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Epigenetic resistance

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https://www.readbyqxmd.com/read/29667069/the-versatile-role-of-exosomes-in-cancer-progression-diagnostic-and-therapeutic-implications
#1
REVIEW
Vignesh Sundararajan, Fazlul H Sarkar, Thamil Selvee Ramasamy
BACKGROUND: Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming...
April 17, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29666300/a-pan-cancer-landscape-of-interactions-between-solid-tumors-and-infiltrating-immune-cell-populations
#2
David Tamborero, Carlota Rubio-Perez, Ferran Muiños, Radhakrishnan Sabarinathan, Josep Maria Piulats, Aura Muntasell, Rodrigo Dienstmann, Nuria Lopez-Bigas, Abel Gonzalez-Perez
PURPOSE: Throughout their development tumors are challenged by the immune system and they acquire features to evade its surveillance. A systematic view of these traits which sheds light on how tumors respond to immunotherapies is still lacking. EXPERIMENTAL DESIGN: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immune-phenotypes...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29666172/genetic-editing-of-colonic-organoids-provides-a-molecularly-distinct-and-orthotopic-preclinical-model-of-serrated-carcinogenesis
#3
Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein...
April 17, 2018: Gut
https://www.readbyqxmd.com/read/29662485/our-environment-shapes-us-the-importance-of-environment-and-sex-differences-in-regulation-of-autoantibody-production
#4
REVIEW
Michael Edwards, Rujuan Dai, S Ansar Ahmed
Consequential differences exist between the male and female immune systems' ability to respond to pathogens, environmental insults or self-antigens, and subsequent effects on immunoregulation. In general, females when compared with their male counterparts, respond to pathogenic stimuli and vaccines more robustly, with heightened production of antibodies, pro-inflammatory cytokines, and chemokines. While the precise reasons for sex differences in immune response to different stimuli are not yet well understood, females are more resistant to infectious diseases and much more likely to develop autoimmune diseases...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29651407/combination-therapy-with-histone-deacetylase-inhibitors-hdaci-for-the-treatment-of-cancer-achieving-the-full-therapeutic-potential-of-hdaci
#5
REVIEW
Amila Suraweera, Kenneth J O'Byrne, Derek J Richard
Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29649500/cancer-development-and-therapy-resistance-spotlights-on-the-dark-side-of-the-genome
#6
REVIEW
Eleonora Leucci
Cancer research has been focusing so far on genetic alterations in protein-coding genes. However, mounting evidence underlines the importance of epigenetic and post-transcriptional events in cancer progression and therapy resistance. Moreover, recent genome-wide studies show that disease-causing mutations and chromosome rearrangements often span areas of the genome that do not contain any known protein-coding gene. This finding is not surprising, considering that even though the vast majority of the human genome is transcribed, only a minor portion (accounting for less than 2%) encodes for proteins...
April 9, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29649127/gene-therapy-for-chronic-hbv-can-we-eliminate-cccdna
#7
REVIEW
Kristie Bloom, Mohube Betty Maepa, Abdullah Ely, Patrick Arbuthnot
Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions...
April 12, 2018: Genes
https://www.readbyqxmd.com/read/29643973/epigenetic-versus-genetic-deregulation-of-the-keap1-nrf2-axis-in-solid-tumors-focus-on-methylation-and-noncoding-rnas
#8
REVIEW
F P Fabrizio, A Sparaneo, D Trombetta, L A Muscarella
Oxidative and electrophilic changes in cells are mainly coordinated by the KEAP1/NRF2 (Kelch-like erythroid-derived cap-n-collar homology- (ECH-) associated protein-1/nuclear factor (erythroid-derived 2)-like 2) axis. The physical interaction between these two proteins promotes the expression of several antioxidant defense genes in response to exogenous and endogenous insults. Recent studies demonstrated that KEAP1/NRF2 axis dysfunction is also strongly related to tumor progression and chemo- and radiotherapy resistance of cancer cells...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29627453/role-of-circulating-tumor-dna-in-the-management-of-patients-with-colorectal-cancer
#9
Emilie Moati, Valérie Taly, Audrey Didelot, Géraldine Perkins, Hélène Blons, Julien Taieb, Pierre Laurent-Puig, Aziz Zaanan
Colorectal cancer is a major health burden with a prognosis that has been improved with the progresses in diagnosis and the advance of chemotherapy and personalized medicine. However, because of intra-tumor heterogeneity, clonal evolution and selection, tumors often develop resistance to treatments. "Liquid biopsy" is a minimally invasive method, based on analysis of tumor-specific material in peripheral blood samples of patients. Analysis of tumor specific genetic or epigenetic alterations in cell-free circulating nucleic acids may reflect the molecular heterogeneity of the underlying disease process and serial testing could allow to monitor its temporal genomic changing without using re-biopsy...
