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prostate cancer methylation

Shashank Gorityala, Shuming Yang, Monica M Montano, Yan Xu
Androgens play a vital role in prostate cancer development, and their elimination and blockade are essential in the disease management. DHT is the key ligand for androgen receptor (AR) in the prostate. It is locally synthesized from testosterone. In the prostate, DHT is predominantly metabolized to α-diol and β-diol. Recent studies indicate that impaired DHT catabolism is associated with prostate cancer, signifying the necessity of a sensitive quantitative method for the determination of DHT and its metabolites...
May 16, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Katrina L Clines, Gregory A Clines
Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis...
May 14, 2018: Translational Oncology
Maksims Yevglevskis, Guat L Lee, Amit Nathubhai, Yoana D Petrova, Tony D James, Michael D Threadgill, Timothy J Woodman, Matthew D Lloyd
α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the 'racemisation' reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no structure-activity relationship study has been performed. This paper describes the first structure-activity relationship study, in which a series of 23 known and potential rational AMACR inhibitors were evaluated...
April 30, 2018: Bioorganic Chemistry
Abisola Abisoye-Ogunniyan, Huxian Lin, Anghesom Ghebremedhin, Ahmad Salam, Balasubramanyam Karanam, Shaniece Theodore, Jacqueline Jones-Trich, Melissa Davis, William Grizzle, Honghe Wang, Clayton Yates
The loss of miR-200 family, through DNA methylation, results in cancer cells undergoing an epithelial to mesenchymal transition (EMT), and metastasis. In this study, we established that the transcriptional repressor Kaiso directly binds methylated regions of the miR-200 family, and this is reversed with 5-aza treatment. sh-Kaiso PC-3 cells display increased miR-200-a/b/c, miR-141, and miR-429 expression, with miR-200c demonstrating the most significant increase. Interestingly, overexpression of EGFR or treatment with EGF decreases miR-200c expression and this is reversed after treatment with EGFR specific kinase inhibitor PD153035...
May 8, 2018: Cancer Letters
Rafael Sebastián Fort, Cecilia Mathó, Carolina Oliveira-Rizzo, Beatriz Garat, José Roberto Sotelo-Silveira, María Ana Duhagon
Prostate cancer is a major health problem worldwide due to its high incidence morbidity and mortality. There is currently a need of improved biomarkers, capable to distinguish mild versus aggressive forms of the disease, and thus guide therapeutic decisions. Although miRNAs deregulated in cancer represent exciting candidates as biomarkers, its scientific literature is frequently fragmented in dispersed studies. This problem is aggravated for miRNAs belonging to miRNA gene clusters with shared target genes. The miRNA cluster composed by hsa-mir-130b and hsa-mir-301b precursors was recently involved in prostate cancer pathogenesis, yet different studies assigned it opposite effects on the disease...
2018: Experimental Hematology & Oncology
Bino Varghese, Erik Velez, Bhushan Desai, Hossein Jadvar
We report on an incidental detection of a meningioma on [F]-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (F-FMAU) PET/CT scan that was performed during a prospective investigation of F-FMAU PET/CT for targeted biopsy of potential sites of tumor in men with suspected prostate cancer based on elevated prostate-specific antigen level. Neither prostate multiparamteric MRI nor F-FMAU PET/CT localized small volume Gleason 3 + 3 tumor deposits. However, an incidental focal high accumulation of F-FMAU was observed in high right parietal lobe that displayed characteristics of a meningioma on a subsequent brain MRI...
May 7, 2018: Clinical Nuclear Medicine
Emily A Teslow, Bin Bao, Greg Dyson, Christophe Legendre, Cristina Mitrea, Wael Sakr, John D Carpten, Isaac Powell, Aliccia Bollig-Fischer
African American men (AAM) are at higher risk of being diagnosed with prostate cancer (PCa) and are at higher risk of dying from the disease compared to European American men (EAM).We sought to better understand PCa molecular diversity that may be underlying these disparities. We performed RNA-sequencing analysis on high-grade PCa to identify genes showing differential tumor versus noncancer adjacent tissue expression patterns unique to AAM or EAM. We observed that interleukin-6 (IL6) was upregulated in the nonmalignant adjacent tissue in AAM, but in EAM IL6 expression was higher in PCa tissue...
