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prostate cancer methylation

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https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#1
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28795320/ezh2-promotes-cell-proliferation-by-regulating-the-expression-of-runx3-in-laryngeal-carcinoma
#2
Rong Lian, Huimin Ma, Zhiyan Wu, Guozheng Zhang, Lei Jiao, Wenjie Miao, Qianqian Jin, Ruixue Li, Ping Chen, Haixu Shi, Wenfa Yu
Enhancer of zeste homolog 2 (EZH2) is a highly conserved histone methyltransferase, which is overexpressed in different types of cancers such as breast and prostate cancer. It is reported that EZH2 can directly down-regulate RUNX3 by increasing histone H3 methylation. However, the role of EZH2 in the development and progression of laryngeal carcinoma has not yet been investigated, and the relationship between EZH2 and RUNX3 in laryngeal carcinoma is rarely reported. The current study aims to determine the role of EZH2 in the progression of laryngeal carcinoma, and investigate the interaction between EZH2 and the tumor suppressor RUNX3...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28775315/pan-urologic-cancer-genomic-subtypes-that-transcend-tissue-of-origin
#3
Fengju Chen, Yiqun Zhang, Dominick Bossé, Aly-Khan A Lalani, A Ari Hakimi, James J Hsieh, Toni K Choueiri, Don L Gibbons, Michael Ittmann, Chad J Creighton
Urologic cancers include cancers of the bladder, kidney, prostate, and testes, with common molecular features spanning different types. Here, we show that 1954 urologic cancers can be classified into nine major genomic subtypes, on the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy number, and RNA and protein expression). Tissue dominant effects are first removed computationally in order to define these subtypes, which reveal common processes-reflecting in part tumor microenvironmental influences-driving cellular behavior across tumor lineages...
August 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28768240/c-met-creb1-and-egfr-are-involved-in-mir-493-5p-inhibition-of-emt-via-akt-gsk-3%C3%AE-snail-signaling-in-prostate-cancer
#4
Song Wang, Xiao Wang, Jiangfeng Li, Shuai Meng, Zhen Liang, Xin Xu, Yi Zhu, Shiqi Li, Jian Wu, Mingjie Xu, Alin Ji, Yiwei Lin, Ben Liu, Xiangyi Zheng, Bo Xie, Liping Xie
miR-493-5p downregulation has emerged as a critical player in cancer progression yet, the underlying mechanisms of miR-493-5p expression pattern and its function in prostate cancer remains to be elucidated. Here, we illustrate that miR-493-5p is frequently downregulated in prostate cancer, at least partially due to altered DNA methylation. miR-493-5p functions as a tumor suppressor in prostate cancer cells. c-Met, CREB1 and EGFR are downstream target genes of miR-493-5p. miR-493-5p inhibits EMT via AKT/GSK-3β/Snail signaling in prostate cancer...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28762545/epigenetic-risk-score-improves-prostate-cancer-risk-assessment
#5
Leander Van Neste, Jack Groskopf, William E Grizzle, George W Adams, Mark S DeGuenther, Peter N Kolettis, James E Bryant, Gary P Kearney, Michael C Kearney, Wim Van Criekinge, Sandra M Gaston
BACKGROUND: Early detection of aggressive prostate cancer (PCa) remains crucial for effective treatment of patients. However, PCa screening remains controversial due to a high rate of overdiagnosis and overtreatment. To better reconcile both objectives, more effective methods for assessing disease severity at the time of diagnosis are needed. METHODS: The relationship between DNA-methylation and high-grade PCa was examined in a cohort of 102 prospectively enrolled men who received standard 12-core prostate biopsies...
