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https://www.readbyqxmd.com/read/29050323/histone-deacetylase-inhibitor-thailandepsin-a-activates-notch-signaling-and-suppresses-neuroendocrine-cancer-cell-growth-in-vivo
#1
Samuel Jang, Andrew Janssen, Zviadi Aburjania, Matthew B Robers, April Harrison, Ajitha Dammalapati, Yi-Qiang Cheng, Herbert Chen, Renata Jaskula-Sztul
Novel therapies for neuroendocrine (NE) cancers are desperately needed as they frequently present as metastatic disease and cause debilitating symptoms by secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive effect in NE cancer cell lines, and we have observed that histone deacetylase inhibitors (HDACi) potently activate Notch. In this study, we describe the potential for Burkholderia thailandensis-derived class I HDACi thailandepsin A (TDP-A) as a Notch activator and therapeutic agent against NE cancer...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049420/production-of-proinflammatory-mediators-in-activated-microglia-is-synergistically-regulated-by-notch-1-glycogen-synthase-kinase-gsk-3%C3%AE-and-nf-%C3%AE%C2%BAb-p65-signalling
#2
Qiong Cao, Aparna Karthikeyan, S Thameem Dheen, Charanjit Kaur, Eng-Ang Ling
Microglia activation and associated inflammatory response are involved in the pathogenesis of different neurodegenerative diseases. We have reported that Notch-1 and NF-κB/p65 signalling pathways operate in synergy in regulating the production of proinflammatory mediators in activated microglia. In the latter, there is also evidence by others that glycogen synthase kinase 3β (GSK-3β) mediates the release of proinflammatory cytokines but the interrelationships between the three signalling pathways have not been fully clarified...
2017: PloS One
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#3
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048643/novel-transduction-of-nutrient-stress-to-notch-pathway-by-rasgrp3-promotes-malignant-aggressiveness-in-human-esophageal-squamous-cell-carcinoma
#4
Ge Hu, Yuepeng Zhou, Yu Zhu, Ling Zhou, Rui Ling, Dan Wu, Lei Mi, Xuefeng Wang, Dongfang Dai, Chaoming Mao, Deyu Chen
In the process of enlarging of tumors, the dissolving tissue structures and remodeling endothelial cells for restoring gas exchange and nutritional support, further facilitate tumor cell invasion and metastasis. Activation of Ras plays a critical role in the development of esophageal squamous cell carcinoma (ESCC), but the underlying mechanisms remain poorly understood. We therefore investigated whether Ras guanyl-releasing protein 3 (RasGRP3), a Ras activator, could promote metastasis by inducing vascular regeneration and further epithelial-mesenchymal transition under nutrient stress (NS)...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29047786/integrated-reconfigurable-photonic-filters-based-on-interferometric-fractional-hilbert-transforms
#5
C Sima, B Cai, B Liu, Y Gao, Y Yu, J C Gates, M N Zervas, P G R Smith, D Liu
In this paper, we present integrated reconfigurable photonic filters using fractional Hilbert transformers (FrHTs) and optical phase tuning structure within the silica-on-silicon platform. The proposed structure, including grating-based FrHTs, an X-coupler, and a pair of thermal tuning filaments, is fabricated through the direct UV grating writing technique. The thermal tuning effect is realized by the controllable microheaters located on the two arms of the X-coupler. We investigate the 200 GHz maximum bandwidth photonic FrHTs based on apodized planar Bragg gratings, and analyze the reflection spectrum responses...
October 1, 2017: Applied Optics
https://www.readbyqxmd.com/read/29047461/hematopoietic-stem-cell-derived-exosomes-promote-hematopoietic-differentiation-of-mouse-embryonic-stem-cells-in-vitro-via-inhibiting-the-mir126-notch1-pathway
#6
Feng-Ling Liao, Lin Tan, Hua Liu, Jin-Ju Wang, Xiao-Tang Ma, Bin Zhao, Yan-Fang Chen, Ji Bihl, Yi Yang, Ri-Ling Chen
Cell-derived exosomes (EXs) can modulate target cell differentiation via microRNAs (miRs) that they carried. Previous studies have shown that miR126 is highly expressed in hematopoietic stem cells (HSCs) and plays a role in hematopoiesis via modulating the Notch pathway that participates in progenitors' cell fate decisions. In this study we investigated whether HSC-derived EXs (HSC-EXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into HSCs. We prepared HSC-EXs(con), HSC-EXs(sc) and HSC-EXs(miR126) from control HSCs and the HSCs transfected with scramble control or miR126 mimics, respectively...
