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https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#1
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but due to a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: Our objective was to establish an in vitro method for studying differentiation of bipotential gonadal progenitors using human embryonic stem cells (hESCs), and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28930610/rps6ka4-mir1237-and-aurkc-promoter-regions-are-differentially-methylated-in-wilms-tumor
#2
Hanna S Pereira, Sheila C Soares Lima, Paulo S de Faria, Leila Ca Cardoso, Hector N Seuanez
Wilms' tumor (WT) is the most frequent renal cancer in childhood, the occurrence of which is characterized by a relatively low frequency of associated mutations. While epigenetic alterations have been postulated to play a relevant role in the emergence of this tumor, the mechanisms involved in WT development remain largely unknown. In this study, the DNA methylation profile of WT was characterized with Beadchip array. Comparisons between WT with normal kidney identified 827 differentially methylated regions, most of which were attributable in hypermethylation in CpG islands...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28927158/regulation-of-htra2-on-wt1-gene-expression-under-imatinib-stimulation-and-its-effects-on-the-cell-biology-of-k562-cells
#3
Lixia Zhang, Yan Li, Xiaoyan Li, Qing Zhang, Shaowei Qiu, Qi Zhang, Min Wang, Haiyan Xing, Qing Rao, Zheng Tian, Kejing Tang, Jianxiang Wang, Yingchang Mi
The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923882/mutational-profiling-of-acute-myeloid-leukemia-with-normal-cytogenetics-in-brazilian-patients-the-value-of-next-generation-sequencing-for-genomic-classification
#4
Thiago Rodrigo de Noronha, Miguel Mitne-Neto, Maria de Lourdes Chauffaille
Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients' risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28923666/validation-of-a-molecular-risk-score-for-prognosis-of-patients-with-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-and-chemotherapy-containing-regimens
#5
Anna Hecht, Seraphina Doll, Heidi Altmann, Daniel Nowak, Eva Lengfelder, Christoph Röllig, Gerhard Ehninger, Karsten Spiekermann, Wolfgang Hiddemann, Christel Weiß, Wolf-Karsten Hofmann, Florian Nolte, Uwe Platzbecker
INTRODUCTION: Although treatment of acute promyelocytic leukemia (APL) has evolved dramatically during the past decades, especially with the introduction of all-trans retinoic acid, risk stratification remains an important issue. To date, relapse risk can be predicted by leukocyte and platelet counts only. In the present report, we present a validation study on 3 candidate genes and a newly developed molecular risk score for APL in 2 independent patient cohorts. PATIENTS AND METHODS: An integrative risk score combining the expression levels of BAALC, ERG, and WT1 was calculated for 79 de novo APL patients from the original cohort and 76 de novo APL patients from a validation cohort...
August 15, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28921387/analysis-of-24-genes-reveals-a-monogenic-cause-in-11-1-of-cases-with-steroid-resistant-nephrotic-syndrome-at-a-single-center
#6
Weizhen Tan, Svjetlana Lovric, Shazia Ashraf, Jia Rao, David Schapiro, Merlin Airik, Shirlee Shril, Heon Yung Gee, Michelle Baum, Ghaleb Daouk, Michael A Ferguson, Nancy Rodig, Michael J G Somers, Deborah R Stein, Asaf Vivante, Jillian K Warejko, Eugen Widmeier, Friedhelm Hildebrandt
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of end-stage renal disease (ESRD) among patients manifesting at under 25 years of age. We performed mutation analysis using a high-throughput PCR-based microfluidic technology in 24 single-gene causes of SRNS in a cohort of 72 families, who presented with SRNS before the age of 25 years. METHODS: Within an 18-month interval, we obtained DNA samples, pedigree information, and clinical information from 77 consecutive children with SRNS from 72 different families seen at Boston Children's Hospital (BCH)...