August 1, 2017: Prostate
https://www.readbyqxmd.com/read/28750683/identification-of-novel-prostate-cancer-drivers-using-regnetdriver-a-framework-for-integration-of-genetic-and-epigenetic-alterations-with-tissue-specific-regulatory-network
#6
Priyanka Dhingra, Alexander Martinez-Fundichely, Adeline Berger, Franklin W Huang, Andre Neil Forbes, Eric Minwei Liu, Deli Liu, Andrea Sboner, Pablo Tamayo, David S Rickman, Mark A Rubin, Ekta Khurana
We report a novel computational method, RegNetDriver, to identify tumorigenic drivers using the combined effects of coding and non-coding single nucleotide variants, structural variants, and DNA methylation changes in the DNase I hypersensitivity based regulatory network. Integration of multi-omics data from 521 prostate tumor samples indicated a stronger regulatory impact of structural variants, as they affect more transcription factor hubs in the tissue-specific network. Moreover, crosstalk between transcription factor hub expression modulated by structural variants and methylation levels likely leads to the differential expression of target genes...
July 27, 2017: Genome Biology
https://www.readbyqxmd.com/read/28744401/polyisoprenylated-cysteinyl-amide-inhibitors-induce-caspase-3-7-and-8-mediated-apoptosis-and-inhibit-migration-and-invasion-of-metastatic-prostate-cancer-cells
#7
Rosemary A Poku, Olufisayo O Salako, Felix Amissah, Augustine T Nkembo, Elizabeth Ntantie, Nazarius S Lamango
Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive and deadly form of prostate cancer. It is characterized by the overexpression of epidermal growth factor receptors whose signals are mediated by small monomeric G proteins of the Ras superfamily. These require polyisoprenylation for functional activity. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) of polyisoprenylated methylated protein methyl esterase (PMPMEase) were developed as potential targeted therapies to mitigate excessive growth signaling in mCRPC either by inhibiting PMPMEase and/or perturbing the polyisoprenylation-dependent functional interactions...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28732347/histone-demethylase-jmjd2c-epigenetic-regulators-in-tumors
#8
REVIEW
Chengcheng Zhang, Zhongqi Wang, Qing Ji, Qi Li
Histone methylation is one of the major epigenetic modifications, and various histone methylases and demethylases participate in the epigenetic regulating. JMJD2C has been recently identified as one of the histone lysine demethylases. As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28728135/prostate-cancer-risk-and-dna-methylation-signatures-in-aging-rats-following-developmental-bpa-exposure-a-dose-response-analysis
#9
Gail S Prins, Shu-Hua Ye, Lynn Birch, Xiang Zhang, Ana Cheong, Han Lin, Esther Calderon-Gierszal, Jacob Groen, Wen-Yang Hu, Shuk-Mei Ho, Richard B van Breemen
BACKGROUND: Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. OBJECTIVES: A complete BPA dose-response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes...
July 11, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28727579/enhanced-anticancer-efficacy-of-histone-deacetyl-inhibitor-suberoylanilide-hydroxamic-acid-in-combination-with-a-phosphodiesterase-inhibitor-pentoxifylline-in-human-cancer-cell-lines-and-in-vivo-tumor-xenografts
#10
Saranya Nidhyanandan, Boreddy S Thippeswamy, Kottapalli B Chandrasekhar, Neetinkumar D Reddy, Nagaraj M Kulkarni, Kandasamy Karthikeyan, Farhin R Khan, Jayaprakash Raghul, Govindharajan Vijaykanth, Shridhar Narayanan
Vorinostat [suberoylanilide hydroxamic acid (SAHA)], a histone deacetylase inhibitor, shows limited clinical activity against solid tumors when used alone. The methyl xanthine drug, pentoxifylline (PENT), has been described to have antitumor properties. The aim of this study was to look for the enhanced anticancer activities of both agents when used in combination at doses lower than their respective efficacy dose when used alone. We investigated the antitumor potential of this novel combination in vitro and in vivo...
