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https://www.readbyqxmd.com/read/28079897/tsc1-expression-by-dendritic-cells-is-required-to-preserve-t-cell-homeostasis-and-response
#1
Yuechen Luo, Wenwen Li, Gang Yu, Juan Yu, Ling Han, Ting Xue, Zhina Sun, Song Chen, Chunming Fang, Chunxiao Zhao, Qing Niu, Fei Yang, Zhongchao Han, Tao Cheng, Yun Zeng, Fang Liao, Guogang Xu, Xiaoming Feng
Dendritic cells (DCs) are pivotal to the induction of adaptive T-cell immune responses. Recent evidence highlights a critical role of tuberous sclerosis complex 1 (Tsc1), a primarily upstream negative regulator of mammalian target of rapamycin (mTOR), in DC development, but whether and how Tsc1 directly regulate mature DC function in vivo remains elusive. Here we show that selective disruption of Tsc1 in DCs results in a lymphoproliferative disorder with the spontaneous activation of T cells. Tsc1 deficiency results in the activation of mTORC1-PPARγ pathway, which leads to the upregulation of neuropilin-1 (Nrp1) expression on DCs to stimulate naive T-cell proliferation...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28062852/a-proteomic-approach-to-identify-endosomal-cargoes-controlling-cancer-invasiveness
#2
Jesica Diaz-Vera, Sarah Palmer, Juan Ramon Hernandez-Fernaud, Emmanuel Dornier, Louise E Mitchell, Iain Macpherson, Joanne Edwards, Sara Zanivan, Jim C Norman
We have previously shown that Rab17 - a small GTPase associated with epithelial polarity - is specifically suppressed by ERK2 signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this are not known. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp-8 is associated with Rab17 at late endosomes...
January 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28025892/tandem-peptide-based-on-structural-modification-of-poly-arginine-for-enhancing-tumor-targeting-efficiency-and-therapeutic-effect
#3
Yayuan Liu, Zhengze Lu, Ling Mei, Qianwen Yu, Xiaowei Tai, Yang Wang, Kairong Shi, Zhirong Zhang, Qin He
The non-selectivity of cell penetrating peptides had greatly limited the application in systemic administration. By conjugating a dGR motif to the C-terminal of octa-arginine, the formed tandem peptide R8-dGR had been proved to specifically recognize both integrin αvβ3 and neuropilin-1 receptors. However, the positive charge of poly-arginine would still inevitably lead to rapid clearance in the circulation system. Therefore in this study, we tried to reduce the positive charge of poly-arginine by decreasing the number of arginine, thus to achieve improved tumor targeting efficiency...
December 27, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28000859/131i-labeled-monoclonal-antibody-targeting-neuropilin-receptor-type-2-for-tumor-spect-imaging
#4
Lichun Chen, Liangliang Wang, Jianghua Yan, Chao Ma, Jing Lu, Guoqiang Chen, Shengyou Chen, Fu Su, Weixing Wang, Xinhui Su
As a co-receptor for vascular endothelial growth factor‑3 (VEGF‑3), neuropilin receptor type‑2 (NRP‑2) plays a central role in lymphangiogenesis and angiogenesis. Recently, mounting data of evidence show that NRP‑2 is overexpressed in several human cancers, and its overexpression is often associated with poor prognosis. Therefore, it is necessary for us to develop an affinity reagent for noninvasive imaging of NRP‑2 expression because it may be possible to provide early cancer diagnosis, more accurate prognosis, and better treatment planning...
December 16, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27974617/hermes-regulates-axon-sorting-in-the-optic-tract-by-post-trancriptional-regulation-of-neuropilin-1
#5
Hanna Hörnberg, Jean-Michel Cioni, William A Harris, Christine E Holt
: The establishment of precise topographic maps during neural development is facilitated by the presorting of axons in the pathway before they reach their targets. In the vertebrate visual system, such topography is seen clearly in the optic tract (OT) and in the optic radiations. However, the molecular mechanisms involved in pretarget axon sorting are poorly understood. Here, we show in zebrafish that the RNA-binding protein Hermes, which is expressed exclusively in retinal ganglion cells (RGCs), is involved in this process...