October 19, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#7
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29046480/epigenetic-mechanisms-underlying-maternal-diabetes-associated-risk-of-congenital-heart-disease
#8
Madhumita Basu, Jun-Yi Zhu, Stephanie LaHaye, Uddalak Majumdar, Kai Jiao, Zhe Han, Vidu Garg
Birth defects are the leading cause of infant mortality, and they are caused by a combination of genetic and environmental factors. Environmental risk factors may contribute to birth defects in genetically susceptible infants by altering critical molecular pathways during embryogenesis, but experimental evidence for gene-environment interactions is limited. Fetal hyperglycemia associated with maternal diabetes results in a 5-fold increased risk of congenital heart disease (CHD), but the molecular basis for this correlation is unknown...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29045844/a-b-cell-regulome-links-notch-to-downstream-oncogenic-pathways-in-small-b-cell-lymphomas
#9
Russell J H Ryan, Jelena Petrovic, Dylan M Rausch, Yeqiao Zhou, Caleb A Lareau, Michael J Kluk, Amanda L Christie, Winston Y Lee, Daniel R Tarjan, Bingqian Guo, Laura K H Donohue, Shawn M Gillespie, Valentina Nardi, Ephraim P Hochberg, Stephen C Blacklow, David M Weinstock, Robert B Faryabi, Bradley E Bernstein, Jon C Aster, Warren S Pear
Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045640/action-potential-contour-contributes-to-species-differences-in-repolarization-response-to-%C3%AE-adrenergic-stimulation
#10
Luca Sala, Bence Hegyi, Chiara Bartolucci, Claudia Altomare, Marcella Rocchetti, Krisztina Váczi, Gaspare Mostacciuolo, Norbert Szentandrássy, Stefano Severi, Péter Pál Nánási, Antonio Zaza
Aim: Repolarization response to β-adrenergic (β-AR) stimulation differs between guinea-pig and canine myocytes and, within the latter, between myocardial layers. Correlative analysis suggests that this may be due to differences in action potential (AP) contour. Here we tested whether AP contour may set the response of current and of repolarization to β-AR stimulation (10 nM isoproterenol, ISO). Methods and Results: The responses of AP and current to ISO were measured under I-clamp and "AP-clamp" in guinea-pig (GP), dog epicardial (DEPI) and dog subendocardial (DENDO) myocytes...
October 17, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29045533/liposuction-augmentation-mammaplasty
#11
Ryan Harris, Peter Raphael, Scott W Harris
Background: The female breast loses superior fullness and becomes more ptotic over time. Women often present to their plastic surgeon requesting reversal of this evolution. While liposuction alone has been proven to lift the breast, no solution combining augmentation and liposuction has been reported. Objectives: Herein, we introduce a technique called liposuction-augmentation mammaplasty (LAM) that can achieve "scarless" lifting or simply volume equalization prior to inserting same-sized implants...
October 16, 2017: Aesthetic Surgery Journal
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#12
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29042972/expression-and-association-of-vegf-notch-pathways-in-infantile-hemangiomas
#13
Shangbin Li, Guangqi Xu, Feng Gao, Jianhai Bi, Ran Huo
The vascular endothelial growth factor (VEGF) and Notch signaling pathways have been identified to be involved in the neovascularization, and angiogenesis of various tumor types. However, there is little data regarding their roles and association in infantile hemangiomas (IHs). In the present study, the significance and association of the VEGF-VEGF receptor (R)2, and δ like canonical Notch ligand 4 (Dll4)-Notch1 pathways in different clinical phases of IHs were investigated. Specimens in the proliferating phase (n=15) and involuting phase (n=12) were collected...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042932/cardioprotective-effect-of-notch-signaling-on-the-development-of-myocardial-infarction-complicated-by-diabetes-mellitus
#14
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/29042479/retraction-eya1-controls-cell-polarity-spindle-orientation-cell-fate-and-notch-signaling-in-distal-embryonic-lung-epithelium-development-doi-10-1242-dev-058479
#15
Ahmed Hk El-Hashash, Gianluca Turcatel, Denise Al Alam, Sue Buckley, Hiroshi Tokumitsu, Saverio Bellusci, David Warburton
No abstract text is available yet for this article.