July 19, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28727412/host-guest-recognition-assisted-electrochemical-release-its-reusable-sensing-application-based-on-dna-cross-configuration-fueled-target-cycling-and-strand-displacement-reaction-amplification
#11
Yuanyuan Chang, Ying Zhuo, Yaqin Chai, Ruo Yuan
In this work, an elegantly designed host-guest recognition-assisted electrochemical release was established and applied in a reusable electrochemical biosensor for the detection of microRNA-182-5p (miRNA-182-5p), a prostate cancer biomarker in prostate cancer, based on the DNA cross configuration-fueled target cycling and strand displacement reaction (SDR) amplification. With such a design, the single target miRNA input could be converted to large numbers of single-stranded DNA (S1-Trp and S2-Trp) output, which could be trapped by cucurbit[8]uril methyl viologen (CB-8-MV(2+)) based on the host-guest recognition, significantly enhancing the sensitivity for miRNA detection...
July 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28724269/association-of-human-methionine-synthase-a2756g-transition-with-prostate-cancer-a-case-control-study-and-in-silico-analysis
#12
Arezou Ebrahimi, Abasalt Hosseinzadeh Colagar, Mohammad Karimian
Methionine synthase (MTR) is one of the key enzymes of folate pathway, which play a key role in the construction, repair, and methylation of DNA. In this study, an association of MTR A2756G gene transition with prostate cancer in men populations of Kashan-Iran was investigated by a case-control study and an in silico analysis. The 200 samples including 100 patients with prostate cancer, as case group and 100 healthy men, as control group included in this study. MTR-A2756G genotyping was performed by PCR-RFLP technique...
May 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28722823/rational-design-of-a-highly-potent-and-selective-peptide-inhibitor-of-pace4-by-salt-bridge-interaction-with-d160-at-position-p3
#13
Vahid Dianati, Azar Shamloo, Anna Kwiatkowska, Roxane Desjardins, Armand Soldera, Robert Day, Yves L Dory
PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH2 . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal...
July 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28717648/response-detection-of-castrate-resistant-prostate-cancer-to-clinically-utilised-and-novel-treatments-by-monitoring-phospholipid-metabolism
#14
Tim A D Smith, Su M Phyu, Kholoud S Alzyoud, Chih-Chung Tseng
Androgen receptor (AR) activation is the primary driving factor in prostate cancer which is initially responsive to castration but then becomes resistant (castration-resistant prostate cancer (CRPC)). CRPC cells still retain the functioning AR which can be targeted by other therapies. A recent promising development is the use of inhibitors (Epi-1) of protein-protein interaction to inhibit AR-activated signalling. Translating novel therapies into the clinic requires sensitive early response indicators. Here potential response markers are explored...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28706131/structure-based-design-synthesis-and-activity-studies-of-small-hybrid-molecules-as-hdac-and-g9a-dual-inhibitors
#15
Lanlan Zang, Shukkoor M Kondengaden, Qing Zhang, Xiaobo Li, Dilep K Sigalapalli, Shameer M Kondengadan, Kenneth Huang, Keqin Kathy Li, Shanshan Li, Zhongying Xiao, Liuqing Wen, Hailiang Zhu, Bathini N Babu, Lijuan Wang, Fengyuan Che, Peng George Wang
Aberrant enzymatic activities or expression profiles of epigenetic regulations are therapeutic targets for cancers. Among these, histone 3 lysine 9 methylation (H3K9Me2) and global de-acetylation on histone proteins are associated with multiple cancer phenotypes including leukemia, prostatic carcinoma, hepatocellular carcinoma and pulmonary carcinoma. Here, we report the discovery of the first small molecule capable of acting as a dual inhibitor targeting both G9a and HDAC. Our structure based design, synthesis, and screening for the dual activity of the small molecules led to the discovery of compound 14 which displays promising inhibition of both G9a and HDAC in low micro-molar range in cell based assays...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705714/aristeromycin-and-dznep-cause-growth-inhibition-of-prostate-cancer-via-induction-of-mir-26a
#16
Noriko Uchiyama, Yukiya Tanaka, Tomohiro Kawamoto
Most prostate cancers initially respond to androgen deprivation therapy, but then progress from androgen-dependent to androgen-independent prostate cancers. In the present study, a differential cytotoxicity screen of hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells, identified a small molecule compound, Aristeromycin (a derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and L-homocysteine...
