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https://www.readbyqxmd.com/read/28325782/aibp-limits-angiogenesis-thorough-%C3%AE-secretase-mediated-upregulation-of-notch-signaling
#1
Renfang Mao, Shu Meng, Qilin Gu, Raquel Araujo-Gutierrez, Sandeep Kumar, Qing Yan, Felicidad Almazan, Keith A Youker, Yingbin Fu, Henry J Pownall, John P Cooke, Yury I Miller, Longhou Fang
Rationale: Angiogenesis improves perfusion to the ischemic tissue following acute vascular obstruction. Angiogenesis in pathophysiological settings reactivates signaling pathways involved in developmental angiogenesis. We showed previously that apoA-I binding protein (AIBP)-regulated cholesterol efflux in endothelial cells (ECs) controls zebrafish embryonic angiogenesis. Objective: This study is to determine whether loss of AIBP affects angiogenesis in mice during development and under pathological conditions, and to explore the underlying molecular mechanism...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28319529/the-notch-signaling-system-is-involved-in-the-regulation-of-reparative-angiogenesis-in-the-zone-of-stasis
#2
Ozan Luay Abbas, Orhan Özatik, Yunus Kasm Terzi, Fikriye Yasemin Özatik, Rukiye Nar, Gamze Turna
The Notch pathway ligand Delta-like 4 (Dll4) functions as an antiangiogenic factor, inhibiting vascular endothelial growth factor (VEGF)-induced angiogenesis. This function is documented in tumor and embryonic vasculature. However, its implication in burn wounds remains unexplored. Our objective was to explore the involvement of the Notch in the healing of zone of stasis burns. We hypothesized that anti-Dll4 therapy would prevent progressive necrosis in the stasis zone by promoting angiogenesis. Burns were created in 21 rats using the comb burn model...
March 13, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28319046/t-cells-take-directions-from-supporting-cast-in-graft-versus-host-disease
#3
Derk Amsen
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only treatment option for several severe hematological malignancies. The development of graft-versus-host disease (GVHD) is a common complication of the procedure and results when donor T cells become activated against recipient-specific antigens. The factors that drive the alloreactive T cell response are not completely understood. In this issue of the JCI, Chung and colleagues present evidence that stromal cells within lymphoid tissue express the Notch ligands Delta-like 1/4 (DLL1 and DLL4), which in turn directly activate T cells...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319044/fibroblastic-niches-prime-t-cell-alloimmunity-through-delta-like-notch-ligands
#4
Jooho Chung, Christen L Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R Blazar, Alex Y Huang, Todd V Brennan, D Keith Bishop, Burkhard Ludewig, Christian W Siebel, Freddy Radtke, Sanjiv A Luther, Ivan Maillard
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28288569/endothelial-dll4-overexpression-reduces-vascular-response-and-inhibits-tumor-growth-and-metastasization-in-vivo
#5
Alexandre Trindade, Dusan Djokovic, Joana Gigante, Liliana Mendonça, António Duarte
BACKGROUND: The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models. METHODS: We used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced...
March 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28279221/notch-signaling-plays-a-crucial-role-in-cancer-stem-like-cells-maintaining-stemness-and-mediating-chemotaxis-in-renal-cell-carcinoma
#6
Wei Xiao, Zhiyong Gao, Yixing Duan, Wuxiong Yuan, Yang Ke
BACKGROUND: Cancer stem cells (CSCs) are correlated with the initiation, chemoresistance and relapse of tumors. Notch pathway has been reported to function in CSCs maintenance, but whether it is involved in renal cell carcinoma (RCC) CSCs maintaining stemness remain unclear. This study aims to explore the effect of Notch pathway on stemness of CSCs in RCC and the underlying mechanisms. METHODS: The CD133(+)/CD24(+) cells were isolated from RCC ACHN and Caki-1 cell line using Magnetic-activated cell sorting and identified by Flow cytometry analysis...
March 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28277073/enhancement-of-vascular-endothelial-growth-factor-s-angiogenic-capacity-by-the-therapeutic-modulation-of-notch-signalling-improves-tram-flap-survival-in-rats-submitted-to-nicotine
#7
Ozan Luay Abbas, Yunus Kasım Terzi, Orhan Özatik, Fikriye Yasemin Özatik, Gamze Turna, Rukiye Nar, Ahmet Musmul
BACKGROUND: Smoke of cigarettes, and specifically nicotine, has been shown to diminish pedicled transverse rectus abdominis musculocutaneous (TRAM) flap survival. Considering that Notch signalling through its ligand Delta-like 4 (Dll4) functions as anti-angiogenic factor by inhibiting the pro-angiogenic effects of vascular endothelial growth factor (VEGF), it is hypothesised that inhibition of the Notch would promote angiogenesis and increase TRAM flap survival in rats submitted to nicotine...
