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https://www.readbyqxmd.com/read/28544366/enumeration-of-wt1-specific-cd8-t-cells-for-clinical-application-using-an-mhc-streptamer-based-no-wash-single-platform-flow-cytometric-assay
#1
Sarah Matko, Madeleine Teichert, Antje Tunger, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
The advent of novel strategies to generate leukemia-associated-antigen (LAA)-specific T cells for adoptive immunotherapies creates a demand for standardized good laboratory practice (GLP)-compliant enumeration assays to provide a secure clinical environment-whether it is to identify potential donors, define therapeutic doses for transplantation, or monitor clinical success. Here, we introduce a no-wash assay based on single-platform cell enumeration and Streptamer staining to determine the Wilms' tumor antigen 1 (WT1)-specific T cell immunity in clinical samples...
May 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28543860/a-unique-case-of-bilateral-ovarian-splenosis-and-review-of-the-literature
#2
Maria Giulia Disanto, Francesca Mercalli, Andrea Palicelli, Alberto Arnulfo, Renzo Boldorini
Splenosis is an acquired anomaly related to heterotopic auto-transplantation of splenic tissue following abdominal trauma or splenectomy. We report the first definitive bilateral ovarian case in a 65-year-old woman who underwent splenectomy following a motor vehicle accident 44 years prior to presentation. We review the literature and discuss the main differential diagnoses. Gross examination revealed a 1-cm well-circumscribed dark nodule on the surface of each ovary. Paraffin-embedded, formalin-fixed blocks were sectioned and stained with hematoxylin-eosin and immunostains (CK5/6, Calretinin, WT1, Vimentin)...
May 25, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28542793/the-genetic-factors-contributing-to-the-development-of-wilm-s-tumor-and-their-clinical-utility-in-its-diagnosis-and-prognosis
#3
REVIEW
Afsane Bahrami, Marjan Joodi, Mina Maftooh, Gordon A Ferns, Mehrdad Ahmadi, Seyed Mahdi Hassanian, Amir Avan
Mutations in the Wilm's tumor 1 (WT1) gene are associated with a wide spectrum of renal manifestations, ultimately leading to end-stage kidney failure. There is an inadequate understanding of the molecular functions of WT1 in renal development, and this has limited the potential for therapeutic interventions in WT1-related diseases. In this review we discuss the existing data on the genetic and epigenetic abnormalities that have been described in WTs and their potential utility as biomarkers for risk stratification, prediction and prognosis in patients withWTs...
May 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28534317/wt1-alternative-splicing-role-of-its-isoforms-in-neuroblastoma
#4
REVIEW
Daniela Maria Rasà, Agata Grazia D'Amico, Grazia Maugeri, Sebastiano Cavallaro, Velia D'Agata
Wilms tumor 1 (WT1), a tumor suppressor gene, was originally identified in the homonymous renal neoplasm but is also involved in other cancers. Its function is still unclear, since it acts both as a pro- and an anti-oncogene. At least 14 WT1 transcriptional variants have been described; yet most investigations have focused on a small number of isoforms. We describe their structural features and review the evidence of their involvement in cancer with emphasis on neuroblastoma. In future, full characterization of all WT1 isoforms is expected to identify new molecular tumor markers and/or therapeutic targets...
May 22, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28527702/crispr-cas9-induced-disruption-of-wt1a-and-wt1b-reveals-their-different-roles-in-kidney-and-gonad-development-in-nile-tilapia
#5
Dongneng Jiang, Jinlin Chen, Zheng Fan, Dejie Tan, Jiue Zhao, Hongjuan Shi, Zhilong Liu, Wenjing Tao, Minghui Li, Deshou Wang
Wilms tumor 1 (Wt1) is an essential factor for urogenital system development. Teleosts have two wt1s, named as wt1a and wt1b. In this study, the expression pattern of wt1a and wt1b and their functions on the urogenital system were analyzed by in situ hybridization and CRISPR/Cas9. wt1a was found to be expressed in the glomerulus at 3 dah (days after hatching), earlier than wt1b. wt1a and wt1b were simultaneously expressed in the somatic cells of gonads at 3 dah, while their cell locations were similar, but not identical in adult fish gonads...