September 18, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28913845/urinary-wt1-positive-cells-as-a-non-invasive-biomarker-of-crescent-formation
#7
T Fujita, T Sofue, M Moritoki, Y Nishijima, Y Tokuhara, H Wakisaka, Y Kushida, R Haba, H Ohsaki
OBJECTIVE: The purpose of this study was to assess the relationship between urinary WT1-positive cells (podocytes and active parietal epithelial cells) and WT1-positive cells in renal biopsy to investigate whether urinary WT1-positive cells are useful for detection of crescent formation. METHODS: Fifty-two patients with kidney disease were investigated (15 cases with crescentic lesions and 37 cases with non-crescentic lesions) for immunoenzyme staining using anti-WT1 antibody for urine cytology and renal biopsy...
September 15, 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/28892074/replacing-reprogramming-factors-with-antibodies-selected-from-combinatorial-antibody-libraries
#8
Joel W Blanchard, Jia Xie, Nadja El-Mecharrafie, Simon Gross, Sohyon Lee, Richard A Lerner, Kristin K Baldwin
The reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) is usually achieved by exogenous induction of transcription by factors acting in the nucleus. In contrast, during development, signaling pathways initiated at the membrane induce differentiation. The central idea of this study is to identify antibodies that can catalyze cellular de-differentiation and nuclear reprogramming by acting at the cell surface. We screen a lentiviral library encoding ∼100 million secreted and membrane-bound single-chain antibodies and identify antibodies that can replace either Sox2 and Myc (c-Myc) or Oct4 during reprogramming of mouse embryonic fibroblasts into iPSCs...
September 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28878596/nucleotide-transition-390c-t-in-the-wilms-tumor-1-gene-a-risk-factor-of-hypospadias
#9
Gergely Buglyó, Ágnes Magyar, Sándor Biró, István Csízy, Dániel Beyer, Kinga Molnár, Éva Oláh
INTRODUCTION: The gene Wilms' tumor 1 (WT1) encodes a unique transcription factor. Its defects are known to cause a wide range of complex genitourinary malformations and may contribute to non-syndromic forms of hypospadias. MATERIALS AND METHODS: We performed WT1 mutation analysis and copy number analysis of WT1-interacting protein in 13 Hungarian patients diagnosed with isolated hypospadias. RESULTS: Sequencing of WT1 revealed a high frequency of heterozygosity for transition 390C-T (5 heterozygotes out of 13 patients, including 2 brothers)...
August 2017: Current Urology
https://www.readbyqxmd.com/read/28860210/safety-and-persistence-of-wt1-specific-t-cell-receptor-gene-transduced-lymphocytes-in-patients-with-aml-and-mds
#10
Isao Tawara, Shinichi Kageyama, Yoshihiro Miyahara, Hiroshi Fujiwara, Tetsuya Nishida, Yoshiki Akatsuka, Hiroaki Ikeda, Kazushi Tanimoto, Seitaro Terakura, Makoto Murata, Yoko Inaguma, Masahiro Masuya, Naoki Inoue, Tomohide Kidokoro, Sachiko Okamoto, Daisuke Tomura, Hideto Chono, Ikuei Nukaya, Junichi Mineno, Tomoki Naoe, Nobuhiko Emi, Masaki Yasukawa, Naoyuki Katayama, Hiroshi Shiku
WT1 is constantly expressed in leukemic cells of acute leukemia and myelodysplastic syndrome (MDS). A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-in human trial of TCR-gene transduced T cell (TCR-T cell) transfer in patients with refractory acute myeloblastic leukemia (AML) and high-risk MDS to investigate the safety and cell kinetics of the T cells. The WT1-specific TCR-gene was transduced to T cells using a retroviral vector encoding siRNAs for endogenous TCR genes...