May 9, 2018: Molecular Oncology
Erfan Aref-Eshghi, Laila C Schenkel, Peter Ainsworth, Hanxin Lin, David I Rodenhiser, Jean-Claude Cutz, Bekim Sadikovic
Introduction: The current methodology involving diagnosis of prostate cancer (PCa) relies on the pathology examination of prostate needle biopsies, a method with high false negative rates partly due to temporospatial, molecular, and morphological heterogeneity of prostate adenocarcinoma. It is postulated that molecular markers have a potential to assign diagnosis to a considerable portion of undetected prostate tumors. This study examines the genome-wide DNA methylation changes in PCa in search of genomic markers for the development of a diagnostic algorithm for PCa screening...
2018: Frontiers in Oncology
Leandro S D'Abronzo, Paramita M Ghosh
Prostate cancer (PCa) progression involves a shift from endocrine to paracrine and eventually autocrine control resulting from alterations in molecular mechanisms in the cells. Deregulation of RNA translation is crucial for tumor cells to grow and proliferate; therefore, overactivation of the translation machinery is often observed in cancer. The two most important signal transduction pathways regulating PCa progression are PI3K/Akt/mTOR and Ras/MAPK. These two pathways converge on the eukaryotic translation initiation factor 4E (eIF4E) which binds to the protein scaffold eIF4G upon mechanistic target of rapamycin (mTOR) activation and is phosphorylated by the mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1/2)...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
Lingling Fan, Fengbo Zhang, Songhui Xu, Xiaolu Cui, Arif Hussain, Ladan Fazli, Martin Gleave, Xuesen Dong, Jianfei Qi
Formation of the androgen receptor splicing variant 7 (AR-V7) is one of the major mechanisms by which resistance of prostate cancer to androgen deprivation therapy occurs. The histone demethylase JMJD1A (Jumonji domain containing 1A) functions as a key coactivator for AR by epigenetic regulation of H3K9 methylation marks. Here, we describe a role for JMJD1A in AR-V7 expression. While JMJD1A knockdown had no effect on full-length AR (AR-FL), it reduced AR-V7 levels in prostate cancer cells. Reexpression of AR-V7 in the JMJD1A-knockdown cells elevated expression of select AR targets and partially rescued prostate cancer cell growth in vitro and in vivo...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ângela Marques-Magalhães, Inês Graça, Rui Henrique, Carmen Jerónimo
Urological cancers are a heterogeneous group of malignancies accounting for a considerable proportion of cancer-related morbidity and mortality worldwide. Aberrant epigenetic traits, especially altered DNA methylation patterns constitute a hallmark of these tumors. Nonetheless, these alterations are reversible, and several efforts have been carried out to design and test several epigenetic compounds that might reprogram tumor cell phenotype back to a normal state. Indeed, several DNMT inhibitors are currently under evaluation for therapeutic efficacy in clinical trials...
2018: Frontiers in Pharmacology
Louise Katrine Larsen, Jørn Skibsted Jakobsen, Ahmad Abdul-Al, Per Guldberg
PURPOSE: With the aim of developing a noninvasive test for detection of clinically significant prostate cancer, we investigated the potential of capturing cells from urine by microfiltration coupled with analysis of DNA-methylation biomarkers. MATERIALS AND METHODS: In this prospective study, urine from men suspected of prostate cancer and scheduled for transrectal ultrasonography-guided biopsy of the prostate was collected before (n=99) or after (n=58) digital rectal examination (DRE), or from a urethral catheter (n=7)...
April 24, 2018: Journal of Urology
Hui Zhou, Guanqing Wu, Xueyou Ma, Jun Xiao, Gan Yu, Chunguang Yang, Nan Xu, Bao Zhang, Jun Zhou, Zhangqun Ye, Zhihua Wang
BACKGROUND: Dysregulation of transforming growth factor β (TGF-β) signaling and hypoxic microenvironment have respectively been reported to be involved in disease progression in malignancies of prostate. Emerging evidence indicates that downregulation of TGFBR2, a pivotal regulator of TGF-β signaling, may contribute to carcinogenesis and progression of prostate cancer (PCa). However, the biological function and regulatory mechanism of TGFBR2 in PCa remain poorly understood. In this study, we propose to investigate the crosstalk of hypoxia and TGF-β signaling and provide insight into the molecular mechanism underlying the regulatory pathways in PCa...
April 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yan Cheng, Cátia Monteiro, Andreia Matos, Jiaying You, Avelino Fraga, Carina Pereira, Victoria Catalán, Amaia Rodríguez, Javier Gómez-Ambrosi, Gema Frühbeck, Ricardo Ribeiro, Pingzhao Hu
Background: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m-2 ) and normal weight (NW, BMI < 25 kg m-2 ) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling...
