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https://www.readbyqxmd.com/read/29332214/targeted-next-generation-sequencing-in-patients-with-non-syndromic-congenital-heart-disease
#1
Silvia Pulignani, Cecilia Vecoli, Andrea Borghini, Ilenia Foffa, Lamia Ait-Alì, Maria Grazia Andreassi
Congenital heart disease (CHD) is a genetically heterogeneous disease. Targeted next-generation sequencing (NGS) offers a unique opportunity to sequence multiple genes at lower cost and effort compared to Sanger sequencing. We tested a targeted NGS of a specific gene panel in a relatively large population of non-syndromic CHD patients. The patient cohort comprised 68 CHD patients (45 males; 8.3 ± 1.7 years). Amplicon libraries for 16 CHD-strictly related genes were generated using a TruSeq® Custom Amplicon kit (Illumina, CA) and sequenced using the Illumina MiSeq platform...
January 13, 2018: Pediatric Cardiology
https://www.readbyqxmd.com/read/29331751/comprehensive-genomic-profiling-of-head-and-neck-squamous-cell-carcinoma-reveals-fgfr1-amplifications-and-tumour-genomic-alterations-burden-as-prognostic-biomarkers-of-survival
#2
C Dubot, V Bernard, M P Sablin, S Vacher, W Chemlali, A Schnitzler, G Pierron, K Ait Rais, N Bessoltane, E Jeannot, J Klijanienko, O Mariani, T Jouffroy, V Calugaru, C Hoffmann, M Lesnik, N Badois, F Berger, C Le Tourneau, M Kamal, I Bieche
BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29331299/the-regulatory-roles-of-notch-in-osteocyte-differentiation-via-the-crosstalk-with-canonical-wnt-pathways-during-the-transition-of-osteoblasts-to-osteocytes
#3
Jin Shao, Yinghong Zhou, Yin Xiao
Osteocytes comprise more than 90% of the cells in bone and are differentiated from osteoblasts via an unknown mechanism. Recently, it was shown that Notch signaling plays an important role in osteocyte functions. To gain insights into the mechanisms underlying the functions of Notch in regulating the transition of osteoblasts to osteocytes, we performed a luciferase assay by cloning the proximal E11 and dentin matrix acidic phosphoprotein 1 (DMP1) promotor regions into pGluc-Basic 2 vectors, which were subsequently transfected into the IDG-SW3 (osteocytes), MC3T3 (osteoblasts) and 293T (non-osteoblastic cells) cell lines...
January 10, 2018: Bone
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#4
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29328395/bioinformatic-identification-of-chemoresistance-associated-micrornas-in-breast-cancer-based-on-microarray-data
#5
Ya-Wen Wang, Weiguo Zhang, Rong Ma
Breast cancer is the most commonly diagnosed cancer among females, and chemoresistance constitutes a major clinical obstacle to the treatment of this disease. MicroRNAs (miRNAs) are related to human cancer development, progression and drug resistance. To identify breast cancer chemoresistance-associated miRNAs, miRNA microarray dataset GSE71142, including five chemoresistant breast cancer tissues and five chemosensitive tissues, was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs) were obtained by t-test and the potential target genes were predicted by miRWalk2...
