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https://www.readbyqxmd.com/read/28210006/a-novel-lsd1-inhibitor-ncd38-ameliorates-mds-related-leukemia-with-complex-karyotype-by-attenuating-leukemia-programs-via-activating-super-enhancers
#1
N Sugino, M Kawahara, G Tatsumi, A Kanai, H Matsui, R Yamamoto, Y Nagai, S Fujii, Y Shimazu, M Hishizawa, T Inaba, A Andoh, T Suzuki, A Takaori-Kondo
Lysine-specific demethylase 1 (LSD1) regulates gene expression by affecting histone modifications and is a promising target for acute myeloid leukemia (AML) with specific genetic abnormalities. Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDS) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and AML oncogenic programs, and commonly upregulated 62 genes in several leukemia cells...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28206829/validity-of-low-contrast-letter-acuity-as-a-visual-performance-outcome-measure-for-multiple-sclerosis
#2
Laura J Balcer, Jenelle Raynowska, Rachel Nolan, Steven L Galetta, Raju Kapoor, Ralph Benedict, Glenn Phillips, Nicholas LaRocca, Lynn Hudson, Richard Rudick
Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual disability in multiple sclerosis (MS) research. As visual dysfunction is one of the most common manifestations of MS, sensitive visual outcome measures are important in examining the effect of treatment. Low-contrast acuity captures visual loss not seen in high-contrast visual acuity (HCVA) measurements. These issues are addressed by the MS Outcome Assessments Consortium (MSOAC), including representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28205557/experimental-study-of-the-biological-properties-of-human-embryonic-stem-cell-derived-retinal-progenitor-cells
#3
Jingzhi Shao, Peng-Yi Zhou, Guang-Hua Peng
Retinal degenerative diseases are among the leading causes of blindness worldwide, and cell replacement is considered as a promising therapeutic. However, the resources of seed cells are scarce. To further explore this type of therapy, we adopted a culture system that could harvest a substantial quantity of retinal progenitor cells (RPCs) from human embryonic stem cells (hESCs) within a relatively short period of time. Furthermore, we transplanted these RPCs into the subretinal spaces of Royal College of Surgeons (RCS) rats...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205530/retinal-structure-and-function-in-eyes-with-optic-nerve-hypoplasia
#4
Satoshi Katagiri, Sachiko Nishina, Tadashi Yokoi, Masashi Mikami, Yuri Nakayama, Michiko Tanaka, Noriyuki Azuma
We investigated retinal structure and function in eyes with optic nerve hypoplasia (ONH). Twenty-nine eyes of 18 patients with ONH and 21 eyes of 21 control patients were analyzed. Spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (FF-ERG), and focal macular ERG (FM-ERG) were performed. SD-OCT analysis of the macular region showed significant ganglion cells complex (GCC) thinning nasally and temporally (P < 0.05), but the thickness from the inner nuclear layer (INL) to the retinal pigment epithelium (RPE) became thinner only nasally (P < 0...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199885/evaluation-of-polyesteramide-pea-and-polyester-plga-microspheres-as-intravitreal-drug-delivery-systems-in-albino-rats
#5
Tobias Peters, Seong-Woo Kim, Vinicius Castro, Krunoslav Stingl, Torsten Strasser, Sylvia Bolz, Ulrich Schraermeyer, George Mihov, MengMeng Zong, Vanessa Andres-Guerrero, Rocio Herrero Vanrell, Aylvin A Dias, Neil R Cameron, Eberhart Zrenner
PURPOSE: To study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone-loaded PEA microspheres (PEA + DEX) were also evaluated. METHODS: Forty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n = 12); PLGA group (n = 12); PEA + DEX group (n = 8); and control group (no injection, n = 8)...
February 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28198785/evaluation-of-full-field-electroretinogram-reductions-after-ocriplasmin-treatment-results-of-the-oasis-trial-erg-substudy
#6
David G Birch, Matthew S Benz, Daniel M Miller, Andrew N Antoszyk, Joseph Markoff, Petra Kozma, Esmeralda Meunier, Robert C Sergott
PURPOSE: To explore a possible association between full-field electroretinograms with vitreomacular adhesion resolution and best-corrected visual acuity as part of the prospective, randomized, double-masked, sham-controlled Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial studying ocriplasmin. METHODS: The ERG substudy enrolled 62 of 220 OASIS subjects (randomized 2:1) and analyzed full-field electroretinograms and their association with both vitreomacular adhesion resolution and best-corrected visual acuity from baseline through Month 24...
