Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression to Breast Cancer in African American Women.

Background/aim: Methylation in the estrogen receptor alpha (ESRα) promoter is an epigenetic abnormality associated with breast cancer (BCa), whereas hypermethylation results in the loss of ER expression.

Materials And Methods: Pyrosequencing was used to investigate a potential link between aberrant methylation in the P0/P1 promoters of ESRα and the risk of progression of benign fibrocystic and fibroadenoma tumors to BCa.

Results: Results showed a significantly elevated level of DNA methylation in ESRα P1 promoter (=0.

Transcriptomic Analysis of Alzheimer's Disease Pathways in a Pakistani Population.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan.

Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population.

Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array;  = 33 subjects) coupled with Affymetrix Arrays ( = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways.

Mechanism of Antitumor Effects of Saffron in Human Prostate Cancer Cells.

Prostate cancer is the most common cancer and the second leading cause of cancer deaths among men in the USA. Several studies have demonstrated the antitumor properties of saffron in different types of cancers, including prostate cancer. The oral administration of saffron extract has been reported to have antitumor effects on aggressive prostate-cancer-cell-line-derived xenografts in nude male mice.

Transcriptomics of MASLD Pathobiology in African American Patients in the Washington DC Area .

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is becoming the most common chronic liver disease worldwide and is of concern among African Americans (AA) in the United States. This pilot study evaluated the differential gene expressions and identified the signature genes in the disease pathways of AA individuals with MASLD. Blood samples were obtained from MASLD patients ( = 23) and non-MASLD controls ( = 24) along with their sociodemographic and medical details.

Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer.

African American (AA) men have the highest incidence and mortality rate from Prostate cancer (PCa) than any other racial/ethnic group. To date, PCa genomic studies have largely under-represented tumour samples from AA men. We measured genome-wide DNA methylation in benign and tumor prostate tissues from AA men using the Illumina Infunium 850 K EPIC array.

Sex differences in saliva-based DNA methylation changes and environmental stressor in young African American adults.

Background: Low socioeconomic status neighborhood exposure to stress and violence may be sources of negative stimuli that poses significant health risks for children, adolescents and throughout the life course of an individual. The study aims to investigate if aberrant epigenetic DNA methylation changes may be a potential mechanism for regulating neighborhood exposures and health outcomes.

Methods: Exposure to environmental stressors identified in 98 young African American (AA) adults aged 18-25 years old from the Washington D.

Aerobic Exercise Training-Induced Changes on DNA Methylation in Mild Cognitively Impaired Elderly African Americans: Gene, Exercise, and Memory Study - GEMS-I.

Background: DNA methylation at CpG sites is a vital epigenetic modification of the human genome affecting gene expression, and potentially, health outcomes. However, evidence is just budding on the effects of aerobic exercise-induced adaptation on DNA methylation in older mild cognitively impaired (MCI) elderly African American (AAs). Therefore, we examined the effects of a 6-month aerobic exercise-intervention on genome-wide DNA methylation in elderly AA MCI volunteers.

RASAL2 suppresses the proliferative and invasive ability of PC3 prostate cancer cells.

The RAS protein activator like 2 (RASAL2) negatively regulates RAS proto-oncogene which is activated by high mutation rate in cancer. Thus, RASAL2 expression could potentially limit the function of RAS in prostate cancer (PCa). Genome-wide DNA methylation analysis demonstrated that RASAL2 is differentially hypermethylated in PCa tissues compared to benign prostate tissues.

DNA methylation and exposure to violence among African American young adult males.

Unlabelled: Exposure to violence (ETV) has been linked to epigenomics mechanisms such as DNA methylation (DNAm). We used epigenetic profiling of blood collected from 32 African American young adult males who lived in Washington DC to determine if changes in DNAm at CpG sites affiliated with nervous and immune system were associated with exposure to violence. Pathway analysis of differentially methylated regions comparing high and low ETV groups revealed an enrichment of gene sets annotated to nervous system and immune ontologies.

Interactions Between Obesity and One-Carbon Metabolism Genes in Predicting Prostate Cancer Outcomes Among White and Black Patients.

Background: One-carbon metabolism genes are linked to several cancers, but the association with prostate cancer (PCa) is less clear. Studies examining the relationship have not accounted for obesity, a risk factor for advanced PCa and altered methylation patterns. We hypothesized that obesity could moderate the association between one-carbon metabolism genes and PCa outcomes.

Androgen-induced Epigenetic Profiles of Polycomb and Trithorax Genes in Prostate Cancer Cells.

Background/aim: Androgens are essential for the growth of most prostate cancers (PCa). As a result, androgen ablation is the mainstay of the treatment of PCa. Proteins of the polycomb and trithorax family are master epigenetic regulators of cell type specific gene expression including androgen receptor.

Association of Genetic Ancestry With DNA Methylation Changes in Prostate Cancer Disparity.

Background: We hypothesized that ancestry-mediated methylated DNA changes may drive racial and ethnic disparity in prostate cancer (PCa). To test this hypothesis, we analyzed genetic ancestry and association with DNA methylation changes in PCa disparity.

Materials And Methods: Pyrosequencing and ancestry informative markers were used for DNA methylation and genetic ancestry testing, respectively.

