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https://www.readbyqxmd.com/read/27926866/inflammation-induced-oxidative-stress-mediates-gene-fusion-formation-in-prostate-cancer
#1
Ram S Mani, Mohammad A Amin, Xiangyi Li, Shanker Kalyana-Sundaram, Brendan A Veeneman, Lei Wang, Aparna Ghosh, Adam Aslam, Susmita G Ramanand, Bradley J Rabquer, Wataru Kimura, Maxwell Tran, Xuhong Cao, Sameek Roychowdhury, Saravana M Dhanasekaran, Nallasivam Palanisamy, Hesham A Sadek, Payal Kapur, Alisa E Koch, Arul M Chinnaiyan
Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27922627/blood-based-and-urinary-prostate-cancer-biomarkers-a-review-and-comparison-of-novel-biomarkers-for-detection-and-treatment-decisions
#2
REVIEW
R J Hendriks, I M van Oort, J A Schalken
BACKGROUND: The diagnosis of prostate cancer (PCa) is currently based on serum PSA testing and/or abnormal digital rectal examination and histopathologic evaluation of prostate biopsies. The main drawback of PSA testing is the lack of specificity for PCa. To improve early detection of PCa more specific biomarkers are needed. In the past few years, many new promising biomarkers have been identified; however, to date, only a few have reached clinical practice. METHODS: In this review, we discuss new blood-based and urinary biomarker models that are promising for usage in PCa detection, follow-up and treatment decision-making...
December 6, 2016: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/27918826/long-term-protection-of-genetically-ablated-rabbit-retinal-degeneration-by-sustained-transscleral-unoprostone-delivery
#3
Nobuhiro Nagai, Eri Koyanagi, Yasuko Izumida, Junjun Liu, Aya Katsuyama, Hirokazu Kaji, Matsuhiko Nishizawa, Noriko Osumi, Mineo Kondo, Hiroko Terasaki, Yukihiko Mashima, Toru Nakazawa, Toshiaki Abe
Purpose: To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). Methods: The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27917337/identification-characterization-and-phylogenetic-analysis-of-antifungal-trichoderma-from-tomato-rhizosphere
#4
Shalini Rai, Prem Lal Kashyap, Sudheer Kumar, Alok Kumar Srivastava, Pramod W Ramteke
The use of Trichoderma isolates with efficient antagonistic activity represents a potentially effective and alternative disease management strategy to replace health hazardous chemical control. In this context, twenty isolates were obtained from tomato rhizosphere and evaluated by their antagonistic activity against four fungal pathogens (Fusarium oxysporum f. sp. lycopersici, Alternaria alternata, Colletotrichum gloeosporoides and Rhizoctonia solani). The production of extracellular cell wall degrading enzymes of tested isolates was also measured...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27916661/tetrameric-assembly-of-k-channels-requires-er-located-chaperone-proteins
#5
Kai Li, Qiang Jiang, Xue Bai, Yi-Feng Yang, Mei-Yu Ruan, Shi-Qing Cai
Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K(+) channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K(+) channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4...
November 30, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27916292/cancer-prognosis-defined-by-the-combined-analysis-of-8q-pten-and-erg
#6
Maria P Silva, João D Barros-Silva, Elin Ersvær, Wanja Kildal, Tarjei Sveinsgjerd Hveem, Manohar Pradhan, Joana Vieira, Manuel R Teixeira, Håvard E Danielsen
Overtreatment is a major concern in men diagnosed with prostate cancer. The aim of this study was to evaluate the combined prognostic role of three frequent molecular alterations in prostate cancer, namely relative 8q gain, ERG overexpression, and loss of PTEN expression, in a series of 136 patients with prostate cancer treated with prostatectomy and with a long follow-up. Fluorescent in situ hybridization was used to detect the relative copy number of 8q and immunohistochemistry was used for quantitative assessment of ERG and PTEN expression...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27915475/how-precisely-can-prostate-cancer-be-managed
#7
REVIEW
Liyan Zhuang, Matthew T Johnson
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27913052/evaluation-of-erg-and-pten-protein-expression-in-cribriform-architecture-prostate-carcinomas
#8
Michelle R Downes, Swati Satturwar, Dominique Trudel, Theo H van der Kwast
ERG and PTEN have been suggested as potential prognostic markers in prostatic adenocarcinoma. We assessed the relationship between ERG and PTEN protein expression in cribriform architecture prostatic carcinomas and adjacent acinar non-cribriform carcinoma and determined the interobserver variability in assessment of these markers. A contemporary cohort of radical prostatectomy cases (n=246) were reviewed and cribriform architecture carcinomas (intraductal carcinoma and cribriform Gleason 4 carcinomas) were identified and confirmed with triple cocktail immunostaining...