January 10, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327707/appendiceal-goblet-cell-carcinoids-and-adenocarcinomas-ex-goblet-cell-carcinoid-are-genetically-distinct-from-primary-colorectal-type-adenocarcinoma-of-the-appendix
#6
Moritz Jesinghaus, Björn Konukiewitz, Sebastian Foersch, Albrecht Stenzinger, Katja Steiger, Alexander Muckenhuber, Claudia Groß, Martin Mollenhauer, Wilfried Roth, Sönke Detlefsen, Wilko Weichert, Günter Klöppel, Nicole Pfarr, Anna Melissa Schlitter
The appendix gives rise to goblet cell carcinoids, which represent special carcinomas with distinct biological and histological features. Their genetic background and molecular relationship to colorectal adenocarcinoma is largely unknown. We therefore performed a next-generation sequencing analysis of 25 appendiceal carcinomas including 11 goblet cell carcinoids, 7 adenocarcinomas ex-goblet cell carcinoid, and 7 primary colorectal-type adenocarcinomas, using a modified Colorectal Cancer specific Panel comprising 32 genes linked to colorectal and neuroendocrine tumorigenesis...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29321718/a-novel-notch1-missense-mutation-c1133y-in-the-abruptex-domain-exhibits-enhanced-proliferation-and-invasion-in-oral-squamous-cell-carcinoma
#7
Yang Zheng, Zhao Wang, Xu Ding, Wei Zhang, Gang Li, Laikui Liu, Heming Wu, Wenyi Gu, Yunong Wu, Xiaomeng Song
Background: Notch1 has been regarded as a fundamental regulator in tissue differentiation and stem cell properties. Recently, Notch1 mutations have been reported intensively both in solid tumors and in hematopoietic malignancies. However, little is known about the biological effect and the clinical implication of these reported mutations. Previously, we discovered several missense mutations in the Notch1 receptor in a Chinese population with oral squamous cell carcinoma (OSCC). Methods: We selected a 'hotspot' mutation in the Abruptex domain (C1133Y)...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29321650/rna-seq-analysis-and-comparison-of-corneal-epithelium-in-keratoconus-and-myopia-patients
#8
Jingjing You, Susan M Corley, Li Wen, Chris Hodge, Roland Höllhumer, Michele C Madigan, Marc R Wilkins, Gerard Sutton
Keratoconus is a common degenerative corneal disease that can lead to significant visual morbidity, and both genetic and environmental factors have been implicated in its pathogenesis. We compared the transcriptome of keratoconus and control epithelium using RNA-Seq. Epithelial tissues were obtained prior to surgery from keratoconus and myopia control patients, undergoing collagen cross-linking and photorefractive keratectomy, respectively. We identified major differences in keratoconus linked to cell-cell communication, cell signalling and cellular metabolism...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321062/notch-signaling-triggered-via-the-ligand-dll4-impedes-m2-macrophage-differentiation-and-promotes-their-apoptosis
#9
Sylvain Pagie, Nathalie Gérard, Béatrice Charreau
BACKGROUND: Notch signaling controls many cellular processes, including cell fate determination, cell differentiation, proliferation and apoptosis. In mammals, four Notch receptors (Notch 1-4) can interact with five distinct ligands [Jagged1, Jagged2, Delta-like 1 (DLL1), DLL3, and DLL4]. We previously reported that Notch activation is modulated in endothelial cells and monocytes during inflammation and showed that inflammation upregulates DLL4 on endothelial cells. DLL4 promotes differentiation of blood monocytes into proinflammatory M1 macrophages...
January 10, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29313423/rho-guanosine-nucleotide-exchange-factors-are-not-such-bad-guys-after-all-in-cancera
#10
Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo
Rho GDP/GTP exchange factors (GEFs), the enzymes that trigger the stimulation of Rho GTPases during cell signaling, are widely deemed as potential therapeutic targets owing to their protumorigenic functions. However, the sparse use of animal models has precluded a full understanding of their pathophysiological roles at the organismal level. In a recent article in Cancer Cell, we have reported that the Vav1 GEF unexpectedly acts as a tumor suppressor by mediating the noncatalytic nucleation of cytoplasmic complexes between the E3 ubiquitin ligase Cbl-b and the active Notch1 intracellular domain (ICN1)...
