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https://www.readbyqxmd.com/read/29043381/transformed-follicular-lymphoma
#1
REVIEW
Thais Fischer, Natalia Pin Chuen Zing, Carlos Sergio Chiattone, Massimo Federico, Stefano Luminari
Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation into an aggressive lymphoma, which is expected to occur at a rate of 2 to 3% each year, is associated with rapid progression, treatment resistance, and poor prognosis. Recent modifications to the physiopathologic mechanism of transformed follicular lymphoma (t-FL) have been proposed, including genetic and epigenetic mechanisms as well as a role for the microenvironment...
October 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29035388/a-novel-her2-gene-body-enhancer-contributes-to-her2-expression
#2
Q Liu, M V Kulak, N Borcherding, P K Maina, W Zhang, R J Weigel, H H Qi
The transcriptional regulation of the human epidermal growth factor receptor-2 (HER2) contributes to an enhanced HER2 expression in HER2-positive breast cancers with HER2 gene amplification and HER2-low or HER2-negative breast cancers following radiotherapy or endocrine therapy, and this drives tumorigenesis and the resistance to therapy. Epigenetic mechanisms are critical for transcription regulation, however, such mechanisms in the transcription regulation of HER2 are limited to the involvement of tri-methylated histone 3 lysine 4 (H3K4me3) and acetylated histone 3 lysine 9 (H3K9ac) at the HER2 promoter region...
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29035371/lncrna-mir100hg-derived-mir-100-and-mir-125b-mediate-cetuximab-resistance-via-wnt-%C3%AE-catenin-signaling
#3
Yuanyuan Lu, Xiaodi Zhao, Qi Liu, Cunxi Li, Ramona Graves-Deal, Zheng Cao, Bhuminder Singh, Jeffrey L Franklin, Jing Wang, Huaying Hu, Tianying Wei, Mingli Yang, Timothy J Yeatman, Ethan Lee, Kenyi Saito-Diaz, Scott Hinger, James G Patton, Christine H Chung, Stephan Emmrich, Jan-Henning Klusmann, Daiming Fan, Robert J Coffey
De novo and acquired resistance, which are largely attributed to genetic alterations, are barriers to effective anti-epidermal-growth-factor-receptor (EGFR) therapy. To generate cetuximab-resistant cells, we exposed cetuximab-sensitive colorectal cancer cells to cetuximab in three-dimensional culture. Using whole-exome sequencing and transcriptional profiling, we found that the long non-coding RNA MIR100HG and two embedded microRNAs, miR-100 and miR-125b, were overexpressed in the absence of known genetic events linked to cetuximab resistance...
October 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29035367/targeting-glioma-stem-cells-through-combined-bmi1-and-ezh2-inhibition
#4
Xun Jin, Leo J Y Kim, Qiulian Wu, Lisa C Wallace, Briana C Prager, Tanwarat Sanvoranart, Ryan C Gimple, Xiuxing Wang, Stephen C Mack, Tyler E Miller, Ping Huang, Claudia L Valentim, Qi-Gang Zhou, Jill S Barnholtz-Sloan, Shideng Bao, Andrew E Sloan, Jeremy N Rich
Glioblastomas are lethal cancers defined by angiogenesis and pseudopalisading necrosis. Here, we demonstrate that these histological features are associated with distinct transcriptional programs, with vascular regions showing a proneural profile, and hypoxic regions showing a mesenchymal pattern. As these regions harbor glioma stem cells (GSCs), we investigated the epigenetic regulation of these two niches. Proneural, perivascular GSCs activated EZH2, whereas mesenchymal GSCs in hypoxic regions expressed BMI1 protein, which promoted cellular survival under stress due to downregulation of the E3 ligase RNF144A...
October 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29033534/multicellular-tumor-spheroids-of-human-uveal-melanoma-induce-genes-associated-with-anoikis-resistance-lipogenesis-and-ssxs
#5
Charlotte Ness, Øystein Garred, Nils A Eide, Theresa Kumar, Ole K Olstad, Thomas P Bærland, Goran Petrovski, Morten C Moe, Agate Noer
PURPOSE: Uveal melanoma (UM) has a high propensity for metastatic spread, and approximately 40-50% of patients die of metastatic disease. Metastases can be found at the time of diagnosis but also several years after the tumor has been removed. The survival of disseminated cancer cells is known to be linked to anchorage independence, anoikis resistance, and an adaptive cellular metabolism. The cultivation of cancer cells as multicellular tumor spheroids (MCTS) by anchorage-independent growth enriches for a more aggressive phenotype...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29032717/bet-inhibitors-in-metastatic-prostate-cancer-therapeutic-implications-and-rational-drug-combinations
#6
Mark C Markowski, Angelo M De Marzo, Emmanuel S Antonarakis
The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas Covered: We speculate that a combination approach using BET inhibition with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer...