Correlating blood-based DNA methylation markers and prostate cancer risk in African-American men.

The objective of this work was to investigate the clinical significance of promoter gene DNA methylation changes in whole blood from African-American (AA) men with prostate cancer (PCa). We used high throughput pyrosequencing analysis to quantify percentage DNA methylation levels in a panel of 8 genes (RARβ2, TIMP3, SPARC, CDH13, HIN1, LINE1, CYB5R2 and DRD2) in blood DNA obtained from PCa and non-cancerous controls cases. Correlations of methylation status and various clinicopathological features were evaluated.

Sex steroid-induced DNA methylation changes and inflammation response in prostate cancer.

Sex steroid hormones have been reported to induce inflammation causing dysregulation of cytokines in prostate cancer cells. However, the underlying epigenetic mechanism has not well been studied. The objective of this study was to evaluate the effect of sex steroid hormones on epigenetic DNA methylation changes in prostate cancer cells using a signature PCR methylation array panel that correspond to 96 genes with biological function in the human inflammatory and autoimmune signals in prostate cancer.

Design, synthesis and cytotoxicity studies of dithiocarbamate ester derivatives of emetine in prostate cancer cell lines.

A small library of emetine dithiocarbamate ester derivatives were synthesized in 25-86% yield via derivatization of the N2'- position of emetine. Anticancer evaluation of these compounds in androgen receptor positive LNCaP and androgen receptor negative PC3 and DU145 prostate cancer cell lines revealed time dependent and dose-dependent cytotoxicity. With the exception of compound 4c, all the dithiocarbamate ester analogs in this study showed appreciable potency in all the prostate cancer cell lines (regardless of whether it is androgen receptor positive or negative) with a cytotoxicity IC50 value ranging from 1.

Genome-wide differentially methylated genes in prostate cancer tissues from African-American and Caucasian men.

Increasing evidence suggests that aberrant DNA methylation changes may contribute to prostate cancer (PCa) ethnic disparity. To comprehensively identify DNA methylation alterations in PCa disparity, we used the Illumina 450K methylation platform to interrogate the methylation status of 485,577 CpG sites focusing on gene-associated regions of the human genome. Genomic DNA from African-American (AA; 7 normal and 3 cancers) and Caucasian (Cau; 8 normal and 3 cancers) was used in the analysis.

DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC study.

Background: Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD).

Methods: We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate.

Results: The mean eGFR slope was 2.

Identification of novel DNA-methylated genes that correlate with human prostate cancer and high-grade prostatic intraepithelial neoplasia.

Background: Prostate cancer (PCa) harbors a myriad of genomic and epigenetic defects. Cytosine methylation of CpG-rich promoter DNA is an important mechanism of epigenetic gene inactivation in PCa. There is considerable amount of data to suggest that DNA methylation-based biomarkers may be useful for the early detection and diagnosis of PCa.

Design, synthesis, and evaluation of pH-dependent hydrolyzable emetine analogues as treatment for prostate cancer.

The N-2' position of the natural product emetine has been derivatized to thiourea, urea, sulfonamide, dithiocarbamate, carbamate, and pH responsive hydrolyzable amide analogues. In vitro studies of these analogues in PC3 and LNCaP prostate cancer cell lines showed that the analogues are generally less cytotoxic (average IC(50) ranging from 0.079 to 10 μM) than emetine (IC(50) ranging from 0.

Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer.

Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women).

Humanizing π-class glutathione S-transferase regulation in a mouse model alters liver toxicity in response to acetaminophen overdose.

Background: Glutathione S-transferases (GSTs) metabolize drugs and xenobiotics. Yet despite high protein sequence homology, expression of π-class GSTs, the most abundant of the enzymes, varies significantly between species. In mouse liver, hepatocytes exhibit high mGstp expression, while in human liver, hepatocytes contain little or no hGSTP1 mRNA or hGSTP1 protein.

Transcriptional and post-transcriptional regulation of Sprouty1, a receptor tyrosine kinase inhibitor in prostate cancer.

Sprouty1 (Spry1) is a negative regulator of fibroblast growth factor signaling with a potential tumor suppressor function in prostate cancer (PCa). Spry1 is downregulated in human PCa, and Spry1 expression can markedly inhibit PCa proliferation in vitro. We have reported DNA methylation as a mechanism for controlling Spry1 expression.

Identification of differentially methylated genes in normal prostate tissues from African American and Caucasian men.

Purpose: Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males.

Experimental Design: We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARbeta2, SPARC, TIMP3, and NKX2-5.

DNA methylation and aberrant expression of Sprouty1 in human prostate cancer.

Sprouty1 is a negative regulator of fibroblast growth factor signaling with a potential tumor suppressor function in prostate cancer (PCa). Sprouty1 is downregulated in human PCa and Sprouty1 expression can markedly inhibit PCa proliferation in vitro. The aim of this study was to investigate the role of DNA methylation in Sprouty1 expression in human prostate tumors.

Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation.

Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based histone H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation and these histone modifications is not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) in prostate cancer cells compared to normal prostate, we found that up to 5% of promoters (16% CpG islands and 84% non-CpG islands) were enriched with H3K27triM.