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https://www.readbyqxmd.com/read/29026302/ultrasmall-aguix-theranostic-nanoparticles-for-vascular-targeted-interstitial-photodynamic-therapy-of-glioblastoma
#1
Eloïse Thomas, Ludovic Colombeau, Mickaël Gries, Thibaut Peterlini, Clélia Mathieu, Noémie Thomas, Cédric Boura, Céline Frochot, Régis Vanderesse, François Lux, Muriel Barberi-Heyob, Olivier Tillement
Despite combined treatments, glioblastoma outcome remains poor with frequent local recurrences, indicating that a more efficient and local therapy is needed. In this way, vascular-targeted photodynamic therapy (VTP) could help tumor eradication by destroying its neovessels. In this study, we designed a polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI) contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR) targeting neuropilin-1 (NRP-1), a receptor overexpressed by angiogenic endothelial cells of the tumor vasculature...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29025973/dynamic-multi-site-phosphorylation-by-fyn-and-abl-drives-the-interaction-between-crkl-and-the-novel-scaffolding-receptors-dcbld1-and-dcbld2
#2
Anna M Schmoker, Jaye L Weinert, Kyle J Kellett, Hannah E Johnson, Ryan M Joy, Marion E Weir, Alicia M Ebert, Bryan A Ballif
Discoidin, CUB, and LCCL Domain-containing (DCBLD) 2 is a neuropilin-like transmembrane scaffolding receptor with known and anticipated roles in vascular remodeling and neuronal positioning. DCBLD2 is also upregulated in several cancers and can drive glioblastomas downstream of activated Epidermal Growth Factor Receptor. While a few studies have shown either a positive or negative role for DCBLD2 in regulating growth factor receptor signaling, little is known about the conserved signaling features of DCBLD family members that drive their molecular activities...
October 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29018206/tumor-penetrating-delivery-of-sirna-against-tnf%C3%AE-to-human-vestibular-schwannomas
#3
Yin Ren, Jessica E Sagers, Lukas D Landegger, Sangeeta N Bhatia, Konstantina M Stankovic
Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle, and it typically presents with sensorineural hearing loss. The genomic landscape of schwannoma is complex and many of the molecules implicated in VS pathogenesis represent targets not amenable to antibody-based or small molecule therapeutics. Tumor-targeted delivery of small interfering RNA (siRNA) therapeutics provides a direct and effective means to interrogate targets while minimizing off-target effects. To establish a preclinical model for therapeutic inhibition of putative targets in VS, archived tumor specimens, fresh tumor cells derived from patients with sporadic VS, and an established schwannoma cell line were screened...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29018205/genetic-status-of-kras-modulates-the-role-of-neuropilin-1-in-tumorigenesis
#4
Sneha Vivekanandhan, Lijuan Yang, Ying Cao, Engfeng Wang, Shamit K Dutta, Anil K Sharma, Debabrata Mukhopadhyay
Neuropilin-1 (NRP1), a non-tyrosine kinase receptor, is overexpressed in many cancers including pancreatic and lung cancers. Inhibition of NRP1 expression, however, has differing pro-tumor vs. anti-tumor effects, depending on the cancer types. To understand the differential role of NRP1 in tumorigenesis process, we utilized cells from two different cancer types, pancreatic and lung, each containing either wild type KRAS (KRAS (wt)) or mutant KRAS (KRAS (mt)). Inhibition of NRP1 expression by shRNA in both pancreatic and lung cancer cells containing dominant active KRAS (mt) caused increased cell viability and tumor growth...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29017512/metastatic-pathway-and-the-microvascular-and-physicochemical-microenvironments-of-human-melanoma-xenografts
#5
Ruixia Huang, Lise Mari K Andersen, Einar K Rofstad
BACKGROUND: Malignant melanoma of the skin can metastasize through blood vessels and lymphatics. The primary tumor develops a vascular microenvironment characterized by abnormal blood vessels and lymphatics and a physicochemical microenvironment characterized by low oxygen tension, regions with hypoxic tissue, and high interstitial fluid pressure (IFP). This study aimed at identifying relationships between the metastatic route of melanomas and characteristic features of the microvascular and physicochemical microenvironments of the primary tumor...