December 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27940520/exploring-the-benefit-risk-associated-with-antiangiogenic-agents-for-the-treatment-of-non-small-cell-lung-cancer-patients
#6
Razelle Kurzrock, David J Stewart
Following the approval of bevacizumab, an antibody targeting vascular endothelial growth factor-A (VEGF-A), for advanced non-squamous non-small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)-targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti-VEGFR-½/3, platelet-derived growth factor receptor (PDGFR)-α/β, fibroblast growth factor receptor (FGFR)-½/3 angiokinase inhibitor indicated for adenocarcinoma of the lung in the European Union...
December 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27937055/curcumin-loaded-nanoliposomes-linked-to-homing-peptides-for-integrin-targeting-and-neuropilin-1-mediated-internalization
#7
Sogol Kangarlou, Sorour Ramezanpour, Saeed Balalaie, Shahla Roudbar Mohammadi, Ismaeil Haririan
CONTEXT: Curcumin, a naturally occurring polyphenol, has been extensively studied for its broad-spectrum anticancer effects. The potential benefits are, however, limited due to its poor water solubility and rapid degradation which result in low bioavailability on administration. OBJECTIVES: This study encapsulates curcumin in nanoliposomes including an integrin-homing peptide combined with a C end R neuropilin-1 targeting motif for targeted delivery and receptor-mediated internalization, respectively...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27921359/modulation-of-vegf-signaling-in-a-mouse-model-of-diabetes-by-xanthohumol-and-8-prenylnaringenin-unveiling-the-angiogenic-paradox-and-metabolism-interplay
#8
Raquel Costa, Ilda Rodrigues, Luísa Guardão, Joana Quelhas Lima, Emília Sousa, Raquel Soares, Rita Negrão
SCOPE: Imbalance in kidney and heart neovascularization is common in type2 Diabetes (T2DM) patients. Nevertheless, the mechanisms governing this angiogenic paradox have not been elucidated. Xanthohumol (XN) and 8-prenylnaringenin (8PN) beer polyphenols modulate angiogenesis, being thus targets for T2DM-related complications. Our work examined whether polyphenols consumption affects angiogenic paradox and metabolism in a T2DM mouse model. METHODS AND RESULTS: An increase in kidney and a reduction in left ventricle (LV) microvessels of diabetic C57Bl/6 mice were observed...
December 6, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27912840/the-semaphorins-and-their-receptors-as-modulators-of-tumor-progression
#9
Gera Neufeld, Yelena Mumblat, Tanya Smolkin, Shira Toledano, Inbal Nir-Zvi, Keren Ziv, Ofra Kessler
The semaphorins were initially characterized as repulsive axon guidance factors. However, they are currently also recognized as important regulators of diverse biological processes which include regulation of immune responses, angiogenesis, organogenesis, and a variety of additional physiological and developmental functions. The semaphorin family consists of more than 20 genes divided into seven subfamilies, all of which contain the sema domain signature. They usually transduce signals by activation of receptors belonging to the plexin family, either directly, or indirectly following the binding of some semaphorins to receptors of the neuropilin family which subsequently associate with plexins...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27906605/current-drug-design-to-target-the-semaphorin-neuropilin-plexin-complexes
#10
Lionel A T Meyer, Justine Fritz, Marie Pierdant-Mancera, Dominique Bagnard
The Semaphorin/Neuropilin/Plexin (SNP) complexes control a wide range of biological processes. Consistently, activity deregulation of these complexes is associated with many diseases. The increasing knowledge on SNP had in turn validated these molecular complexes as novel therapeutic targets. Targeting SNP activities by small molecules, antibodies and peptides or by soluble semaphorins have been proposed as new therapeutic approach. This review is focusing on the latest demonstration of this potential and discusses some of the key questions that need to be addressed before translating SNP targeting into clinically relevant approaches...
