (HF + RO) diet for 9 wks and skeletal muscle Pgc-1α isoform expression and DNA methylation were determined...
2017: PPAR Research
https://www.readbyqxmd.com/read/28187790/retinoic-acid-and-tgf-%C3%AE-signalling-cooperate-to-overcome-mycn-induced-retinoid-resistance
#8
David J Duffy, Aleksandar Krstic, Melinda Halasz, Thomas Schwarzl, Anja Konietzny, Kristiina Iljin, Desmond G Higgins, Walter Kolch
BACKGROUND: Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance...
February 10, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28180300/epigenetic-changes-in-histone-acetylation-underpin-resistance-to-the-topoisomerase-i-inhibitor-irinotecan
#9
Cornelia Meisenberg, Mohamed E Ashour, Lamia El-Shafie, Chunyan Liao, Adam Hodgson, Alice Pilborough, Syed A Khurram, Jessica A Downs, Simon E Ward, Sherif F El-Khamisy
No abstract text is available yet for this article.
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28176653/multimodal-hdac-inhibitors-with-improved-anticancer-activity
#10
Rainer Schobert, Bernhard Biersack
Histone deacetylases (HDACs) play a significant role in the proliferation and dissemination of cancer and represent promising epigenetic drug targets. The HDAC inhibitor vorinostat featuring a zinc-binding hydroxamate fragment was already clinically approved. However, HDAC inhibitors containing hydroxamic acids are often hampered by acquired or intrinsic drug resistance and may lead to enhanced tumor aggressiveness. In order to overcome these drawbacks of hydroxamate HDAC inhibitors a series of multimodal derivatives of this compound class, including such with different zinc-binding groups, was recently developed and showed promising anticancer activity...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176651/lung-cancer-stem-cells-an-epigenetic-perspective
#11
Samriddhi Shukla, Sajid Khan, Sonam Sinha, Syed Musthapa Meeran
Lung cancer remains the major cause of human mortality among all the cancer types despite the colossal amount of efforts to prevent the cancer onset and to provide the appropriate cure. Recent reports have identified that important contributors of lung cancer-related mortality are the drug resistance and aggressive tumor relapse, the characteristics contributed by the presence of lung cancer stem cells (CSCs). The identification of lung CSCs is inherently complex due to the quiescent nature of lung epithelium, which makes the distinction between the normal lung epithelium and lung CSCs difficult...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#12
Kirsty J Flower, Sadaf Ghaem-Maghami, Robert Brown
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28167670/salmonella-typhi-lipopolysaccharide-o-antigen-modifications-impact-on-serum-resistance-and-antibody-recognition
#13
Erica Kintz, Christian Heiss, Ian Black, Nicholas Donohue, Naj Brown, Mark R Davies, Parastoo Azadi, Stephen Baker, Paul M Kaye, Marjan van der Woude
Salmonella Typhi is a human restricted Gram-negative bacterial pathogen, responsible for causing an estimated 27 million cases of typhoid fever annually leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28167050/changing-mutational-and-adaptive-landscapes-and-the-genesis-of-cancer
#14
L Alexander Liggett, James DeGregori
By the time the process of oncogenesis has produced an advanced cancer, tumor cells have undergone extensive evolution. The cellular phenotypes resulting from this evolution have been well studied, and include accelerated growth rates, apoptosis resistance, immortality, invasiveness, and immune evasion. Yet with all of our current knowledge of tumor biology, the details of early oncogenesis have been difficult to observe and understand. Where different oncogenic mutations may work together to enhance the survival of a tumor cell, in isolation they are often pro-apoptotic, pro-differentiative or pro-senescent, and therefore often, somewhat paradoxically, disadvantageous to a cell...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28159741/biology-and-relevance-of-human-acute-myeloid-leukemia-stem-cells
#15
Daniel Thomas, Ravindra Majeti
Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly two decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse, and implies that approaches to treatment must eradicate LSCs for cure...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28154240/epigenetic-regulation-of-antagonistic-receptors-confers-rice-blast-resistance-with-yield-balance
#16
Yiwen Deng, Keran Zhai, Zhen Xie, Dongyong Yang, Xudong Zhu, Junzhong Liu, Xin Wang, Peng Qin, Yuanzhu Yang, Guomin Zhang, Qun Li, Jianfu Zhang, Shuangqing Wu, Joëlle Milazzo, Bizeng Mao, Ertao Wang, Huaan Xie, Didier Tharreau, Zuhua He
Crop breeding aims to balance disease resistance with yield, however single resistance (R) genes can lead to resistance breakdown and R gene pyramiding may impact growth fitness. Here we report that the rice Pigm locus contains a cluster of genes encoding nucleotide-binding leucine-rich repeat (NLR) receptors that confer durable resistance to the fungus Magnaporthe oryzae without yield penalty. In the cluster, PigmR confers broad-spectrum resistance, whereas PigmS competitively attenuates PigmR homodimerization to suppress resistance...
