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Notch pathway

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https://www.readbyqxmd.com/read/28732358/lenalidomide-restores-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-from-multiple-myeloma-patients-via-deactivating-notch-signaling-pathway
#1
Juan Guo, Chengming Fei, Youshan Zhao, Sida Zhao, Qingqing Zheng, Jiying Su, Dong Wu, Xiao Li, Chunkang Chang
Multiple myeloma (MM) always presents osteolytic bone lesions, resulting from the abnormal osteoblastic and osteoclastic function in patients. MM patients exhibit the impairment of osteogenic differentiation of BMMSCs (bone marrow mesenchymal stem cells) and osteoblast deficiency. Effects of the drug, lenalidomide on the osteoblastic functions and the involved mechanisms remain unexplored. In the present study, it is observed that the osteogenic differentiation of BMMSCs from MM patients (MM-MSCs) is impaired and activation of Notch signaling pathway in MM-MSCs is abnormal...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730338/jagged1-promotes-aromatase-inhibitor-resistance-by-modulating-tumor-associated-macrophage-differentiation-in-breast-cancer-patients
#2
Hang Liu, Jingxuan Wang, Minghui Zhang, Qijia Xuan, Zhipeng Wang, Xin Lian, Qingyuan Zhang
PURPOSE: Endocrine resistance limits the efficacy of anti-estrogen therapies. Notch signaling is involved in modulating tumor-associated macrophage (TAM) differentiation and is upregulated in endocrine-resistant breast cancer cells. Here, we analyzed the role of Jagged1 in the regulation of TAM polarization to investigate whether the Jagged1-Notch pathway promotes the acquisition of aromatase inhibitor (AI) resistance by upregulating TAM infiltration. METHODS: The Jagged1 expression levels and M2 TAM infiltration density, in 203 tumor samples from ER-positive postmenopausal patients, who received AI treatment, were evaluated by immunohistochemical staining and the results were compared with clincopathological parameters and survival...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28729422/o-glycosylation-modulates-the-stability-of-epidermal-growth-factor-like-repeats-and-thereby-regulates-notch-trafficking
#3
Hideyuki Takeuchi, Hongjun Yu, Huilin Hao, Megumi Takeuchi, Atsuko Ito, Huilin Li, Robert S Haltiwanger
Glycosylation in the endoplasmic reticulum (ER) is closely associated with protein folding and quality control. We recently described a non-canonical ER quality control mechanism for folding of thrombospondin type 1 repeats by Protein O-fucosyltransferase 2 (POFUT2). Epidermal Growth Factor-like (EGF) repeats are also small, cysteine rich protein motifs that can be O-glycosylated by several ER-localized enzymes including Protein O-glucosyltransferase 1 (POGLUT1) and POFUT1. Both POGLUT1 and POFUT1 modify the Notch receptor on multiple EGF repeats and are essential for full Notch function...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724574/the-microvascular-niche-instructs-t-cells-in-large-vessel-vasculitis-via-the-vegf-jagged1-notch-pathway
#4
Zhenke Wen, Yi Shen, Gerald Berry, Farhad Shahram, Yinyin Li, Ryu Watanabe, Yaping Joyce Liao, Jörg J Goronzy, Cornelia M Weyand
Microvascular networks in the adventitia of large arteries control access of inflammatory cells to the inner wall layers (media and intima) and thus protect the immune privilege of the aorta and its major branches. In autoimmune vasculitis giant cell arteritis (GCA), CD4 T helper 1 (TH1) and TH17 cells invade into the wall of the aorta and large elastic arteries to form tissue-destructive granulomas. Whether the disease microenvironment provides instructive cues for vasculitogenic T cells is unknown. We report that adventitial microvascular endothelial cells (mvECs) perform immunoregulatory functions by up-regulating the expression of the Notch ligand Jagged1...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28723653/inhibition-of-notch-1-pathway-is-involved-in-rottlerin-induced-tumor-suppressive-function-in-nasopharyngeal-carcinoma-cells
#5
Yingying Hou, Shaoyan Feng, Lixia Wang, Zhe Zhao, Jingna Su, Xuyuan Yin, Nana Zheng, Xiuxia Zhou, Jun Xia, Zhiwei Wang
Recent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Therefore, regulation of Notch pathway could be beneficial for the treatment of human cancer. The aims of our current study were to explore whether rottlerin could suppress Notch-1 expression, which leads to inhibition of cell proliferation, migration and invasion in nasopharyngeal carcinoma cells...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720126/a-small-molecule-cytokine-combination-enhances-hematopoietic-stem-cell-proliferation-via-inhibition-of-cell-differentiation
#6
Lan Wang, Xin Guan, Huihui Wang, Bin Shen, Yu Zhang, Zhihua Ren, Yupo Ma, Xinxin Ding, Yongping Jiang
BACKGROUND: Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. METHODS: Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34(+) cell expansion ex vivo...
