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https://www.readbyqxmd.com/read/29951828/igf2-and-igf1r-identified-as-novel-tip-cell-genes-in-primary-microvascular-endothelial-cell-monolayers
#1
Marchien G Dallinga, Bahar Yetkin-Arik, Richelle P Kayser, Ilse M C Vogels, Patrycja Nowak-Sliwinska, Arjan W Griffioen, Cornelis J F van Noorden, Ingeborg Klaassen, Reinier O Schlingemann
Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34+ cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4...
June 27, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29924900/elucidating-the-genetic-architecture-of-adams-oliver-syndrome-in-a-large-european-cohort
#2
Josephina A N Meester, Maja Sukalo, Kim C Schröder, Denny Schanze, Gareth Baynam, Guntram Borck, Nuria C Bramswig, Duygu Duman, Brigitte Gilbert-Dussardier, Muriel Holder-Espinasse, Peter Itin, Diana S Johnson, Shelagh Joss, Hannele Koillinen, Fiona McKenzie, Jenny Morton, Heike Nelle, Willie Reardon, Claudia Roll, Mustafa A Salih, Ravi Savarirayan, Ingrid Scurr, Miranda Splitt, Elizabeth Thompson, Hannah Titheradge, Colm P Travers, Lionel Van Maldergem, Margo Whiteford, Dagmar Wieczorek, Geert Vandeweyer, Richard Trembath, Lut Van Laer, Bart L Loeys, Martin Zenker, Laura Southgate, Wim Wuyts
Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts is currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort...
June 20, 2018: Human Mutation
https://www.readbyqxmd.com/read/29899427/treating-the-intestine-with-oral-apoa-i-mimetic-tg6f-reduces-tumor-burden-in-mouse-models-of-metastatic-lung-cancer
#3
Arnab Chattopadhyay, Xinying Yang, Pallavi Mukherjee, Dawoud Sulaiman, Hannah R Fogelman, Victor Grijalva, Steven Dubinett, Tonya C Wasler, Manash K Paul, Ramin Salehi-Rad, Julia J Mack, M Luisa Iruela-Arispe, Mohamad Navab, Alan M Fogelman, Srinivasa T Reddy
Having demonstrated that apolipoprotein A-I (apoA-I) mimetic peptides ameliorate cancer in mouse models, we sought to determine the mechanism for the anti-tumorigenic function of these peptides. CT-26 cells (colon cancer cells that implant and grow into tumors in the lungs) were injected into wild-type BALB/c mice. The day after injection, mice were either continued on chow or switched to chow containing 0.06% of a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F). After four weeks, the number of lung tumors was significantly lower in Tg6F-fed mice...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29897969/gene-expression-analysis-of-nidus-of-cerebral-arteriovenous-malformations-reveals-vascular-structures-with-deficient-differentiation-and-maturation
#4
Jaya Mary Thomas, Sumi Surendran, Mathew Abraham, Dhakshmi Sasankan, Sridutt Bhaadri, Arumugam Rajavelu, Chandrasekharan C Kartha
OBJECTIVE: Arteriovenous malformations (AVMs) are characterised by tangles of dysplastic blood vessels which shunt blood from arteries to veins with no intervening capillary bed. It is not known at what stage of development and differentiation, AVM vessels became aberrant. To address this, we have analysed the expression of vascular differentiation, vascular maturation and brain capillary specific genes in AVM nidus. METHODOLOGY: We performed immunohistochemistry and western blot analysis of vascular differentiation (HEY2, DLL4, EFNB2, and COUP-TFII), vascular maturation (ENG and KLF2) and brain capillary specific genes (GGTP and GLUT1) on ten surgically excised human brain AVMs and ten normal human brain tissues...
2018: PloS One
https://www.readbyqxmd.com/read/29896227/expression-of-notch-receptors-and-their-ligands-in-pancreatic-ductal-adenocarcinoma
#5
Hai-Yan Song, Ying Wang, Hong Lan, Yu-Xiang Zhang
Pancreatic cancer is the fourth leading cause of cancer-associated mortality in developed countries. Pancreatic ductal adenocarcinoma (PDAC) accounts for ~90% of all pancreatic cancer cases. The Notch signaling pathway serves a crucial role in embryonic development, as well as during the tumorigenesis of different types of cancer. However, Notch signaling serves either oncogenic or tumor suppressor roles depending on the tissue type. There are four Notch receptors (Notch1-4) and five ligands [Jagged1, Jagged2, δ-like ligand protein (DLL)1, DLL3 and DLL4]; therefore, it has been suggested that the different Notch receptors serve distinct roles in the same type of tissue...
