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https://www.readbyqxmd.com/read/28102366/aurora-kinase-a-is-a-biomarker-for-bladder-cancer-detection-and-contributes-to-its-aggressive-behavior
#1
Aaron Mobley, Shizhen Zhang, Jolanta Bondaruk, Yan Wang, Tadeusz Majewski, Nancy P Caraway, Li Huang, Einav Shoshan, Guermarie Velazquez-Torres, Giovanni Nitti, Sangkyou Lee, June Goo Lee, Enrique Fuentes-Mattei, Daniel Willis, Li Zhang, Charles C Guo, Hui Yao, Keith Baggerly, Yair Lotan, Seth P Lerner, Colin Dinney, David McConkey, Menashe Bar-Eli, Bogdan Czerniak
The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069802/genomic-profiling-of-a-large-set-of-diverse-pediatric-cancers-identifies-known-and-novel-mutations-across-tumor-spectra
#2
Juliann Chmielecki, Mark Bailey, Jie He, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, James Suh, Garrett M Frampton, James X Sun, Samantha Morley, Daniel Spritz, Siraj Ali, Laurie Gay, Rachel L Erlich, Jeffrey S Ross, Joana Buxhaku, Hilary Davies, Vinny Faso, Alexis Germain, Blair Glanville, Vincent A Miller, Philip J Stephens, Katherine A Janeway, John M Maris, Soheil Meshinchi, Trevor J Pugh, Jack F Shern, Doron Lipson
Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28058850/molecular-diagnostics-in-the-management-of-rhabdomyosarcoma
#3
Michael A Arnold, Fredric G Barr
A classification of rhabdomyosarcoma (RMS) with prognostic relevance has primarily relied on clinical features and histologic classification as either embryonal or alveolar RMS. The PAX3-FOXO1 and PAX7-FOXO1 gene fusions occur in 80% of cases with the alveolar subtype and are more predictive of outcome than histologic classification. Identifying additional molecular hallmarks that further subclassify RMS is an active area of research. Areas Covered: The authors review the current state of the PAX3-FOXO1 and PAX7-FOXO1 fusions as prognostic biomarkers...
January 6, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28043919/a-spontaneous-and-novel-pax3-mutant-mouse-that-models-waardenburg-syndrome-and-neural-tube-defects
#4
Tetsuo Ohnishi, Ikuo Miura, Hisako Ohba, Chie Shimamoto, Yoshimi Iwayama, Shigeharu Wakana, Takeo Yoshikawa
BACKGROUND: Genes responsible for reduced pigmentation phenotypes in rodents are associated with human developmental defects, such as Waardenburg syndrome, where patients display congenital deafness along with various abnormalities mostly related to neural crest development deficiency. OBJECTIVE: In this study, we identified a spontaneous mutant mouse line Rwa, which displays variable white spots on mouse bellies and white digits and tail, on a C57BL/6N genetic background...
December 30, 2016: Gene
https://www.readbyqxmd.com/read/28035744/impact-of-fusion-gene-status-versus-histology-on-risk-stratification-for-rhabdomyosarcoma-retrospective-analyses-of-patients-on-uk-trials
#5
Joanna Selfe, David Olmos, Reem Al-Saadi, Khin Thway, Julia Chisholm, Anna Kelsey, Janet Shipley
BACKGROUND: Long-term toxicities from current treatments are a major issue in paediatric cancer. Previous studies, including our own, have shown prognostic value for the presence of PAX3/7-FOXO1 fusion genes in rhabdomyosarcoma (RMS). It is proposed to introduce PAX3/7-FOXO1 positivity as a component of risk stratification, rather than alveolar histology, in future clinical trials. PROCEDURE: To assess the potential impact of this reclassification, we have determined the changes to risk category assignment of 210 histologically reviewed patients treated in the UK from previous malignant mesenchymal tumour clinical trials for non-metastatic RMS based on identification of PAX3/7-FOXO1 by fluorescence in situ hybridisation and/or reverse transcription PCR...
December 30, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28029168/trends-in-regenerative-medicine-repigmentation-in-vitiligo-through-melanocyte-stem-cell-mobilization
#6
REVIEW
Stanca A Birlea, Gertrude-E Costin, Dennis R Roop, David A Norris
Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin...
December 28, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28025671/retinoic-acid-maintains-human-skeletal-muscle-progenitor-cells-in-an-immature-state
#7
Marina El Haddad, Cécile Notarnicola, Brendan Evano, Nour El Khatib, Marine Blaquière, Anne Bonnieu, Shahragim Tajbakhsh, Gérald Hugon, Barbara Vernus, Jacques Mercier, Gilles Carnac
Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor...
