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Notch pathway

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https://www.readbyqxmd.com/read/29451718/kiaa0247-inhibits-growth-migration-invasion-of-non-small-cell-lung-cancer-through-regulating-the-notch-pathway
#1
Yitong Xu, Hongjiu Ren, Jun Jiang, Qiongzi Wang, Muli Wudu, Qingfu Zhang, Hongbo Su, Chenglong Wang, Lihong Jiang, Xueshan Qiu
Lung cancer remains the leading cause of cancer-related death worldwide. Previous studies have shown that the novel KIAA0247 gene potentially targeted by the tumor suppressor p53 may inhibit the development of several cancers. However, the exact function of KIAA0247 in non-small-cell lung cancer (NSCLC) is unknown. The purpose of this study was to clarify the role of KIAA0247 in NSCLC. KIAA0247 expression was evaluated in tumors and adjacent normal tissues of 197 NSCLC patients by immunohistochemistry and real-time PCR and analyzed for association with clinicopathological parameters...
February 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29449332/inhibition-of-endothelial-notch1-signaling-attenuates-inflammation-by-reducing-cytokine-mediated-histone-acetylation-at-inflammatory-enhancers
#2
Lars la Cour Poulsen, Reidunn Jetne Edelmann, Stig Krüger, Rodrigo Diéguez-Hurtado, Akshay Shah, Tor Espen Stav-Noraas, Anastasia Renzi, Monika Szymanska, Junbai Wang, Manuel Ehling, Rui Benedito, Monika Kasprzycka, Espen Bækkevold, Olav Sundnes, Kim S Midwood, Helge Scott, Philippe Collas, Christian W Siebel, Ralf H Adams, Guttorm Haraldsen, Eirik Sundlisæter, Johanna Hol
OBJECTIVE: Endothelial upregulation of adhesion molecules serves to recruit leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however, current models based on interactions between active NOTCH1 and NF-κB components cannot explain the transcriptional selectivity exerted by NOTCH1 in this context. APPROACH AND RESULTS: Observing that Cre/Lox-induced conditional mutations of endothelial Notch modulated inflammation in murine contact hypersensitivity, we found that IL (interleukin)-1β stimulation induced rapid recruitment of RELA to genomic sites occupied by NOTCH1-RBPJ and that NOTCH1 knockdown reduced H3K27 acetylation at a subset of NF-κB-directed inflammatory enhancers...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29449267/single-cell-transcriptome-analyses-reveal-endothelial-cell-heterogeneity-in-tumors-and-changes-following-anti-angiogenic-treatment
#3
Qi Zhao, Alexandra Eichten, Asma A Parveen, Christina Adler, Ying Huang, Wei Wang, Yueming Ding, Alexander Adler, Thomas Nevins, Min Ni, Yi Wei, Gavin Thurston
Angiogenesis involves dynamic interactions between specialized endothelial tip and stalk cells that are believed to be regulated in part by VEGF and Dll4-Notch signaling. However, our understanding of this process is hampered by limited knowledge of the heterogeneity of endothelial cells and the role of different signaling pathways in specifying endothelial phenotypes. Here we characterized by single cell transcriptomics the heterogeneity of mouse endothelial cells and other stromal cells during active angiogenesis in xenograft tumors as well as from adult normal heart, following pharmacologic inhibition of VEGF and Dll4-Notch signaling...
February 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29448933/the-curious-case-of-vacuolar-atpase-regulation-of-signaling-pathways
#4
REVIEW
Sahithi Pamarthy, Arpita Kulshrestha, Gajendra K Katara, Kenneth D Beaman
The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. The structure of V-ATPase has been highly conserved among all eukaryotic cells and is involved in diverse functions across species. V-ATPase is best known for its acidification of endosomes and lysosomes and is also important for luminal acidification of specialized cells. Several reports have suggested the involvement of V-ATPase in maintaining an alkaline intracellular and acidic extracellular pH thereby aiding in proliferation and metastasis of cancer cells respectively...
