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Cancer epigenetics

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https://www.readbyqxmd.com/read/27926866/inflammation-induced-oxidative-stress-mediates-gene-fusion-formation-in-prostate-cancer
#1
Ram S Mani, Mohammad A Amin, Xiangyi Li, Shanker Kalyana-Sundaram, Brendan A Veeneman, Lei Wang, Aparna Ghosh, Adam Aslam, Susmita G Ramanand, Bradley J Rabquer, Wataru Kimura, Maxwell Tran, Xuhong Cao, Sameek Roychowdhury, Saravana M Dhanasekaran, Nallasivam Palanisamy, Hesham A Sadek, Payal Kapur, Alisa E Koch, Arul M Chinnaiyan
Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926531/an-annotated-list-of-bivalent-chromatin-regions-in-human-es-cells-a-new-tool-for-cancer-epigenetic-research
#2
Franck Court, Philippe Arnaud
CpG islands (CGI) marked by bivalent chromatin in stem cells are believed to be more prone to aberrant DNA methylation in tumor cells. The robustness and genome-wide extent of this instructive program in different cancer types remain to be determined. To address this issue we developed a user-friendly approach to integrate the stem cell chromatin signature in customized DNA methylation analyses. We used publicly available ChIP-sequencing datasets of several human embryonic stem cell (hESC) lines to determine the extent of bivalent chromatin genome-wide...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926517/suberoylanilide-hydroxamic-acid-induced-specific-epigenetic-regulation-controls-leptin-induced-proliferation-of-breast-cancer-cell-lines
#3
Xiuyan Feng, Han Han, Dan Zou, Jiaming Zhou, Weiqiang Zhou
Breast cancer is one of the most common malignancies among women in the world, investigating the characteristics and special transduction pathways is important for better understanding breast development and tumorigenesis. Leptin, a peptide hormone secreted from white adipocytes, may be an independent risk factor for breast cancer.Here, we treated suberoylanilide hydroxamic acid (SAHA) on Leptin-induced cell proliferation and invasion in the estrogen-receptor-positive breast cancer cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926516/frequent-silencing-of-the-candidate-tumor-suppressor-trim58-by-promoter-methylation-in-early-stage-lung-adenocarcinoma
#4
Koichiro Kajiura, Kiyoshi Masuda, Takuya Naruto, Tomohiro Kohmoto, Miki Watabnabe, Mitsuhiro Tsuboi, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku, Issei Imoto
In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926510/genetic-and-epigenetic-characterization-of-the-brca1-gene-in-brazilian-women-at-risk-for-hereditary-breast-cancer
#5
Paula Silva Felicio, Matias Eliseo Melendez, Lidia Maria Rebolho Batista Arantes, Ligia Maria Kerr, Dirce Maria Carraro, Rebeca Silveira Grasel, Natalia Campacci, Cristovam Scapulatempo-Neto, Gabriela Carvalho Fernandes, Ana Carolina de Carvalho, Edenir Inêz Palmero
This study aimed to characterize women at-risk for hereditary BC regarding their clinical and molecular characteristics (mutation and methylation in the BRCA1 gene) and correlate the gene expression levels with histopathological, clinical and family history information. BRCA1 real time qPCR was performed to evaluate methylation status and gene expression. The study included 88 women grouped according to the BRCA1 mutational status: 23 BRCA1 mutated, 22 with a Variant of Unknown Significance (VUS) in BRCA1 and 43 BRCA1 WT...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926488/blocking-ezh2-methylation-transferase-activity-by-gsk126-decreases-stem-cell-like-myeloma-cells
#6
Delong Zeng, Maoxing Liu, Jingxuan Pan
EZH2 is a critical epigenetic regulator that is deregulated in various types of cancers including multiple myeloma (MM). In the present study, we hypothesized that targeting EZH2 might induce apoptosis in myeloma cells including stem cell-like cells (CSCs). We investigated the effect of EZH2 inhibition on MM cells using a potent inhibitor (GSK126). The results showed that GSK126 effectively abrogated the methylated histone 3 (H3K27me3) level in MM.1S and LP1 cells, and inhibited the number of live cells and colony formation in soft agar of six MM cell lines...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924730/congenital-malformations-attributed-to-prenatal-exposure-to-cyclophosphamide
#7
Padmanabhan Rengasamy
Cyclophosphamide (CPA) remains one of the most widely prescribed anticancer drugs. It is also used in the treatment of rheumatoid arthritis, childhood nephrotic syndrome and systemic lupus erythematosus. It is a potent immunosuppressive agent. It is commonly used in blood and bone marrow transplantation. With the growing trend among women postponing childbearing, the number of women who are diagnosed with breast cancer is also increasing thus escalating the chances of exposure of the unborn child to antineoplastic drugs...