August 31, 2017: Blood
https://www.readbyqxmd.com/read/28859078/the-wagr-syndrome-gene-prrg4-is-a-functional-homologue-of-the-commissureless-axon-guidance-gene
#11
Elizabeth D Justice, Sarah J Barnum, Thomas Kidd
WAGR syndrome is characterized by Wilm's tumor, aniridia, genitourinary abnormalities and intellectual disabilities. WAGR is caused by a chromosomal deletion that includes the PAX6, WT1 and PRRG4 genes. PRRG4 is proposed to contribute to the autistic symptoms of WAGR syndrome, but the molecular function of PRRG4 genes remains unknown. The Drosophila commissureless (comm) gene encodes a short transmembrane protein characterized by PY motifs, features that are shared by the PRRG4 protein. Comm intercepts the Robo axon guidance receptor in the ER/Golgi and targets Robo for degradation, allowing commissural axons to cross the CNS midline...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28852936/down-regulation-of-pax2-promotes-in-vitro-differentiation-of-podocytes-from-human-cd34-cells
#12
Manne Mudhu Sunitha, Lokanathan Srikanth, Pasupuleti Santhosh Kumar, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma
Podocytes are major kidney cells that help in glomerular filtration and any damage or loss is a major event in the progression of kidney diseases. Understanding podocytes development will help in designing therapeutic strategies against these renal diseases. Therefore, in vitro generation of podocytes from adult hematopoietic CD34(+) stem cells is explored in the present study. Apheretically, isolated human HSCs from peripheral blood showed the presence of CD34 surface glycoprotein through immunocytochemistry (ICC) and flowcytometry...
August 29, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28846953/post-remissional-and-pre-transplant-role-of-minimal-residual-disease-detected-by-wt1-in-acute-myeloid-leukemia-a-retrospective-cohort-study
#13
Chiara Frairia, Semra Aydin, Ernesta Audisio, Ludovica Riera, Sabrina Aliberti, Bernardino Allione, Alessandro Busca, Stefano D'Ardia, Chiara Maria Dellacasa, Anna Demurtas, Andrea Evangelista, Giovannino Ciccone, Paola Francia di Celle, Barbara Nicolino, Alessandra Stacchini, Filippo Marmont, Umberto Vitolo
In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) is still under investigation. The aim of the present retrospective study was to assess the role of Wilms tumor gene 1 (WT1) overexpression in a large monocentric cohort of AML patients. Among 255 enrolled patients, MRD was investigated in those in complete remission (CR) with an available WT1 at baseline (>250 copies) and at two further time-points: after induction (n=117) and prior allogeneic hematopoietic cell transplantation (allo-HCT), n=65...
August 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28844009/anatomical-and-electrophysiological-characterization-of-a-population-of-di6-interneurons-in-the-neonatal-mouse-spinal-cord
#14
Anna Griener, Wei Zhang, Henry Kao, Farhia Haque, Simon Gosgnach
The locomotor central pattern generator is a neural network located in the ventral aspect of the caudal spinal cord that underlies stepping in mammals. While many genetically defined interneurons that are thought to comprise this neural network have been identified and characterized, the dI6 cells- which express the transcription factors WT1 and/or DMRT3- are one population that settle in this region, are active during locomotion, whose function is poorly understood. These cells were originally hypothesized to be commissural premotor interneurons, however evidence in support of this is sparse...
August 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28840388/molecular-screening-of-multidrug-resistance-tuberculosis-by-a-designated-public-health-laboratory-in-taiwan
#15
H-C Lin, C-L Perng, Y-W Lai, F-G Lin, C-J Chiang, H-A Lin, R Jou, T-S Chiueh
This manuscript describes our experience in early identifying MDR-TB cases in high-risk populations by setting up a single-referral molecular diagnosis laboratory in Taiwan. Taiwan Centers for Disease Control designated a single-referral laboratory to provide the GenoType MTBDRplus test for screening high-risk MDR-TB populations nationwide in 2012-2015. A total of 5,838 sputum specimens from 3,308 patients were tested within 3 days turnaround time. Compared with the conventional culture and drug susceptibility testing, the overall performance of the GenoType MTBDRplus test for detecting TB infection showed accuracy of 70...
