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https://www.readbyqxmd.com/read/29465803/olaparib-is-effective-in-combination-with-and-as-maintenance-therapy-after-first-line-endocrine-therapy-in-prostate-cancer-cells
#1
Gertrud E Feiersinger, Kristina Trattnig, Peter D Leitner, Fabian Guggenberger, Alexander Oberhuber, Sarah Peer, Martin Hermann, Ira Skvortsova, Jana Vrbkova, Jan Bouchal, Zoran Culig, Frédéric R Santer
A number of prostate cancer (PCa)-specific genomic aberrations (denominated BRCAness genes) have been discovered implicating sensitivity to PARP inhibition within the concept of synthetic lethality. Recent clinical studies show favorable results for the PARP inhibitor Olaparib used as single agent for treatment of metastatic castration-resistant PCa. Using 2D and 3D cell culture models mimicking the different treatment and progression stages of PCa we evaluated a potential use for Olaparib in combination with first-line endocrine treatments, androgen deprivation and complete androgen blockade, and as a maintenance therapy following on from endocrine therapy...
February 21, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29453313/multigene-profiling-of-ctcs-in-mcrpc-identifies-a-clinically-relevant-prognostic-signature
#2
Udit Singhal, Yugang Wang, James Henderson, Yashar S Niknafs, Yuanyuan Qiao, Amy Gursky, Alexander Zaslavsky, Jae-Seung Chung, David C Smith, R Jeffrey Karnes, S Laura Chang, Felix Y Feng, Ganesh S Palapattu, Russell S Taichman, Arul M Chinnaiyan, Scott A Tomlins, Todd M Morgan
The trend towards precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer related genes...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29442332/issues-related-to-the-frequency-of-exploratory-analyses-by-evidence-review-groups-in-the-nice-single-technology-appraisal-process
#3
Eva Kaltenthaler, Christopher Carroll, Daniel Hill-McManus, Alison Scope, Michael Holmes, Stephen Rice, Micah Rose, Paul Tappenden, Nerys Woolacott
BACKGROUND: Evidence Review Groups (ERGs) critically appraise company submissions as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal (STA) process. As part of their critique of the evidence submitted by companies, the ERGs undertake exploratory analyses to explore uncertainties in the company's model. The aim of this study was to explore pre-defined factors that might influence or predict the extent of ERG exploratory analyses. OBJECTIVE: The aim of this study was to explore predefined factors that might influence or predict the extent of ERG exploratory analyses...
June 2017: PharmacoEconomics Open
https://www.readbyqxmd.com/read/29440700/age-related-changes-in-the-response-of-retinal-structure-function-and-blood-flow-to-pressure-modification-in-rats
#4
Da Zhao, Christine T O Nguyen, Zheng He, Vickie H Y Wong, Anna K van Koeverden, Algis J Vingrys, Bang V Bui
Age-related changes to the balance between the pressure inside the eye (intraocular pressure, IOP) and the pressure inside the brain (intracranial pressure, ICP) can modify the risk of glaucoma. In this study, we consider whether the optic nerve in older rat eyes is more susceptible to acute IOP and ICP modification. We systematically manipulate both ICP and IOP and quantify their effects on ganglion cell function (electroretinography, ERG), optic nerve structure (optical coherence tomography, OCT) and retinal blood flow (Doppler OCT)...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29437727/unique-case-of-gyrate-atrophy-with-a-well-preserved-electroretinogram-erg
#5
Kirti M Jasani, Neil R A Parry, Graeme Black, Simon P Kelly
Gyrate atrophy is a rare autosomal recessive disorder caused by a mutation in the ornithine-δ-amino transferase gene. We present an interesting case of a 33-year-old woman who presented with increasing myopia, nyctalopia and failing vision. Examination revealed posterior subscapsular cataracts, narrowed peripheral visual fields and scalloped atrophic peripheral chorioretinal lesions. Blood investigations showed a raised plasma ornithine level at 917 μmol/L (normal range: 32-88 μmol/L) confirming the diagnosis of gyrate atrophy...
