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https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#1
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#2
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/28811834/high-risk-human-papilloma-viruses-hpvs-are-present-in-benign-prostate-tissues-before-development-of-hpv-associated-prostate-cancer
#3
Wendy K Glenn, Christopher C Ngan, Timothy G Amos, Richard J Edwards, Joshua Swift, Louise Lutze-Mann, Fei Shang, Noel J Whitaker, James S Lawson
BACKGROUND: Although high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28805821/opposing-effects-of-cancer-type-specific-spop-mutants-on-bet-protein-degradation-and-sensitivity-to-bet-inhibitors
#4
Hana Janouskova, Geniver El Tekle, Elisa Bellini, Namrata D Udeshi, Anna Rinaldi, Anna Ulbricht, Tiziano Bernasocchi, Gianluca Civenni, Marco Losa, Tanya Svinkina, Craig M Bielski, Gregory V Kryukov, Luciano Cascione, Sara Napoli, Radoslav I Enchev, David G Mutch, Michael E Carney, Andrew Berchuck, Boris J N Winterhoff, Russell R Broaddus, Peter Schraml, Holger Moch, Francesco Bertoni, Carlo V Catapano, Matthias Peter, Steven A Carr, Levi A Garraway, Peter J Wild, Jean-Philippe P Theurillat
It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants...
August 14, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28802562/current-research-development-of-single-cell-genome-in-urological-tumor
#5
Ziyi Cao, Song Wu
The technique of whole genome amplification is advancing rapidly and generating attention on detecting genomic lesions in individual cancer cells. Also, single-cell genome could label the uniqueness of each cell, its individual mutations and structural variations especially in cancer studies. In this Review, we provide the insight into the current state of single-cell genome in urological tumor mainly including kidney cancer, bladder cancer and prostate cancer. We put more forward on the new progress of the technique used by single-cell genomes and different results of the genes transform on random tumor tissue from single cell isolated on account of tumor heterogeneity...
August 9, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28802252/exploiting-radiation-induced-signaling-to-increase-the-susceptibility-of-resistant-cancer-cells-to-targeted-drugs-akt-and-mtor-inhibitors-as-an-example
#6
Iris Eke, Adeola Y Makinde, Molykutty J Aryankalayil, Veit Sandfort, Sanjeewani T Palayoor, Barbara H Rath, Lance Liotta, Mariaelena Pierobon, Emanuel F Petricoin, Matthew F Brown, Jayne M Stommel, Mansoor M Ahmed, C Norman Coleman
Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate pro-survival pathways which can help tumor cells to adapt and thereby survive treatment. Therefore, we aimed to identify changes in signaling induced by radiation and evaluate the potential of targeting these changes with small molecules to increase the therapeutic efficacy on cancer cell survival...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28794807/prognostic-and-predictive-biomarkers-in-prostate-cancer-latest-evidence-and-clinical-implications
#7
REVIEW
Naoki Terada, Shusuke Akamatsu, Takashi Kobayashi, Takahiro Inoue, Osamu Ogawa, Emmanuel S Antonarakis
Advances in our understanding of the mechanisms driving castration-resistant prostate cancer have promoted the development of several new drugs including androgen receptor-directed therapy and chemotherapy. Concomitant docetaxel treatment at the beginning of hormonal therapy for metastatic prostate cancer has resulted in longer overall survival than with hormonal therapy alone. Elucidating an appropriate treatment sequence using these therapies is important for maximizing clinical benefit in castration-sensitive and castration-resistant prostate cancer patients...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28794468/the-mir-183-family-cluster-alters-zinc-homeostasis-in-benign-prostate-cells-organoids-and-prostate-cancer-xenografts
#8
Shweta Dambal, Bethany Baumann, Tara McCray, LaTanya Williams, Zachary Richards, Ryan Deaton, Gail S Prins, Larisa Nonn
The miR-183 cluster, which is comprised of paralogous miRs-183, -96 and -182, is overexpressed in many cancers, including prostate adenocarcinoma (PCa). Prior studies showed that overexpression of individual pre-miRs-182, -96 and -183 in prostate cells decreased zinc import, which is a characteristic feature of PCa tumours. Zinc is concentrated in healthy prostate 10-fold higher than any other tissue, and an >80% decrease in zinc is observed in PCa specimens. Here, we studied the effect of overexpression of the entire 4...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783165/tmprss2-erg-fusion-co-opts-master-transcription-factors-and-activates-notch-signaling-in-primary-prostate-cancer
#9
Ken J Kron, Alexander Murison, Stanley Zhou, Vincent Huang, Takafumi N Yamaguchi, Yu-Jia Shiah, Michael Fraser, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow, Mathieu Lupien
TMPRSS2-ERG (T2E) structural rearrangements typify ∼50% of prostate tumors and result in overexpression of the ERG transcription factor. Using chromatin, genomic and expression data, we show distinct cis-regulatory landscapes between T2E-positive and non-T2E primary prostate tumors, which include clusters of regulatory elements (COREs). This difference is mediated by ERG co-option of HOXB13 and FOXA1, implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression...