December 6, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27924065/the-more-the-messier-centrosome-amplification-as-a-novel-biomarker-for-personalized-treatment-of-colorectal-cancers
#8
REVIEW
Monica M Mahathre, Padmashree Cg Rida, Ritu Aneja
Colon cancer is currently the third most common cancer and second most fatal cancer in the United States, resulting in approximately 600,000 deaths annually. Though colorectal cancer death rates are decreasing by about 3% every year, disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis, the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments. Colon carcinogenesis is notably a slow process that can take decades...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27923712/regulation-of-microrna-1-mir-1-expression-in-human-cancer
#9
REVIEW
Chao Han, Jacson K Shen, Francis J Hornicek, Quancheng Kan, Zhenfeng Duan
MicroRNAs (miRs) have been found to play important roles in tumorigenesis, apoptosis, metastasis, and drug resistance in cancer. Among a number of miRs, miR-1 was shown to be predominantly downregulated in almost all examined human cancers. As a tumor suppressor miR involved in post-transcriptional regulation of crucial tumor associated gene expression, miR-1 represents a promising target for anticancer therapy. Re-expression of miR-1 can suppress cancer cell proliferation, promote apoptosis, and reverse drug resistance in cancers both in vitro and in vivo...
December 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27923508/surfacing-role-of-probiotics-in-cancer-prophylaxis-and-therapy-a-systematic-review
#10
REVIEW
Subramanyam Dasari, Chandrasekhar Kathera, Avilala Janardhan, Arthala Praveen Kumar, Buddolla Viswanath
Cancers figure among the most important causes of morbidity and mortality worldwide. Cancer and its associated infections are always complicated even when specific cancer regimens are available. It is well proved that Lactobacillus and other probiotic bacteria can modulate-ameliorate specific mechanisms against various infections including cancers. The present systematic review is intended to focus on the 'cellular and molecular mechanisms' of probiotic bacteria in the prevention and treatment of various cancers...
November 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27922854/identification-of-hiv-infection-related-dna-methylation-sites-and-advanced-epigenetic-aging-in-hiv-treatment-na%C3%A3-ve-u-s-veterans
#11
Kristin N Nelson, Qin Hui, David Rimland, Ke Xu, Matthew S Freiberg, Amy C Justice, Vincent C Marconi, Yan V Sun
OBJECTIVE: HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNAm age, an aging marker involving multiple age-related CpG sites, among antiretroviral treatment (ART) naïve HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study (VACS)...
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27922451/direct-screening-for-chromatin-status-on-dna-barcodes-in-yeast-delineates-the-regulome-of-h3k79-methylation-by-dot1
#12
Hanneke Vlaming, Thom M Molenaar, Tibor van Welsem, Deepani W Poramba-Liyanage, Desiree E Smith, Arno Velds, Liesbeth Hoekman, Tessy Korthout, Sjoerd Hendriks, Af Maarten Altelaar, Fred van Leeuwen
Given the frequent misregulation of chromatin in cancer, it is important to understand the cellular mechanisms that regulate chromatin structure. However, systematic screening for epigenetic regulators is challenging and often relies on laborious assays or indirect reporter read-outs. Here we describe a strategy, Epi-ID, to directly assess chromatin status in thousands of mutants. In Epi-ID, chromatin status on DNA barcodes is interrogated by chromatin immunoprecipitation followed by deep sequencing, allowing for quantitative comparison of many mutants in parallel...
