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https://www.readbyqxmd.com/read/28435676/understanding-cd8-t-cell-responses-toward-the-native-and-alternate-hla-a-02-01-restricted-wt1-epitope
#1
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
https://www.readbyqxmd.com/read/28426816/ex-vivo-cultures-combined-with-vivo-morpholino-induced-gene-knockdown-provide-a-system-to-assess-the-role-of-wt1-and-gata4-during-gonad-differentiation
#2
Lucas J Rudigier, Christof Dame, Holger Scholz, Karin M Kirschner
Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper gonadal development. Here we address the contributions of GATA4 and WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo technique for cultivating gonads in hanging droplets of media that were supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in combination at the same developmental stage...
2017: PloS One
https://www.readbyqxmd.com/read/28413448/genetic-and-epigenetic-characterization-of-the-tumors-in-a-patient-with-a-tongue-primary-tumor-a-recurrence-and-a-pharyngoesophageal-second-primary-tumor
#3
Ilda P Ribeiro, Francisco Marques, Leonor Barroso, Jorge Miguéis, Francisco Caramelo, André Santos, Maria J Julião, Joana B Melo, Isabel M Carreira
BACKGROUND: The choice of therapeutic modality for oral carcinoma in recurrent or second primary tumors remains controversial, as the treatment modalities available might be reduced by the treatment of the first tumor, and the overall survival is lower when compared with patients with a single or first tumor. Identifying biomarkers that predict the risk of relapse and the response to treatment is an emerging clinical issue. CASE PRESENTATION: A Caucasian 49-years-old man was treated with chemotherapy followed by chemoradiotherapy for a primary left side tongue tumor, achieving a complete response...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28400619/dysfunction-of-the-wt1-meg3-signaling-promotes-aml-leukemogenesis-via-p53-dependent-and-independent-pathways
#4
Y Lyu, J Lou, Y Yang, J Feng, Y Hao, S Huang, L Yin, J Xu, D Huang, B Ma, D Zou, Y Wang, Y Zhang, B Zhang, P Chen, K Yu, Ew-F Lam, X Wang, Q Liu, J Yan, B Jin
Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified by the recent finding that lncRNA MEG3 inhibits tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults, and TP53 mutations or loss are frequently detected in patients with therapy-related AML or AML with complex karyotype. Here, we reveal that MEG3 is significantly down-regulated in AML and suppresses leukemogenesis in not only a p53-dependent, but also a p53-independent manner...
April 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28398607/wagr-syndrome-and-congenital-hypothyroidism-in-a-child-with-a-mosaic-11p13-deletion
#5
Minh Tuan Huynh, Elise Boudry-Labis, Bénédicte Duban, Joris Andrieux, Cong Toai Tran, Heidi Tampere, Delphine Ceraso, Sylvie Manouvrier, Gérard Tachdjian, Catherine Roche-Lestienne, Catherine Vincent-Delorme
Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, a rare genetic disorder, is caused by the loss of 11p13 region including PAX6 and WT1. We report novel findings in a 28-month-old boy with aniridia, Wilm's tumor, congenital hypothyroidism, and sublingual thyroid ectopia. He was found to have a mosaic 5.28 Mb interstitial deletion of chromosome 11p13 deleting PAX6 and WT1. In order to clarify the mechanism underlying his thyroid dysgenesis, sequence analysis of candidate thyroid developmental genes was performed...
April 11, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28395566/wt1-protein-is-cleaved-by-caspase-3-in-apoptotic-leukemic-cells
#6
Jichen Ruan, Shenmeng Gao, Junjun Yang, Haiying Li, He Huang, Xiaoqun Zheng
The aberrant overexpression of Wilms' tumor-1 gene (WT1) plays an important role in blast cell survival and resistance to chemotherapy in acute myeloid leukemia (AML). Here, we found in chemotherapeutic drug etoposide-induced apoptosis, WT1 protein was cleaved into smaller fragment by caspase-3 in leukemic cells. The cleavage was blocked by pan-caspase inhibitor and special caspase-3 inhibitor, suggesting that caspase-3 might cleave WT1 protein. Furthermore, recombinant active caspase-3 cleaved the Flag-WT1 and GST-WT1 proteins in vitro...