May 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28522325/generation-of-chromosomal-translocations-that-lead-to-conditional-fusion-protein-expression-using-crispr-cas9-and-homology-directed-repair
#6
Fabio Vanoli, Maria Jasin
Recurrent chromosomal translocations often lead to expression of fusion proteins associated with oncogenic transformation. To study translocations and downstream events, genome editing techniques have been developed to generate chromosomal translocations through non-homologous end joining of DNA double-strand breaks introduced at the two participating endogenous loci. However, the frequencies at which these events occur is usually too low to efficiently clone cells carrying the translocation. This article provides a detailed method using CRISPR-Cas9 technology and homology-directed repair to efficiently isolate cells harboring a chromosomal translocation...
May 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28521413/chromosome-t-7-11-p15-p15-translocation-in-acute-myeloid-leukemia-coexisting-with-multilineage-dyspoiesis-and-mutations-in-nras-and-wt1-a-case-report-and-literature-review
#7
Jingke Yang, Xiaodong Lyu, Xinghu Zhu, Xiangguang Meng, Wenli Zuo, Hao Ai, Mei Deng
The chromosomal translocation t(7;11)(p15;p15) and the resulting nucleoporin 98-homeobox A9 (NUP98-HOXA9) gene fusion is rare but recurrent genetic abnormity in acute myeloid leukemia (AML). The present study describes a case of AML plus maturation (-M2) with multilineage dyspoiesis in a 30-year-old male in whom a 46,XY,t(7;11)(p15;p15) karyotype was detected through chromosome analysis. Subsequent molecular and sequencing analysis demonstrated a NUP98-HOXA9 fusion gene with a type I fusion between NUP98 exon 12 and HOXA9 exon 1b, and mutations in neuroblastoma V-Ras oncogene homolog and Wilms tumor 1...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28505004/a-subset-of-malignant-mesotheliomas-in-young-adults-are-associated-with-recurrent-ewsr1-fus-atf1-fusions
#8
Patrice Desmeules, Philippe Joubert, Lei Zhang, Hikmat A Al-Ahmadie, Christopher D Fletcher, Efsevia Vakiani, Deborah F Delair, Natasha Rekhtman, Marc Ladanyi, William D Travis, Cristina R Antonescu
Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28498419/mir-590-regulates-wt1-during-proliferation-of-g401-cells
#9
Liyi Hong, Xu Zhao, Xuejun Shao, Hong Zhu
Nephroblastoma (Wilms' tumor) is frequently associated with mortality in children. MicroRNAs (miRNAs) are important for tumor development serving as oncogenes or tumor suppressors. In the present study, miRNA‑590 (miR‑590) was identified to be upregulated in Wilms' tumor tissues compared with the normal adjacent tissues. Additionally, the levels of miR‑590 were consistent with their clinical stage. Wilms' tumor 1 (WT1) was considered to be a tumor suppressor in certain tumor types, and it has been detected at low expression levels in various types of cancer with high cell proliferation and aggressive behavior...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28495917/combining-flow-cytometry-and-wt1-assessment-improves-the-prognostic-value-of-pre-transplant-minimal-residual-disease-in-acute-myeloid-leukemia
#10
Fabio Guolo, Paola Minetto, Marino Clavio, Maurizio Miglino, Federica Galaverna, Anna Maria Raiola, Carmen Di Grazia, Nicoletta Colombo, Sarah Pozzi, Adalberto Ibatici, Samuele Bagnasco, Daniela Guardo, Annalisa Kunkl, Filippo Ballerini, Chiara Ghiggi, Roberto M Lemoli, Marco Gobbi, Andrea Bacigalupo
No abstract text is available yet for this article.
May 11, 2017: Haematologica
https://www.readbyqxmd.com/read/28494767/intestinal-differentiated-mucinous-adenocarcinoma-of-the-endometrium-with-sporadic-msi-high-status-a-case-report
#11
Mafalda Trippel, Sara Imboden, Andrea Papadia, Michael D Mueller, Nando Mertineit, Kirsi Härmä, Alina Nicolae, Erik Vassella, Tilman T Rau
BACKGROUND: Intestinal differentiation of primary mucinous adenocarcinoma of the uterine corpus is exceedingly rare in comparison to the approximately 25% rate in endocervical and ovarian mucinous carcinoma. Additionally, little is known about the related genetic and epigenetic alterations, even though large-scale molecular characterisation of the different types of endometrial cancer took place in the TCGA project along the entities defined by the recent WHO classification. CASE PRESENTATION: We present a 62-year-old patient harbouring a primary mucinous carcinoma of the uterine corpus with a morphological resemblance to mucinous colorectal adenocarcinoma...