December 6, 2016: ELife
https://www.readbyqxmd.com/read/27919711/epigenetic-dysfunctional-diseases-and-therapy-for-infection-and-inflammation
#13
REVIEW
Saheli Samanta, Sheeja Rajasingh, Thuy Cao, Buddhadeb Dawn, Johnson Rajasingh
Even though the discovery of the term 'epigenetics' was in the 1940s, it has recently become one of the most promising and expanding fields to unravel the gene expression pattern in several diseases. The most well studied example is cancer, but other diseases like metabolic disorders, autism, or inflammation-associated diseases such as lung injury, autoimmune disease, asthma, and type-2 diabetes display aberrant gene expression and epigenetic regulation during their occurrence. The change in the epigenetic pattern of a gene may also alter gene function because of a change in the DNA status...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27918237/gpx3-promoter-methylation-predicts-platinum-sensitivity-in-colorectal-cancer
#14
Lorraine Pelosof, Sashidhar Yerram, Todd Armstrong, Nina Chu, Ludmila Danilova, Breann Yanagisawa, Manuel Hidalgo, Nilofer Azad, James G Herman
Epigenetic control of gene expression is a major determinant of tumor phenotype and has been found to influence sensitivity to individual chemotherapeutic agents. Glutathione peroxidase 3 (GPX3, plasma glutathione peroxidase) is a key component of cellular antioxidant regulation and its gene has been reported to be methylated in specific tumor types. GPX3 role in oxidative damage has been associated with sensitivity to platinums in other tumors but its importance in colorectal cancer (CRC) has not been determined...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27917697/current-and-future-biomarkers-in-the-treatment-of-colorectal-cancer
#15
Pieter-Jan Cuyle, Hans Prenen
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. CRC develops as a consequence of genomic instability, characterized by various genetic and epigenetic alterations. Its molecular heterogeneity explains the large variability in patient prognosis and treatment response, emphasizing the need for development of accurate prognostic and predictive biomarkers. This article delineates the different pathways of colorectal carcinogenesis and its molecular subtype classification. With this review, we aim to provide a comprehensive overview of the current and future biomarkers guiding clinical decision-making and CRC treatment...
December 5, 2016: Acta Clinica Belgica
https://www.readbyqxmd.com/read/27917406/genomics-of-colorectal-cancer-in-african-americans
#16
Hassan Brim, Hassan Ashktorab
Genome-wide studies are increasingly becoming a must, especially for complex diseases such as cancer where multiple genes and diverse molecular mechanisms are known to be involved in genes' function alteration. In this review, we report our latest genomic and epigenomic findings in African-American colorectal cancer patients. This population suffers a higher burden of the disease and most investigators in this field are looking for the underlying genetic and epigenetic targets that might be responsible for this disparity...
September 2016: Next Generation, Sequencing & Applications
https://www.readbyqxmd.com/read/27916892/molecular-mechanisms-of-p53-deregulation-in-cancer-an-overview-in-multiple-myeloma
#17
REVIEW
Ana B Herrero, Elizabeta A Rojas, Irena Misiewicz-Krzeminska, Patryk Krzeminski, Norma C Gutiérrez
The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916548/high-expression-of-cpt1a-predicts-adverse-outcomes-a-potential-therapeutic-target-for-acute-myeloid-leukemia
#18
Jinlong Shi, Huaping Fu, Zhilong Jia, Kunlun He, Lin Fu, Weidong Wang
Carnitine palmitoyl transferase 1A (CPT1A) protein catalyzes the rate-limiting step of Fatty-acid oxidation (FAO) pathway, which can promote cell proliferation and suppress apoptosis. Targeting CPT1A has shown remarkable anti-leukemia activity. But, its prognostic value remains unclear in Acute Myeloid Leukemia (AML). In two independent cohorts of cytogenetically normal AML (CN-AML) patients, compared to low expression of CPT1A (CPT1A(low)), high expression of CPT1A (CPT1A(high)) was significantly associated with adverse outcomes, which was also shown in European Leukemia Network (ELN) Intermediate-I category...
November 22, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27915976/strategies-to-strike-survival-networks-in-cancer
#19
Marzia Pennati, Graziella Cimino-Reale, Laura Gatti, Giuliana Cassinelli
The machinery that maintains cellular and tissue homeostasis in a healthy individual is recruited and hijacked by cancer cells to support tumor growth and progression. Activation of often unpredictable alternative or complementary signaling pathways allows cancer cells to bypass the intrinsic self-destructive machinery and the limited replicative potential present in every cell for correct homeostasis maintenance. Therefore, evasion/resistance to apoptosis/cell death, self-sufficiency in growth/survival signals, and limitless replicative potential remain undoubted hallmarks of cancer, contributing to drug resistance...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27915480/genetic-and-epigenetic-alterations-in-bladder-cancer
#20
REVIEW
Hong-Tao Li, Christopher E Duymich, Daniel J Weisenberger, Gangning Liang
Bladder cancer is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes as a result of relapse. Bladder cancer patients require lifelong invasive monitoring and treatment, making bladder cancer one of the most expensive malignancies. Lines of evidence increasingly point to distinct genetic and epigenetic alteration patterns in bladder cancer, even between the different stages and grades of disease. In addition, genetic and epigenetic alterations have been demonstrated to play important roles during bladder tumorigenesis...
November 2016: International Neurourology Journal
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