April 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28390675/promotion-of-wilms-tumor-cells-migration-and-invasion-by-mono-2-ethyhexyl-phthalate-mehp-via-activation-of-nf-%C3%AE%C2%BAb-signals
#7
Zhansheng Wang, Minkun Shao, Yulu Liu
Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5-10% of cases. There is an urgent need to illustrate risk factors which can trigger the motility of Wilms tumor cells. Our present study revealed that mono-(2-ethylhexyl) phthalate (MEHP) exposure can significantly increase the in vitro migration and invasion of G401 and WiT49 cells. Real time PCR and western blot analysis revealed that MEHP treatment can increase the expression of metalloproteinase-2 (MMP-2) and MMP-9, while had no effect on the expression of MMP-1, MMP-3, or MMP-12...
April 6, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28388552/myelodysplastic-syndromes-advantages-of-a-combined-cytogenetic-and-molecular-diagnostic-workup
#8
Elena Ciabatti, Angelo Valetto, Veronica Bertini, Maria Immacolata Ferreri, Alice Guazzelli, Susanna Grassi, Francesca Guerrini, Iacopo Petrini, Maria Rita Metelli, Maria Adelaide Caligo, Simona Rossi, Sara Galimberti
In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383760/nephrogenic-rests-in-wilms-tumors-treated-with-preoperative-chemotherapy-the-uk-siop-wilms-tumor-2001-trial-experience
#9
Gordan M Vujanić, John R Apps, Veronica Moroz, Federica Ceroni, Richard D Williams, Neil J Sebire, Kathy Pritchard-Jones
BACKGROUND: Nephrogenic rests (NRs) are abnormally persistent foci of embryonal cells, thought to be the precursor lesion of Wilms tumors (WTs). To date, their presence has not been systematically examined in WTs treated with preoperative chemotherapy. METHODS: A systematic analysis of the data on NRs in WTs treated with preoperative chemotherapy obtained from the UK cohort of the International Society of Pediatric Oncology (SIOP) WT 2001 Trial. The study was based on central pathology review of full sets of slides from pathological specimens, with a median of 28 slides reviewed per case...
April 6, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28376587/-epithelioid-sarcoma-with-mesothelial-and-lymphatic-endothelial-differentiation-a-clinicopathologic-analysis-of-10-cases
#10
Z Y Ke, S J Yang
Objective: To investigate the multidirectional differentiation potential in epithelioid sarcoma (ES), with special emphasis on its mesothelial and lymphatic endothelial markers expression. Methods: Ten cases of distal-type ES were included. The clinical, histological, and immunohistochemical(including mesothelial and lymphatic endothelial markers expression)features and follow-up data were evaluated. Results: The patients aged between 8 to 66 years. Five cases were male and five were female. The tumors were located at the palm (2 cases), wrist (3 cases), upper arm (2 cases), poplitealfossa (1 case), lower leg (1 case) and thigh (1 case), respectively...
April 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28370670/origin-and-characterization-of-alpha-smooth-muscle-actin-positive-cells-during-murine-lung-development
#11
Alena Moiseenko, Vahid Kheirollahi, Cho-Ming Chao, Negah Ahmadvand, Jennifer Quantius, Jochen Wilhelm, Susanne Herold, Katrin Ahlbrecht, Rory E Morty, Albert A Rizvanov, Parviz Minoo, Elie El Agha, Saverio Bellusci
ACTA2 expression identifies pulmonary airway and vascular smooth muscle cells (SMCs) as well as alveolar myofibroblasts (MYF). Mesenchymal progenitors expressing fibroblast growth factor 10 (Fgf10), Wilms tumor 1 (Wt1), or glioma-associated oncogene 1 (Gli1) contribute to SMC formation from early stages of lung development. However, their respective contribution and specificity to the SMC and/or alveolar MYF lineages remain controversial. In addition, the contribution of mesenchymal cells undergoing active WNT signaling remains unknown...