February 15, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29448248/lncrna-gas5-overexpression-reverses-lps-induced-inflammatory-injury-and-apoptosis-through-up-regulating-klf2-expression-in-atdc5-chondrocytes
#5
Feng Li, Jianguang Sun, Shilei Huang, Gao Su, Guofu Pi
BACKGROUND/AIMS: Osteoarthritis (OA) is the most frequently occurring joint disease and characterized by degeneration of cartilage. As the unique cell type in cartilage, chondrocytes play a crucial role during OA. Our study explored the influence of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) on lipopolysaccharides (LPS)-induced injury in ATDC5 cells. METHODS: Cell viability, apoptosis and expression of inflammatory cytokines were all assessed to evaluate LPS-induce inflammatory injury...
February 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29448069/micro-environmental-signals-directing-human-epidermal-langerhans-cell-differentiation
#6
REVIEW
Herbert Strobl, Corinna Krump, Izabela Borek
Human Langerhans cells (LC) can be generated ex vivo from hematopoietic precursor cells in response to cytokines and cell-membrane associated ligands. These in vitro differentiation models provided mechanistic insights into the molecular and cellular pathways underlying the development of this unique, epithelia-associated dendritic cell subset. Notably, the human epidermal microenvironment is fully sufficient to induce LC differentiation from hematopoietic progenitors. Hence, dissecting the molecular characteristics of the human epithelial/epidermal LC niche, and testing defined ligands for their capacity to induce LC differentiation, led to a refined molecular model of LC lineage commitment...
February 12, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29447233/notch-signaling-inhibitor-dapt-provides-protection-against-acute-craniocerebral-injury
#7
Hong-Mei Zhang, Pei Liu, Cheng Jiang, Xiao-Qing Jin, Rui-Ning Liu, Shun-Qing Li, Yan Zhao
Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased...
2018: PloS One
https://www.readbyqxmd.com/read/29441951/lncrna-hulc-promotes-epithelial-and-smooth-muscle-like-differentiation-of-adipose-derived-stem-cells-by-upregulation-of-bmp9
#8
Yongwei Li, Zhengfei Shan, Bin Yang, Diandong Yang, Changping Men, Yuanshan Cui, Jitao Wu
AIMS: Adipose-derived stem cells (ADSCs), a source of mesenchymal stem cells, are able to differentiate into numerous cell lineages, including epithelial and smooth muscle cells. The use of ADSCs in tissue engineering technology has become the most promising therapeutic approach for urethral reconstruction. This study aimed to explore the effect of lncRNA highly upregulated in liver cancer (HULC) on the induction of ADSCs to differentiate into epithelial and smooth-muscle-like cells. METHODS: ADSCs were isolated from a male dog, and the expression of HULC in ADSCs was overexpressed by transfection with HULC expressing vector lentivirus...
January 2, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29441061/profiling-of-human-molecular-pathways-affected-by-retrotransposons-at-the-level-of-regulation-by-transcription-factor-proteins
#9
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29440175/pan-cancer-molecular-classes-transcending-tumor-lineage-across-32-cancer-types-multiple-data-platforms-and-over-10-000-cases
#10
Chad J Creighton, Fengju Chen, Yiqun Zhang, Don L Gibbons, Benjamin Deneen, David Kwiatkowski, Michael Ittmann
PURPOSE: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. EXPERIMENTAL DESIGN: On the basis of gene expression data, we classified 10224 cancers, representing 32 major types, into ten molecular-based "classes."  Molecular patterns representing tissue or histologic dominant effects were first removed computationally, with the resulting classes representing emergent themes across tumor lineages...
February 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29439807/could-notch-signaling-pathway-be-a-potential-therapeutic-option-in-renal-diseases
#11
Laura Marquez-Exposito, Elena Cantero-Navarro, Carolina Lavoz, Marta Fierro-Fernández, Jonay Poveda, Sandra Rayego-Mateos, Raúl R Rodrigues-Diez, José Luis Morgado-Pascual, Macarena Orejudo, Sergio Mezzano, Marta Ruiz-Ortega
Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells...
