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https://www.readbyqxmd.com/read/29769567/genomic-alterations-of-ground-glass-nodular-lung-adenocarcinoma
#1
Hyun Lee, Je-Gun Joung, Hyun-Tae Shin, Duk-Hwan Kim, Yujin Kim, Hojoong Kim, O Jung Kwon, Young Mog Shim, Ho Yun Lee, Kyung Soo Lee, Yoon-La Choi, Woong-Yang Park, D Neil Hayes, Sang-Won Um
In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29767458/overlapping-but-distinct-roles-for-notch-receptors-in-human-cardiovascular-disease
#2
REVIEW
J A N Meester, A Verstraeten, M Alaerts, D Schepers, L Van Laer, B L Loeys
The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. NOTCH1 mutations have been described in bicuspid aortic valve disease, left-sided congenital heart disease, and Adams-Oliver syndrome...
May 16, 2018: Clinical Genetics
https://www.readbyqxmd.com/read/29740045/exosome-markers-associated-with-immune-activation-and-oxidative-stress-in-hiv-patients-on-antiretroviral-therapy
#3
Sukrutha Chettimada, David R Lorenz, Vikas Misra, Simon T Dillon, R Keith Reeves, Cordelia Manickam, Susan Morgello, Gregory D Kirk, Shruti H Mehta, Dana Gabuzda
Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29702197/mutations-in-the-estrogen-receptor-alpha-hormone-binding-domain-promote-stem-cell-phenotype-through-notch-activation-in-breast-cancer-cell-lines
#4
L Gelsomino, S Panza, C Giordano, I Barone, G Gu, E Spina, S Catalano, S Fuqua, S Andò
The detection of recurrent mutations affecting the hormone binding domain (HBD) of estrogen receptor alpha (ERα/ESR1) in endocrine therapy-resistant and metastatic breast cancers has prompted interest in functional characterization of these genetic alterations. Here, we explored the role of HBD-ESR1 mutations in influencing the behaviour of breast cancer stem cells (BCSCs), using various BC cell lines stably expressing wild-type or mutant (Y537 N, Y537S, D538G) ERα. Compared to WT-ERα clones, mutant cells showed increased CD44+ /CD24- ratio, mRNA levels of stemness genes, Mammosphere Forming Efficiency (MFE), Self-Renewal and migratory capabilities...
April 24, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29693251/notch4-regulates-colorectal-cancer-proliferation-invasiveness-and-determines-clinical-outcome-of-patients
#5
Zixi Zhang, Xin Bu, Jingyi Yang, Shaojun Zhu, Shuixiang He, Jianyong Zheng, Weizhong Wang, Dake Chu
Notch signal has complex roles in human malignancies, which might be attributed to the diversity of Notch receptors. Here, we set out to identify the association of NOTCH4 with colorectal cancer (CRC). In the hospital-based study cohort, we investigated NOTCH4 mRNA levels in primary CRC, as well as its association with clinicopathologic characteristics. Besides, NOTCH4 cDNA and siRNA was transfected into colorectal cancer cell line to elucidate its impact on tumor cell proliferation and migration. Results revealed a statistically significant lower expression of NOTCH4 mRNA in tumor specimens compared with that in control...
April 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29627423/a-jagged1-notch4-molecular-switch-mediates-airway-inflammation-by-ultrafine-particles
#6
Mingcan Xia, Hani Harb, Arian Saffari, Constantinos Sioutas, Talal A Chatila
BACKGROUND: Exposure to traffic-related particulate matter (PM) promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which PM exposure acts to mediate these effects remain unclear. OBJECTIVE: We sought to elucidate the cellular targets and signaling pathways critical for the augmentation of allergic airway inflammation induced by ambient ultra fine particles (UFP). METHODS: We employed in vitro cell culture assays using lung-derived antigen presenting cells and allergen-specific T cells, and in vivo mouse models of allergic airway inflammation that employed myeloid lineage-specific gene deletions, cellular reconstitution approaches and antibody inhibition studies...
April 5, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29590145/genomic-profiling-of-bovine-corpus-luteum-maturation
#7
Sigal Kfir, Raghavendra Basavaraja, Noa Wigoda, Shifra Ben-Dor, Irit Orr, Rina Meidan
To unveil novel global changes associated with corpus luteum (CL) maturation, we analyzed transcriptome data for the bovine CL on days 4 and 11, representing the developing vs. mature gland. Our analyses revealed 681 differentially expressed genes (363 and 318 on day 4 and 11, respectively), with ≥2 fold change and FDR of <5%. Different gene ontology (GO) categories were represented prominently in transcriptome data at these stages (e.g. days 4: cell cycle, chromosome, DNA metabolic process and replication and on day 11: immune response; lipid metabolic process and complement activation)...