December 26, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28017376/myogenic-potential-of-mouse-embryonic-stem-cells-lacking-functional-pax7-tested-in-vitro-by-5-azacitidine-treatment-and-in-vivo-in-regenerating-skeletal-muscle
#8
Anita Helinska, Maciej Krupa, Karolina Archacka, Areta M Czerwinska, Wladyslawa Streminska, Katarzyna Janczyk-Ilach, Maria A Ciemerych, Iwona Grabowska
Regeneration of skeletal muscle relies on the presence of satellite cells. Satellite cells deficiency accompanying some degenerative diseases is the reason for the search for the "replacement cells" that can be used in the muscle therapies. Due to their unique properties embryonic stem cells (ESCs), as well as myogenic cells derived from them, are considered as a promising source of therapeutic cells. Among the factors crucial for the specification of myogenic precursor cells is Pax7 that sustains proper function of satellite cells...
December 15, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27984116/microrna-and-gene-co-expression-networks-characterize-biological-and-clinical-behavior-of-rhabdomyosarcomas
#9
Edoardo Missiaglia, Chris J Shepherd, Ewa Aladowicz, David Olmos, Joanna Selfe, Gaëlle Pierron, Olivier Delattre, Zoe Walters, Janet Shipley
Rhabdomyosarcomas (RMS) in children and adolescents are heterogeneous sarcomas broadly defined by skeletal muscle features and the presence/absence of PAX3/7-FOXO1 fusion genes. MicroRNAs are small non-coding RNAs that regulate gene expression in a cell context specific manner. Sequencing analyses of microRNAs in 64 RMS revealed expression patterns separating skeletal muscle, fusion gene positive and negative RMS. Integration with parallel gene expression data assigned biological functions to 12 co-expression networks/modules that reassuringly included myogenic roles strongly correlated with microRNAs known in myogenesis and RMS development...
October 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27978878/-pax3-gene-mutation-analysis-for-two-waardenburg-syndrome-type-%C3%A2-families-and-their-prenatal-diagnosis
#10
Y Bai, N Liu, X D Kong, J Yan, Z B Qin, B Wang
Objective: To analyze the mutations of PAX3 gene in two Waardenburg syndrome type Ⅰ (WS1) pedigrees and make prenatal diagnosis for the high-risk 18-week-old fetus. Methods:PAX3 gene was first analyzed by Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) for detecting pathogenic mutation of the probands of the two pedigrees. The mutations were confirmed by MLPA and Sanger in parents and unrelated healthy individuals.Prenatal genetic diagnosis for the high-risk fetus was performed by amniotic fluid cell after genotyping...
December 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/27938609/-sox10-mutation-is-relevant-to-inner-ear-malformation-in-patients-with-waardenburg-syndrome
#11
G Y Xu, Q Q Hao, L L Zhong, W Ren, Y Yan, R Y Liu, J N Li, W W Guo, H Zhao, S M Yang
Objective: To determine the relevance between the SOX10 mutation and Waardenburg syndrome (WS) accompanied with inner ear abnormality by analyzing the inner ear imaging results and molecular and genetic results of the WS patients with the SOX10 mutation. Methods: This study included 36 WS in patients during 2001 and 2015 in the department of otorhinolaryngology head and neck surgery, Chinese Peoples's Liberation Army General Hospital. The condition of the inner ear of each patient was assessed by analyzing HRCT scans of the temporal bone and MRI scans of the brain and internal auditory canal...
November 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/27906583/isolation-of-bovine-skin-derived-precursor-cells-and-their-developmental-potential-after-nuclear-transfer
#12
Jiajia Xiao, Qiaoqiao Li, Pengxiang Qu, Zihan Zhang, Shaohui Pan, Yongsheng Wang, Yong Zhang
Nuclei from less differentiated stem cells yield high cloning efficiency. However, pluripotent stem cells are rather difficult to obtain from bovines. Skin-derived precursor (SKPs) cells exhibit a certain degree of pluripotency, which has been shown to enhance the efficiency of nuclear transfer (NT) in pigs. In this study, bovine SKPs were isolated and characterized. Results showed that bovine SKPs expressed nestin, fibronectin, vimentin, pluripotency-related genes, and characteristic neural crest markers, such as NGFR, PAX3, SOX9, SNAI2, and OCT4...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27906130/braf-activates-pax3-to-control-muscle-precursor-cell-migration-during-forelimb-muscle-development
#13
Jaeyoung Shin, Shuichi Watanabe, Soraya Hoelper, Marcus Krüger, Sawa Kostin, Jochen Pöling, Thomas Kubin, Thomas Braun
Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. We found that a fraction of BRAF accumulates in the nucleus after activation and endosomal transport to a perinuclear position. Mass spectrometry based screening for potential interaction partners revealed that BRAF interacts and phosphorylates PAX3...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27864937/pax3-overexpression-induces-cell-aggregation-and-perturbs-commissural-axon-projection-during-embryonic-spinal-cord-development
#14
Juntang Lin, Sulei Fu, Ciqing Yang, Christoph Redies
Pax3 is a transcription factor that belongs to the paired box family. In the developing spinal cord, it is expressed in the dorsal commissural neurons, which project ascending axons contralaterally to form proper spinal cord-brain circuitry. While it has been shown that Pax3 induces cell aggregation in vitro, little is known about the role of Pax3 in cell aggregation and spinal circuit formation in vivo. We have reported that Pax3 is involved in neuron differentiation and that its overexpression induces ectopic cadherin-7 expression...