February 10, 2018: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/29438372/a-phase-i-trial-of-the-%C3%AE-secretase-inhibitor-mk-0752-in-combination-with-gemcitabine-in-patients-with-pancreatic-ductal-adenocarcinoma
#12
Natalie Cook, Bristi Basu, Donna-Michelle Smith, Aarthi Gopinathan, Jeffry Evans, William P Steward, Daniel Palmer, David Propper, Balaji Venugopal, Mirela Hategan, D Alan Anthoney, Lisa V Hampson, Michael Nebozhyn, David Tuveson, Hayley Farmer-Hall, Helen Turner, Robert McLeod, Sarah Halford, Duncan Jodrell
BACKGROUND: The Notch pathway is frequently activated in cancer. Pathway inhibition by γ-secretase inhibitors has been shown to be effective in pre-clinical models of pancreatic cancer, in combination with gemcitabine. METHODS: A multi-centre, non-randomised Bayesian adaptive design study of MK-0752, administered per os weekly, in combination with gemcitabine administered intravenously on days 1, 8 and 15 (28 day cycle) at 800 or 1000 mg m -2 , was performed to determine the safety of combination treatment and the recommended phase 2 dose (RP2D)...
February 13, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29437519/molecular-analysis-of-gli3-ihh-rab23-and-jag1-in-a-rabbit-model-of-craniosynostosis-likely-exclusion-as-the-loci-of-origin
#13
James R Gilbert, Gwen M Taylor, Joseph E Losee, Mark P Mooney, Gregory M Cooper
OBJECTIVE: Craniosynostosis (CS) involves the premature fusion of one or more cranial sutures. The etiology of CS is complex and mutations in more than 50 distinct genes have been causally linked to the disorder. Many of the genes that have been associated with CS in humans play an essential role in tissue patterning and early craniofacial development. Among these genes are members of the Hedgehog (HH) and Notch signal transduction pathways, including the GLI family member Gli3, Indian Hedgehog ( Ihh), the RAS oncogene family member Rab23, and the Notch ligand JAGGED1 ( Jag1)...
March 2018: Cleft Palate-craniofacial Journal
https://www.readbyqxmd.com/read/29437009/the-bhlh-protein-nulp1-is-essential-for-femur-development-via-acting-as-a-cofactor-in-wnt-signaling-in-drosophila
#14
Q Zeng, Y Wan, P Zhu, M Zhao, F Jiang, J Chen, M Tang, X Zhu, Y Li, H Zha, Y Wang, M Hu, X Mo, Y Zhang, Y Deng, Y Chen, X Fan, Y Chen, X Ye, R Bodmer, K Ocorr, Z Jiang, J Zhuang, W Yuan, X Wu
The basic helix-loop-helix (bHLH) protein families are a large class of transcription factors, which are associated with cell proliferation, tissue differentiation, and other important development process. We reported that the Nuclear localized protein-1 (Nulp1) might act as a novel bHLH transcriptional factor to mediate cellular functions. However, its role in development in vivo remains unknown. Here we show that Drosophila Nulp1 (dNulp1) mutants, generated by CRISPR/Cas9 targeting the Domain of Unknown Function (DUF654) in its C terminal, are partially homozygous lethal and the rare escapers have bent femurs, which are similar to the major manifestation of congenital bent-bone dysplasia in human Stuve-Weidemann syndrome...
February 12, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/29436668/kynurenine-promotes-the-goblet-cell-differentiation-of-ht-29-colon-carcinoma-cells-by-modulating-wnt-notch-and-ahr-signals
#15
Joo-Hung Park, Jeong-Min Lee, Eun-Jin Lee, Da-Jeong Kim, Won-Bhin Hwang
Various amino acids regulate cell growth and differentiation. In the present study, we examined the ability of HT-29 cells to differentiate into goblet cells in RPMI and DMEM which are largely different in the amounts of numerous amino acids. Most of the HT-29 cells differentiated into goblet cells downregulating the stem cell marker Lgr5 when cultured in DMEM, but remained undifferentiated in RPMI. The goblet cell differentiation in DMEM was inhibited by 1-methyl-tryptophan (1-MT), an inhibitor of indoleamine 2,3 dioxygenase-1 which is the initial enzyme in tryptophan metabolism along the kynurenine (KN) pathway, whereas tryptophan and KN induced goblet cell differentiation in RPMI...