February 5, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29427188/molecular-characteristic-of-acute-leukemias-with-t-16-21-fus-erg
#6
Elena Zerkalenkova, Agnesa Panfyorova, Anna Kazakova, Pavel Baryshev, Larisa Shelihova, Irina Kalinina, Galina Novichkova, Michael Maschan, Aleksey Maschan, Yulia Olshanskaya
T(16;21)(p11;q22)/FUS-ERG is a rare but recurrent translocation in acute leukemias and in some types of solid tumors. Due to multiple types of FUS-ERG transcripts, PCR-based minimal residual disease detection is impeded. In this study, we evaluated a cohort of pediatric patients with t(16;21)(p11;q22)/FUS-ERG and revealed fusion gene breakpoints. We implemented next-generation sequencing (NGS) on long PCR amplicons for the detection of fusion genes with unknown partners or DNA breakpoints. That allowed us to describe different fusion variants of FUS/ERG in different patients and to detect MRD on both RNA and DNA levels...
February 9, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29427004/immunohistochemically-detected-idh1r132h-mutation-is-rare-and-mostly-heterogeneous-in-prostate-cancer
#7
Andrea Hinsch, Meta Brolund, Claudia Hube-Magg, Martina Kluth, Ronald Simon, Christina Möller-Koop, Guido Sauter, Stefan Steurer, Andreas Luebke, Alexander Angerer, Corinna Wittmer, Emily Neubauer, Cosima Göbel, Franziska Büscheck, Sarah Minner, Waldemar Wilczak, Thorsten Schlomm, Frank Jacobsen, Till Sebastian Clauditz, Till Krech, Maria Christina Tsourlakis, Cornelia Schroeder
BACKGROUND: IDH1 mutations are oncogenic through induction of DNA damage and genome instability. They are of therapeutic interest because they confer increased sensitivity to radiation and cytotoxic therapy and hold potential for vaccination therapy. METHODS: In this study, we analyzed more than 17,000 primary prostate cancer tissues with a mutation-specific antibody for the IDH1R132H mutation. RESULTS: IDH1 mutation-specific staining was found in 42 of 15,531 (0...
February 9, 2018: World Journal of Urology
https://www.readbyqxmd.com/read/29422768/retinal-phenotypic-characterization-of-patients-with-abca4-retinopathydue-to-the-homozygous-p-ala1773val-mutation
#8
Salvador López-Rubio, Oscar F Chacon-Camacho, Rodrigo Matsui, Dalia Guadarrama-Vallejo, Mirena C Astiazarán, Juan C Zenteno
Purpose: To describe the retinal clinical features of a group of Mexican patients with Stargardt disease carrying the uncommon p.Ala1773Val founder mutation in ABCA4. Methods: Ten patients carrying the p.Ala1773Val mutation, nine of them homozygously, were included. Visual function studies included best-corrected visual acuity, electroretinography, Goldmann kinetic visual fields, and full-field electroretinography (ERG). In addition, imaging studies, such as optical coherence tomography (OCT), short-wave autofluorescence imaging, and quantitative analyses of hypofluorescence, were performed in each patient...
2018: Molecular Vision
https://www.readbyqxmd.com/read/29422418/incorporation-of-urinary-prostate-cancer-antigen-3-and-tmprss2-erg-into-prostate-cancer-prevention-trial-risk-calculator
#9
Donna P Ankerst, Martin Goros, Scott A Tomlins, Dattatraya Patil, Ziding Feng, John T Wei, Martin G Sanda, Jonathan Gelfond, Ian M Thompson, Robin J Leach, Michael A Liss
BACKGROUND: The Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) is a commonly used risk tool for predicting the outcome on biopsy based on the established risk factors. OBJECTIVE: To determine whether incorporation of the novel urinary markers prostate cancer antigen 3 (PCA3) and TMPRSS2:ERG (T2:ERG) into the PCPTRC improves its discrimination, accuracy, and clinical net benefit. DESIGN, SETTING, AND PARTICIPANTS: Since PCA3 and T2:ERG were not measured as part of the PCPTRC, a Bayesian modeling approach was used to combine data where the markers were measured in a Michigan cohort with the PCPTRC as prior probabilities to form an updated PCPTRC...