February 13, 2017: Journal of Plastic Surgery and Hand Surgery
https://www.readbyqxmd.com/read/28275186/cpg-in-combination-with-an-inhibitor-of-notch-signaling-suppresses-fi-rsv-enhanced-airway-hyperresponsiveness-and-inflammation-through-inhibiting-th17-memory-responses-and-promoting-tissue-resident-memory-cells-in-lungs
#8
Lei Zhang, Hongyong Li, Yan Hai, Wei Yin, Wenjian Li, Boyang Zheng, Xiaomin Du, Na Li, Zhengzheng Zhang, Yuqing Deng, Ruihong Zeng, Lin Wei
Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross-talk between TLR and Notch signaling pathways results in fine tuning of TLR-triggered innate inflammatory responses...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28265853/response-derived-input-function-estimation-for-dynamic-contrast-enhanced-mri-demonstrated-by-anti-dll4-treatment-in-a-murine-u87-xenograft-model
#9
Matthew D Silva, Brittany Yerby, Jodi Moriguchi, Albert Gomez, H Toni Jun, Angela Coxon, Sharon E Ungersma
PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is an accepted method to evaluate tumor perfusion and permeability and anti-vascular cancer therapies. However, there is no consensus on the vascular input function estimation method, which is critical to kinetic modeling and K (trans) estimation. This work proposes a response-derived input function (RDIF) estimated from the response of the tumor, modeled as a linear, time-invariant (LTI) system. PROCEDURES: In an LTI system, an unknown input can be estimated from the system response...
March 6, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28262821/notch-ligand-dll4-alleviates-allergic-airway-inflammation-via-induction-of-a-homeostatic-regulatory-pathway
#10
Miao-Tzu Huang, Yi-Lien Chen, Chia-I Lien, Wei-Liang Liu, Li-Chung Hsu, Hideo Yagita, Bor-Luen Chiang
Notch is a pleiotropic signaling family that has been implicated in pathogenesis of allergic airway diseases; however, the distinct function of individual Notch ligands remains elusive. We investigated whether Notch ligands, Jagged1 and DLL4, exert differential effects in OVA-induced allergic asthma. We found that whilst Jagged1 inhibition mitigated Th2-dominated airway inflammation, blockage of DLL4 aggravated the Th2-mediated asthma phenotypes. Additionally, Jagged1 signaling blockage enhanced IL-17 production and neutrophilic airway infiltration...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216678/the-cul3-spop-daxx-axis-is-a-novel-regulator-of-vegfr2-expression-in-vascular-endothelial-cells
#11
Tomohisa Sakaue, Iori Sakakibara, Takahiro Uesugi, Ayako Fujisaki, Koh-Ichi Nakashiro, Hiroyuki Hamakawa, Eiji Kubota, Takashi Joh, Yu-Ki Imai, Hironori Izutani, Shigeki Higashiyama
Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28185609/olfactory-ensheathing-cells-inhibit-gliosis-in-retinal-degeneration-by-down-regulation-of-the-m%C3%A3-ller-cell-notch-signaling-pathway
#12
Jing Xie, Shujia Huo, Yijian Li, Jiaman Dai, Haiwei Xu, Zheng Qin Yin
Retinal regeneration and self-repair, whether in response to injury or degenerative disease, are severely impeded by glial scar formation by Müller cells (specialized retinal macroglia). We have previously demonstrated that the activation of Müller cells and gliosis in the degenerative retina are significantly suppressed by the subretinal transplantation of a mixture of olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts. However, the underlying molecular mechanism has remained elusive. Here, we transplanted purified rat OECs into the subretinal space of pigmented Royal College of Surgeons (RCS) rats, a classic rodent model of retinal degeneration...
February 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28177944/metformin-depresses-overactivated-notch1-hes1-signaling-in-colorectal-cancer-patients-with-type-2-diabetes-mellitus
#13
Bin Yang, Can-Ze Huang, Tao Yu, Sheng-Ning Zhou, Qi Liu, Gao-Jie Liu, Shuang Chen, Fang-Hai Han
The function of metformin in colorectal cancer (CRC) patients with diabetes mellitus (DM) remains a controversial topic because studies are increasingly focusing on epidemiologic features. We examined Notch1/Hes1 signaling in CRC with DM (DM-CRC) and investigated alterations in signaling caused by metformin treatment. For this purpose, information on pathological characteristics was collected from each patient. The proliferation of epithelium labeled with proliferating cell nuclear antigen and the differentiation of goblet cells were investigated using immunohistochemistry and periodic acid-Schiff staining, respectively...