2018: PloS One
https://www.readbyqxmd.com/read/29577422/notch4-is-a-possible-novel-susceptibility-gene-for-dilated-cardiomyopathy-in-the-chinese-population-a-case-control-study
#8
Xiaoqing Shi, Yang Zhang, Bingjie Li, Mengle Peng, Yingying Yuan, Ximing Wang, Xinqiang Li, Dongze Yu, Yongzhe Li, Dongchun Qin
BACKGROUND: The incidence of dilated cardiomyopathy (DCM) has increased in recent years, and many studies have sought to further improve the general understanding of this condition. Previous studies have demonstrated that some single nucleotide polymorphisms (SNPs) associated with systemic lupus erythematosus also affect susceptibility to DCM, suggesting that immune-related diseases may share similar genetic susceptibility. Recent large-scale and genome-wide association studies have identified NCR3, NOTCH4, CYP1A2, ITGA1, OPRM1, ST8SIA2, and LINC00704 as genetic risk factors associated with cardiac manifestations of neonatal lupus...
March 26, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29333477/notch-ligand-binding-assay-using-flow-cytometry
#9
Shweta Varshney, Pamela Stanley
Notch signaling is an evolutionary conserved signaling pathway that plays an indispensable role during development, and in the maintenance of homeostatic processes, in a wide variety of tissues (Kopan, 2012; Hori et al., 2013). The multifaceted roles of Notch signaling are stringently regulated at different levels. One of the most important aspects of regulation is the binding of different Notch ligands to each Notch receptor (NOTCH1-NOTCH4). Canonical ligands Delta or Serrate (in Drosophila ), and Delta-like (DLL1 and DLL4) or Jagged (JAG1 and JAG2) (in mammals), are transmembrane glycoproteins...
December 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29228365/notch4-negatively-regulates-the-inflammatory-response-to-mycobacterium-tuberculosis-infection-by-inhibiting-tak1-activation
#10
Ruijuan Zheng, Haipeng Liu, Yilong Zhou, Dapeng Yan, Jianxia Chen, Dapeng Ma, Yonghong Feng, Lianhua Qin, Feng Liu, Xiaochen Huang, Jie Wang, Baoxue Ge
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection remains a global threat to human health, but knowledge of the molecular mechanisms underlying the pathogenesis of TB is still limited. Although Notch4, a member of the Notch receptor family, is involved in the initiation of mammary tumors, its function in Mtb infection remains unclear. In this study, we found that Notch4-deficient mice were more resistant to Mtb infection with a much lower bacterial burden and less pathological changes in the lungs...
December 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29162408/downregulation-of-notch4-a-prognostic-marker-in-distinguishing-oral-verrucous-carcinoma-from-oral-squamous-cell-carcinoma
#11
M K Harishankar, A Mathan Mohan, A Vinod Krishnan, Arikketh Devi
INTRODUCTION: Oral verrucous carcinoma is a special form of well-differentiated squamous cell carcinoma which possesses specific clinical, morphologic and cytokinetic features that differ from other types of oral cancers and hence diagnosis requires immense experience in histopathology. Hence it is certainly important to distinguish such a lesion from other oral tumors as treatment strategies vary widely between them. OBJECTIVE: In search of a critical diagnostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma, Notch4 receptor, one of the key regulatory molecules of the Notch signaling family has been aberrantly activated in the progression of several types of tumors...
October 31, 2017: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/29146722/the-notch4-hey1-pathway-induces-epithelial-mesenchymal-transition-in-head-and-neck-squamous-cell-carcinoma
#12
Takahito Fukusumi, Theresa W Guo, Akihiro Sakai, Mizuo Ando, Shuling Ren, Sunny Haft, Chao Liu, Panomwat Amornphimoltham, J Silvio Gutkind, Joseph A Califano
Purpose: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood. Experimental Design: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4 , we performed in vitro proliferation, cisplatin viability, apoptosis, and cell-cycle assays...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29142904/kras-g12d-upregulates-notch-signaling-to-induce-gallbladder-tumorigenesis-in-mice
#13
Wen-Cheng Chung, Junqing Wang, Yunyun Zhou, Keli Xu
Background: Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context. Methods: We determined Cre recombination activity of Pdx1-Cre in the gallbladder using a reporter strain and examined gallbladder tumor development in the KrasLSL- G12D/+ ;Pdx1-Cre mice...
September 2017: Oncoscience
https://www.readbyqxmd.com/read/29101237/human-notch4-is-a-key-target-of-runx1-in-megakaryocytic-differentiation
#14
Yueying Li, Chen Jin, Hao Bai, Yongxing Gao, Shu Sun, Lei Chen, Lei Qin, Paul P Liu, Linzhao Cheng, Qian-Fei Wang
Megakaryocytes (MKs) in adult marrow produce platelets that play important roles in blood coagulation and hemostasis. Monoallelic mutations of the master transcription factor gene RUNX1 lead to familial platelet disorder (FPD) characterized by defective MK and platelet development. However, the molecular mechanisms of FPD remain unclear. Previously, we generated human induced pluripotent stem cells (iPSCs) from patients with FPD containing a RUNX1 nonsense mutation. Production of MKs from the FPD-iPSCs was reduced, and targeted correction of the RUNX1 mutation restored MK production...