February 14, 2017: Retina
https://www.readbyqxmd.com/read/28198784/choroidal-thickness-in-patients-with-stargardt-disease
#7
Esra Vural, Ugur Acar, Mehmet K Sevinc, Mesut Erdurmus, Bekir Kucuk, Seckin Aykas, Gungor Sobaci
PURPOSE: To investigate the relationship between choroidal thicknesses (CT), central foveal thicknesses, multifocal electroretinography (mf-ERG) responses, and best-corrected visual acuity levels in patients with Stargardt disease (STGD). METHODS: A total of 30 eyes of 30 patients with STGD, and 30 age- and sex-matched healthy controls were included in the study. All participants underwent detailed ophthalmic examination including best-corrected visual acuity and spectral domain optical coherence tomography measurements, and also patients with STGD were performed mf-ERG...
February 14, 2017: Retina
https://www.readbyqxmd.com/read/28198469/garp2-accelerates-retinal-degeneration-in-rod-cgmp-gated-cation-channel-%C3%AE-subunit-knockout-mice
#8
Marci L DeRamus, Delores A Stacks, Youwen Zhang, Carrie E Huisingh, Gerald McGwin, Steven J Pittler
The Cngb1 locus-encoded β-subunit of rod cGMP-gated cation channel and associated glutamic acid rich proteins (GARPs) are required for phototransduction, disk morphogenesis, and rod structural integrity. To probe individual protein structure/function of the GARPs, we have characterized several transgenic mouse lines selectively restoring GARPs on a Cngb1 knockout (X1(-/-)) mouse background. Optical coherence tomography (OCT), light and transmission electron microscopy (TEM), and electroretinography (ERG) were used to analyze 6 genotypes including WT at three and ten weeks postnatal...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197724/histological-and-immunohistochemical-characteristics-of-undifferentiated-small-round-cell-sarcomas-associated-with-cic-dux4-and-bcor-ccnb3-fusion-genes
#9
Yuichi Yamada, Masaaki Kuda, Kenichi Kohashi, Hidetaka Yamamoto, Junkichi Takemoto, Takeaki Ishii, Kunio Iura, Akira Maekawa, Hirofumi Bekki, Takamichi Ito, Hiroshi Otsuka, Makoto Kuroda, Yumi Honda, Shinji Sumiyoshi, Takeshi Inoue, Naoe Kinoshita, Atsushi Nishida, Kyoko Yamashita, Ichiro Ito, Shizuo Komune, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda
CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH...
February 14, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28196695/impact-of-erg3-mutations-and-expression-of-ergosterol-genes-controlled-by-upc2-and-ndt80-in-candida-parapsilosis-azole-resistance
#10
Joana Branco, Mihaela Ola, Raquel M Silva, Elizangela Fonseca, Nuno C Gomes, Cláudia Martins-Cruz, Ana P Silva, Ana Silva-Dias, Cidália Pina-Vaz, Claire Erraught, Lorraine Brennan, Acácio Gonçalves Rodrigues, Geraldine Butler, Isabel M Miranda
OBJECTIVES: C. parapsilosis is a health care related fungal pathogen particularly common among immunocompromised patients. Our understanding of antifungal resistance mechanisms in C. parapsilosis remains very limited. We previously described an azole-resistant strain of C. parapsilosis (BC014RPSC), obtained following exposure in vitro to posaconazole. Resistance was associated with overexpression of ergosterol biosynthetic genes (ERG genes), together with the transcription factors UPC2 (CPAR2-207280) and NDT80 (CPAR2-213640)...