February 2, 2017: Science
https://www.readbyqxmd.com/read/28150715/epigenetic-regulation-of-nitric-oxide-synthase-2-inducible-nos2-by-nlrc4-inflammasomes-involves-parp1-cleavage
#17
Carina de Lima Buzzo, Tiago Medina, Laura M Branco, Silvia L Lage, Luís Carlos de Souza Ferreira, Gustavo P Amarante-Mendes, Michael O Hottiger, Daniel D De Carvalho, Karina R Bortoluci
Nitric oxide synthase 2, inducible (Nos2) expression is necessary for the microbicidal activity of macrophages. However, NOS2 over-activation causes multiple inflammatory disorders, suggesting a tight gene regulation is necessary. Using cytosolic flagellin as a model for inflammasome-dependent NOS2 activation, we discovered a surprising new role for NLRC4/caspase-1 axis in regulating chromatin accessibility of the Nos2 promoter. We found that activation of two independent mechanisms is necessary for NOS2 expression by cytosolic flagellin: caspase-1 and NF-κB activation...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148257/epigenetics-in-cancer-stem-cells
#18
REVIEW
Tan Boon Toh, Jhin Jieh Lim, Edward Kai-Hua Chow
Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells...
February 1, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#19
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28135237/the-eed-protein-protein-interaction-inhibitor-a-395-inactivates-the-prc2-complex
#20
Yupeng He, Sujatha Selvaraju, Michael L Curtin, Clarissa G Jakob, Haizhong Zhu, Kenneth M Comess, Bailin Shaw, Juliana The, Evelyne Lima-Fernandes, Magdalena M Szewczyk, Dong Cheng, Kelly L Klinge, Huan-Qiu Li, Marina Pliushchev, Mikkel A Algire, David Maag, Jun Guo, Justin Dietrich, Sanjay C Panchal, Andrew M Petros, Ramzi F Sweis, Maricel Torrent, Lance J Bigelow, Guillermo Senisterra, Fengling Li, Steven Kennedy, Qin Wu, Donald J Osterling, David J Lindley, Wenqing Gao, Scott Galasinski, Dalia Barsyte-Lovejoy, Masoud Vedadi, Fritz G Buchanan, Cheryl H Arrowsmith, Gary G Chiang, Chaohong Sun, William N Pappano
Polycomb repressive complex 2 (PRC2) is a regulator of epigenetic states required for development and homeostasis. PRC2 trimethylates histone H3 at lysine 27 (H3K27me3), which leads to gene silencing, and is dysregulated in many cancers. The embryonic ectoderm development (EED) protein is an essential subunit of PRC2 that has both a scaffolding function and an H3K27me3-binding function. Here we report the identification of A-395, a potent antagonist of the H3K27me3 binding functions of EED. Structural studies demonstrate that A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2...
January 30, 2017: Nature Chemical Biology
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