April 4, 2018: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29626011/centromere-transcription-allows-cenp-a-to-transit-from-chromatin-association-to-stable-incorporation
#10
Georg O M Bobkov, Nick Gilbert, Patrick Heun
Centromeres are essential for chromosome segregation and are specified epigenetically by the presence of the histone H3 variant CENP-A. In flies and humans, replenishment of the centromeric mark is uncoupled from DNA replication and requires the removal of H3 "placeholder" nucleosomes. Although transcription at centromeres has been previously linked to the loading of new CENP-A, the underlying molecular mechanism remains poorly understood. Here, we used Drosophila melanogaster tissue culture cells to show that centromeric presence of actively transcribing RNA polymerase II temporally coincides with de novo deposition of dCENP-A...
April 6, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29625794/the-role-of-epigenetic-therapies-in-colorectal-cancer
#11
REVIEW
Marina Baretti, Nilofer Saba Azad
Although developments in the diagnosis and therapy of colorectal cancer (CRC) have been made in the last decade, much work remains to be done as it remains the second leading cause of cancer death. It is now well established that epigenetic events, together with genetic alterations, are key events in initiation and progression of CRC. Epigenetics refers to heritable alterations in gene expression that do not involve changes in the DNA sequence. These alterations include DNA methylation, histone alterations, chromatin remodelers, and noncoding RNAs...
March 12, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29623853/repositioning-of-difluorinated-propanediones-as-inhibitors-of-histone-methyltransferases-and-their-biological-evaluation-in-human-leukemic-cell-lines
#12
Tanushree Pal, Asmita Sharda, Bharat Khade, C S Ramaa, Sanjay Gupta
Cancer chemotherapy is associated with limitations like dose dependent host-tissue toxicity, multiple drug resistance and tumor heterogeneity. Hence, it is imperative to unearth novel targets to cure cancer. At present, 'pharmaco-epigenomics' constitutes the hope in cancer treatment owing to epigenetic deregulation- a reversible process, suspected of playing a role in malignancy. In this research work, we have used the fundamentals of drug repurposing for a set of our previously synthesized difluorinated propanediones and evaluated them for their histone methyltransferase inhibitory potential in leukemic cell lines...
April 4, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29618904/current-opinions-on-chemoresistance-an-overview
#13
Saba Hasan, Ruba Taha, Halima El Omri
Sub population of cancer cells, referred to as Cancer stem cells (CSCs) or tumor initiating cells, have enhanced metastatic potential that drives tumor progression. CSCs have been found to hold intrinsic resistance to present chemotherapeutic strategies. This resistance is attributed to DNA reparability, slower cell cycle and high levels of detoxifying enzymes. Hence, CSCs pose an obstacle against chemotherapy. The increasing prevalence of drug resistant cancers necessitates further research and treatment development...
2018: Bioinformation
https://www.readbyqxmd.com/read/29616383/progression-of-conventional-hepatic-cell-culture-models-to-bioengineered-hepg2-cells-for-evaluation-of-herbal-bioactivities
#14
REVIEW
Pardeep Kaur, Robin, Rajendra G Mehta, Saroj Arora, Balbir Singh
Cancer cell lines of human tissue origin have been extensively used to investigate antiproliferative activity and toxicity of herbal extracts, isolated compounds, and anticancer drugs. These cell lines are genetically and/or epigenetically well characterized to determine the altered expression of proteins within given cellular pathways and critical genes in cancer. Human derived hepatoma (HepG2) cell line has been extensively exploited to examine cytoprotective, antioxidative, hepatoprotective, anti-hepatoma, hypocholesterolemic, anti-steatosis, bioenergetic homeostatic and anti-insulin resistant properties...