February 13, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29434912/notch-signaling-via-regulation-of-rb-and-p-akt-but-not-pik3cg-contributes-to-mia-paca-2-cell-growth-and-migration-to-affect-pancreatic-carcinogenesis
#16
Shubing Zhang, Jingjiang Liu, Keli Xu, Zhijian Li
Pancreatic cancer is one of the leading causes of cancer-associated mortality. The understanding of the expression pattern of key protein factors and their function in pancreatic cancer cells is therefore vital for the diagnosis and treatment of this malignancy. The results of the present study reveal that the levels of neurogenic locus notch homolog protein 2 (Notch2) and phosphorylated (p)-SMAD family member 2 decreased, whereas the expression of Notch3 and phosphoinositide-3 kinase catalytic subunit-γ protein increased in human pancreatic cancer tissues compared with tumor-adjacent tissues...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434883/lncrna-fam83h-as1-is-associated-with-the-prognosis-of-colorectal-carcinoma-and-promotes-cell-proliferation-by-targeting-the-notch-signaling-pathway
#17
Song Lu, Wei Dong, Pei Zhao, Zhenjun Liu
The long non-coding RNA, FAM83H antisense RNA 1 (head to head) (FAM83H-AS1), has exhibited a functional role as an oncogene in a number of different types of cancer. The aim of the present study was to reveal the dysregulation of FAM83H-AS1 in colorectal carcinoma (CRC) samples and elucidate its underlying associations with the Notch signaling pathway. The expression profiles of FAM83H-AS1 and two Notch signaling-associated molecules, Notch1 and Hes family basic-helix-loop-helix transcription factor 1 (Hes1), were measured by reverse transcription-polymerase chain reaction and western blot analysis...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29432996/lncrna-let-inhibits-cell-viability-migration-and-emt-while-induces-apoptosis-by-up-regulation-of-timp2-in-human-granulosa-like-tumor-cell-line-kgn
#18
Qingfang Han, Wenke Zhang, Jinlai Meng, Li Ma, Aihua Li
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease characterized by hyperandrogenism, irregular menses, and polycystic ovaries. Several long non-coding RNAs (lncRNAs) are aberrantly expressed in PCOS patients; however, little is known about the effects of the lncRNA-low expression in tumor (lncRNA-LET) on PCOS. We aimed to explore the effects of lncRNA-LET on human granulosa-like tumor cell line, KGN. METHODS: Expression of lncRNA-LET in normal IOSE80 cells and granulosa cells was determined by qRT-PCR...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29425642/effect-of-dioscin-on-promoting-liver-regeneration-via-activating-notch1-jagged1-signal-pathway
#19
Lina Xu, Lina Gu, Xufeng Tao, Youwei Xu, Yan Qi, Lianhong Yin, Xu Han, Jinyong Peng
BACKGROUND: Development of novel candidates to promote liver regeneration is critical important after partial hepatectomy (PH). Dioscin, a natural product, shows potent effect on liver protection in our previous works. PURPOSE: This work aimed to investigate the effect and underlying mechanisms of dioscin on liver regeneration. METHODS: The promoting proliferation effects of dioscin on mouse hepatocytem AML12 cells, rat primary hepatocytes, rats and mice after 70% PH were evaluated...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29425042/pushing-the-limits-of-structure-based-models-prediction-of-non-globular-protein-folding-and-fibrils-formation-with-go-model-simulations
#20
Lokesh Kumar Baweja, Julien Roche
The development of computational efficient models is essential to obtain a detailed characterization of the mechanisms underlying the folding of proteins and the formation of amyloid fibrils. Structure based computational models (Go-model) with Cα or all-atom resolutions have been able to successfully delineate the mechanisms of folding of several globular proteins and offer an interesting alternative to computationally intensive simulations with explicit solvent description. We are exploring here the limits of Go-model predictions by analyzing the folding of the non-globular repeat domain proteins Notch Ankyrin and p16INK4 and the formation of human islet polypeptide (hIAPP) fibrils...
February 9, 2018: Journal of Physical Chemistry. B
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