October 15, 2017: Development
https://www.readbyqxmd.com/read/29042443/mammalian-numb-protein-antagonizes-notch-by-controlling-postendocytic-trafficking-of-the-notch-ligand-delta-like-4
#16
Ximing Shao, Zhihao Ding, Ming Zhao, Ke Liu, Haiyan Sun, Juntao Chen, Xianming Liu, Yuzhen Zhang, Yang Hong, Huashun Li, Hongchang Li
The biological antagonism between the signaling proteins Numb and Notch has been implicated in the regulation of many developmental processes, especially in asymmetric cell division. Mechanistic studies show that Numb inactivates Notch via endocytosis and proteasomal degradation that directly reduce Notch protein levels at the cell surface. However, some aspects of how Numb antagonizes Notch remain unclear. Here, we report a novel mechanism in which Numb acts as a Notch antagonist by controlling the intracellular destination and stability of the Notch ligand Delta-like 4 (Dll4) through a postendocytic-sorting process...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29040816/lamin-a-c-mutation-associated-with-lipodystrophy-influences-adipogenic-differentiation-of-stem-cells-through-interaction-with-notch-signaling
#17
Ksenia Perepelina, Renata I Dmitrieva, Elena Ignatieva, Aleksandra Borodkina, Anna Kostareva, Anna Malashicheva
Lamin A/C is involved in many cellular functions due to its ability to bind chromatin and transcription factors and affect their properties. Mutations of LMNA gene encoding lamin A/C affect differentiation capacity of stem cells. However, signaling pathways involved in interaction with lamins in cellular differentiation remain unclear. Lipodystrophy associated with LMNA mutation R482L causes loss of fat tissue. In this study we investigated the role of LMNA mutation R482L in modulating Notch signaling activity in adipogenic differentiation of mesenchymal stem cells...
October 17, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29040223/effect-of-losartan-on-the-acute-response-of-human-elderly-skeletal-muscle-to-exercise
#18
Mette Flindt Heisterberg, Jesper L Andersen, Peter Schjerling, Jacob Bülow, Jeppe Bo Lauersen, Heidi L Roeber, Michael Kjaer, Abigail L Mackey
PURPOSE: To investigate the effect of blocking the angiotensin II type I receptor (AT1R) upon the response to acute heavy resistance exercise in elderly human skeletal muscle. The hypothesis was that AT1R blocking would result in a superior myogenic response accompanied by downregulation of TGF-β and upregulation of IGF-1 signalling. METHODS: 28 healthy elderly men (+64 years) were randomized into two groups, consuming either AT1R blocker (Losartan, 100mg/day) or Placebo for 18 days prior to exercise...
October 16, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/29040126/reverse-total-shoulder-arthroplasty-for-massive-irreparable-rotator-cuff-tears-before-the-age-of-60-years-long-term-results
#19
Lukas Ernstbrunner, Aline Suter, Sabrina Catanzaro, Stefan Rahm, Christian Gerber
BACKGROUND: There has been serious concern regarding the longevity and durability of outcomes of reverse total shoulder arthroplasty (RTSA) in younger patients. It was the purpose of this study to analyze long-term outcomes and complications of RTSA for irreparable rotator cuff tears in patients younger than 60 years. METHODS: Twenty patients (23 shoulders) with a mean age of 57 years (range, 47 to 59 years) were evaluated at a mean of 11.7 years (range, 8 to 19 years) after RTSA...
October 18, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/29039612/long-non-coding-rna-steroid-receptor-rna-activator-sra-induces-tumor-proliferation-and-invasion-through-the-notch-pathway-in-cervical-cancer-cell-lines
#20
Kyung Jin Eoh, Jiheum Paek, Sang Wun Kim, Hee Jung Kim, Hye Yeon Lee, Sang Kil Lee, Young Tae Kim
Contemporary research has focused on the function of long non-coding RNAs (lncRNAs) in carcinogenesis. However, the involvement of the lncRNA, steroid receptor RNA activator (SRA), in cervical carcinogenesis remains to be elucidated. In the present study, we investigated the bio-functional consequences of lncRNA SRA knockdown in vitro. To verify the role of lncRNA SRA in cell proliferation, migration, and invasion, lncRNA RNA interference was utilized to knock down lncRNA SRA expression in cervical cancer cell lines, resulting in our discovery that lncRNA SRA knockdown inhibited cell proliferation, cell migration and tumor invasion in the cervical cancer cell lines...
October 11, 2017: Oncology Reports
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