October 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28977999/platelet-derived-growth-factor-c-promotes-human-melanoma-aggressiveness-through-activation-of-neuropilin-1
#6
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28961428/the-neuropilins-and-their-ligands-in-hematogenous-metastasis-of-salivary-adenoid-cystic-carcinoma-an-immunohistochemical-study
#7
Qianwei Ni, Jinlong Sun, Chao Ma, Yun Li, Jun Ju, Moyi Sun
PURPOSE: We investigated the expression of neuropilin-1 (NRP1), neuropilin-2 (NRP2), vascular endothelial growth factor-A (VEGF-A), semaphorin-3A (Sema-3A), and semaphorin-3F (Sema-3F) in normal salivary gland (NSG) tissue, nonmetastatic salivary adenoid cystic carcinoma (SACC), and metastatic SACC to better understand their role in intratumoral angiogenesis and hematogenous metastasis of SACC. PATIENTS AND METHODS: The study included 60 SACC patients, equally divided between nonmetastatic SACC and metastatic SACC...
September 7, 2017: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28954991/antiangiogenic-agent-sunitinib-induces-epithelial-to-mesenchymal-transition-and-accelerates-motility-of-colorectal-cancer-cells
#8
Chisato Tomida, Naoko Yamagishi, Hikaru Nagano, Takayuki Uchida, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo
Although vascular endothelial growth factor receptor (VEGF-R)-targeted antiangiogenic agents are important treatment for a number of human malignancies, there is accumulating evidence that the therapies may promote disease progression, such as invasion and metastasis. How tumors become to promote their evasiveness remains fully uncertain. One of possible mechanisms for the adaptation may be a direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. To elucidate a direct effect of VEGF-R-targeting drug (sunitinib), we established a human colorectal cancer cell model adapted to sunitinib...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28951988/a-genomic-screen-for-angiosuppressor-genes-in-the-tumor-endothelium-identifies-a-multifaceted-angiostatic-role-for-bromodomain-containing-7-brd7
#9
Judy R van Beijnum, Patrycja Nowak-Sliwinska, Maaike van Berkel, Tse J Wong, Arjan W Griffioen
Tumor angiogenesis is characterized by deregulated gene expression in endothelial cells (EC). While studies until now have mainly focused on overexpressed genes in tumor endothelium, we here describe the identification of transcripts that are repressed in tumor endothelium and thus have potential suppressive effects on angiogenesis. We identified nineteen putative angiosuppressor genes, one of them being bromodomain containing 7 (BRD7), a gene that has been assigned tumor suppressor properties. BRD7 was studied in more detail, and we demonstrate that BRD7 expression is inversely related to EC activation...
September 26, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28938007/neuropilin-1-modulates-tgf%C3%AE-signaling-to-drive-glioblastoma-growth-and-recurrence-after-anti-angiogenic-therapy
#10
Sam C Kwiatkowski, Paola A Guerrero, Shinya Hirota, Zhihua Chen, John E Morales, Manish Aghi, Joseph H McCarty
Glioblastoma (GBM) is a rapidly progressive brain cancer that exploits the neural microenvironment, and particularly blood vessels, for selective growth and survival. Anti-angiogenic agents such as the vascular endothelial growth factor-A (VEGF-A) blocking antibody bevacizumab yield short-term benefits to patients due to blood vessel regression and stabilization of vascular permeability. However, tumor recurrence is common, and this is associated with acquired resistance to bevacizumab. The mechanisms that drive acquired resistance and tumor recurrence in response to anti-angiogenic therapy remain largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28933986/the-antiangiogenesis-effect-of-pirfenidone-in-wound-healing-in-vitro
#11
Xiao'an Liu, Yangfan Yang, Xiujuan Guo, Liling Liu, Kaili Wu, Minbin Yu
Abstracts Background: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring...