October 16, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29032385/exercise-training-response-heterogeneity-physiological-and-molecular-insights
#7
REVIEW
Lauren M Sparks
The overall beneficial effects of exercise are well studied, but why some people do not respond favourably to exercise is less understood. The National Institutes of Health Common Fund has recently launched the large-scale discovery project 'Molecular Transducers of Physical Activity in Humans' to examine the physiological and molecular (i.e. genetic, epigenetic, lipidomic, metabolomic, proteomic, etc.) responses to exercise training. A nationwide, multicentre clinical trial such as this one also provides a unique opportunity to robustly investigate the non-response to exercise in thousands of individuals that have undergone supervised aerobic- and resistance-based exercise training interventions...
October 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/29031714/dwarfism-and-insulin-resistance-in-male-offspring-caused-by-%C3%AE-1-adrenergic-antagonism-during-pregnancy
#8
Rebecca Oelkrug, Beate Herrmann, Cathleen Geissler, Lisbeth Harder, Christiane Koch, Hendrik Lehnert, Henrik Oster, Henriette Kirchner, Jens Mittag
OBJECTIVE: Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29029592/pharmacoepigenetics-and-toxicoepigenetics-novel-mechanistic-insights-and-therapeutic-opportunities
#9
Volker M Lauschke, Isabel Barragan, Magnus Ingelman-Sundberg
Pharmacological treatment and exposure to xenobiotics can cause substantial changes in epigenetic signatures. The majority of these epigenetic changes, caused by the compounds in question, occur downstream of transcriptional activation mechanisms, whereby the epigenetic alterations can create a transcriptional memory and stably modulate cell function. The increasing understanding of epigenetic mechanisms and their importance in disease has prompted the development of therapeutic interventions that target epigenetic modulatory mechanisms, particularly in oncology where inhibitors of epigenetic-modifying proteins (epidrugs) have been successfully used in treatment, mostly in combination with standard-of-care chemotherapy, provoking either direct cytotoxicity or inhibiting resistance to anticancer drugs...
October 13, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/29028222/role-of-rbp2-induced-er-and-igf1r-erbb-signaling-in-tamoxifen-resistance-in-breast-cancer
#10
Hee-Joo Choi, Hyeong-Seok Joo, Hee-Young Won, Kyueng-Whan Min, Hyung-Yong Kim, Taekwon Son, Young-Ha Oh, Jeong-Yeon Lee, Gu Kong
Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764)...
April 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29027833/trichostatin-a-and-5-aza-2-deoxycytidine-influence-the-expression-of-cold-induced-genes-in-arabidopsis
#11
Yuan Song, Lijun Liu, Gaopeng Li, Lizhe An, Lining Tian
The expression of cold-induced genes is critical for plants to survive under freezing stress. However, the underlying mechanisms for the decision of when, where, and which genes to express are unclear when a plant meets a sudden temperature drop. Previous studies have demonstrated epigenetics to play a central role in the regulation of gene expression in plant responses to environmental stress. DNA methylation and histone deacetylation are the two most important epigenetic modifications. This study was conducted to investigate the effects of inhibiting DNA methylation and histone deacetylation on gene expression, and to explore the potential role of epigenetics in plant responses to cold stress...
October 13, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29027617/zebrafish-as-a-model-to-study-neuroblastoma-development
#12
REVIEW
Mattie J Casey, Rodney A Stewart
Neuroblastoma is a pediatric solid tumor arising from embryonic neural crest progenitor cells that normally generate the peripheral sympathetic nervous system. As such, the location of neuroblastoma tumors is correlated with the distribution of major post-ganglionic clusters throughout the sympathetic chain, with the highest incidence in the adrenal medulla or lumbar sympathetic ganglia (~65%). Neuroblastoma is an enigmatic tumor that can spontaneously regress with minimal treatment or become highly metastatic and develop resistance to aggressive treatments, including radiation and high-dose chemotherapy...