July 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28719575/non-canonical-notch3-signalling-limits-tumour-angiogenesis
#7
Shuheng Lin, Ana Negulescu, Sirisha Bulusu, Benjamin Gibert, Jean-Guy Delcros, Benjamin Ducarouge, Nicolas Rama, Nicolas Gadot, Isabelle Treilleux, Pierre Saintigny, Olivier Meurette, Patrick Mehlen
Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a fraction of human cancer and our data support the view that Jagged-1, produced by cancer cells, is inhibiting the apoptosis induced by the aberrant Notch3 expression in tumour vasculature...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28718798/co-expression-network-and-pathway-analyses-reveal-important-modules-of-mirnas-regulating-milk-yield-and-component-traits
#8
Duy N Do, Pier-Luc Dudemaine, Ran Li, Eveline M Ibeagha-Awemu
Co-expression network analyses provide insights into the molecular interactions underlying complex traits and diseases. In this study, co-expression network analysis was performed to detect expression patterns (modules or clusters) of microRNAs (miRNAs) during lactation, and to identify miRNA regulatory mechanisms for milk yield and component traits (fat, protein, somatic cell count (SCC), lactose, and milk urea nitrogen (MUN)) via miRNA target gene enrichment analysis. miRNA expression (713 miRNAs), and milk yield and components (Fat%, Protein%, lactose, SCC, MUN) data of nine cows at each of six different time points (day 30 (D30), D70, D130, D170, D230 and D290) of an entire lactation curve were used...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28717251/transdifferentiated-human-vascular-smooth-muscle-cells-are-a-new-potential-cell-source-for-endothelial-regeneration
#9
Xuechong Hong, Andriana Margariti, Alexandra Le Bras, Laureen Jacquet, Wei Kong, Yanhua Hu, Qingbo Xu
Endothelial dysfunction is widely implicated in cardiovascular pathological changes and development of vascular disease. In view of the fact that the spontaneous endothelial cell (EC) regeneration is a slow and insufficient process, it is of great interest to explore alternative cell sources capable of generating functional ECs. Vascular smooth muscle cell (SMC) composes the majority of the vascular wall and retains phenotypic plasticity in response to various stimuli. The aim of this study is to test the feasibility of the conversion of SMC into functional EC through the use of reprogramming factors...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714363/portulaca-oleracea-extract-can-inhibit-nodule-formation-of-colon-cancer-stem-cells-by-regulating-gene-expression-of-the-notch-signal-transduction-pathway
#10
Heiying Jin, Li Chen, Shuiming Wang, Deng Chao
To investigate whether Portulaca oleracea extract affects tumor formation in colon cancer stem cells and its chemotherapy sensitivity. In addition, to analyze associated genetic changes within the Notch signal transduction pathway. Serum-free cultures of colon cancer cells (HT-29) and HT-29 cancer stem cells were treated with the chemotherapeutic drug 5-fluorouracil to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and note its characteristics. In addition, the effect of different concentrations of P...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28714033/evaluation-of-velvet-antler-total-protein-effect-on-bone-marrow%C3%A2-derived-endothelial-progenitor-cells
#11
Xiang Xiao, Lin Li, Shuqiang Xu, Min Mao, Ruiyan Pan, Yanjun Li, Jiayun Wu, Li Huang, Xiaoyun Zheng
Lu Rong, velvet antler (VA), is a traditional Chinese medicine, which is used as a food supplement and therapeutic drug in China, Japan, Russia, New Zealand and Southeast Asia. The regenerative characteristics of VA have resulted in great research interest, particularly regarding the fields of organ grafting and stem cell differentiation. Various VA proteomic studies verified that proteins act as the primary bioactive components of VA. The present study aimed to investigate if VA proteins (VA‑pro) influence endothelial progenitor cell (EPC) viability...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28714011/mangiferin-induces-apoptosis-in-human-ovarian-adenocarcinoma-ovcar3-cells-via-the-regulation-of-notch3
#12
Bingyu Zou, Hailian Wang, Yilong Liu, Ping Qi, Tiantian Lei, Minghan Sun, Yi Wang
Ovarian cancer is the most lethal gynecological malignancy in the world. Our previous studies showed that mangiferin, purified from plant source, possessed anti-neoplasm effect on human lung adenocarcinoma A549 cells. This study aimed to determine the apoptosis-inducing effect of mangiferin on human ovarian carcinoma OVCAR3 cells. By in vitro studies, we found mangiferin significantly inhibited viability of OVCAR3 cells, and remarkably increased the sensitivity of OVCAR3 cells to cisplatin. In addition, the activation of caspase-dependent apoptosis was observed in mangiferin treated ovarian cancer cells...