October 26, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27913051/erg-expression-in-multiple-myeloma-a-potential-diagnostic-pitfall
#9
Juliana Knief, Katharina Reddemann, Jan Gliemroth, Swantje Brede, Tobias Bartscht, Christoph Thorns
INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions...
November 3, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27911079/trans-acting-epigenetic-effects-of-chromosomal-aneuploidies-lessons-from-down-syndrome-and-mouse-models
#10
Catherine Do, Zhuo Xing, Y Eugene Yu, Benjamin Tycko
An important line of postgenomic research seeks to understand how genetic factors can influence epigenetic patterning. Here we review epigenetic effects of chromosomal aneuploidies, focusing on findings in Down syndrome (DS, trisomy 21). Recent work in human DS and mouse models has shown that the extra chromosome 21 acts in trans to produce epigenetic changes, including differential CpG methylation (DS-DM), in specific sets of downstream target genes, mostly on other chromosomes. Mechanistic hypotheses emerging from these data include roles of chromosome 21-linked methylation pathway genes (DNMT3L and others) and transcription factor genes (RUNX1, OLIG2, GABPA, ERG and ETS2) in shaping the patterns of DS-DM...
December 2, 2016: Epigenomics
https://www.readbyqxmd.com/read/27910803/the-prognostic-and-predictive-value-of-tmprss2-erg-gene-fusion-and-erg-protein-expression-in-prostate-cancer-biopsies
#11
Kasper Drimer Berg
BACKGROUND: The clinical course of prostate carcinoma (PCa) is very heterogeneous. Consequently, a personalised approach for risk stratification and treatment planning is important. Recently, it has become evident that PCa, also at the genomic level, is heterogeneous. An early and common alteration is the gene fusion between the transmembrane protease serine 2 (TMPRSS2) gene and the v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene resulting in expression of the oncoprotein ERG...
December 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27906189/distinct-outcomes-of-crl-nedd8-pathway-inhibition-reveal-cancer-cell-plasticity
#12
Anastasia V Rulina, Frédérique Mittler, Patricia Obeid, Sophie Gerbaud, Laurent Guyon, Eric Sulpice, Frédérique Kermarrec, Nicole Assard, Monika E Dolega, Xavier Gidrol, Maxim Y Balakirev
Inhibition of protein degradation by blocking Cullin-RING E3 ligases (CRLs) is a new approach in cancer therapy though of unknown risk because CRL inhibition may stabilize both oncoproteins and tumor suppressors. Probing CRLs in prostate cancer cells revealed a remarkable plasticity of cells with TMPRSS2-ERG translocation. CRL suppression by chemical inhibition or knockdown of RING component RBX1 led to reversible G0/G1 cell cycle arrest that prevented cell apoptosis. Conversely, complete blocking of CRLs at a higher inhibitor dose-induced cytotoxicity that was amplified by knockdown of CRL regulator Cand1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906070/subretinal-adipose-tissue-derived-mesenchymal-stem-cell-implantation-in-advanced-stage-retinitis-pigmentosa-a-phase-i-clinical-safety-study
#13
Ayse Oner, Z Burcin Gonen, Neslihan Sinim, Mustafa Cetin, Yusuf Ozkul
BACKGROUND: This prospective clinical case series aimed to investigate the safety of subretinal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in advanced stage retinitis pigmentosa (RP). METHODS: This study included 11 patients with end-stage RP who received subretinal implantation of ADMSCs. All patients had a total visual field defect and five of them only had light perception. The best corrected visual acuity (BCVA) in the study was 20/2000...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27905344/concurrent-retinitis-pigmentosa-and-pigmented-paravenous-retinochoroidal-atrophy-phenotypes-in-the-same-patient
#14
Dhanashree Ratra, Dhileesh P Chandrasekharan, P Aruldas, Vineet Ratra
We report a unique case of a patient with retinitis pigmentosa (RP) phenotype in one eye and pigmented paravenous retinochoroidal atrophy (PPRCA) phenotype in the other eye. We describe in detail the symptoms, clinical findings, and investigations done for a 32-year-old Indian woman. This patient had phenotypical picture resembling typical RP in the right eye, with characteristic symptoms of night blindness and constricted field of vision and a nonrecordable electroretinogram (ERG). The left eye of the same patient revealed typical PPRCA phenotype, with no night blindness, normal field, and normal ERG...
