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https://www.readbyqxmd.com/read/27922122/identification-of-critical-paralog-groups-with-indispensable-roles-in-the-regulation-of-signaling-flow
#1
Dezso Modos, Johanne Brooks, David Fazekas, Eszter Ari, Tibor Vellai, Peter Csermely, Tamas Korcsmaros, Katalin Lenti
Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#2
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27916718/loss-of-the-opa-interacting-protein-5-inhibits-breast-cancer-proliferation-through-mir-139-5p-notch1-pathway
#3
Hong-Chang Li, Ya-Feng Chen, Wen Feng, Han Cai, Yi Mei, Yi-Ming Jiang, Teng Chen, Ke Xu, Dian-Xu Feng
Opa interacting protein 5 (OIP5) has been reported to be over-expressed in several kinds of human cancer. However, the biological function and clinical significance of OIP5 in human breast cancer remains unknown. In this study, we found that OIP5 was notably over-expressed in breast cancer tissues compared with their corresponding nontumorous tissues. Statistical analysis showed a significant correlation of OIP5 expression with advanced clinical stage. Ablation OIP5 inhibited the proliferation of breast cancer cells...
December 1, 2016: Gene
https://www.readbyqxmd.com/read/27915972/resistance-to-cell-death-and-its-modulation-in-cancer-stem-cells
#4
Ahmad R Safa
Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#5
Tushar D Bhagat, Yiyu Zou, Shizeng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Wejuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, Maria C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq dataset also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27904680/enhancement-of-early-cardiac-differentiation-of-dedifferentiated-fat-cells-by-dimethyloxalylglycine-via-notch-signaling-pathway
#6
Fuhai Li, Zongzhuang Li, Zhi Jiang, Ye Tian, Zhi Wang, Wei Yi, Chenyun Zhang
Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27901496/cancer-initiating-cells-are-enriched-in-the-ca9-positive-fraction-of-primary-cervix-cancer-xenografts
#7
Delphine Tamara Marie-Egyptienne, Naz Chaudary, Tuula Kalliomäki, David William Hedley, Richard Peter Hill
Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901093/macrophage-dependent-tumor-cell-transendothelial-migration-is-mediated-by-notch1-mena-inv-initiated-invadopodium-formation
#8
Jeanine Pignatelli, Jose Javier Bravo-Cordero, Minna Roh-Johnson, Saumil J Gandhi, Yarong Wang, Xiaoming Chen, Robert J Eddy, Alice Xue, Robert H Singer, Louis Hodgson, Maja H Oktay, John S Condeelis
The process of intravasation involving transendothelial migration is a key step in metastatic spread. How the triple cell complex composed of a macrophage, Mena over-expressing tumor cell and endothelial cell, called the tumor microenvironment of metastasis (TMEM), facilitates tumor cell transendothelial migration is not completely understood. Previous work has shown that the physical contact between a macrophage and tumor cell results in the formation of invadopodia, actin-rich matrix degrading protrusions, important for tumor cell invasion and transendothelial migration and tumor cell dissemination...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901069/molecular-profiling-of-circulating-tumour-cells-identifies-notch1-as-a-principal-regulator-in-advanced-non-small-cell-lung-cancer
#9
Javier Mariscal, Marta Alonso-Nocelo, Laura Muinelo-Romay, Jorge Barbazan, Maria Vieito, Alicia Abalo, Antonio Gomez-Tato, Casares de Cal Maria de Los Angeles, Tomas Garcia-Caballero, Carmela Rodriguez, Elena Brozos, Francisco Baron, Rafael Lopez-Lopez, Miguel Abal
Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900092/primary-orbital-precursor-t-cell-lymphoblastic-lymphoma-report-of-a-unique-case
#10
Lisa Stenman, Marta Persson, Fredrik Enlund, Erik Clasen-Linde, Göran Stenman, Steffen Heegaard
Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical examination revealed left-sided exophthalmus, periorbital edema, chemosis, and reduced motility of the left eye. A magnetic resonance imaging scan revealed thickening of the left orbital muscles and a positron emission tomography-computed tomography scan also demonstrated activity in a subclavicular lymph node...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27894350/gant61-a-gli-inhibitor-sensitizes-glioma-cells-to-the-temozolomide-treatment
#11
Jianlong Li, Jinquan Cai, Shihong Zhao, Kun Yao, Ying Sun, Yongli Li, Lingchao Chen, Ruiyan Li, Xiuwei Zhai, Junhe Zhang, Chuanlu Jiang
BACKGROUND: The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms. METHODS: The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively...
November 28, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27890934/egr2-mutations-define-a-new-clinically-aggressive-subgroup-of-chronic-lymphocytic-leukemia
#12
E Young, D Noerenberg, L Mansouri, V Ljungström, M Frick, L-A Sutton, S J Blakemore, J Galan-Sousa, K Plevova, P Baliakas, D Rossi, R Clifford, D Roos-Weil, V Navrkalova, B Dörken, C A Schmitt, K E Smedby, G Juliusson, B Giacopelli, J S Blachly, C Belessi, P Panagiotidis, N Chiorazzi, F Davi, A W Langerak, D Oscier, A Schuh, G Gaidano, P Ghia, W Xu, L Fan, O A Bernard, F Nguyen-Khac, L Rassenti, J Li, T J Kipps, K Stamatopoulos, S Pospisilova, T Zenz, C C Oakes, J C Strefford, R Rosenquist, F Damm
Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888718/characterization-of-peritoneal-leukemia-associated-macrophages-in-notch1-induced-mouse-t-cell-acute-lymphoblastic-leukemia
#13
Shayan Chen, Xiao Yang, Wenli Feng, Feifei Yang, Rong Wang, Chong Chen, Lina Wang, Yongmin Lin, Qian Ren, Guoguang Zheng
Macrophages, which have remarkable plasticity, are indispensable cellular components and play essential roles in both innate and adaptive immune responses. Peritoneal macrophages show unique gene expression profile and peritoneal cavity is also involved in leukemia. However, the characteristics of peritoneal leukemia-associated macrophages (Per LAMs) have not been established. Here we studied the phenotype of Per LAMs, their subpopulations in Notch1-induced acute lymphoblastic leukemia mice and compared with LAMs from BM or spleen in the same model...