July 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29879147/interrogation-of-transcriptomic-changes-associated-with-drug-induced-hepatic-sinusoidal-dilatation-in-colorectal-cancer
#6
Monika A Jarzabek, William R Proctor, Jennifer Vogt, Rupal Desai, Patrick Dicker, Gary Cain, Rajiv Raja, Jens Brodbeck, Dale Stevens, Eric P van der Stok, John W M Martens, Cornelis Verhoef, Priti S Hegde, Annette T Byrne, Jacqueline M Tarrant
Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively...
2018: PloS One
https://www.readbyqxmd.com/read/29874128/laminin-dystroglycan-signaling-regulates-retinal-arteriogenesis
#7
Saptarshi Biswas, Jared Watters, Galina Bachay, Shweta Varshney, Dale D Hunter, Huaiyu Hu, William J Brunken
Proper arteriovenous morphogenesis is crucial for maintaining normal tissue perfusion. However, our understanding of how arterial morphogenesis is regulated in the CNS is incomplete. In this study, we asked whether vascular basement membrane (BM) laminins, specifically the γ3-containing isoforms, regulate retinal arterial morphogenesis. We provide evidence that Laminin-γ3 is deposited at both arterial and venous BMs during arteriogenesis. Vascular BM Laminin-γ3 bound dystroglycan (DG), a laminin receptor preferentially expressed by arterial endothelial cells (ECs) during arteriogenesis...
June 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29861167/gata2-is-dispensable-for-specification-of-hemogenic-endothelium-but-promotes-endothelial-to-hematopoietic-transition
#8
HyunJun Kang, Walatta-Tseyon Mesquitta, Ho Sun Jung, Oleg V Moskvin, James A Thomson, Igor I Slukvin
The transcriptional factor GATA2 is required for blood and hematopoietic stem cell formation during the hemogenic endothelium (HE) stage of development in the embryo. However, it is unclear if GATA2 controls HE lineage specification or if it solely regulates endothelial-to-hematopoietic transition (EHT). To address this problem, we innovated a unique system, which involved generating GATA2 knockout human embryonic stem cell (hESC) lines with conditional GATA2 expression (iG2-/- hESCs). We demonstrated that GATA2 activity is not required for VE-cadherin+ CD43- CD73+ non-HE or VE-cadherin+ CD43- CD73- HE generation and subsequent HE diversification into DLL4+ arterial and DLL4- non-arterial lineages...
July 10, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29791856/activation-of-the-arterial-program-drives-development-of-definitive-hemogenic-endothelium-with-lymphoid-potential
#9
Mi Ae Park, Akhilesh Kumar, Ho Sun Jung, Gene Uenishi, Oleg V Moskvin, James A Thomson, Igor I Slukvin
Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC) technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29749499/stable-silencing-of-dll4-gene-suppresses-the-growth-and-metastasis-of-esophagus-cancer-cells-by-attenuating-akt-phosphorylation
#10
Xianzhi Guo, Yingchun Duan, Xiaolei Ye, Lina Hu, Tong Xu, Li Tong, Minghua Yu
δ‑Like ligand 4 (DLL4) has recently been reported to be involved in the process of cancer angiogenesis and considered to play a vital role in vascular endothelial growth factor (VEGF) signaling, while the role of DLL4 in cancer metastasis and growth has not been systematically studied. In the present study, the esophagus cancer cell line Eca109 was infected in vitro with a lentiviral vector loaded with dll4‑shRNA to obtain a stable cell line of DLL4 expression which was downregulated through puromycin screening...
July 2018: Oncology Reports
https://www.readbyqxmd.com/read/29744869/isolation-and-identification-of-chemotherapy-enriched-sphere-forming-cells-from-a-patient-with-gastric-cancer
#11
Vahid Bagheri, Bahram Memar, Ramezan Behzadi, Mohsen Aliakbarian, Ali Jangjoo, Mostafa Mehrabi Bahar, Samaneh Talebi, Mehran Gholamin, Mohammad R Abbaszadegan
Gastric cancer (GC) is the third and fifth cause of cancer-associated mortality for men and women throughout the world, respectively. Despite the use of surgery and chemotherapy for GC therapy, there are no efficient therapeutic protocols for it to date. Cancer stem cells (CSCs) due to their pivotal role in tumor initiation, growth, progression, invasion, distant metastasis, recurrence and resistance to anticancer drugs are very appealing targets for cancer therapies. Here, we isolated and identified CSCs from a chemotherapy-treated patient...