January 11, 2018: Blood
https://www.readbyqxmd.com/read/29069725/notch4-and-mhc-class-ii-polymorphisms-are-associated-with-hcv-related-benign-and-malignant-lymphoproliferative-diseases
#15
Laura Gragnani, Elisa Fognani, Valli De Re, Massimo Libra, Adriana Garozzo, Patrizio Caini, Guia Cerretelli, Andrea Giovannelli, Serena Lorini, Monica Monti, Silvia Bagnoli, Irene Piaceri, Anna Linda Zignego
Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign, lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma (NHL). Significant associations were found between two single nucleotide polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776 in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection without lymphoproliferative disorders. We found a positive relationship between NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 14...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29058285/notch4-inhibition-suppresses-invasion-and-vasculogenic-mimicry-formation-of-hepatocellular-carcinoma-cells
#16
Rui Cheng, Xin-Ran Cai, Kun Ke, Yan-Ling Chen
Vasculogenic mimicry (VM) is a process by which aggressive tumor cells generate non-endothelial cell-lined channels in malignant tumors including hepatocellular carcinoma (HCC). It has provided new insights into tumor behavior and has surfaced as a potential target for drug therapy. The molecular events underlying the process of VM formation are still poorly understood. In this study, we attempted to elucidate the relationship between Notch4 and VM formation in HCC. An effective siRNA lentiviral vector targeting Notch4 was constructed and transfected into Bel7402, a HCC cell line...
October 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/29054964/gene-expression-profiling-of-the-notch-ahr-il22-axis-at-homeostasis-and-in-response-to-tissue-injury
#17
Marc Weidenbusch, Severin Rodler, Shangqing Song, Simone Romoli, Julian A Marschner, Franziska Kraft, Alexander Holderied, Santosh Kumar, Shrikant R Mulay, Mohsen Honarpisheh, Satish Kumar Devarapu, Maciej Lech, Hans-Joachim Anders
Notch and interleukin-22 (IL-22) signaling are known to regulate tissue homeostasis and respond to injury in humans and mice, and the induction of endogenous aryl hydrocarbon receptor (Ahr) ligands through Notch links the two pathways in a hierarchical fashion. However in adults, the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TNF-α ADAM metalloprotease converting enzyme (TACE), PSEN1, basigin (BSG)/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL-22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in ten mature murine and human organs...
December 22, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29052507/metabolic-shift-in-density-dependent-stem-cell-differentiation
#18
Simar J Singh, William Turner, Drew E Glaser, Kara E McCloskey, Fabian V Filipp
BACKGROUND: Vascular progenitor cells (VPCs) derived from embryonic stem cells (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies. During the optimization of endothelial cell (EC) inductions from mouse ESCs using our staged and chemically-defined induction methods, we found that cell seeding density but not VEGF treatment between 10 ng/mL and 40 ng/mL was a significant variable directing ESCs into FLK1+ VPCs during stage 1 induction. Here, we examine potential contributions from cell-to-cell signaling or cellular metabolism in the production of VPCs from ESCs seeded at different cell densities...
October 20, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29042932/cardioprotective-effect-of-notch-signaling-on-the-development-of-myocardial-infarction-complicated-by-diabetes-mellitus
#19
Fang Wu, Bo Yu, Xu Zhang, Yuelan Zhang
The present study aimed to elucidate the role of Notch signaling in the development of myocardial infarction (MI) concomitant with diabetes in vivo and in vitro and evaluated the therapeutic effect of the Notch signaling in vitro . Streptozotocin-induced diabetic rats were subjected to 25 min of ischemia and 2 h of reperfusion. Cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) isoenzyme levels were detected. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining. Myocardial apoptosis and fibrosis were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Masson Trichrome staining, respectively...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29036275/porcupine-dependent-wnt-activity-within-the-uterine-epithelium-is-essential-for-fertility
#20
Omar Farah, Steffen Biechele, Janet Rossant, Daniel Dufort
The secretion of mammalian Wnt ligands within the cell is dependent on the activity of Porcupine, a gene located on the X-chromosome that encodes for a membrane-bound O-acyl transferase. Here, we report that postnatal ablation of Porcupine in the uterine luminal epithelium alone results in the decrease in endometrial gland number. Despite having uterine glands, mutant females are completely infertile. Epithelial ablation of Porcupine causes defects in timely apposition of the lumen, along with failure to respond to artificial decidual induction...
November 1, 2017: Biology of Reproduction
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