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https://www.readbyqxmd.com/read/28944671/prioritizing-popular-proteins-in-liver-cancer-remodelling-one-carbon-metabolism
#1
María Isabel Mora, Manuela Molina, Leticia Odriozola, Felix Elortza, Jose M Mato, Barbara Sitek, Pumin Zhang, Fuchu He, Maria Uxue Latasa, Matías Avila, Fernando Corrales
Primary liver cancer (HCC) is recognized as the fifth most common neoplasm and the second leading cause of cancer deaths worldwide. Most risk factors are known and the molecular pathogenesis has been widely studied in the last decade; however, the underlying molecular mechanisms remain to be unveiled, as they will facilitate definition of novel biomarkers and clinical targets for more effective patient management. In this study, we utilize the B/D-HPP popular protein strategy. We report a list of popular proteins that have been highly co-cited with the expression "liver cancer"...
September 25, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28943948/analysis-of-the-expression-level-and-methylation-of-tumor-protein-p53-phosphatase-and-tensin-homolog-and-muts-homolog-2-in-n-methyl-n-nitrosourea-induced-thymic-lymphoma-in-c57bl-6-mice
#2
Xueyun Huo, Zhenkun Li, Shuangyue Zhang, Changlong Li, Meng Guo, Jing Lu, Jianyi Lv, Xiaoyan Du, Zhenwen Chen
Tumorigenesis is often caused by somatic mutation or epigenetic changes in genes that regulate aspects of cell death, proliferation and survival. Although the functions of multiple tumor suppressor genes have been well studied in isolation, how these genes cooperate during the progression of a single tumor remains unclear in numerous cases. The present study used N-methyl-N-nitrosourea (MNU), one of the most potent mutagenic nitrosourea compounds, to induce thymic lymphoma in C57BL/6J mice. Subsequently, the protein expression levels of phosphatase and tensin homolog (PTEN), transformation protein 53 and mutS homolog 2 (MSH2) were evaluated concomitantly in the thymus, liver, kidney and spleen of MNU-treated mice by western blotting...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943305/targeting-the-cancer-epigenome-synergistic-therapy-with-bromodomain-inhibitors
#3
REVIEW
Mahalakshmi Ramadoss, Vijayalakshmi Mahadevan
Epigenetic and genomic alterations regulate the transcriptional landscape of cells during cancer onset and progression. Recent clinical studies targeting the epigenetic 'readers' (bromodomains) for cancer therapy have established the effectiveness of bromodomain (BRD) extraterminal (BET) inhibitors in treating several types of cancer. In this review, we discuss key mechanisms of BET inhibition and synergistic combinations of BET inhibitors with histone deacetylase inhibitors (HDACi), histone methyltransferase inhibitors (HMTi), DNA methyltransferase inhibitors (DNMTi), kinase, B-cell lymphoma 2 (Bcl-2) and proteosome inhibitors, and immunomodulatory drugs for cancer therapy...
September 21, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28943239/how-to-effectively-treat-acute-leukemia-patients-bearing-mll-rearrangements
#4
REVIEW
Dieter Steinhilber, Rolf Marschalek
Chromosomal translocations - leading to the expression of fusion genes - are well-studied genetic abberrations associated with the development of leukemias. Most of them represent altered transcription factors that affect transcription or epigenetics, while others - like BCR-ABL - are enhancing signaling. BCR-ABL has become the prototype for rational drug design, and drugs like Imatinib and subsequently improved drugs have a great impact on cancer treatments. By contrast, MLL-translocations in acute leukemia patients are hard to treat, display a high relapse rate and the overall survival rate is still very poor...
September 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28942676/epigenetics-of-cancer-associated-muscle-catabolism
#5
Ryan M Carr, Elisa Enriquez-Hesles, Rachel Lo Olson, Aminah Jatoi, Jason Doles, Martin E Fernandez-Zapico
Cancer patients are commonly affected by cachexia, a wasting process involving muscle and fat. Specifically, loss of the muscle compartment has been associated with poor prognosis and suboptimal response to therapy. Nutritional support has been ineffective in treating this process leading to investigations into the underlying molecular processes governing muscle catabolism. In this commentary, we discuss the molecular mechanisms of cancer-associated muscle metabolism and the epigenetic processes responsible for the muscle wasting phenotype...
September 25, 2017: Epigenomics
https://www.readbyqxmd.com/read/28940884/involvement-of-pdgf-ligands-and-receptors-in-tumorigenesis
#6
REVIEW
Carl-Henrik Heldin, Johan Lennartsson, Bengt Westermark
Platelet-derived growth factor (PDGF) isoforms and their receptors have important roles during embryogenesis, particularly in the development of various mesenchymal cell types in different organs. In the adult, PDGF stimulates wound healing and regulates tissue homeostasis. However, over-activity of PDGF signaling is associated with malignancies and other diseases characterized by excessive cell proliferation, such as fibrotic conditions and atherosclerosis. In certain tumors, genetic or epigenetic alterations of the genes for PDGF ligands and receptors drives tumor cell proliferation and survival...