August 24, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28830889/dendritic-cell-vaccination-as-post-remission-treatment-to-prevent-or-delay-relapse-in-acute-myeloid-leukemia
#16
Sébastien Anguille, Ann L Van de Velde, Evelien L Smits, Viggo F Van Tendeloo, Gunnar Juliusson, Nathalie Cools, Griet Nijs, Barbara Stein, Eva Lion, Ann Van Driessche, Irma Vandenbosch, Anke Verlinden, Alain P Gadisseur, Wilfried A Schroyens, Ludo Muylle, Katrien Vermeulen, Marie-Berthe Maes, Kathleen Deiteren, Ronald Malfait, Emma Gostick, Martin Lammens, Marie M Couttenye, Philippe Jorens, Herman Goossens, David A Price, Kristin Ladell, Yoshihiro Oka, Fumihiro Fujiki, Yusuke Oji, Haruo Sugiyama, Zwi N Berneman
Relapse is a major problem in acute myeloid leukemia (AML) and adversely impacts survival. In this phase II study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) mRNA as post-remission treatment in 30 AML patients at very high risk of relapse. There was a demonstrable anti-leukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which are sustained after a median follow-up of 109...
August 22, 2017: Blood
https://www.readbyqxmd.com/read/28830460/gene-mutational-pattern-and-expression-level-in-560-acute-myeloid-leukemia-patients-and-their-clinical-relevance
#17
Yong-Mei Zhu, Pan-Pan Wang, Jin-Yan Huang, Yun-Shuo Chen, Bing Chen, Yu-Jun Dai, Han Yan, Yi Hu, Wen-Yan Cheng, Ting-Ting Ma, Sai-Juan Chen, Yang Shen
BACKGROUND: Cytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML. METHODS: In this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1...
August 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28825729/a-children-s-oncology-group-and-target-initiative-exploring-the-genetic-landscape-of-wilms-tumor
#18
Samantha Gadd, Vicki Huff, Amy L Walz, Ariadne H A G Ooms, Amy E Armstrong, Daniela S Gerhard, Malcolm A Smith, Jaime M Guidry Auvil, Daoud Meerzaman, Qing-Rong Chen, Chih Hao Hsu, Chunhua Yan, Cu Nguyen, Ying Hu, Leandro C Hermida, Tanja Davidsen, Patee Gesuwan, Yussanne Ma, Zusheng Zong, Andrew J Mungall, Richard A Moore, Marco A Marra, Jeffrey S Dome, Charles G Mullighan, Jing Ma, David A Wheeler, Oliver A Hampton, Nicole Ross, Julie M Gastier-Foster, Stefan T Arold, Elizabeth J Perlman
We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A...
August 21, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28811308/wilms-tumour-1-wt1-in-development-homeostasis-and-disease
#19
REVIEW
Nicholas D Hastie
The study of genes mutated in human disease often leads to new insights into biology as well as disease mechanisms. One such gene is Wilms' tumour 1 (WT1), which plays multiple roles in development, tissue homeostasis and disease. In this Primer, I summarise how this multifaceted gene functions in various mammalian tissues and organs, including the kidney, gonads, heart and nervous system. This is followed by a discussion of our current understanding of the molecular mechanisms by which WT1 and its two major isoforms regulate these processes at the transcriptional and post-transcriptional levels...
August 15, 2017: Development
https://www.readbyqxmd.com/read/28810922/pleural-epithelioid-angiosarcoma-with-lymphatic-differentiation-arisen-after-radiometabolic-therapy-for-thyroid-carcinoma-immunohistochemical-findings-and-review-of-the-literature
#20
REVIEW
Daniela Cabibi, Giulia Pipitone, Rossana Porcasi, Sabrina Ingrao, Ignazio Benza, Calogero Porrello, Massimo Cajozzo, Antonino Giulio Giannone
BACKGROUND: Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. CASE PRESENTATION: A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases...
August 15, 2017: Diagnostic Pathology
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