May 12, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28493961/aldosterone-signaling-regulates-the-over-expression-of-claudin-4-and-8-at-the-distal-nephron-from-type-1-diabetic-rats
#12
Eduardo Molina-Jijón, Rafael Rodríguez-Muñoz, Ricardo González-Ramírez, Carmen Namorado-Tónix, José Pedraza-Chaverri, Jose L Reyes
Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3-21. Twenty-one days after STZ injection the rats were sacrificed...
2017: PloS One
https://www.readbyqxmd.com/read/28493604/cic-break-apart-fluorescence-in-situ-hybridisation-misses-a-subset-of-cic-dux4-sarcomas-a-clinicopathological-and-molecular-study
#13
Akihiko Yoshida, Yasuhito Arai, Eisuke Kobayashi, Kan Yonemori, Koichi Ogura, Natsuko Hama, Wakako Mukai, Toru Motoi, Akira Kawai, Tatsuhiro Shibata, Nobuyoshi Hiraoka
AIMS: Approximately 60-70% of high-grade round-cell sarcomas that lack the EWSR1 rearrangement harbour a rearrangement of the CIC gene, most commonly CIC-DUX4. Recent studies have established that CIC-rearranged sarcomas constitute a distinct group characterised by recognisable histology and immunoprofiles, such as positivity for ETV4 and WT1 and negativity for NKX2.2. Although these sarcomas are increasingly diagnosed in practice by fluorescence in situ hybridisation (FISH) with CIC break-apart probes, the optimal modality to diagnose these sarcomas has not been determined...
May 11, 2017: Histopathology
https://www.readbyqxmd.com/read/28477011/simultaneous-in-vitro-generation-of-cd8-and-cd4-t-cells-specific-to-three-universal-tumor-associated-antigens-of-wt1-survivin-and-tert-and-adoptive-t-cell-transfer-for-the-treatment-of-acute-myeloid-leukemia
#14
Hyun-Jung Sohn, Ji Yoon Lee, Hyun-Joo Lee, Dae-Hee Sohn, Hyun-Il Cho, Hee-Je Kim, Tai-Gyu Kim
Previously, we found that most patients with acute myeloid leukemia (AML) expressed at least one of the leukemic associated antigens (LAAs) WT1, survivin and TERT, and different combinations of the three LAAs predicted negative clinical outcomes. Multi-tumor antigen-specific T cells were generated to overcome antigenic variation and may be sufficient to maximize antitumoral effects. To generate triple antigen-specific (Tri)-T cells that recognize three LAAs, dendritic cells (DCs) were transfected with three tumor antigen-encoding RNAs...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28476686/mutation-spectrum-of-genes-associated-with-steroid-resistant-nephrotic-syndrome-in-chinese-children
#15
Ying Wang, Xiqiang Dang, Qingnan He, Yan Zhen, Xiaoxie He, Zhuwen Yi, Kuichun Zhu
Approximately 20% of children with idiopathic nephrotic syndrome do not respond to steroid therapy. More than 30 genes have been identified as disease-causing genes for the steroid-resistant nephrotic syndrome (SRNS). Few reports were from the Chinese population. The coding regions of genes commonly associated with SRNS were analyzed to characterize the gene mutation spectrum in children with SRNS in central China. The first phase study involved 38 children with five genes (NPHS1, NPHS2, PLCE1, WT1, and TRPC6) by Sanger sequencing...
May 2, 2017: Gene
https://www.readbyqxmd.com/read/28475434/enhancing-acute-myeloid-leukemia-therapy-monitoring-response-using-residual-disease-testing-as-a-guide-to-therapeutic-decision-making
#16
Benjamin Tomlinson, Hillard M Lazarus
Current standards for monitoring the response of acute myeloid leukemia (AML) are based on morphologic assessments of the bone marrow and recovery of peripheral blood counts. A growing experience is being developed to enhance the detection of small amounts of AML, or minimal residual disease (MRD). Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD...