October 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29026446/dna-methylation-links-genetics-fetal-environment-and-an-unhealthy-lifestyle-to-the-development-of-type-2-diabetes
#13
REVIEW
Emma Nilsson, Charlotte Ling
Type 2 diabetes is a complex trait with both environmental and hereditary factors contributing to the overall pathogenesis. One link between genes, environment, and disease is epigenetics influencing gene transcription and, consequently, organ function. Genome-wide studies have shown altered DNA methylation in tissues important for glucose homeostasis including pancreas, liver, skeletal muscle, and adipose tissue from subjects with type 2 diabetes compared with nondiabetic controls. Factors predisposing for type 2 diabetes including an adverse intrauterine environment, increasing age, overweight, physical inactivity, a family history of the disease, and an unhealthy diet have all shown to affect the DNA methylation pattern in target tissues for insulin resistance in humans...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29022903/alternative-mechanisms-of-mir-34a-regulation-in-cancer
#14
REVIEW
Eva Slabáková, Zoran Culig, Ján Remšík, Karel Souček
MicroRNA miR-34a is recognized as a master regulator of tumor suppression. The strategy of miR-34a replacement has been investigated in clinical trials as the first attempt of miRNA application in cancer treatment. However, emerging outcomes promote the re-evaluation of existing knowledge and urge the need for better understanding the complex biological role of miR-34a. The targets of miR-34a encompass numerous regulators of cancer cell proliferation, survival and resistance to therapy. MiR-34a expression is transcriptionally controlled by p53, a crucial tumor suppressor pathway, often disrupted in cancer...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022901/bcr-abl1-induced-downregulation-of-wasp-in-chronic-myeloid-leukemia-involves-epigenetic-modification-and-contributes-to-malignancy
#15
Welbert O Pereira, Daniel D De Carvalho, Maria Emilia Zenteno, Beatriz F Ribeiro, Jacqueline F Jacysyn, Luiz R Sardinha, Maria A Zanichelli, Nelson Hamerschlak, Gareth E Jones, Katia B Pagnano, Fabiola A Castro, Yolanda Calle, Gustavo P Amarante-Mendes
Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the BCR-ABL1 tyrosine kinase (TK). The development of TK inhibitors (TKIs) revolutionized the treatment of CML patients. However, TKIs are not effective to those at advanced phases when amplified BCR-ABL1 levels and increased genomic instability lead to secondary oncogenic modifications. Wiskott-Aldrich syndrome protein (WASP) is an important regulator of signaling transduction in hematopoietic cells and was shown to be an endogenous inhibitor of the c-ABL TK...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022893/mycn-contributes-to-the-malignant-characteristics-of-erythroleukemia-through-ezh2-mediated-epigenetic-repression-of-p21
#16
Li Liu, Feng Xu, Chun-Kang Chang, Qi He, Ling-Yun Wu, Zheng Zhang, Xiao Li
MYC proto-oncogene family including c-myc and n-myc (MYCN) are critical for normal cell development and tumorigenesis. Overexpression of c-myc causes acute erythroleukemia in vivo. However, the role of MYCN in acute erythroleukemia remains poorly understood. In this study, we found that the patients with erythroleukemia showed higher expression of MYCN than normal controls. In vitro experiments, knockdown of MYCN resulted in decreased cell proliferation, elevated autonomously cell apoptosis and increased P21-mediated cell senescence...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29018149/hypothesis-stimulation-of-trained-immunity-as-adjunctive-immunotherapy-in-cancer
#17
REVIEW
Mihai G Netea, Leo A B Joosten, Jos W M van der Meer
Cancer immunotherapy has steadily progressed during the past decades, with checkpoint inhibitor therapy becoming the latest and one of the most promising treatments. Despite the progress, most of the patients do not respond or develop resistance, and novel additional approaches are needed to improve the clinical effectiveness of immunotherapy. Trained immunity (TI) has been described recently as a process of epigenetic and metabolic reprogramming that induces a long-term enhanced function of innate immune cells...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28987628/nutrient-regulation-of-pancreatic-%C3%AE-cell-proliferation
#18
Valentine S Moullé, Julien Ghislain, Vincent Poitout
Excess consumption of energy-dense foods combined with a sedentary lifestyle is driving an obesity epidemic. Although obesity is closely associated with insulin resistance, most individuals meet the insulin demand by increasing their functional β-cell mass. Those who eventually develop type 2 diabetes are distinguished by a failure in this compensatory process. Although a causal role of insulin resistance in compensatory β-cell responses has received considerable experimental support, precisely how the β cell senses changes in the metabolic environment is still unknown...
October 4, 2017: Biochimie
https://www.readbyqxmd.com/read/28987322/an-insight-into-the-complex-roles-of-metallothioneins-in-malignant-diseases-with-emphasis-on-sub-isoforms-isoforms-and-epigenetics-phenomena
#19
REVIEW
Sona Krizkova, Marta Kepinska, Gabriella Emri, Tomas Eckschlager, Marie Stiborova, Petra Pokorna, Zbynek Heger, Vojtech Adam
Metallothioneins (MTs) belong to a group of small cysteine-rich proteins that are ubiquitous throughout all kingdoms. The main function of MTs is scavenging of free radicals and detoxification and homeostating of heavy metals. In humans, 16 genes localized on chromosome 16 have been identified to encode four MT isoforms labelled by numbers (MT-1 - MT-4). MT-2, MT-3 and MT-4 proteins are encoded by a single gene. MT-1 comprises many (sub)isoforms. The known active MT-1 genes are MT-1A, -1B, -1E, -1F, -1G, -1H, -1M and -1X...
October 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28986361/regulating-microrna-expression-at-the-heart-of-diabetes-mellitus-and-the-mitochondrion
#20
Quincy A Hathaway, Mark V Pinti, Andrya J Durr, Shanawar Waris, Danielle L Shepherd, John M Hollander
Type 2 diabetes mellitus is a major risk factor for cardiovascular disease and mortality. Uncontrolled type 2 diabetes mellitus results in a systemic milieu of increased circulating glucose and fatty acids. The development of insulin resistance in cardiac tissue decreases cellular glucose import and enhances mitochondrial fatty acid uptake. While triacylglycerol and cytotoxic lipid species begin to accumulate in the cardiomyocyte, the energy substrate utilization ratio of free fatty acids (FFAs) to glucose changes to almost entirely FFAs...
October 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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