October 2016: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/27899403/meta-analysis-of-genome-wide-association-studies-for-abdominal-aortic-aneurysm-identifies-four-new-disease-specific-risk-loci
#15
Gregory T Jones, Gerard Tromp, Helena Kuivaniemi, Solveig Gretarsdottir, Annette F Baas, Betti Giusti, Ewa Strauss, Femke N van 't Hof, Thomas Webb, Robert Erdman, Marylyn D Ritchie, James R Elmore, Anurag Verma, Sarah Pendergrass, Iftikhar J Kullo, Zi Ye, Peggy L Peissig, Omri Gottesman, Shefali S Verma, Jennifer Malinowski, Laura J Rasmussen-Torvik, Kenneth Borthwick, Diane T Smelser, David R Crosslin, Mariza de Andrade, Evan J Ryer, Catherine A McCarty, Erwin P Bottinger, Jennifer A Pacheco, Dana C Crawford, David S Carrell, Glenn S Gerhard, David P Franklin, David J Carey, Victoria L Phillips, Michael J Williams, Wenhua Wei, Ross Blair, Andrew A Hill, Thodur M Vasudevan, David R Lewis, Ian A Thomson, Jo Krysa, Geraldine B Hill, Justin Roake, Tony R Merriman, Grzegorz Oszkinis, Silvia Galora, Claudia Saracini, Rosanna Abbate, Raffaele Pulli, Carlo Pratesi, Athanasios Saratzis, Anna Verissimo, Suzannah J Bumpstead, Stephen A Badger, Rachel E Clough, Gillian W Cockerill, Hany Hafez, D J Scott, T S Futers, Simon P Romaine, Katherine Bridge, Kathryn J Griffin, Marc A Bailey, Alberto Smith, Matt M Thompson, Frank van Bockxmeer, Stefan E Matthiasson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jan D Blankensteijn, Joep A Teijink, Cisca Wijmenga, Jacqueline de Graaf, Lambertus A Kiemeney, Jes S Lindholt, Anne E Hughes, Declan T Bradley, Kathleen Stirrups, Jonathan Golledge, Paul E Norman, Janet T Powell, Steve E Humphries, Stephen E Hamby, Alison H Goodall, Christopher P Nelson, Natzi Sakalihasan, Audrey Courtois, Robert E Ferrell, Per Eriksson, Lasse Folkersen, Anders Franco-Cereceda, John D Eicher, Andrew D Johnson, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Eric Schadt, Johan L Björkegren, Leonard Lipovich, Anne M Drolet, Eric Verhoeven, Clark J Zeebregts, Robert H Geelkerken, Marc R van Sambeek, Steven M van Sterkenburg, Jean-Paul P de Vries, Kari Stefansson, John R Thompson, Paul I de Bakker, Panos Deloukas, Robert D Sayers, Seamus Harrison, Andre M van Rij, Nilesh J Samani, Matthew J Bown
RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). METHODS AND RESULTS: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32...