2018: Clinical Epigenetics
Sukanya Panja, Sheida Hayati, Nusrat J Epsi, James Scott Parrott, Antonina Mitrofanova
Therapeutic resistance is a central problem in clinical oncology. We have developed a systematic genome-wide computational methodology to allow prioritization of patients with favorable and poor therapeutic response. Our method, which integrates DNA methylation and mRNA expression data, uncovered a panel of 5 differentially methylated sites, which explain expression changes in their site-harboring genes, and demonstrated their ability to predict primary resistance to androgen-deprivation therapy (ADT) in the TCGA prostate cancer patient cohort (hazard ratio = 4...
April 12, 2018: EBioMedicine
Agata Karolina Pietrzak, Rafal Czepczynski, Ewa Wierzchoslawska, Witold Cholewinski
PURPOSE: The objective was to compare the efficacy of 99mTc-MDP-BS, 18F-FDG-PET/CT and 18F-FCH-PET/CT in detecting bone metastases in prostate cancer patients. MATERIALS AND METHODS: 56 patients diagnosed with prostate cancer underwent 99mTc-methylendiphosphonates bone scintigraphy (99mTc-MDP-BS) and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) or fluorine-18-fluorocholine PET/CT (18F-FCH-PET/CT) within six weeks...
April 22, 2018: Urology Journal
Bruna Dos Santos Rodrigues, Renato Ivan de Ávila, Polyana Lopes Benfica, Ludmila Pires Bringel, Cecília Maria Alves de Oliveira, Fábio Vandresen, Cleuza Conceição da Silva, Marize Campos Valadares
AIMS: This study evaluated parameters of toxicity and antiproliferative effects of (+)-N(1)-4-fluorobenzaldehyde-N(4)-{1-methyl-1-[(1R)-4-methylcyclohexene-3-il]-ethyl}-thiossemicarbazone (4-FTSC) in PC-3 adenocarcinoma prostate cells. MAIN METHODS: Cytotoxicity of 4-FTSC in PC-3 cells was evaluated using MTT assay. Morphology examination of PC-3 cells treated with 4-FTSC was also performed as well as the cell death mechanisms induced were investigated using flow cytometry...
April 16, 2018: Life Sciences
Hussain Mohamad Awwad, Carsten-Henning Ohlmann, Michael Stoeckle, Juergen Geisel, Rima Obeid
BACKGROUND: Folate is required for synthesis of methyl groups and DNA in growing cells. The association between folate and prostate cancer (PCa) is not conclusive. METHODS: We investigated concentrations of folate vitamers, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) in blood of men with PCa (n = 129) or benign prostatic hyperplasia (BPH) (n = 73) who were recruited just after the first diagnosis. RESULTS: In younger subjects <65 years, concentrations of (6S)-5-CH3 -H4 folate (15...
April 16, 2018: Clinical Biochemistry
Yuehua Xu, Xueting Cai, Bin Zong, Rui Feng, Yali Ji, Gang Chen, Zhongxing Li
Qianlie Xiaozheng decoction (QLXZD), a traditional Chinese medicinal formula, has been used clinically to treat advanced prostate cancer (PCa) for more than 10 years. However, experimental evidence supporting its efficacy is lacking. Here, we investigated the anticancer properties and molecular mechanism of QLXZD in vitro in a human PCa cell line (PC3) and in vivo using PC3 xenografts in nude mice. We confirmed the antineoplastic activity of QLXZD by analyzing cell viability and tumor volume growth, which decreased significantly compared to that of the controls...
2018: Frontiers in Pharmacology
Chee W Ong, Pamela Maxwell, Muhammad A Alvi, Stephen McQuaid, David Waugh, Ian Mills, Manuel Salto-Tellez
Accurate identification of intermediate risk (Gleason 3 + 4 = 7) prostate cancer patients with low risk of disease progression is an unmet challenge in treatment decision making. Here we describe a gene signature that could guide clinicians in the selection of patients with intermediate stage clinically localized prostate cancer for active surveillance. We examined six major drivers of aggressive disease - PTEN, MYC, RB1, TP53, AURKA, AR - by immunohistochemistry in a focused (N = 69) cohort predominantly consisting of intermediate risk prostate cancer...
April 2018: Journal of Pathology. Clinical Research
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