April 3, 2017: Stem Cells
https://www.readbyqxmd.com/read/28367736/expression-of-wt1-and-pax8-in-the-epithelial-tumours-of-malaysian-women-with-ovarian-cancer
#12
Anthony Rhodes, Narayanan Vallikkannu, Pailoor Jayalakshmi
BACKGROUND: Ovarian cancer is particularly lethal due to late stage at presentation. The subtypes behave differently with respect to their biology and response to treatment. Two recent markers reported to be useful in assisting in the diagnosis are WT1 and PAX8. Malaysia, with its multi-ethnic population provides an opportunity to study the expression of these biomarkers in ovarian cancer in the three most populous ethnicities in Asia and ascertain their usefulness in the diagnosis of ovarian carcinoma...
April 2017: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/28366834/the-wilms-tumor-protein-wt1-stimulates-transcription-of-the-gene-encoding-insulin-like-growth-factor-binding-protein-5-igfbp5
#13
Miriam Müller, Anja Bondke Persson, Katharina Krueger, Karin M Kirschner, Holger Scholz
Insulin-like growth factor (IGF) binding proteins (IGFBPs) constitute a family of six secreted proteins that regulate the signaling of insulin-like growth factors (IGFs). IGFBP5 is the most conserved family member in vertebrates and the major IGF binding protein in bone. IGFBP5 is required for normal development of the musculoskeletal system, and various types of cancer frequently express high levels of IGFP5. Here we identify the gene encoding IGFBP5 as a novel downstream target of the Wilms tumor protein WT1...
March 30, 2017: Gene
https://www.readbyqxmd.com/read/28364352/effects-of-bufalin-on-up-regulating-methylation-of-wilm-s-tumor-1-gene-in-human-erythroid-leukemic-cells
#14
Li-Pei Wang, Yan-Na Zhao, Xin Sun, Rui-Lan Gao
OBJECTIVE: To explore the effects of bufalin on inhibiting proliferation, up-regulating methylation of Wilm' tumor 1 gene (WT1) as well as its possible mechanisms in human erythroid leukemic (HEL) cells. METHODS: The HEL cells were treated with bufalin at various concentrations to observe cellular morphology, proliferation assay and cell cycle. The mRNA and protein expression levels of WT1 were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry, DNA methylation of WT1 and protein expression levels of DNA methyltransferase 3a (DNMT3a) and DNMT3b were analyzed by methylation-specific PCR, and Western blot respectively...
April 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28346326/sarcomas-with-cic-rearrangements-are-a-distinct-pathologic-entity-with-aggressive-outcome-a-clinicopathologic-and-molecular-study-of-115-cases
#15
Cristina R Antonescu, Adepitan A Owosho, Lei Zhang, Sonja Chen, Kemal Deniz, Joseph M Huryn, Yu-Chien Kao, Shih-Chiang Huang, Samuel Singer, William Tap, Inga-Marie Schaefer, Christopher D Fletcher
CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available...