November 29, 2016: Circulation Research
https://www.readbyqxmd.com/read/27899256/erlotinib-has-tumor-inhibitory-effect-in-human-retinoblastoma-cells
#16
Yi Shao, Yao Yu, Rongrong Zong, Luowa Quyang, Hui He, Qiong Zhou, Chonggang Pei
AIM: In this study, we explored the effect of erlotinib on the development of retinoblastoma (RB) cells both in vitro and in vivo. METHOD: RB cell lines, Y79 and WERI cells were treated with various concentrations of erlotinib in vitro to assess their cytotoxic profiles. In vitro proliferation, cell-cycle transition and migration were compared between RB cells treated with erlotinib and cells without erlotinib treatment. In in vivo tumorigenicity assay, mice were injected with Y79 cells and orally fed with erlotinib for 28days...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27896899/characterization-of-a-novel-form-of-progressive-retinal-atrophy-in-whippet-dogs-a-clinical-electroretinographic-and-breeding-study
#17
André Tavares Somma, Juan Carlos Duque Moreno, Mario Teruo Sato, Blanche Dreher Rodrigues, Marianna Bacellar-Galdino, Laurence Mireille Occelli, Simon Michael Petersen-Jones, Fabiano Montiani-Ferreira
OBJECTIVE: To describe a form of progressive retinal atrophy (PRA) in Whippets including clinical, electroretinographic, optical coherence tomographic changes and pedigree analysis. ANIMALS STUDIED: Client-owned Whippet dogs (n = 51) living in Brazil. PROCEDURES: All animals were submitted for routine ophthalmic screening for presumed inherited ocular disease, which included the following: visual tests, such as obstacle course tests, in scotopic and photopic conditions, cotton ball test, dazzle reflex, ocular fundus evaluation by indirect ophthalmoscopy followed by fundus photography...
November 29, 2016: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/27893831/retinal-pre-conditioning-by-cd59a-knockout-protects-against-light-induced-photoreceptor-degeneration
#18
Delu Song, Brooks Wilson, Liangliang Zhao, Rupak Bhuyan, Mausumi Bandyopadhyay, Arkady Lyubarsky, Chen Yu, Yafeng Li, Levi Kanu, Takashi Miwa, Wen-Chao Song, Silvia C Finnemann, Bärbel Rohrer, Joshua L Dunaief
Complement dysregulation plays a key role in the pathogenesis of age-related macular degeneration (AMD), but the specific mechanisms are incompletely understood. Complement also potentiates retinal degeneration in the murine light damage model. To test the retinal function of CD59a, a complement inhibitor, CD59a knockout (KO) mice were used for light damage (LD) experiments. Retinal degeneration and function were compared in WT versus KO mice following light damage. Gene expression changes, endoplasmic reticulum (ER) stress, and glial cell activation were also compared...
2016: PloS One
https://www.readbyqxmd.com/read/27893096/chemogenetic-activation-of-iprgcs-drives-changes-in-dark-adapted-scotopic-electroretinogram
#19
Nina Milosavljevic, Annette E Allen, Jasmina Cehajic-Kapetanovic, Robert J Lucas
Purpose: The purpose of this study was to investigate the impact of activating melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) on dark-adapted (scotopic) electroretinograms (ERG). Methods: We used mice (Opn4Cre/+) expressing cre recombinase in melanopsin-expressing cells for a targeted gene delivery of a chemogenetic Gq-coupled receptor, hM3Dq, to ipRGCs. Intraperitoneal injection of clozapine N-oxide (CNO) at 5 mg/kg was used for acute activation of hM3Dq and thus excitation of ipRGCs in darkness...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27884354/computing-methods-for-composite-clinical%C3%A2-endpoints-in-unprotected-left-main-coronary-artery-revascularization-a-post-hoc-analysis-of-the-delta-registry
#20
Davide Capodanno, Giuseppe Gargiulo, Sergio Buccheri, Alaide Chieffo, Emanuele Meliga, Azeem Latib, Seung-Jung Park, Yoshinobu Onuma, Piera Capranzano, Marco Valgimigli, Inga Narbute, Raj R Makkar, Igor F Palacios, Young-Hak Kim, Pawel E Buszman, Tarun Chakravarty, Imad Sheiban, Roxana Mehran, Christoph Naber, Ronan Margey, Arvind Agnihotri, Sebastiano Marra, Martin B Leon, Jeffrey W Moses, Jean Fajadet, Thierry Lefèvre, Marie-Claude Morice, Andrejs Erglis, Ottavio Alfieri, Patrick W Serruys, Antonio Colombo, Corrado Tamburino
OBJECTIVES: The study sought to investigate the impact of different computing methods for composite endpoints other than time-to-event (TTE) statistics in a large, multicenter registry of unprotected left main coronary artery (ULMCA) disease. BACKGROUND: TTE statistics for composite outcome measures used in ULMCA studies consider only the first event, and all the contributory outcomes are handled as if of equal importance. METHODS: The TTE, Andersen-Gill, win ratio (WR), competing risk, and weighted composite endpoint (WCE) computing methods were applied to ULMCA patients revascularized by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) at 14 international centers...
November 28, 2016: JACC. Cardiovascular Interventions
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