August 7, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28780673/investigating-the-genetic-relationship-between-alzheimer-s-disease-and-cancer-using-gwas-summary-statistics
#10
Yen-Chen Anne Feng, Kelly Cho, Sara Lindstrom, Peter Kraft, Jean Cormack, Liming Liang, Jane A Driver
Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer's disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; r g = 0...
August 5, 2017: Human Genetics
https://www.readbyqxmd.com/read/28775315/pan-urologic-cancer-genomic-subtypes-that-transcend-tissue-of-origin
#11
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/28775145/bypassing-drug-resistance-mechanisms-of-prostate-cancer-with-small-molecules-that-target-androgen-receptor-chromatin-interactions
#12
Kush Dalal, Meixia Che, Nanette S Que, Aishwariya Sharma, Rendong Yang, Nada Lallous, Hendrik Borgmann, Deniz Ozistanbullu, Ronnie Tse, Fuqiang Ban, Huifang Li, Kevin J Tam, Mani Roshan-Moniri, Eric Leblanc, Martin E Gleave, Daniel T Gewirth, Scott M Dehm, Artem Cherkasov, Paul S Rennie
Human androgen receptor (AR) is a hormone-activated transcription factor that is an important drug-target in the treatment of prostate cancer. Current small molecule AR-antagonists, such as enzalutamide, compete with androgens that bind to the steroid binding pocket of the AR ligand binding domain (LBD). In castration-resistant prostate cancer (CRPC), drug-resistance can manifest through AR-LBD mutations that convert AR-antagonists into agonists, or by expression of AR-variants lacking the LBD. Such treatment resistance underscores the importance of novel ways of targeting the AR...
August 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28762374/molecular-alterations-in-prostate-cancer-and-association-with-mri-features
#13
D Lee, J Fontugne, N Gumpeni, K Park, T Y MacDonald, B D Robinson, A Sboner, M A Rubin, J M Mosquera, C E Barbieri
BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has been increasingly used for prostate cancer (PCa). Recent studies identified distinct molecular subclasses of PCa with recurrent genomic alterations. However, the associations between molecular alterations in PCa and characteristics on mpMRI are unknown. Therefore, the objective of this study was to investigate recurrent molecular alterations in PCa and their associations with mpMRI features. METHODS: Sixty-two PCa nodules >0...
August 1, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28754872/tunicamycin-induced-endoplasmic-reticulum-stress-promotes-apoptosis-of-prostate-cancer-cells-by-activating-mtorc1
#14
Prasun Guha, Engin Kaptan, Padmaja Gade, Dhananjaya V Kalvakolanu, Hafiz Ahmed
Studies suggest that tunicamycin may work as a therapeutic drug to cancer cells by inducing stress in the endoplasmic reticulum (ER) through unfolded protein response (UPR) and thereby promoting apoptosis. However, mechanisms of the prolonged activation of the UPR under sustained ER stress in the regulation of cell apoptosis are largely unknown. To delineate the role of candidate genes in the apoptotic process under ER stress and to search for new therapeutic strategies to treat metastatic castration resistant prostate cancer, we performed whole genome expression microarray analysis in tunicamycin treated metastatic androgen-insensitive prostate cancer cells, PC-3...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754843/hormone-induced-dna-damage-response-and-repair-mediated-by-cyclin-d1-in-breast-and-prostate-cancer
#15
REVIEW
Gabriele Di Sante, Agnese Di Rocco, Claudia Pupo, Mathew C Casimiro, Richard G Pestell
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA [1]. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753864/predicting-prostate-cancer-progression-as-a-function-of-ets-related-gene-status-race-and-obesity-in-a-longitudinal-patient-cohort
#16
Jennifer Cullen, Denise Young, Yongmei Chen, Michael Degon, James Farrell, Jason Sedarsky, Wagner Baptiste, Philip Rosen, Vladimir Tolstikov, Michael Kiebish, Jacob Kagan, Sudhir Srivastava, Huai-Ching Kuo, Joel T Moncur, Inger L Rosner, Niven Narain, Viatcheslav Akmaev, Gyorgy Petrovics, Albert Dobi, David G McLeod, Shiv Srivastava, Isabell A Sesterhenn
BACKGROUND: ETS-related gene (ERG) oncogenic activation is the most common genomic alteration in prostate cancer (CaP) although it occurs less frequently in African American (AA) versus Caucasian (CA) patients, and the potential role of ERG as a prognostic marker has not been confirmed. OBJECTIVE: This study was conducted to confirm strong racial variation in the prevalence of ERG oncoprotein expression and to examine ERG oncoprotein expression, race, and body mass index as independent and joint predictors of CaP biochemical recurrence (BCR) following radical prostatectomy (RP)...