July 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28700329/decreased-expression-of-mt1e-is-a-potential-biomarker-of-prostate-cancer-progression
#17
Rita Demidenko, Kristina Daniunaite, Arnas Bakavicius, Rasa Sabaliauskaite, Aiste Skeberdyte, Donatas Petroska, Arvydas Laurinavicius, Feliksas Jankevicius, Juozas R Lazutka, Sonata Jarmalaite
Differentiation of indolent and aggressive prostate carcinoma (PCa) at the time of diagnosis is currently one of the major challenges. This study aimed at identification of prognostic biomarkers to aid in predicting biochemical recurrence (BCR) of the disease. Microarray-based gene expression profiling in tissues of 8 BCR and 8 No-BCR cases revealed expression differences of 455 genes, most of which were down-regulated in BCR cases. Eleven genes were selected for validation by real-time PCR in the first PCa cohort (N = 55), while seven of them were further validated in the second, independent, PCa cohort (N = 53)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28693181/distinct-dna-methylation-alterations-are-associated-with-cribriform-architecture-and-intraductal-carcinoma-in-gleason-pattern-4-prostate-tumors
#18
Ekaterina Olkhov-Mitsel, Farshid Siadat, Ken Kron, Liyang Liu, Andrea J Savio, John Trachtenberg, Neil Fleshner, Theodorus van der Kwast, Bharati Bapat
The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28685147/genotyping-the-high-altitude-mestizo-ecuadorian-population-affected-with-prostate-cancer
#19
REVIEW
Andrés López-Cortés, Alejandro Cabrera-Andrade, Carolina Salazar-Ruales, Ana Karina Zambrano, Santiago Guerrero, Patricia Guevara, Paola E Leone, César Paz-Y-Miño
Prostate cancer (PC) is the second most commonly diagnosed type of cancer in males with 1,114,072 new cases in 2015. The MTHFR enzyme acts in the folate metabolism, which is essential in methylation and synthesis of nucleic acids. MTHFR C677T alters homocysteine levels and folate assimilation associated with DNA damage. Androgens play essential roles in prostate growth. The SRD5A2 enzyme metabolizes testosterone and the V89L polymorphism reduces in vivo SRD5A2 activity. The androgen receptor gene codes for a three-domain protein that contains two polymorphic trinucleotide repeats (CAG, GGC)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28641156/mild-c-sp-3-h-functionalization-of-dihydrosanguinarine-and-dihydrochelerythrine-for-development-of-highly-cytotoxic-derivatives
#20
Adriana Romo-Pérez, Luis Demetrio Miranda, Alma D Chávez-Blanco, Alfonso Dueñas-González, María Del Rayo Camacho-Corona, Alejandrina Acosta-Huerta, Abraham García
A series of C(6)-substituted dihydrobenzo[c]phenanthridines were synthesized by mild copper-catalyzed C(sp(3))-H functionalization of dihydrosanguinarine (2) and dihydrochelerythrine (3) with certain nucleophiles selected to enhance cytotoxicity against human breast, colorectal, and prostate cancer cell lines. We also investigated the cytotoxicity of our previously reported C(6)-functionalized N-methyl-5,6-dihydrobenzo[c]phenanthridines 1a-1e to perform structure-activity relationship (SAR) studies. Among the target compounds, five β-aminomalonates (1a, 1b, 2a, 2b, and 3b), one α-aminophosphonate (2c), and one nitroalkyl derivative (2h) exhibited half maximal inhibitory concentration (IC50) values in the range of 0...
June 13, 2017: European Journal of Medicinal Chemistry
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