May 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29739946/notch-signaling-specifies-arterial-type-definitive-hemogenic-endothelium-from-human-pluripotent-stem-cells
#12
Gene I Uenishi, Ho Sun Jung, Akhilesh Kumar, Mi Ae Park, Brandon K Hadland, Ethan McLeod, Matthew Raymond, Oleg Moskvin, Catherine E Zimmerman, Derek J Theisen, Scott Swanson, Owen J Tamplin, Leonard I Zon, James A Thomson, Irwin D Bernstein, Igor I Slukvin
NOTCH signaling is required for the arterial specification and formation of hematopoietic stem cells (HSCs) and lympho-myeloid progenitors in the embryonic aorta-gonad-mesonephros region and extraembryonic vasculature from a distinct lineage of vascular endothelial cells with hemogenic potential. However, the role of NOTCH signaling in hemogenic endothelium (HE) specification from human pluripotent stem cell (hPSC) has not been studied. Here, using a chemically defined hPSC differentiation system combined with the use of DLL1-Fc and DAPT to manipulate NOTCH, we discover that NOTCH activation in hPSC-derived immature HE progenitors leads to formation of CD144+ CD43- CD73- DLL4+ Runx1 + 23-GFP+ arterial-type HE, which requires NOTCH signaling to undergo endothelial-to-hematopoietic transition and produce definitive lympho-myeloid and erythroid cells...
May 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29686270/spatial-patterning-of-the-notch-ligand-dll4-controls-endothelial-sprouting-in-vitro
#13
L A Tiemeijer, J-P Frimat, O M J A Stassen, C V C Bouten, C M Sahlgren
Angiogenesis, the formation of new blood vessels, is a vital process for tissue growth and development. The Notch cell-cell signalling pathway plays an important role in endothelial cell specification during angiogenesis. Dll4 - Notch1 signalling directs endothelial cells into migrating tip or proliferating stalk cells. We used the directing properties of Dll4 to spatially control endothelial cell fate and the direction of endothelial sprouts. We created linear arrays of immobilized Dll4 using micro contact printing...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29674611/inhibition-of-dll4-notch1-pathway-promotes-angiogenesis-of-masquelet-s-induced-membrane-in-rats
#14
Qian Tang, Haimin Jin, Minji Tong, Gang Zheng, Zhongjie Xie, Shangkun Tang, Jialei Jin, Ping Shang, Huazi Xu, Liyan Shen, Yu Zhang, Haixiao Liu
The Masquelet's induced membrane technique for repairing bone defects has been demonstrated to be a promising treatment strategy. Previous studies have shown that the vessel density of induced membrane is decreased in the late stage of membrane formation, which consequently disrupts the bone healing process. However, relatively little is known about certain mechanisms of vessel degeneration in the induced membrane tissue and whether promotion of angiogenesis in induced membranes can improve bone regeneration...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29629872/radical-and-lunatic-fringes-modulate-notch-ligands-to-support-mammalian-intestinal-homeostasis
#15
Preetish Kadur Lakshminarasimha Murthy, Tara Srinivasan, Matthew S Bochter, Rui Xi, Anastasia Kristine Varanko, Kuei-Ling Tung, Fatih Semerci, Keli Xu, Mirjana Maletic-Savatic, Susan E Cole, Xiling Shen
Notch signalling maintains stem cell regeneration at the mouse intestinal crypt base and balances the absorptive and secretory lineages in the upper crypt and villus. Here we report the role of Fringe family of glycosyltransferases in modulating Notch activity in the two compartments. At the crypt base, RFNG is enriched in the Paneth cells and increases cell surface expression of DLL1 and DLL4. This promotes Notch activity in the neighbouring Lgr5 + stem cells assisting their self-renewal. Expressed by various secretory cells in the upper crypt and villus, LFNG promotes DLL surface expression and suppresses the secretory lineage ...