February 11, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28195618/preclinical-acute-ocular-safety-study-of-combined-intravitreal-carboplatin-and-etoposide-phosphate-for-retinoblastoma
#11
Brian G Mohney, Victor M Elner, Andrew B Smith, J William Harbour, Brian D Smith, David C Musch, Stephen J Smith
BACKGROUND AND OBJECTIVE: To describe the ocular toxicity of intravitreal carboplatin and etoposide phosphate (VP16P) in Dutch-Belted rabbits. MATERIALS AND METHODS: Twenty-two adult male Dutch-Belted rabbits (Cohort 1) each received a single, bilateral intravitreal injection (0.05 mL). For Cohort 1, safety was assessed via electroretinograms (ERGs) and ocular examination. Of nine total groups in Cohort 1, the first five received the following single agents: Group 1: normal saline; Group 2: VP16P 75 µg; Group 3: VP16P 100 µg; Group 4: carboplatin 4 µg; and Group 5: carboplatin 8 µg...
February 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28191285/autoantibodies-against-oncogenic-erg-protein-in-prostate-cancer-potential-use-in-diagnosis-and-prognosis-in-a-panel-with-c-myc-amacr-and-herv-k-gag
#12
Anshu Rastogi, Amina Ali, Shyh-Han Tan, Sreedatta Banerjee, Yongmei Chen, Jennifer Cullen, Charles P Xavier, Ahmed A Mohamed, Lakshmi Ravindranath, Jigisha Srivastav, Denise Young, Isabell A Sesterhenn, Jacob Kagan, Sudhir Srivastava, David G McLeod, Inger L Rosner, Gyorgy Petrovics, Albert Dobi, Shiv Srivastava, Alagarsamy Srinivasan
Overdiagnosis and overtreatment of prostate cancer (CaP) is attributable to widespread reliance on PSA screening in the US. This has prompted us and others to search for improved biomarkers for CaP, to facilitate early detection and disease stratification. In this regard, autoantibodies (AAbs) against tumor antigens could serve as potential candidates for diagnosis and prognosis of CaP. Towards this, our goals were: i) To investigate whether AAbs against ERG oncoprotein (overexpressed in 25-50% of Caucasian American and African American CaP) are present in the sera of CaP patients; ii) To evaluate an AAb panel to enhance CaP detection...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28186998/somatic-molecular-subtyping-of-prostate-tumors-from-hoxb13-g84e-carriers
#13
Tamara L Lotan, Alba Torres, Miao Zhang, Jeffrey J Tosoian, Liana B Guedes, Helen Fedor, Jessica Hicks, Charles M Ewing, Sarah D Isaacs, Dorhyun Johng, Angelo M De Marzo, William B Isaacs
A recurrent germline mutation (G84E) in the HOXB13 gene is associated with early onset and family history-positive prostate cancer in patients of European descent, occurring in up to 5% of prostate cancer families. To date, the molecular features of prostate tumors occurring in HOXB13 G84E carriers have not been studied in a large cohort of patients. We identified 101 heterozygous carriers of G84E who underwent radical prostatectomy for prostate cancer between 1985 and 2011 and matched these men by race, age and tumor grade to 99 HOXB13 wild-type controls...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177849/the-clinical-evaluation-of-infantile-nystagmus-what-to-do-first-and-why
#14
Morgan Bertsch, Michael Floyd, Taylor Kehoe, Wanda Pfeifer, Arlene V Drack
INTRODUCTION: Infantile nystagmus has many causes, some life threatening. We determined the most common diagnoses in order to develop a testing algorithm. METHODS: Retrospective chart review. Exclusion criteria were no nystagmus, acquired after 6 months, or lack of examination. DATA COLLECTED: pediatric eye examination findings, ancillary testing, order of testing, referral, and final diagnoses. Final diagnosis was defined as meeting published clinical criteria and/or confirmed by diagnostic testing...
January 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28176188/adalimumab-for-treating-moderate-to-severe-hidradenitis-suppurativa-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#15
REVIEW
Paul Tappenden, Christopher Carroll, John W Stevens, Andrew Rawdin, Sabine Grimm, Mark Clowes, Eva Kaltenthaler, John R Ingram, Fiona Collier, Mohammad Ghazavi
As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG)...