November 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27895796/promotion-of-metastasis-of-thyroid-cancer-cells-via-nrp-2-mediated-induction
#11
Dom-Gene Tu, Wen-Wei Chang, Ming-Shiou Jan, Chi-Wen Tu, Yin-Che Lu, Chien-Kuo Tai
Tumor-node-metastasis is one of the leading causes of morbidity and mortality in thyroid cancer patients. Upregulation of vascular endothelial growth factor-C (VEGF-C) increases the migratory ability of thyroid cancer cells to lymph nodes. Expression of neuropilin-2 (NRP-2), the co-receptor of VEGF-C, has been reported to be correlated with lymph node metastasis in human thyroid cancer. The present study investigated the role of VEGF-C/NRP-2 signaling in the regulation of metastasis of two different types of human thyroid cancer cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27889287/structure-activity-relationship-study-of-a-small-cyclic-peptide-h-c-lys-pro-glu-arg-oh-a-potent-inhibitor-of-vascular-endothelial-growth-factor-interaction-with-neuropilin-1
#12
Karolina Grabowska, Anna K Puszko, Piotr F J Lipiński, Anna K Laskowska, Beata Wileńska, Ewa Witkowska, Gerard Y Perret, Aleksandra Misicka
Inhibition of angiogenesis is one of the most promising approaches in anticancer therapy. It was recently suggested that Neuropilin-1 (NRP-1) in tumour cells may serve as a separate receptor for Vascular Endothelial Growth Factor-165 (VEGF165) which is one of the main pro-angiogenic agents in the organism. Therefore molecules inhibiting VEGF165 binding to NRP-1 could be potential candidates for new antiangiogenic and anticancer drugs. Here we present a structure-activity relationship study of the peptide H-c[Lys-Pro-Glu]-Arg-OH which showed high inhibitory effect on VEGF165/NRP-1 binding (IC50=0...
January 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27880905/semaphorin-3g-provides-a-repulsive-guidance-cue-to-lymphatic-endothelial-cells-via-neuropilin-2-plexind1
#13
Xinyi Liu, Akiyoshi Uemura, Yoko Fukushima, Yutaka Yoshida, Masanori Hirashima
The vertebrate circulatory system is composed of closely related blood and lymphatic vessels. It has been shown that lymphatic vascular patterning is regulated by blood vessels during development, but its molecular mechanisms have not been fully elucidated. Here, we show that the artery-derived ligand semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced lymphatic vascular branching...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27879479/identify-signature-regulatory-network-for-glioblastoma-prognosis-by-integrative-mrna-and-mirna-co-expression-analysis
#14
Zhi-Tong Bing, Guang-Hui Yang, Jie Xiong, Ling Guo, Lei Yang
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults. Patients with this disease have a poor prognosis. The objective of this study is to identify survival-related individual genes (or miRNAs) and miRNA -mRNA pairs in GBM using a multi-step approach. First, the weighted gene co-expression network analysis and survival analysis are applied to identify survival-related modules from mRNA and miRNA expression profiles, respectively. Subsequently, the role of individual genes (or miRNAs) within these modules in GBM prognosis are highlighted using survival analysis...
December 2016: IET Systems Biology
https://www.readbyqxmd.com/read/27863391/nordihydroguaiaretic-acid-impairs-prostate-cancer-cell-migration-and-tumor-metastasis-by-suppressing-neuropilin-1
#15
Xin Li, Shengjun Fan, Xueyang Pan, Yilixiati Xiaokaiti, Jianhui Duan, Yundi Shi, Yan Pan, Lu Tie, Xin Wang, Yuhua Li, Xuejun Li
Tumor metastasis is a major cause leading to the deaths of cancer patients. Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated to show therapeutic values in multiple diseases. In this study, we report that NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA suppresses NRP1 function by downregulating its expression, which leads to attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells. Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also impairs angiogenesis function of endothelial cells and fibronectin assembly by fibroblasts, both of which are critical to promote metastasis...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27858201/semaphorin3a-neuropilin1-signalling-is-involved-in-the-generation-of-cortical-interneurons
#16
William D Andrews, Melissa Barber, Marion Nemitz, Fani Memi, John G Parnavelas
Cortical interneurons are generated predominantly in the medial ganglionic eminence of the ventral telencephalon and migrate to the cortex during embryonic development. These cells express neuropilin (Nrp1 and Nrp2) receptors which mediate their response to the chemorepulsive class 3 semaphorin (Sema) ligands. We show here that semaphorins Sema3A and Sema3F are expressed in layers adjacent to cortical interneuron migratory streams as well as in the striatum, suggesting they may have a role in guiding these cells throughout their journey...