January 9, 2018: Small GTPases
https://www.readbyqxmd.com/read/29312733/longitudinal-study-of-esophageal-mucosal-damage-after-esophagectomy-and-gastric-interposition-relationship-between-reflux-related-mucosal-injury-and-notch-signaling
#11
Yong Yuan, Tie-Jun Tong, Xiao-Xi Zeng, Yu-Shang Yang, Zhi-Qiang Wang, Yun-Cang Wang, Jun-He Gou, Long-Qi Chen
Background: Esophagectomy with gastric interposition could serve as a good human reflux model to study the molecular pathogenesis of esophageal mucosal damage induced by gastroesophageal reflux. This study was to investigate the role of Notch signaling in reflux injury of esophageal mucosa. Methods: Patients undergoing Ivor-Lewis esophagectomy for early stage esophageal squamous cell carcinoma were included. Follow-ups were scheduled at 6, 18, 36 and 48 months postoperatively, including reflux symptom assessment, endoscopic and histological evaluation of esophageal mucosal damage...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29311361/multiple-levels-of-control-determine-how-e4bp4-nfil3-regulates-nk-cell-development
#12
Tomasz Kostrzewski, Aaron J Borg, Yiran Meng, Iva Filipovic, Victoria Male, Andreas Wack, Peter A DiMaggio, Hugh J M Brady
The transcription factor E4bp4/Nfil3 has been shown to have a critical role in the development of all innate lymphoid cell types including NK cells. In this study, we show that posttranslational modifications of E4bp4 by either SUMOylation or phosphorylation have profound effects on both E4bp4 function and NK cell development. We examined the activity of E4bp4 mutants lacking posttranslational modifications and found that Notch1 was a novel E4bp4 target gene. We observed that abrogation of Notch signaling impeded NK cell production and the total lack of NK cell development from E4bp4-/- progenitors was completely rescued by short exposure to Notch peptide ligands...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29307821/lncrna-gas5-regulates-ischemic-stroke-as-a-competing-endogenous-rna-for-mir-137-to-regulate-the-notch1-signaling-pathway
#13
Fenghui Chen, Lixin Zhang, Erwei Wang, Chaofeng Zhang, Xiaoting Li
Ischemic stroke is related to a variety of physiological and pathological processes including autophagy and apoptosis. Growth arrest-specific 5 (GAS5), a long non-coding RNA (lncRNA), is known to negatively regulate cell survival and plays a key role in the pathogenesis of numerous diseases. However, the function and molecular mechanism of lncRNA GAS5 in ischemic stroke have not been reported. Real-time PCR was used to detect GAS5 and microRNA-137 (miR-137) expression in the brain tissues of mice underwent middle cerebral artery occlusion (MCAO) surgery and oxygen-glucose deprivation (OGD)-treated mouse primary brain neurons...
January 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29307746/orai1-is-critical-for-notch-driven-aggressiveness-under-hypoxic-conditions-in-triple-negative-breast-cancers
#14
Xiaoyu Liu, Teng Wang, Yan Wang, Zhen Chen, Dong Hua, Xiaoqiang Yao, Xin Ma, Peng Zhang
It is believed that hypoxia stimulates triple-negative breast cancers (TNBCs) metastasis, which is associated with a poor prognosis. However, the underlying mechanism remains unclear. Here, we demonstrated that hypoxia up-regulates both the levels of Orai1 and Notch1, and the increase in Orai1 is mediated by Notch1 signaling in TNBCs. Functionally, Orai1 caused a sustained elevation of intracellular Ca2+ via Store-operated Ca2+ entry (SOCE), then activated the calcineurin-nuclear factor of activated T-cell 4 (NFAT4, also named NFATc3) in hypoxic TNBCs...
January 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29305585/sumoylation-of-notch1-represses-its-target-gene-expression-during-cell-stress
#15
Christian J M Antila, Vilma Rraklli, Henri A Blomster, Käthe M Dahlström, Tiina A Salminen, Johan Holmberg, Lea Sistonen, Cecilia Sahlgren
The Notch signaling pathway is a key regulator of stem cells during development, and its deregulated activity is linked to developmental defects and cancer. Transcriptional activation of Notch target genes requires cleavage of the Notch receptor in response to ligand binding, production of the Notch intracellular domain (NICD1), NICD1 migration into the nucleus, and assembly of a transcriptional complex. Post-translational modifications of Notch regulate its trafficking, turnover, and transcriptional activity...