September 21, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28929539/refuting-the-hypothesis-that-semaphorin-3f-neuropilin-2-exclude-blood-vessels-from-the-cap-mesenchyme-in-the-developing-kidney
#12
David A D Munro, Peter Hohenstein, Thomas M Coate, Jamie A Davies
BACKGROUND: During murine kidney development, new cortical blood vessels form and pattern in cycles that coincide with cycles of collecting duct branching and the accompanying splitting of the cap mesenchyme (nephron progenitor cell populations that 'cap' collecting duct ends). At no point in the patterning cycle do blood vessels enter the cap mesenchyme. We hypothesised that the exclusion of blood vessels from the cap mesenchyme may be controlled, at least in part, by an anti-angiogenic signal expressed by the cap mesenchyme cells...
September 20, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28910136/nrp1-accelerates-odontoblast-differentiation-of-dental-pulp-stem-cells-through-classical-wnt-%C3%AE-catenin-signaling
#13
Yihua Song, Xiaojuan Liu, Xingmei Feng, Zhifeng Gu, Yongchun Gu, Min Lian, Jingwen Xiao, Peipei Cao, Ke Zheng, Xiaobing Gu, Dongping Li, Ping He, Chenfei Wang
Neuropilin-1 (NRP1) is one of the members of neuropilin family. It can combine with disparate ligands involved in regulating cell proliferation, apoptosis, and differentiation. The binding of NRP1 to Sema3A stimulates osteoblast differentiation through the classical Wnt/β-catenin pathway. However, the functions of NRP1 in dental pulp stem cells (DPSCs) are not clear. The aim of our study was to investigate how NRP1 controlled odontoblast differentiation in DPSCs and clarified the underlying mechanisms. NRP1 expression was increased in time-dependent manner along with cell odontoblast differentiation...
October 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28893946/a-radial-axis-defined-by-semaphorin-to-neuropilin-signaling-controls-pancreatic-islet-morphogenesis
#14
Philip T Pauerstein, Krissie Tellez, Kirk B Willmarth, Keon Min Park, Brian Hsueh, H Efsun Arda, Xueying Gu, Haig Aghajanian, Karl Deisseroth, Jonathan A Epstein, Seung K Kim
The islets of Langerhans are endocrine organs characteristically dispersed throughout the pancreas. During development, endocrine progenitors delaminate, migrate radially, and cluster to form islets. Despite the distinctive distribution of islets, spatially localized signals that control islet morphogenesis have not been discovered. Here we identify a radial signaling axis that instructs developing islet cells to disperse throughout the pancreas. A screen of pancreatic extracellular signals identified factors that stimulated islet cell development...
September 11, 2017: Development
https://www.readbyqxmd.com/read/28887481/glycosylation-dependent-galectin-1-neuropilin-1-interactions-promote-liver-fibrosis-through-activation-of-tgf-%C3%AE-and-pdgf-like-signals-in-hepatic-stellate-cells
#15
Ming-Heng Wu, Yuh-Ling Chen, Kuen-Haur Lee, Che-Chang Chang, Tsai-Mu Cheng, Szu-Yuan Wu, Chao-Chiang Tu, Wan-Lin Tsui
Concomitant expressions of glycan-binding proteins and their bound glycans regulate many pathophysiologic processes, but this issue has not been addressed in liver fibrosis. Activation of hepatic stellate cells (HSCs) is a rate-limiting step in liver fibrosis and is an important target for liver fibrosis therapy. We previously reported that galectin (Gal)-1, a β-galactoside-binding protein, regulates myofibroblast homeostasis in oral carcinoma and wound healing, but the role of Gal-1 in HSC migration and activation is unclear...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887477/neuropilin-1-is-upregulated-by-wnt-%C3%AE-catenin-signaling-and-is-important-for-mammary-stem-cells
#16
Wei Liu, Ting Wu, Xiaobing Dong, Yi Arial Zeng