November 23, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27888063/notch1-signalling-inhibits-apoptosis-of-human-dental-follicle-stem-cells-via-both-the-cytoplasmic-mitochondrial-pathway-and-nuclear-transcription-regulation
#14
Xuepeng Chen, Songying Li, Zhaobin Zeng, Zexu Gu, Yanfang Yu, Feifei Zheng, Yi Zhou, Huiming Wang
Dental follicle stem cells (DFSCs) have been considered as promising candidate cells for periodontal tissue regeneration. Understanding the signalling pathways underlying the apoptosis of DFSCs will facilitate its biomedical application. Here we showed that Notch1 signalling could inhibit DFSCs apoptosis because the constitutive overexpression of the intracellular domain of Notch1 (ICN1) promoted proliferation and suppressed apoptosis by inhibiting cytoplasmic mitochondrial membrane depolarization, cytochrome c release and activation of caspase-9 and caspase-3...
November 22, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27878968/proprotein-convertase-inhibition-promotes-ciliated-cell-differentiation-a-potential-mechanism-for-the-inhibition-of-notch1-signalling-by-decanoyl-rvkr-chloromethylketone
#15
Sang-Nam Lee, In-Suk Choi, Hyun Jun Kim, Eun Jin Yang, Hyun Jin Min, Joo-Heon Yoon
Chronic repetitive rounds of injury and repair in the airway lead to airway remodelling, including ciliated cell loss and mucous cell hyperplasia. Airway remodelling is mediated by many growth and differentiation factors including Notch1, which are proteolytically processed by proprotein convertases (PCs). The present study evaluated a novel approach for controlling basal cell-type determination based on the inhibition of PCs. It was found that decanoyl-RVKR-chloromethylketone (CMK), a PC inhibitor, promotes ciliated cell differentiation and has no effect on the ciliary beat frequency in air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs)...
November 22, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27878266/cantharidin-induces-g2-m-arrest-and-triggers-apoptosis-in-renal-cell-carcinoma
#16
Yu Ren, Shu-Wei Zhang, Zhen-Hua Xie, Xiao-Ming Xu, Liang-Liang Chen, Zhong-Guan Lou, Guo-Bin Weng, Xu-Ping Yao
The present study aimed to investigate the effects of cantharidin on cell cycle distribution, the induction of apoptosis, and Notch1 and Jagged1 expression in ACHN and Caki‑1 renal cancer cells. Cell viability assay, flow cytometry, cell cycle and western blot analyses were performed for ACHN and Caki‑1 cells. Immunohistochemistry was used to analyze the expression of Notch1 and Jagged1 in RCC tissues The results demonstrated that treatment with cantharidin exerted a dose‑ and time‑dependent effect on cell viability, apoptosis induction and G2/M phase cell cycle arrest...
November 23, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27875565/inhibition-of-notch-signaling-attenuates-schistosomiasis-hepatic-fibrosis-via-blocking-macrophage-m2-polarization
#17
Shaoping Zheng, Peige Zhang, Yixiong Chen, Shaojiang Zheng, Liping Zheng, Zhihong Weng
Macrophages play a key role in the pathogenesis of liver granuloma and fibrosis in schistosomiasis. However, the underlying mechanisms have not been fully characterized. This study revealed that the macrophages infiltrating the liver tissues in a murine model of Schistosoma japonica infection exhibited M2 functional polarization, and Notch1/Jagged1 signaling was significantly upregulated in the M2 polarized macrophages in vivo and in vitro. Furthermore, the blockade of Notch signaling pathway by a γ-secretase inhibitor could reverse macrophage M2 polarization in vitro and alleviate liver granuloma and fibrosis in the murine model of schistosomiasis...
2016: PloS One
https://www.readbyqxmd.com/read/27872499/phosphatase-prl2-promotes-oncogenic-notch1-induced-t-cell-leukemia
#18
M Kobayashi, Y Bai, S Chen, R Gao, C Yao, W Cai, A A Cardoso, J Croop, Z-Y Zhang, Y Liu
Leukemia accepted article preview online, 22 November 2016. doi:10.1038/leu.2016.340.
November 22, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27872496/inactivation-of-klf4-promotes-t-cell-acute-lymphoblastic-leukemia-and-activates-the-map2k7-pathway
#19
Y Shen, C S Park, K Suppipat, T-A Mistretta, M Puppi, T Horton, K Rabin, N S Gray, J P P Meijerink, H D Lacorazza
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL patients exhibit activating mutations in NOTCH1, the cooperating genetic events required to accelerate the onset of leukemia and worsen disease progression are largely unknown. Here, we show that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells...
November 22, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27870570/activating-notch1-mutations-define-a-distinct-subgroup-of-patients-with-adenoid-cystic-carcinoma-who-have-poor-prognosis-propensity-to-bone-and-liver-metastasis-and-potential-responsiveness-to-notch1-inhibitors
#20
Renata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N William, Bonnie S Glisson, Michael J Wick, Ann M Kapoun, Amita Patnaik, Gail Eckhardt, Pamela Munster, Leonardo Faoro, Jakob Dupont, J Jack Lee, Andrew Futreal, Adel K El-Naggar, John V Heymach
Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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