March 24, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28345629/wt1-expression-in-breast-cancer-disrupts-the-epithelial-mesenchymal-balance-of-tumour-cells-and-correlates-with-the-metabolic-response-to-docetaxel
#16
Mara Artibani, Andrew H Sims, Joan Slight, Stuart Aitken, Anna Thornburn, Morwenna Muir, Valerie G Brunton, Jorge Del-Pozo, Linda R Morrison, Elad Katz, Nicholas D Hastie, Peter Hohenstein
WT1 is a transcription factor which regulates the epithelial-mesenchymal balance during embryonic development and, if mutated, can lead to the formation of Wilms' tumour, the most common paediatric kidney cancer. Its expression has also been reported in several adult tumour types, including breast cancer, and usually correlates with poor outcome. However, published data is inconsistent and the role of WT1 in this malignancy remains unclear. Here we provide a complete study of WT1 expression across different breast cancer subtypes as well as isoform specific expression analysis...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344864/an-immunogenic-wt1-derived-peptide-that-induces-t-cell-response-in-the-context-of-hla-a-02-01-and-hla-a-24-02-molecules
#17
Tao Dao, Tatyana Korontsvit, Victoria Zakhaleva, Casey Jarvis, Patrizia Mondello, Claire Oh, David A Scheinberg
The Wilms' tumor oncogene protein (WT1) is a highly validated tumor antigen for immunotherapy. WT1-targeted immunotherapy has been extensively explored in multiple human trials in various cancers. However, clinical investigations using WT1 epitopes have generally focused on two peptides, HLA-restricted to HLA-A*02:01 or HLA-A*24:02. The goal of this study was to identify new epitopes derived from WT1, to expand the potential use of WT1 as a target of immunotherapy. Using computer-based MHC-binding algorithms and in vitro validation of the T cell responses specific for the identified peptides, we found that a recently identified HLA-A*24:02-binding epitope (239-247), NQMNLGATL (NQM), was also a strong CD8(+) T cell epitope for HLA-A*02:01 molecule...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28342843/the-stress-response-molecule-nr4a1-resists-ros-induced-pancreatic-%C3%AE-cells-apoptosis-via-wt1
#18
Chen Zong, Dandan Qin, Cong Yu, Peng Gao, Jicui Chen, Sumei Lu, Yuchao Zhang, Yuantao Liu, Yingfeng Yang, Zeqing Pu, Xia Li, Yuchang Fu, Qingbo Guan, Xiangdong Wang
Pancreatic β-cells often face endoplasmic reticulum stress and/or ROS-associated oxidative stress under adverse conditions. Our previous work has verified that NR4A1 protects pancreatic β-cells from ER-stress induced apoptosis. However, It remains unknown whether NR4A1 is able to protect pancreatic β-cells against ROS-associated oxidative stress. In the present study, our data showed that NR4A1 protein expression rapidly increased in MIN6 cells upon H2O2 treatment, and overexpression of NR4A1 in MIN6 cells conferred resistance to cell apoptosis induced by H2O2...
March 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28337592/head-and-neck-round-cell-sarcomas-a-comparative-clinicopathologic-analysis-of-2-molecular-subsets-ewing-and-cic-rearranged-sarcomas
#19
Adepitan A Owosho, Cherry L Estilo, Joseph M Huryn, Lei Zhang, Christopher D M Fletcher, Cristina R Antonescu
CIC-rearranged sarcoma (CRS) is a relatively new entity defined by its pathognomonic genetic signature and undifferentiated round cell phenotype, initially grouped together with the 'Ewing sarcoma-like tumors'. However, increasing data suggest that these tumors should be regarded as a stand-alone pathologic entity. We conducted a clinicopathologic analysis on molecularly conformed Ewing sarcoma (ES) and CRS arising in the head and neck (HN) and compared to a well characterized cohort of ES and CRS from other locations...
March 23, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28334862/the-wilms-tumor-protein-wt1-contributes-to-female-fertility-by-regulating-oviductal-proteostasis
#20
Abinaya Nathan, Peter Reinhardt, Dagmar Kruspe, Tjard Jörß, Marco Groth, Hendrik Nolte, Andreas Habenicht, Jörg Herrmann, Verena Holschbach, Bettina Toth, Marcus Krüger, Zhao-Qi Wang, Matthias Platzer, Christoph Englert
Although the zinc finger transcription factor Wt1 has been linked to female fertility, its precise role in this process has not yet been understood. We have sequenced the WT1 exons in a panel of patients with idiopathic infertility and have identified a missense mutation in WT1 in one patient out of eight. This mutation leads to an amino acid change within the zinc finger domain and results in reduced DNA binding. We utilized Wt1+/- mice as a model to mechanistically pinpoint the consequences of reduced Wt1 levels for female fertility...
March 1, 2017: Human Molecular Genetics
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