September 22, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28939884/prc2-specifies-ectoderm-lineages-and-maintains-pluripotency-in-primed-but-not-na%C3%A3-ve-escs
#7
Yongli Shan, Zechuan Liang, Qi Xing, Tian Zhang, Bo Wang, Shulan Tian, Wenhao Huang, Yanqi Zhang, Jiao Yao, Yanling Zhu, Ke Huang, Yujian Liu, Xiaoshan Wang, Qianyu Chen, Jian Zhang, Bizhi Shang, Shengbiao Li, Xi Shi, Baojian Liao, Cong Zhang, Keyu Lai, Xiaofen Zhong, Xiaodong Shu, Jinyong Wang, Hongjie Yao, Jiekai Chen, Duanqing Pei, Guangjin Pan
Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages...
September 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28939182/colorectal-cancer-epigenetic-alterations-and-their-clinical-implications
#8
REVIEW
Alberto Puccini, Martin D Berger, Madiha Naseem, Ryuma Tokunaga, Francesca Battaglin, Shu Cao, Diana L Hanna, Michelle McSkane, Shivani Soni, Wu Zhang, Heinz-Josef Lenz
Colorectal cancer (CRC) is a heterogeneous disease with distinct molecular and clinical features, which reflects the wide range of prognostic outcomes and treatment responses observed among CRC patients worldwide. Our understanding of the CRC epigenome has been largely developed over the last decade and it is now believed that among thousands of epigenetic alterations present in each tumor, a small subgroup of these may be considered as a CRC driver event. DNA methylation profiles have been the most widely studied in CRC, which includes a subset of patients with distinct molecular and clinical features now categorized as CpG island methylator phenotype (CIMP)...
September 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28939121/discovery-of-novel-1-2-4-triazolo-4-3-a-quinoxaline-aminophenyl-derivatives-as-bet-inhibitors-for-cancer-treatment
#9
Imran Ali, Jooyun Lee, Areum Go, Gildon Choi, Kwangho Lee
Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3-a]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay...
September 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28939082/epigenetic-therapy-regulates-the-expression-of-aldh1-and-immunologic-response-relevance-to-the-prognosis-of-oral-cancer
#10
Ming-Shao Tsai, Wen-Cheng Chen, Chia-Hsuan Lai, Yu-Yen Chen, Miao-Fen Chen
OBJECTIVES: Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and shown to identify cancer stem cells (CSC)-like cells. We aimed to investigate the significance of ALDH1 in oral squamous cell carcinoma (OSCC) and its correlation with DNMT3b and immune evasion in the present study. METHODS: We retrospectively analyzed the clinical outcomes of OSCC patients and examined its correlation with the levels of ALDH1 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in the peripheral blood...
October 2017: Oral Oncology
https://www.readbyqxmd.com/read/28938489/prognostic-classifier-based-on-genome-wide-dna-methylation-profiling-in-well-differentiated-thyroid-tumors
#11
Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fábio Albuquerque Marchi, Caroline Moraes Beltrami, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto
Context: Even though the majority of well-differentiated thyroid cancer (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidences have suggested that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. Objective: To identify a prognostic epigenetic signature in thyroid cancer. Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 non-neoplastic thyroid tissues (NT), 17 benign thyroid lesions (BTL) and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated and 3 anaplastic)...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938122/genome-regulation-by-polycomb-and-trithorax-70-years-and-counting
#12
REVIEW
Bernd Schuettengruber, Henri-Marc Bourbon, Luciano Di Croce, Giacomo Cavalli
Polycomb (PcG) and Trithorax (TrxG) group proteins are evolutionarily conserved chromatin-modifying factors originally identified as part of an epigenetic cellular memory system that maintains repressed or active gene expression states. Recently, they have been shown to globally control a plethora of cellular processes. This functional diversity is achieved by their ability to regulate chromatin at multiple levels, ranging from modifying local chromatin structure to orchestrating the three-dimensional organization of the genome...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28938089/drug-discovery-and-chemical-biology-of-cancer-epigenetics
#13
REVIEW
Scott Ribich, Darren Harvey, Robert A Copeland
Comprehensive whole-exome sequencing, DNA copy-number determination, and transcriptomic analyses of diverse cancers have greatly expanded our understanding of the biology of many tumor types. In addition to mutations in the common cell-of-origin specific driver mutations, these studies have also revealed a large number of loss-of-function and gain-of-function mutations in chromatin-modifying proteins (CMPs). This has revealed that epigenetic dysregulation is a common feature of most pediatric and adult cancers...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28937961/regulation-of-chromatin-assembly-and-cell-transformation-by-formaldehyde-exposure-in-human-cells
#14
Danqi Chen, Lei Fang, Shenglin Mei, Hongjie Li, Xia Xu, Thomas L Des Marais, Kun Lu, X Shirley Liu, Chunyuan Jin
BACKGROUND: Formaldehyde (FA) is an environmental and occupational chemical carcinogen. Recent studies have shown that exogenous FA causes only a modest increase in DNA adduct formation compared with the amount of adducts formed by endogenous FA, raising the possibility that epigenetic mechanisms may contribute to FA-mediated carcinogenicity. OBJECTIVES: We investigated the effects of FA exposure on histone modifications and chromatin assembly. We also examined the role of defective chromatin assembly in FA-mediated transcription and cell transformation...