February 5, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29420665/electroretinographic-evidence-suggesting-that-the-type-2-diabetic-retinopathy-of-the-sand-rat-psammomys-obesus-is-comparable-to-that-of-humans
#10
Ahmed Dellaa, Maha Benlarbi, Imane Hammoum, Nouha Gammoudi, Mohamed Dogui, Riadh Messaoud, Rached Azaiz, Ridha Charfeddine, Moncef Khairallah, Pierre Lachapelle, Rafika Ben Chaouacha-Chekir
PURPOSE: Type 2 diabetic retinopathy is the main cause of acquired blindness in adults. The aim of this work was to examine the retinal function of the sand rat Psammomys obesus as an animal model of diet-induced type 2 diabetes when subjected to a hypercaloric regimen. MATERIALS AND METHODS: Hyperglycemia was induced in Psammomys obesus by high caloric diet (4 kcal/g). The visual function of control (n = 7) and diabetic (n = 7) adult rodents were followed up during 28 consecutive weeks with full-field electroretinogram(ERG) recordings evoked to flashes of white light according to the standard protocol of the International Society for Clinical Electrophysiology of Vision protocol (ISCEV)...
2018: PloS One
https://www.readbyqxmd.com/read/29411010/discovery-of-a-cynomolgus-monkey-family-with-retinitis-pigmentosa
#11
Yasuhiro Ikeda, Koji M Nishiguchi, Fuyuki Miya, Nobuhiro Shimozawa, Jun Funatsu, Shunji Nakatake, Kohta Fujiwara, Takashi Tachibana, Yusuke Murakami, Toshio Hisatomi, Shigeo Yoshida, Yasuhiro Yasutomi, Tatsuhiko Tsunoda, Toru Nakazawa, Tatsuro Ishibashi, Koh-Hei Sonoda
Purpose: To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. Methods: First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29408880/daily-visual-stimulation-in-the-critical-period-enhances-multiple-aspects-of-vision-through-bdnf-mediated-pathways-in-the-mouse-retina
#12
Amanda M Mui, Victoria Yang, Moe H Aung, Jieming Fu, Adewumi N Adekunle, Brian C Prall, Curran S Sidhu, Han Na Park, Jeffrey H Boatright, P Michael Iuvone, Machelle T Pardue
Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing...
2018: PloS One
https://www.readbyqxmd.com/read/29406432/pseudomyogenic-hemangioendothelioma-case-report-and-review-of-the-literature
#13
Emily Raftopoulos, Michael Royer, Mildred Warren, Jin Zhao, Walter Rush
Pseudomyogenic hemangioendothelioma (PHE; epithelioid sarcoma-like hemangioendothelioma) is a rare entity, with 129 reported cases. It is a rarely metastasizing, low-grade vascular tumor that can histologically mimic epithelioid sarcoma and often presents as multiple discontinuous nodules in the extremities. PHEs characteristically and consistently show immunoreactivity for cytokeratins and endothelial markers. We present a case in the thigh of a 65-year-old-man with a 3-month history of painful lesions in the dermis and review the published literature...
February 2, 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29404551/blue-light-filtered-white-light-induces-depression-like-responses-and-temporary-spatial-learning-deficits-in-rats
#14
Qinghe Meng, Yuzheng Lian, Jianjun Jiang, Wei Wang, Xiaohong Hou, Yao Pan, Hongqian Chu, Lanqin Shang, Xuetao Wei, Weidong Hao
OBJECTIVES: Ambient light has a vital impact on mood and cognitive functions. Blue light has been previously reported to play a salient role in the antidepressant effect via melanopsin. Whether blue light filtered white light (BFW) affects mood and cognitive functions remains unclear. The present study aimed to investigate whether BFW led to depression-like symptoms and cognitive deficits including spatial learning and memory abilities in rats, and whether they were associated with the light-responsive function in retinal explants...