April 3, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29615458/an-effective-epigenetic-parp-inhibitor-combination-therapy-for-breast-and-ovarian-cancers-independent-of-brca-mutations
#15
Nicholas Pulliam, Fang Fang, Ali R Ozes, Jessica Tang, Adeoluwa Adewuyi, Harold N Keer, John F Lyons, Stephen B Baylin, Daniela Matei, Harikrishna Nakshatri, Feyruz V Rassool, Kathy D Miller, Kenneth P Nephew
PURPOSE: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are primarily effective against BRCA1/2-mutated breast and ovarian cancers but resistance due to reversion of mutated BRCA1/2 and other mechanisms is common. Based on previous reports demonstrating a functional role for DNMT1 in DNA repair (DDR) and our previous studies demonstrating DNMTis ability to resensitize tumors to primary therapies, we hypothesized that combining a DNMTi with PARPi would sensitize PARPi resistant breast and ovarian cancers to PARPi therapy, independent of BRCA status...
April 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29603746/mbd2-enables-tumourigenesis-within-the-intestine-while-preventing-tumour-promoting-inflammation
#16
Stephanie May, Heather Owen, Toby J Phesse, Kirsty R Greenow, Gareth-Rhys Jones, Adam Blackwood, Peter C Cook, Christopher Towers, Awen M Gallimore, Geraint T Williams, Michael Stürzl, Nathalie Britzen-Laurent, Owen J Sansom, Andrew S MacDonald, Adrian P Bird, Alan R Clarke, Lee Parry
Epigenetic regulation plays a key role in the link between inflammation and cancer. Here we examine Mbd2, which mediates epigenetic transcriptional silencing by binding to methylated DNA. In separate studies the Mbd2-/- mouse has been shown to be (1) resistant to intestinal tumourigenesis and (2) have an enhanced inflammatory/immune response; observations that are inconsistent with the links between inflammation and cancer. To clarify its role in tumourigenesis and inflammation, we used constitutive and conditional models of Mbd2 deletion to explore its epithelial and non-epithelial roles in the intestine...
March 30, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29602522/high-glycemic-index-metabolic-damage-a-pivotal-role-of-gip-and-glp-1
#17
REVIEW
Andreas F H Pfeiffer, Farnaz Keyhani-Nejad
When glucose-fructose dimers are supplied as the slowly digestible, completely absorbable, low glycemic index (GI) sugar isomaltulose, the detrimental effects of high GI sucrose are avoided. This difference requires the presence of intact glucose-induced insulinotropic peptide receptor (GIPR) and is mediated by the rapid uptake of glucose and the stimulation of GIP release from K cells in the upper small intestine. GIP promotes lipogenesis, fatty liver, insulin resistance, and postprandial inflammation, and reduces fat oxidation in skeletal muscle, partly by hypothalamic interference with energy partitioning and epigenetic programming...
March 27, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29601851/microrna-155-expression-and-function-in-aml-an-evolving-paradigm
#18
REVIEW
Nisha Narayan, Cameron P Bracken, Paul G Ekert
Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that results in dysregulated proliferation. Acute leukemia is the most common form of paediatric cancer, with AML accounting for ~20% of all leukemias in children. The genomic aberrations that drive AML inhibit myeloid differentiation and activate signal transduction pathways that drive proliferation. MicroRNAs, a class of small (~22 nucleotide) non-coding RNA that post-transcriptionally suppress the expression of specifically targeted transcripts, are also frequently dysregulated in AML which may prove useful for the purposes of disease classification, prognosis and future therapeutic approaches...
March 27, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29593783/perinatal-programming-of-circadian-clock-stress-crosstalk
#19
REVIEW
Mariana Astiz, Henrik Oster
An intact communication between circadian clocks and the stress system is important for maintaining physiological homeostasis under resting conditions and in response to external stimuli. There is accumulating evidence for a reciprocal interaction between both-from the systemic to the molecular level. Disruption of this interaction by external factors such as shiftwork, jetlag, or chronic stress increases the risk of developing metabolic, immune, or mood disorders. From experiments in rodents, we know that both systems maturate during the perinatal period...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29589384/pathophysiology-of-type-2-diabetes-in-koreans
#20
REVIEW
Soo Heon Kwak, Kyong Soo Park
The pathophysiology of type 2 diabetes is characterized by variable degrees of insulin resistance and impaired insulin secretion. Both genetic and environmental factors serve as etiologic factors. Recent genetic studies have identified at least 83 variants associated with diabetes. A significant number of these loci are thought to be involved in insulin secretion, either through β-cell development or β-cell dysfunction. Environmental factors have changed rapidly during the past half century, and the increased prevalence of obesity and diabetes can be attributed to these changes...
March 2018: Endocrinology and Metabolism
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