September 21, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28937658/extracellular-vesicle-associated-rna-as-a-carrier-of-epigenetic-information
#15
REVIEW
Carlo Maria Di Liegro, Gabriella Schiera, Italia Di Liegro
Post-transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis-acting signals (zip codes), usually present in their 5'- and 3'-untranslated regions (UTRs). By binding to these signals, trans-acting factors, such as RNA-binding proteins (RBPs), and/or non-coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non-coding RNAs of different sizes...
September 22, 2017: Genes
https://www.readbyqxmd.com/read/28937318/the-crosstalk-between-p38-and-akt-signaling-pathways-orchestrates-emt-by-regulating-satb2-expression-in-nsclc-cells
#16
Hakan Kucuksayan, Hakan Akca
Epithelial-mesenchymal transition is a crucial event for metastasis and could be mediated by several pathways such as phosphoinositide 3-kinase/Akt, mitogen-activated protein kinases, as well as many epigenetic regulators. Special AT-rich sequence-binding protein 2 is an epigenetic regulator involved in epithelial-mesenchymal transition and osteoblastic differentiation. It has been reported that the crosstalk between several pathways is responsible for the regulation of epithelial-mesenchymal transition in cancer cells...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28936481/controlling-epithelial-to-mesenchymal-transition-through-acetylation-of-histone-h2bk5
#17
Robert J Mobley, Amy N Abell
Large-scale epigenetic changes take place when epithelial cells with cell-cell adhesion and apical-basal polarity transition into invasive, individual, mesenchymal cells through a process known as epithelial to mesenchymal transition (EMT). Importantly, cancers with stem cell properties disseminate and form distant metastases by reactivating the developmental EMT program. Recent studies have demonstrated that the epigenetic histone modification, H2BK5 acetylation (H2BK5Ac), is important in the regulation of EMT...
September 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28935813/asxl3-is-a-novel-pluripotency-factor-in-human-respiratory-epithelial-cells-and-a-potential-therapeutic-target-in-small-cell-lung-cancer
#18
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly Stevenson, Emily Reardon, Kaitlin C McLoughlin, Andrew Kaufman, Eden Payabyab, Julie A Hong, Mary Zhang, Sean R Davis, Daniel C Edelman, Guokai Chen, Markku Miettinen, Nicholas Restfo, Thomas Ried, Paul S Meltzer, David S Schrump
In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSC (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAEC. Of particular novelty, we identified the PRC2-associated protein, ASXL3 which was markedly upregulated in Lu-iPSC and small cell lung cancer (SCLC) lines and clinical specimens...
September 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28935149/molecular-aspects-of-cancer-chemopreventive-and-therapeutic-efficacies-of-tea-and-tea-polyphenols
#19
REVIEW
Subhayan Sur, Chinmay Kumar Panda
The natural dietary product tea (Camellia sinensis) and its bioactive polyphenols such as epigallocatechin gallate (EGCG) and theaflavin (TF) demonstrated potential anticancer effects in different preclinical and clinical studies. The aim of the present review was to understand the molecular mechanisms of the tea and tea polyphenol-mediated cancer prevention and therapy. In the setting of in vivo cancer prevention studies, administration of the tea and tea polyphenols at preinitiation stages only showed partial prevention, whereas continuous administration showed potential effect in restriction of carcinogenesis in the body's multiple organs at early premalignant stages throughout the experiment...
November 2017: Nutrition
https://www.readbyqxmd.com/read/28935018/-progress-of-epigenetic-methylation-in-lung-cancer-research
#20
Shaowei Zhang, Zhiqiang Xue
Lung cancer is becoming an increasing threat to Chinese residents and its incidence continues to rise while the treatment effect is far from satisfactory. Hence, it is essential to improve the level of early diagnosis, treatment, prognosis in lung cancer. An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence. The epigenetic studies, such as DNA methylation and histone methylation, are progressing rapidly in oncology research. A comprehensive understanding of its development status and existing problems is of great significance for the future research and the implementation of precision medicine...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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