Wnt/β-catenin signaling is instrumental for the development of mammary gland and the properties of mammary stem cells (MaSCs). The Wnt signaling downstream effectors that engage in regulating MaSCs have not been extensively studied. Here, we report that Neuropilin-1 (Nrp1) expression is induced by Wnt/β-catenin signaling in MaSCs, and its function is critical for the activity of MaSCs. Nrp1 is particularly expressed in MaSCs that are marked by the expression of Protein C Receptor (Procr). Knockdown of Nrp1 by shRNA diminishes MaSCs' in vitro colony formation and in vivo mammary gland reconstitution ability...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887220/enhanced-glioma-therapy-by-synergistic-inhibition-of-autophagy-and-tyrosine-kinase-activity
#17
Xuhui Wang, Yue Qiu, Qianwen Yu, Hui Li, Xiaoxiao Chen, Man Li, Yang Long, Yayuan Liu, Libao Lu, Jiajing Tang, Zhirong Zhang, Qin He
Autophagy is a lysosomal degradation pathway that acts as a cytoprotective mechanism causing treatment resistance in various cancer cells. Recent studies showed that hydroxychloroquine can inhibit the latter step of autophagy and therefore enhance the anti-glioma efficiency of ZD6474, a tyrosine kinase inhibitor. However, the nonselective distribution of ZD6474 in vivo and the low penetrating ability of hydroxychloroquine when crossing the blood-brain barrier restrict their clinical use in glioma therapy. Here we coencapsulated ZD6474 and hydroxychloroquine into R6dGR peptide-modified liposomes (R6dGR-Lip) which can specifically recognize both integrin αvβ3 and neuropilin-1 receptors that are highly expressed on the endothelial cells and glioma cells...
September 5, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28868347/major-effect-of-transcytosis-on-nano-drug-delivery-to-pancreatic-cancer
#18
Xiangsheng Liu, Jinhong Jiang, Andre E Nel, Huan Meng
We demonstrated that activated transcytosis is a major mechanism to complement the classic enhanced permeability and retention effect in pancreatic cancer. This was achieved by using an iRGD peptide that triggers transcytosis pathway at the tumor site. Co-administration of unconjugated iRGD substantially improved the effect of the chemotherapeutics delivering nanocarrier, and resulted in survival improvement in mice. Since the iRGD effect is commensurate with neuropilin-1 expression on tumor vasculature, it is necessary to contemplate a personalized approach to implement this technology...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28843905/role-of-neuropilin-2-in-the-immune-system
#19
REVIEW
S Schellenburg, A Schulz, D M Poitz, M H Muders
Neuropilins (NRPs) are single transmembrane receptors with short cytoplasmic tails and are dependent on receptors like VEGF receptors or Plexins for signal transduction. NRPs are known to be important in angiogenesis, lymphangiogenesis, and axon guidance. The Neuropilin-family consists of two members, Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). They are up to 44 % homologous and conserved in all vertebrates. High levels of NRP2 are found on immune cells. Current research is very limited regarding the functions of NRP2 on these cells...
October 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28835631/neuropilin-1-sequestration-by-neuropathogenic-mutant-glycyl-trna-synthetase-is-permissive-to-vascular-homeostasis
#20
James N Sleigh, Adriana Gómez-Martín, Na Wei, Ge Bai, Xiang-Lei Yang, Giampietro Schiavo
The mechanism by which dominantly inherited mutations in the housekeeping gene GARS, which encodes glycyl-tRNA synthetase (GlyRS), mediate selective peripheral nerve toxicity resulting in Charcot-Marie-Tooth disease type 2D (CMT2D) is still largely unresolved. The transmembrane receptor protein neuropilin 1 (Nrp1) was recently identified as an aberrant extracellular binding partner of mutant GlyRS. Formation of the Nrp1/mutant GlyRS complex antagonises Nrp1 interaction with one of its main natural ligands, vascular endothelial growth factor-A (VEGF-A), contributing to neurodegeneration...
August 23, 2017: Scientific Reports
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