May 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28461089/vascular-lesions-of-the-female-genital-tract-clinicopathologic-findings-and-application-of-the-issva-classification
#17
Georgia Karpathiou, Celine Chauleur, Vanessa Da Cruz, Fabien Forest, Michel Peoc'h
INTRODUCTION: Vascular lesions of the female genital tract are extremely rare and their nomenclature does not widely follow the International Society for the Study of Vascular Anomalies (ISSVA) classification. AIM OF THE STUDY: To describe the clinicopathologic characteristics of vascular lesions of the female genital tract and to apply the ISSVA classification. MATERIAL AND METHODS: 19 vascular lesions were diagnosed during a 20 year period...
April 23, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28458685/fatty-acids-of-cla-enriched-egg-yolks-can-induce-transcriptional-activation-of-peroxisome-proliferator-activated-receptors-in-mcf-7-breast-cancer-cells
#18
Aneta A Koronowicz, Paula Banks, Adam Master, Dominik Domagała, Ewelina Piasna-Słupecka, Mariola Drozdowska, Elżbieta Sikora, Piotr Laidler
In our previous study, we showed that fatty acids from CLA-enriched egg yolks (EFA-CLA) reduced the proliferation of breast cancer cells; however, the molecular mechanisms of their action remain unknown. In the current study, we used MCF-7 breast cancer cell line to determine the effect of EFA-CLA, as potential ligands for peroxisome proliferator-activated receptors (PPARs), on identified in silico PPAR-responsive genes: BCAR3, TCF20, WT1, ZNF621, and THRB (transcript TRβ2). Our results showed that EFA-CLA act as PPAR ligands with agonistic activity for all PPAR isoforms, with the highest specificity towards PPARγ...
2017: PPAR Research
https://www.readbyqxmd.com/read/28454430/wt1-associated-protein-is-a-novel-prognostic-factor-in-pancreatic-ductal-adenocarcinoma
#19
Bing-Qi Li, Shuai Huang, Qian-Qian Shao, Jian Sun, Li Zhou, Lei You, Tai-Ping Zhang, Quan Liao, Jun-Chao Guo, Yu-Pei Zhao
Although Wilms tumor 1 (WT1)-associated protein (WTAP) was initially found to be a specific WT1-binding protein, it has increasingly attracted attention because of its oncogenic role in various types of malignancies, including cholangiocarcinoma, glioblastoma and acute myeloid leukemia. However, the clinical impact of WTAP on pancreatic ductal adenocarcinoma (PDAC) is still unknown. A total of 145 patients who underwent surgical treatment from 2004 to 2008 were enrolled in the present study. The cytoplasmic and nuclear expression of WTAP in tumor and adjacent normal tissues was examined by immunohistochemical analysis in order to investigate the relationship between WTAP and the clinicopathological factors and prognosis of patients with PDAC...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28435676/understanding-cd8-t-cell-responses-toward-the-native-and-alternate-hla-a-02-01-restricted-wt1-epitope
#20
Thi Ho Nguyen, Amabel Cl Tan, Sue D Xiang, Anne Goubier, Kim L Harland, E Bridie Clemens, Magdalena Plebanski, Katherine Kedzierska
The Wilms' tumor 1 (WT1) antigen is expressed in solid and hematological malignancies, but not healthy tissues, making it a promising target for cancer immunotherapies. Immunodominant WT1 epitopes, the native HLA-A2/WT1126-134 (RMFPNAPYL) (HLA-A2/RMFPNAPYL epitope (WT1A)) and its modified variant YMFPNAPYL (HLA-A2/YMFPNAPYL epitope (WT1B)), can induce WT1-specific CD8(+) T cells, although WT1B is more stably bound to HLA-A*02:01. Here, to further determine the benefits of those two targets, we assessed the naive precursor frequencies; immunogenicity and cross-reactivity of CD8(+) T cells directed toward these two WT1 epitopes...
March 2017: Clinical & Translational Immunology
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