February 7, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28169467/radiation-associated-angiosarcoma-in-the-setting-of-breast-cancer-mimicking-radiation-dermatitis-a-diagnostic-pitfall
#16
Brianne H Daniels, Jennifer S Ko, J Jordi Rowe, Erinn Downs-Kelly, Steven D Billings
BACKGROUND: We have encountered cases of postradiation angiosarcoma (PRAS) histologically mimicking radiation dermatitis. METHODS: Cases of PRAS from institutional/consultation archives from 2006-2016 were reviewed. For inclusion, tumors had to have inapparent/subtle tumor at low magnification and scattered individual tumor cells resembling radiation fibroblasts. Prior ancillary studies were reviewed, with additional immunostains performed as needed. RESULTS: Ten met criteria...
February 7, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28168949/erg-28-controls-bk-channel-trafficking-in-the-er-to-regulate-synaptic-function-and-alcohol-response-in-c-elegans
#17
Kelly H Oh, James J Haney, Xiaohong Wang, Chiou-Fen Chuang, Janet E Richmond, Hongkyun Kim
Voltage- and calcium-dependent BK channels regulate calcium-dependent cellular events such as neurotransmitter release by limiting calcium influx. Their plasma membrane abundance is an important factor in determining BK current and thus regulation of calcium-dependent events. In C. elegans, we show that ERG-28, an endoplasmic reticulum (ER) membrane protein, promotes the trafficking of SLO-1 BK channels from the ER to the plasma membrane by shielding them from premature degradation. In the absence of ERG-28, SLO-1 channels undergo aspartic protease DDI-1-dependent degradation, resulting in markedly reduced expression at presynaptic terminals...
February 7, 2017: ELife
https://www.readbyqxmd.com/read/28160194/constant-luminance-cd%C3%A2-s-m-2-versus-constant-retinal-illuminance-td%C3%A2-s-stimulation-in-flicker-ergs
#18
C Quentin Davis, Olga Kraszewska, Colette Manning
PURPOSE: To compare the effect of variable pupil size on the flicker electroretinogram (ERG) between a stimulus having constant luminance and a stimulus having constant retinal illuminance (constant Troland) that compensates for pupil size. METHODS: Subjects (n = 18) were tested with 12 pairs of the stimuli. The stimulus pair consisted of the ISCEV standard constant luminance stimulus (3 cd·s/m(2) with a 30 cd/m(2) background) and a constant retinal illuminance stimulus (32 Td·s with a 320 Td background) selected to provide the same stimulus and background when the pupil diameter is 3...
February 3, 2017: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/28159970/the-clinical-phenotype-of-cnga3-related-achromatopsia-pretreatment-characterization-in-preparation-of-a-gene-replacement-therapy-trial
#19
Ditta Zobor, Annette Werner, Franco Stanzial, Francesco Benedicenti, Günther Rudolph, Ulrich Kellner, Christian Hamel, Sten Andréasson, Gergely Zobor, Torsten Strasser, Bernd Wissinger, Susanne Kohl, Eberhart Zrenner
Purpose: The purpose of this study was to clinically characterize patients with CNGA3-linked achromatopsia (CNGA3-ACHM) in preparation of a gene therapy trial. Methods: Thirty-six patients (age 7-56 years) with complete (cACHM) or incomplete (iACHM) CNGA3-ACHM were examined, including detailed psychophysical tests, extended electrophysiology, and assessment of morphology by fundus autofluorescence and spectral-domain optical coherence tomography (SD-OCT). Results: Mean best-corrected visual acuity was 0...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28156002/lucap-prostate-cancer-patient-derived-xenografts-reflect-the-molecular-heterogeneity-of-advanced-disease-an-d-serve-as-models-for-evaluating-cancer-therapeutics
#20
Holly M Nguyen, Robert L Vessella, Colm Morrissey, Lisha G Brown, Ilsa M Coleman, Celestia S Higano, Elahe A Mostaghel, Xiaotun Zhang, Lawrence D True, Hung-Ming Lam, Martine Roudier, Paul H Lange, Peter S Nelson, Eva Corey
BACKGROUND: Metastatic prostate cancer is a common and lethal disease for which there are no therapies that produce cures or long-term durable remissions. Clinically relevant preclinical models are needed to increase our understanding of biology of this malignancy and to evaluate new agents that might provide effective treatment. Our objective was to establish and characterize patient-derived xenografts (PDXs) from advanced prostate cancer (PC) for investigation of biology and evaluation of new treatment modalities...
February 3, 2017: Prostate
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