April 9, 2018: ELife
https://www.readbyqxmd.com/read/29620522/mpdz-promotes-dll4-induced-notch-signaling-during-angiogenesis
#16
Fabian Tetzlaff, M Gordian Adam, Anja Feldner, Iris Moll, Amitai Menuchin, Juan Rodriguez-Vita, David Sprinzak, Andreas Fischer
Angiogenesis is coordinated by VEGF and Notch signaling. DLL4-induced Notch signaling inhibits tip cell formation and vessel branching. To ensure proper Notch signaling, receptors and ligands are clustered at adherens junctions. However, little is known about factors that control Notch activity by influencing the cellular localization of Notch ligands. Here, we show that the multiple PDZ domain protein (MPDZ) enhances Notch signaling activity. MPDZ physically interacts with the intracellular carboxyterminus of DLL1 and DLL4 and enables their interaction with the adherens junction protein Nectin-2...
April 5, 2018: ELife
https://www.readbyqxmd.com/read/29618931/upregulated-vegfa-and-dll4-act-as-potential-prognostic-genes-for-clear-cell-renal-cell-carcinoma
#17
Xilong Wang, Jun Zhang, Yangyun Wang, Minqi Tu, Ying Wang, Guowei Shi
Purpose: As a typical hypervascular tumor, clear cell renal cell carcinoma (ccRCC) is the most common type of RCC. This study was aimed to explore the prognostic genes for ccRCC, focusing on the roles of vascular endothelial growth factor A ( VEGFA ) and Delta-like ligand 4 ( DLL4 ) in the disease. Materials and methods: The mRNA-sequencing data of kidney renal clear cell carcinoma (KIRC) were obtained from The Cancer Genome Atlas (TCGA) database, including 469 tumor samples and 68 adjacent normal samples...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29606343/the-missed-notch-to-bring-down-diabetes
#18
Peter Mirtschink, Triantafyllos Chavakis
Notch signaling contributes to maintenance of adult tissue homeostasis and is also involved in disease. A recent study demonstrates that inhibition of Dll4-Notch signaling by anti-Dll4 improves pancreatic islet function and insulin production by multiple complementary mechanisms. Thus, anti-Dll4 represents a therapeutic approach for compromised insulin production in diabetes.
March 29, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29599924/asiatic-acid-attenuates-lipopolysaccharide-induced-injury-by-suppressing-activation-of-the-notch-signaling-pathway
#19
Xiong Yuyun, Cheng Xi, Yin Qing, Xia Lin, Rui Ke, Sun Bingwei
Sepsis is a severe multisystem disease with high mortality rates and limited treatment options. However, advances during the last decade have opened opportunities to develop novel therapeutic strategies. The Notch signaling pathway plays a critical role in inflammation, and its inhibition offers an avenue to treat inflammatory diseases, such as sepsis. Asiatic acid (AA), a triterpenoid isolated from Centella asiatica, reportedly exerts anti-oxidant, anti-tumor, and anti-inflammatory effects, but its mechanisms remain unclear...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29592882/abt-165-a-dual-variable-domain-immunoglobulin-dvd-ig-targeting-dll4-and-vegf-demonstrates-superior-efficacy-and-favorable-safety-profiles-in-preclinical-models
#20
Yingchun Li, Jonathan A Hickson, Dominic J Ambrosi, Deanna L Haasch, Kelly D Foster-Duke, Lucia J Eaton, Enrico L DiGiammarino, Sanjay C Panchal, Fang Jiang, Sarah R Mudd, Catherine Zhang, Surekha S Akella, Wenqing Gao, Sherry L Ralston, Louie Naumovski, Jijie Gu, Susan E Morgan-Lappe
Antiangiogenic therapy is a clinically validated modality in cancer treatment. To date, all approved antiangiogenic drugs primarily inhibit the VEGF pathway. Delta-like ligand 4 (DLL4) has been identified as a potential drug target in VEGF-independent angiogenesis and tumor-initiating cell (TIC) survival. A dual-specific biologic targeting both VEGF and DLL4 could be an attractive strategy to improve the effectiveness of anti-VEGF therapy. ABT-165 was uniquely engineered using a proprietary dual-variable domain immunoglobulin (DVD-Ig) technology based on its ability to bind and inhibit both DLL4 and VEGF...
May 2018: Molecular Cancer Therapeutics
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