March 11, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28753860/metabolic-imaging-of-prostate-cancer-reveals-intrapatient-intermetastasis-response-heterogeneity-to-systemic-therapy
#17
Fannie Morin, Jean-Mathieu Beauregard, Michelle Bergeron, Molière Nguile Makao, Louis Lacombe, Vincent Fradet, Yves Fradet, Frédéric Pouliot
Although intrapatient heterogeneity of prostate cancer (PCa) has recently been characterized via genomic and transcriptomic studies, the heterogeneity of systemic treatment responses has yet to be reported or imaged. Our objective was to evaluate the intrapatient intermetastasis response to systemic treatment among patients with metastatic PCa. We evaluated the metabolic response for each individual metastatic lesion (n=165) in 15 patients with metastatic PCa who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography before and at least 3 mo after initiation of a systemic therapy that did not change in that period...
February 23, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28753846/the-landscape-of-whole-genome-alterations-and-pathologic-features-in-genitourinary-malignancies-an-analysis-of-the-cancer-genome-atlas
#18
Mark W Ball, Michael A Gorin, Charles G Drake, Hans J Hammers, Mohamad E Allaf
BACKGROUND: The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival. OBJECTIVE: To investigate the influence of somatic mutation count (MC) and copy number variation (CNV) on pathologic and oncologic outcomes in patients with genitourinary malignancies in The Cancer Genome Atlas (TCGA). DESIGN, SETTING, AND PARTICIPANTS: TCGA data sets for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed via cBioportal...
February 8, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28753844/transcriptome-wide-analysis-of-magnetic-resonance-imaging-targeted-biopsy-and-matching-surgical-specimens-from-high-risk-prostate-cancer-patients-treated-with-radical-prostatectomy-the-target-must-be-hit
#19
Jan Philipp Radtke, Mandeep Takhar, David Bonekamp, Claudia Kesch, Nicholas Erho, Marguerite du Plessis, Christine Buerki, Kaye Ong, Elai Davicioni, Markus Hohenfellner, Boris A Hadaschik
BACKGROUND: The most suspicious lesions on multiparametric magnetic resonance imaging (MRI) may be representative of final pathology. OBJECTIVE: We connect imaging with high-precision spatial annotation of biopsies and genomic cancer signatures to compare the genomic signals of the index lesion and biopsy cores of adjacent and far away locations. DESIGN, SETTING, AND PARTICIPANTS: Eleven patients diagnosed with high-risk prostate cancer on MRI/transrectal ultrasound-fusion biopsy (Bx) and treated with radical prostatectomy (RP)...
January 26, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28753811/risk-of-upgrading-and-upstaging-among-10-000-patients-with-gleason-3-4-favorable-intermediate-risk-prostate-cancer
#20
David D Yang, Brandon A Mahal, Vinayak Muralidhar, Michelle D Nezolosky, Marie E Vastola, Shelby A Labe, Ninjin Boldbaatar, Martin T King, Neil E Martin, Peter F Orio, Clair J Beard, Karen E Hoffman, Quoc-Dien Trinh, Daniel E Spratt, Felix Y Feng, Paul L Nguyen
BACKGROUND: It is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer. OBJECTIVE: To examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. DESIGN, SETTING, AND PARTICIPANTS: The study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent radical prostatectomy...
June 17, 2017: European Urology Focus
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