February 6, 2018: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/29402864/%C3%AE-melanocyte-stimulating-hormone-protects-early-diabetic-retina-from-blood-retinal-barrier-breakdown-and-vascular-leakage-via-mc4r
#15
Siwei Cai, Qianhui Yang, Mengzhu Hou, Qian Han, Hanyu Zhang, Jiantao Wang, Chen Qi, Qiyu Bo, Yusha Ru, Wei Yang, Zhongxiu Gu, Ruihua Wei, Yunshan Cao, Xiaorong Li, Yan Zhang
BACKGROUND/AIMS: Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A)...
January 25, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29397523/iscev-guide-to-visual-electrodiagnostic-procedures
#16
Anthony G Robson, Josefin Nilsson, Shiying Li, Subhadra Jalali, Anne B Fulton, Alma Patrizia Tormene, Graham E Holder, Scott E Brodie
Clinical electrophysiological testing of the visual system incorporates a range of noninvasive tests and provides an objective indication of function relating to different locations and cell types within the visual system. This document developed by the International Society for Clinical Electrophysiology of Vision provides an introduction to standard visual electrodiagnostic procedures in widespread use including the full-field electroretinogram (ERG), the pattern electroretinogram (pattern ERG or PERG), the multifocal electroretinogram (multifocal ERG or mfERG), the electrooculogram (EOG) and the cortical-derived visual evoked potential (VEP)...
February 3, 2018: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/29392925/biological-effect-of-neoadjuvant-androgen-deprivation-therapy-assessed-on-specimens-from-radical-prostatectomy-a-systematic-review
#17
Alessandro Antonelli, Carlotta Palumbo, Alessandro Veccia, Salvatore Grisanti, Luca Triggiani, Stefania Zamboni, Maria Furlan, Claudio Simeone, Stefano Magrini, Alfredo Berruti
INTRODUCTION: Androgen-deprivation therapy (ADT) administered in neoadjuvant setting before radical prostatectomy (RP) represents an ideal in vivo human model to test the efficacy of hormonal treatments in prostate cancer (PCa). This review summarizes the findings from published studies specifically focused on the biological effects of ADT assessed on specimens from RP. The aim is to provide a base of knowledge that might be used to design future studies on neoadjuvant therapy for PCa...
February 1, 2018: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/29392320/a-naturally-fluorescent-mgp-transgenic-mouse-for-angiogenesis-and-glaucoma-longitudinal-studies
#18
Priyadarsini Asokan, Rajendra N Mitra, Ramesh Periasamy, Zongchao Han, Teresa Borrás
Purpose: Our goal was to generate and characterize a new mouse model in which only angiogenesis- and glaucoma-relevant tissues would be naturally fluorescent. The Matrix Gla (MGP) gene is highly expressed in vascular smooth muscle cells (VSMC) and trabecular meshwork (TM). We sought to direct our Mgp-Cre.KI mouse recombinase to VSMC/TM cells to produce their longitudinal fluorescent profiles. Methods: Homozygous Mgp-Cre.KI mice were crossed with Ai9 homozygous reporter mice harboring a loxP-flanked STOP cassette preventing transcription of a DsRed fluorescent protein (tdTomato)...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29392316/mesenchymal-stem-cell-derived-small-extracellular-vesicles-promote-neuroprotection-in-rodent-models-of-glaucoma
#19
Ben Mead, Juan Amaral, Stanislav Tomarev
Purpose: To investigate the benefit of bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEV) as an intravitreal (ivit) therapy in two rat models of glaucoma and to determine and identify candidate miRNA involved in the mechanism. Methods: sEV were isolated from human BMSC and fibroblasts and ivit injected into adult rats after induction of elevated IOP. IOP was elevated using either intracameral injection of microbeads or laser photocoagulation of circumferential limbal vessels and the trabecular meshwork...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29392308/pharmacokinetic-and-safety-evaluation-of-a-transscleral-sustained-unoprostone-release-device-in-monkey-eyes
#20
Nobuhiro Nagai, Shinji Yamada, Junichi Kawasaki, Eri Koyanagi, Saaya Saijo, Hirokazu Kaji, Matsuhiko Nishizawa, Toru Nakazawa, Toshiaki Abe
Purpose: We evaluate the ocular tissue distribution and retinal toxicity of unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes. Methods: The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation...
February 1, 2018: Investigative Ophthalmology & Visual Science
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