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prostate cancer methylation

M G Carta, A Preti, H S Akiskal
Human population is increasing in immense cities with millions of inhabitants, in which life is expected to run 24 hours a day for seven days a week (24/7). Noise and light pollution are the most reported consequences, with a profound impact on sleep patterns and circadian biorhythms. Disruption of sleep and biorhythms has severe consequences on many metabolic pathways. Suppression of melatonin incretion at night and the subsequent effect on DNA methylation may increase the risk of prostate and breast cancer...
2018: Clinical Practice and Epidemiology in Mental Health: CP & EMH
Priscila E Kobayashi, Carlos E Fonseca-Alves, Luis G Rivera-Calderón, Márcio Carvalho, Hellen Kuasne, Silvia R Rogatto, Renée Laufer-Amorim
Prostate cancer is a heterogeneous disease with high levels of clinical and gene heterogeneity, consequently offering several targets for therapy. Dogs with naturally occurring prostate cancer are useful models for molecular investigations and studying new treatment efficacy. Three genes and proteins associated with the WNT pathway (β-catenin, APC and E-cadherin) and Caveolin-1 (CAV-1) were evaluated in canine pre-neoplastic proliferative inflammatory atrophy (PIA), prostate cancer and metastatic disease. The APC gene methylation status was also investigated...
March 5, 2018: Research in Veterinary Science
Wei Sun, Paul Bunn, Chong Jin, Paul Little, Vasyl Zhabotynsky, Charles M Perou, David Neil Hayes, Mengjie Chen, Dan-Yu Lin
We systematically studied the association between somatic copy number aberration (SCNA), DNA methylation and gene expression using -omic data from The Cancer Genome Atlas (TCGA) on six cancer types: breast cancer, colon cancer, glioblastoma, leukemia, lower-grade glioma and prostate cancer. A major challenge for such integrated study is that the association between DNA methylation and gene expression is severely confounded by tumor purity and cell type composition, which are often unobserved and difficult to estimate...
February 26, 2018: Nucleic Acids Research
Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Kinga Anna Urbanek, Kamila Domińska, Agnieszka Wanda Piastowska-Ciesielska
Zearalenone (ZEA), a mycotoxin produced in the genus Fusarium , binds to estrogen receptors (ER) and is therefore regarded as an endocrine disruptor. ZEA has also been found to modulate the proliferation and apoptosis of prostate cancer cells in a dose-dependent manner. This study evaluates whether the effect of a low dose of ZEA (0.1 and 0.001 nM) on the invasion and migration of prostate cancer cell line PC3 is associated with ERs expression. The invasion and migration was evaluated by modified Boyden chamber assay, scratch assay, gelatin zymography, Real Time qPCR (RTqPCR) and Western blot...
February 28, 2018: Toxins
Heba S A Elzahabi, Eman S Nossier, Nagy M Khalifa, Rania A Alasfoury, May A El-Manawaty
An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50 : 0...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Christa Haldrup, Anne Lykke Pedersen, Nadia Øgaard, Siri H Strand, Søren Høyer, Michael Borre, Torben Falck Ørntoft, Karina Dalsgaard Sørensen
Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, leading to overdiagnosis and overtreatment. Aberrant promoter hypermethylation of specific genes has been suggested as novel candidate biomarkers for PC that may improve diagnosis and prognosis. We here analyzed ST6GALNAC3 and ZNF660 promoter methylation in prostate tissues, and ST6GALNAC3, ZNF660, CCDC181, and HAPLN3 promoter methylation in liquid biopsies. First, using four independent patient sample sets, including a total of 110 non-malignant (NM) and 705 PC tissue samples, analyzed by methylation specific qPCR or methylation array, we found that hypermethylation of ST6GALNAC3 and ZNF660 was highly cancer-specific with areas under the curve (AUC) of receiver operated characteristic (ROC) curve analysis of 0...