February 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28160419/adams-oliver-syndrome-review-of-the-literature-refining-the-diagnostic-phenotype
#14
REVIEW
Susan Hassed, Shibo Li, John Mulvihill, Christopher Aston, Susan Palmer
The Adams-Oliver syndrome (AOS) is defined as aplasia cutis congenita (ACC) with transverse terminal limb defects (TTLD). Frequencies of associated anomalies are not well characterized. Six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. We review 385 previously described individuals (139 non-familial and 246 familial probands and family members) and add clinical data on 13 previously unreported individuals with AOS. In addition to ACC and TTLD, the most commonly associated anomalies included a wide variety of central nervous system (CNS) anomalies and congenital heart defects each seen in 23%...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28147322/vegf-promotes-cartilage-angiogenesis-by-phospho-erk1-2-activation-of-dll4-signaling-in-temporomandibular-joint-osteoarthritis-caused-by-chronic-sleep-disturbance-in-wistar-rats
#15
Yabing Dong, Gaoyi Wu, Ting Zhu, Hongyu Chen, Yong Zhu, Guoxiong Zhu, Fabin Han, Huaqiang Zhao
Chronic sleep disturbance (CSD) has been linked to the development of temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis of TMJ-OA is unclear, recent studies indicate that osteochondral angiogenesis is important. We developed a rat model of CSD induced TMJ-OA to investigate the changes caused by sleep disturbance and to correlate them with vascular invasion in the TMJ. We found pathological alterations and an increased microvessel density in the rat TMJ following CSD. VEGF, Dll4 and p-ERK1/2, the expression of angiogenic factors, were highly expressed in the rat mandibular condylar cartilage and their expression increased with CSD...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28124021/data-showing-proliferation-and-differentiation-of-intestinal-epithelial-cells-under-targeted-depletion-of-notch-ligands-in-mouse-intestine
#16
Toru Nakata, Hiromichi Shimizu, Sayaka Nagata, Go Ito, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Fumiaki Ishibashi, Reiko Kuno, Sho Anzai, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Katsuto Hozumi, Mamoru Watanabe, Ryuichi Okamoto
The data on the immunohistochemical analysis of conditional Notch ligand knockout mice is presented. Targeted deletion of Jag1, Dll1, Dll4, or Dll1 plus Dll4 in Lgr5(+ve) cells was induced by a Cre-mediated gene recombination, and differentiation or proliferation of the intestinal epithelial cells was examined by immunohistochemistry. These data are the extension of the data presented and discussed in the paper entitled "Indispensable role of non-canonical Notch signaling in the proliferation of Apc-deficient intestinal tumors" (Nakata et al...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28087639/vegfd-modulates-both-angiogenesis-and-lymphangiogenesis-during-zebrafish-embryonic-development
#17
Neil I Bower, Adam J Vogrin, Ludovic Le Guen, Huijun Chen, Steven A Stacker, Marc G Achen, Benjamin M Hogan
Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, giving rise to veins and lymphatics. Vegfd has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function...
February 1, 2017: Development
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#18
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28077598/notch-ligand-delta-like-4-promotes-regulatory-t-cell-identity-in-pulmonary-viral-infection
#19
Hung-An Ting, Matthew A Schaller, Denise E de Almeida Nagata, Andrew J Rasky, Ivan P Maillard, Nicholas W Lukacs
Regulatory T (Treg) cells establish tolerance, prevent inflammation at mucosal surfaces, and regulate immunopathology during infectious responses. Recent studies have shown that Delta-like ligand 4 (Dll4) was upregulated on APC after respiratory syncytial virus (RSV) infection, and its inhibition leads to exaggerated immunopathology. In the present study, we outline the role of Dll4 in Treg cell differentiation, stability, and function in RSV infection. We found that Dll4 was expressed on CD11b(+) pulmonary dendritic cells in the lung and draining lymph nodes in wild-type BALB/c mice after RSV infection...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28058628/a-pilot-study-on-plasma-levels-of-micro-rnas-involved-in-angiogenesis-and-vascular-maturation-in-patients-with-breast-cancer
#20
Emmanuel Kontomanolis, Achilleas Mitrakas, Alexandra Giatromanolaki, Dimitra Kareli, Marianthi Panteliadou, Stamatia Pouliliou, Michael I Koukourakis
Micro-RNAs (miRNAs) have a complex role in carcinogenesis and tumour progression. Several miRNAs, such as miR-221, miR-27b and miR-132, have been implicated in the regulation of VEGF tumour angiogenic activity. In this pilot study, we assessed angiogenesis and DLL4+ vascular maturation index (VMI) in breast cancer tissues, in parallel with the plasma levels of the above-mentioned miRNAs. Significantly higher than control samples pre-operative levels were recorded in 10/11, 7/11 and 9/11 cases for the miR-221, miR-27b and miR-132, respectively...
February 2017: Medical Oncology
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