January 5, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29301578/notch1-signaling-in-melanoma-cells-promoted-tumor-induced-immunosuppression-via-upregulation-of-tgf-%C3%AE-1
#16
Zike Yang, Yanxia Qi, Nan Lai, Jiahe Zhang, Zehong Chen, Mingyu Liu, Wan Zhang, Rongcheng Luo, Shijun Kang
BACKGROUND: The receptors of Notch family play an important role in controlling the development, differentiation, and function of multiple cell types. The aim of this study is to investigate the role of Notch1 signaling upon immune suppression induced by melanoma cells. METHODS: Melanoma cell line B16 cells were transfected by lentivirus containing mouse Notch1 gene or Notch1 shRNA to generate B16 cell line that highly or lowly expressed Notch1. Notch1 in anti-tumor immune response was comprehensively appraised in murine B16 melanoma tumor model in immunocompetent and immunodeficient mice...
January 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29299142/microrna-34a-promotes-mitochondrial-dysfunction-induced-apoptosis-in-human-lens-epithelial-cells-by-targeting-notch2
#17
Fan Fan, Jianhui Zhuang, Peng Zhou, Xin Liu, Yi Luo
Purpose: Human lens epithelial cell (HLEC) apoptosis is a common pathogenic mechanism in age-related cataracts (ARC). While the function of microRNAs (miRNAs) in the eye is beginning to be explored using miRNA expression array, the role of miR-34a in regulating HLEC apoptosis remains unknown and requires further investigation. Methods: Quantitative reverse-transcript polymerase chain reaction (RT-PCR) was used to determine the expression level of miR-34a in cataractous and control samples...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295997/diabetes-impairs-wound-healing-by-dnmt1-dependent-dysregulation-of-hematopoietic-stem-cells-differentiation-towards-macrophages
#18
Jinglian Yan, Guodong Tie, Shouying Wang, Amanda Tutto, Natale DeMarco, Lyne Khair, Thomas G Fazzio, Louis M Messina
People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29290947/mir-34a-expression-in-human-breast-cancer-is-associated-with-drug-resistance
#19
Zhi-Hua Li, Xueling Weng, Qiu-Yun Xiong, Jian-Hong Tu, An Xiao, Wei Qiu, Yu Gong, Er-Wei Hu, Songyin Huang, Ya-Li Cao
miR-34a is significantly down-regulated in breast cancer tissues and cell lines, which may be correlated with breast cancer multi-drug resistance (MDR). Here, we conducted cell-based experiments and clinical studies in a cohort of 113 breast cancer samples to analyze miR-34a expression and breast cancer MDR. Expression of miR-34a is down-regulated in the multi-drug resistant MDR-MCF-7 cells compared with its parental cells. Patients with miR-34a low expression had poorer overall survival (OS) and disease free survival (DFS) in comparison with those with high expression...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286081/aryl-hydrocarbon-receptor-activation-maintained-the-intestinal-epithelial-barrier-function-through-notch1-dependent-signaling-pathway
#20
Zhongze Liu, Liangzi Li, Weigang Chen, Qimeng Wang, Weidong Xiao, Yuanhang Ma, Baifa Sheng, Xiang Li, Lihua Sun, Min Yu, Hua Yang
Intestinal ischemia/reperfusion (I/R) induces disruption of the intestinal barrier function. Aryl hydrocarbon receptor (AhR) has a vital role in maintaining the intestinal barrier function. However, the precise mechanism by which AhR maintains intestinal barrier function remains unclear. Notch1 signaling is downstream of AhR, and has also been reported to have a role in the development of tight junctions (TJs) and maintenance of intestinal homeostasis. Therefore, we hypothesized that AhR activation may attenuate the intestinal barrier dysfunction through increased activation of Notch1 signaling...
December 22, 2017: International Journal of Molecular Medicine
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