February 21, 2018: Molecular Oncology
Sung A Hong, Yong-June Kim, Sung Jae Kim, Sung Yang
DNA methylation is considered to be a promising marker for the early diagnosis and prognosis of cancer. However, direct detection of the methylated DNAs in clinically relevant samples is still challenging because of its extremely low concentration (~fM). Here, an integrated microfluidic chip is reported, which is capable of pre-concentrating the methylated DNAs using ion concentration polarization (ICP) and electrochemically detecting the pre-concentrated DNAs on a single chip. The proposed chip is the first demonstration of an electrochemical detection of both level and concentration of the methylated DNAs by integrating a DNA pre-concentration unit without gene amplification...
February 1, 2018: Biosensors & Bioelectronics
Jae Kyeom Kim, Marissa A McCormick, Cynthia M Gallaher, Daniel D Gallaher, Sabrina P Trudo
We previously showed rats fed with apiaceous vegetables, but not with their putative chemopreventive phytochemicals, reduced colonic DNA adducts formed by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a dietary procarcinogen. We report here the effects of feeding apiaceous and cruciferous vegetables versus their purified predominant phytochemicals, either alone or combined, on prostate and pancreatic PhIP-DNA adduct formation. In experiment I, male Wistar rats received three supplemented diets: CRU (cruciferous vegetables), API (apiaceous vegetables), and CRU+API (both types of vegetables)...
February 2018: Journal of Medicinal Food
Jolein Mijnes, Jürgen Veeck, Nadine T Gaisa, Eduard Burghardt, Tim C de Ruijter, Sonja Gostek, Edgar Dahl, David Pfister, Sebastian C Schmid, Ruth Knüchel, Michael Rose
Background: Genome-wide studies identified pan-cancer genes and shared biological networks affected by epigenetic dysregulation among diverse tumor entities. Here, we systematically screened for hypermethylation of DNA damage repair (DDR) genes in a comprehensive candidate-approach and exemplarily identify and validate candidate DDR genes as targets of epigenetic inactivation unique to bladder cancer (BLCA), which may serve as non-invasive biomarkers. Methods: Genome-wide DNA methylation datasets (2755 CpG probes of n  = 7819 tumor and n  = 659 normal samples) of the TCGA network covering 32 tumor entities were analyzed in silico for 177 DDR genes...
2018: Clinical Epigenetics
Gaelle Rondeau, Parisa Abedinpour, Adrian Chrastina, Jennifer Pelayo, Per Borgstrom, John Welsh
Treatment of mice harboring PTEN-P2 tumors in the prostate or on prostate tissue in vivo with 5-hydroxy-2-methyl-1,4-naphthoquinone, also known as plumbagin, results in tumor regression in castrated mice, but not in intact mice. This suggested that dihydrotestosterone (DHT) production in the testes may prevent cell death due to plumbagin treatment, but the underlying mechanism is not understood. We performed RNA-seq analysis on cells treated with combinations of plumbagin and DHT, and analyzed differential gene expression, to gain insight into the interactions between androgen and plumbgin...
February 9, 2018: Scientific Reports
Daniela Barros-Silva, Pedro Costa-Pinheiro, Henrique Duarte, Elsa Joana Sousa, Adriane Feijó Evangelista, Inês Graça, Isa Carneiro, Ana Teresa Martins, Jorge Oliveira, André L Carvalho, Márcia M Marques, Rui Henrique, Carmen Jerónimo
Upregulation of MYC and miRNAs deregulation are common in prostate cancer (PCa). Overactive MYC may cause miRNAs' expression deregulation through transcriptional and post-transcriptional mechanisms and epigenetic alterations are also involved in miRNAs dysregulation. Herein, we aimed to elucidate the role of regulatory network between MYC and miRNAs in prostate carcinogenesis. MYC expression was found upregulated in PCa cases and matched precursor lesions. MicroRNA's microarray analysis of PCa samples with opposed MYC levels identified miRNAs significantly overexpressed in high-MYC PCa...
February 7, 2018: Cell Death & Disease
Rafael Sebastián Fort, Cecilia Mathó, Murilo Vieira Geraldo, María Carolina Ottati, Alex Shimura Yamashita, Kelly Cristina Saito, Katia Ramos Moreira Leite, Manuel Méndez, Noemí Maedo, Laura Méndez, Beatriz Garat, Edna Teruko Kimura, José Roberto Sotelo-Silveira, María Ana Duhagon
BACKGROUND: Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer...