November 16, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27864345/pax3-foxo1a-expression-in-rhabdomyosarcoma-is-driven-by-the-targetable-nuclear-receptor-nr4a1
#15
Alexandra Lacey, Aline Rodrigues Hoffman, Stephen Safe
Alveolar rhabdomyosarcoma (ARMS) is a devastating pediatric disease driven by expression of the oncogenic fusion gene PAX3-FOXO1A. In this study, we report overexpression of the nuclear receptor NR4A1 is rhabdomyosarcomas which is sufficient to drive high expression of PAX3-FOXO1A there. RNAi-mediated silencing of NR4A1 decreased expression of PAX3-FOXO1A and its downstream effector genes. Similarly, cell treatment with the NR4A1 small molecule antagonists 1,1-bis(3-indolyl)-1-(p-hydroxy or p-carbomethoxyphenyl)methane (C-DIM) decreased PAX3-FOXO1A...
November 18, 2016: Cancer Research
https://www.readbyqxmd.com/read/27859625/loss-of-microrna-489-3p-promotes-osteosarcoma-metastasis-by-activating-pax3-met-pathway
#16
Qifei Liu, Guochun Yang, Yuying Qian
(OS) remains one deadly disease for many affected patients. MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-489-3p in osteosarcoma (OS) metastasis. MiR-489-3p expression was downregulated in OS cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-489-3p significantly suppressed OS cell invasion and metastasis both in vitro and in vivo...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27834030/does-the-grass-snake-natrix-natrix-squamata-serpentes-natricinae-fit-the-amniotes-specific-model-of-myogenesis
#17
Damian Lewandowski, Magda Dubińska-Magiera, Ewelina Posyniak, Weronika Rupik, Małgorzata Daczewska
In the grass snake (Natrix natrix), the newly developed somites form vesicles that are located on both sides of the neural tube. The walls of the vesicles are composed of tightly connected epithelial cells surrounding the cavity (the somitocoel). Also, in the newly formed somites, the Pax3 protein can be observed in the somite wall cells. Subsequently, the somite splits into three compartments: the sclerotome, dermomyotome (with the dorsomedial [DM] and the ventrolateral [VL] lips) and the myotome. At this stage, the Pax3 protein is detected in both the DM and VL lips of the dermomyotome and in the mononucleated cells of the myotome, whereas the Pax7 protein is observed in the medial part of the dermomyotome and in some of the mononucleated cells of the myotome...
November 10, 2016: Protoplasma
https://www.readbyqxmd.com/read/27816457/inhibition-of-fgf-signaling-accelerates-neural-crest-cell-differentiation-of-human-pluripotent-stem-cells
#18
Thiranut Jaroonwitchawan, Pattamon Muangchan, Parinya Noisa
Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27806318/med12-mutations-in-breast-phyllodes-tumors-evidence-of-temporal-tumoral-heterogeneity-and-identification-of-associated-critical-signaling-pathways
#19
Marick Laé, Sophie Gardrat, Sophie Rondeau, Camille Richardot, Martial Caly, Walid Chemlali, Sophie Vacher, Jérôme Couturier, Odette Mariani, Philippe Terrier, Ivan Bièche
Exome sequencing has recently identified highly recurrent MED12 somatic mutations in fibroadenomas (FAs) and phyllodes tumors (PTs). In the present study, based on a large series, we confirmed the presence of MED12 exon 1 and 2 mutations in 49% (41/83) of PTs, 70% (7/10) of FAs and 9.1% (1/11) of fibromatoses. We show that MED12 mutations are associated with benign behavior of phyllodes tumors, as they are detected less frequently in malignant PTs (27.6%) compared to benign (58.3%) and borderline (63.3%) PTs, respectively (p = 0...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27799565/fusion-transcriptome-profiling-provides-insights-into-alveolar-rhabdomyosarcoma
#20
Zhongqiu Xie, Mihaela Babiceanu, Shailesh Kumar, Yuemeng Jia, Fujun Qin, Frederic G Barr, Hui Li
Gene fusions and fusion products were thought to be unique features of neoplasia. However, more and more studies have identified fusion RNAs in normal physiology. Through RNA sequencing of 27 human noncancer tissues, a large number of fusion RNAs were found. By analyzing fusion transcriptome, we observed close clusterings between samples of same or similar tissues, supporting the feasibility of using fusion RNA profiling to reveal connections between biological samples. To put the concept into use, we selected alveolar rhabdomyosarcoma (ARMS), a myogenic pediatric cancer whose exact cell of origin is not clear...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
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