November 17, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27856318/sympathetic-nerve-repulsion-inhibited-by-designer-molecules-in-vitro-and-role-in-experimental-arthritis
#17
Julia Kunath, Nicolas Delaroque, Michael Szardenings, Ines Neundorf, Rainer H Straub
AIMS: In rheumatoid arthritis and collagen type II arthritis (CIA), sympathetic nerve fibers get lost in inflamed tissue. The process is probably induced by nerve repellent factors like semaphorin 3F (SEMA3F). Repulsion of sympathetic nerve fibers in inflamed tissue has proinflammatory effects due to the loss of anti-inflammatory neurotransmitters. We hypothesized that design molecules like antibodies and specific peptides that inhibit nerve fiber repulsion can ameliorate CIA. MATERIALS AND METHODS: Two blocking antibodies were used and four blocking peptides were generated using the phage display technique with the targets of SEMA3F and plexin-A2...
January 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27853189/a-multiscale-computational-model-predicts-distribution-of-anti-angiogenic-isoform-vegf165b-in-peripheral-arterial-disease-in-human-and-mouse
#18
Liang-Hui Chu, Vijay Chaitanya Ganta, Min H Choi, George Chen, Stacey D Finley, Brian H Annex, Aleksander S Popel
Angiogenesis is the growth of new blood vessels from pre-existing microvessels. Peripheral arterial disease (PAD) is caused by atherosclerosis that results in ischemia mostly in the lower extremities. Clinical trials including VEGF-A administration for therapeutic angiogenesis have not been successful. The existence of anti-angiogenic isoform (VEGF165b) in PAD muscle tissues is a potential cause for the failure of therapeutic angiogenesis. Experimental measurements show that in PAD human muscle biopsies the VEGF165b isoform is at least as abundant if not greater than the VEGF165a isoform...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27844052/neuropilin-1-and-the-positions-of-glomeruli-in-the-mouse-olfactory-bulb
#19
Bolek Zapiec, Olaf Christian Bressel, Mona Khan, Andreas Walz, Peter Mombaerts
It is known since 1996 that mouse odorant receptors (ORs) are involved in determining the positions of the sites of coalescence of axons of olfactory sensory neurons (OSNs)-the thousands of glomeruli in the olfactory bulb. But the molecular and cellular mechanisms of OR-mediated axonal coalescence into glomeruli remain unclear. A model was proposed in 2006-2009 whereby OR-derived cAMP signals, rather than direct action of OR molecules, determine the target destinations (glomeruli) of OSNs in the bulb. This model hypothesizes that OR-derived cAMP signals determine the expression levels of neuropilin 1 (Nrp1) in OSN axon termini; that levels of Nrp1 in glomeruli form a gradient from anterior-low to posterior-high throughout the bulb; and that these Nrp1 levels mechanistically determine anterior-posterior patterning of glomeruli...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27835904/tuftsin-prevents-the-negative-immunoregulation-of-neuropilin-1highcd4-cd25-regulatory-t-cells-and-improves-survival-rate-in-septic-mice
#20
Yu-Lei Gao, Mu-Ming Yu, Song-Tao Shou, Ying Yao, Yan-Cun Liu, Li-Jun Wang, Bin Lu, Yan-Fen Chai
Our previous research showed that neuropilin (Nrp) -1highCD4+CD25+Regulatory T cells (Tregs) exhibited primary negative immunoregulation in sepsis induced immune dysfunction. Tuftsin is the typical ligand of Nrp-1. Herein, we investigated the potential therapeutic value and mechanisms of tuftsin in sepsis. Sepsis per se markedly decreased the serum concentration of tuftsin, administration of tuftsin improved the survival rate of septic mice with cecal ligation and puncture (CLP). In vitro study, tuftsin prevented the negative immunoregulation of Nrp-1highCD4+CD25+Tregs, including weakening the expression of forkhead/winged helix transcription factor (Foxp)- 3/cytotoxic T lymphocyte associated antigen (CTLA)-4, inhibiting the secretion of transforming growth factor (TGF)-β, and weakening the immunosuppressive function of Nrp-1highCD4+CD25+Tregs to conventional CD4+CD25-T cells...
November 9, 2016: Oncotarget
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