February 2, 2018: BMC Cancer
Daoguang Zhang, Solomon Asnake, Jingya Zhang, Per-Erik Olsson, Guisen Zhao
Androgen receptor (AR) signaling functions as a core driving force for the progression of prostate cancer (PCa), and AR has been proved to be an effective therapeutic target even for castration resistant prostate cancer (CRPC). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e, leading to the discovery of a series of 5-methyl-1H-pyrazole derivatives. AR reporter gene assay revealed compounds A13 and A14 as potent AR antagonists. Some of the compounds in this series inhibited growth of PCa LNCaP cells more efficiently than enzalutamide...
February 1, 2018: Chemical Biology & Drug Design
Ning Jiang, Binghu Ke, Kim Hjort-Jensen, Diego Iglesias-Gato, Zhun Wang, Pengcheng Chang, Yang Zhao, Xiaodan Niu, Tao Wu, Bo Peng, Mingdong Jiang, Xiaoshi Li, Zhiqun Shang, Qiang Wang, Chawnshang Chang, Amilcar Flores-Morales, Yuanjie Niu
Castration resistant prostate cancer (CRPC) is a stage of relapse that arises after various forms of androgen ablation therapy (ADT) and causes significant morbidity and mortality. However, the mechanism underlying progression to CRPC remains poorly understood. Here, we report that YAP1, which is negatively regulated by AR, influences prostate cancer (PCa) cell self-renewal and CRPC development. Specifically, we found that AR directly regulates the methylation of YAP1 gene promoter via the formation of a complex with Polycomb group protein EZH2 and DNMT3a...
December 29, 2017: Oncotarget
Lars Tögel, Rebecca Nightingale, Rui Wu, Anderly C Chüeh, Sheren Al-Obaidi, Ian Luk, Mercedes Dávalos-Salas, Fiona Chionh, Carmel Murone, Daniel D Buchanan, Zac Chatterton, Oliver M Sieber, Diego Arango, Niall C Tebbutt, David Williams, Amardeep S Dhillon, John M Mariadason
The ERK signalling pathway regulates key cell fate decisions in the intestinal epithelium and is frequently dysregulated in colorectal cancers (CRCs). Variations in the dynamics of ERK activation can induce different biological outcomes and are regulated by multiple mechanisms, including activation of negative feedback loops involving transcriptional induction of dual-specificity phosphatases (DUSPs). We have found that the nuclear ERK-selective phosphatase DUSP5 is downregulated in colorectal tumours and cell lines, as previously observed in gastric and prostate cancer...
January 29, 2018: Scientific Reports
Shivaputra A Patil, James K Addo, Hemantkumar Deokar, Shan Sun, Jin Wang, Wei Li, D Parker Suttle, Wei Wang, Ruiwen Zhang, John K Buolamwini
Objective: There is an urgent need drugs against particularly difficult to treat solid tumors such as pancreatic, triple negative breast, lung, colon, metastatic prostate cancers and melanoma. Thus, the objective of this study was to synthesize compounds based computational modeling that indicated the pyrido[3,4-b]indole class bind to MDM2, a new cancer target for which there are still no drug on the market. Methods: Compounds were synthesized by established methods and tested for antiproliferative activity against a broad range of human cancer cell lines, comprising HCT116 colon, HPAC, MIA PaCa-2 and Panc-1 pancreatic, MCF-7 and MDA-MB-468 breast, A375 and WM164 melanoma, A549 lung, and LNCaP, DU145 and PC3 prostate cancer lines...
March 2017: Drug Designing: Open Access
Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald P Hart, Ah-Ng Kong
Purpose: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq)...
2018: Cell & Bioscience
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
Lili Zhang, Mei Qi, Tingting Feng, Jing Hu, Lin Wang, Xinjun Li, Wei Gao, Hui Liu, Meng Jiao, Zhen Wu, Xinnuo Bai, Yifan Bie, Long Liu, Bo Han
Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa). Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
Rianne J Hendriks, Siebren Dijkstra, Frank P Smit, Johan Vandersmissen, Hendrik Van de Voorde, Peter F A Mulders, Inge M van Oort, Wim Van Criekinge, Jack A Schalken
BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. METHODS: In this prospective study, patients were included before starting new treatment after developing CRPC...
April 2018: Prostate
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