July 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28711903/notch-system-is-differentially-expressed-and-activated-in-pituitary-adenomas-of-distinct-histotype-tumor-cell-lines-and-normal-pituitaries
#13
Sofia Perrone, Lautaro Zubeldia-Brenner, Elias Gazza, Gianina Demarchi, Leticia Baccarini, Agustin Baricalla, Freya Mertens, Guillermina Luque, Hugo Vankelecom, Silvia Berner, Damasia Becu-Villalobos, Carolina Cristina
Pituitary adenomas are among the most frequent intracranial neoplasms and treatment depends on tumor subtype and clinical features. Unfortunately, non responder cases occur, then new molecular targets are needed.Notch system component expression and activation data are scarce in pituitary tumorigenesis, we therefore aimed to characterize Notch system in pituitary tumors of different histotype. In human pituitary adenomas we showed NOTCH1-4 receptors, JAGGED1 ligand and HES1 target gene expression with positive correlations between NOTCH1,2,4 and HES1, and NOTCH3 and JAGGED1 denoting Notch system activation in a subset of tumors...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708309/bone-healing-in-an-aged-murine-fracture-model-is-characterized-by-sustained-callus-inflammation-and-decreased-cell-proliferation
#14
John H Hebb, Jason W Ashley, Lee McDaniel, Luke A Lopas, John Tobias, Kurt D Hankenson, Jaimo Ahn
Geriatric fractures take longer to heal and heal with more complications than those of younger patients; however, the mechanistic basis for this difference in healing is not well understood. To improve this understanding, we investigated cell and molecular differences in fracture healing between 5 month-old (young adult) and 25 month-old (geriatric) mice healing utilizing high-throughput analysis of gene expression. Mice underwent bilateral tibial fractures and fracture calluses were harvested at 5, 10, and 20 days post fracture (DPF) for analysis...
July 14, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#15
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28707430/multi-genic-pattern-found-in-rare-type-of-hypopituitarism-a-whole-exome-sequencing-study-of-han-chinese-with-pituitary-stalk-interruption-syndrome
#16
Qing-Hua Guo, Cheng-Zhi Wang, Zhi-Qiang Wu, Yan Qin, Bai-Yu Han, An-Ping Wang, Bao-An Wang, Jing-Tao Dou, Xiao-Sheng Wu, Yi-Ming Mu
Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis...
July 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28705915/microarray-analysis-of-bone-marrow-lesions-in-osteoarthritis-demonstrates-upregulation-of-genes-implicated-in-osteochondral-turnover-neurogenesis-and-inflammation
#17
Anasuya Kuttapitiya, Lena Assi, Ken Laing, Caroline Hing, Philip Mitchell, Guy Whitley, Abiola Harrison, Franklyn A Howe, Vivian Ejindu, Christine Heron, Nidhi Sofat
OBJECTIVE: Bone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression. METHODS: We recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls...
July 13, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28698260/phospholipase-c%C3%AE-1-mediates-intima-formation-through-akt-notch1-signaling-independent-of-the-phospholipase-activity
#18
Dongyang Jiang, Jianhui Zhuang, Wenhui Peng, Yuyan Lu, Hao Liu, Qian Zhao, Chen Chi, Xiankai Li, Guofu Zhu, Xiangbin Xu, Chen Yan, Yawei Xu, Junbo Ge, Jinjiang Pang
BACKGROUND: Vascular smooth muscle cell proliferation, migration, and dedifferentiation are critical for vascular diseases. Recently, it was demonstrated that Notch receptors have opposing effects on intima formation after vessel injury. Therefore, it is important to investigate the specific regulatory pathways that activate the different Notch receptors. METHODS AND RESULTS: There was a time- and dose-dependent activation of Notch1 by angiotensin II and platelet-derived growth factor in vascular smooth muscle cells...
July 11, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28697535/cancer-stem-cells-and-epithelial-mesenchymal-transition-in-urothelial-carcinoma-possible-pathways-and-potential-therapeutic-approaches
#19
REVIEW
Dong Fang, Hiroshi Kitamura
There is growing evidence of the presence of cancer stem cells in urothelial carcinoma. Cancer stem cells have the ability to self-renew and to differentiate into all cell types of the original heterogeneous tumor. A panel of diverse cancer stem cell markers might be suitable for simulation studies of urothelial cancer stem cells and for the development of optimized treatment protocols. The present review focuses on the advances in recognizing the markers of urothelial cancer stem cells and possible therapeutic targets...
July 11, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28695891/the-endothelial-transcription-factor-erg-mediates-angiopoietin-1-dependent-control-of-notch-signalling-and-vascular-stability
#20
A V Shah, G M Birdsey, C Peghaire, M E Pitulescu, N P Dufton, Y Yang, I Weinberg, L Osuna Almagro, L Payne, J C Mason, H Gerhardt, R H Adams, A M Randi
Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation and stability. Here we identify the transcription factor ERG as a key regulator of endothelial Notch signalling. We show that ERG controls the balance between Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo, this regulation occurs selectively in the maturing plexus of the mouse developing retina, where Ang1/Tie2 signalling is active. We find that ERG mediates Ang1-dependent regulation of Notch ligands and is required for the stabilizing effects of Ang1 in vivo...
July 11, 2017: Nature Communications
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