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https://www.readbyqxmd.com/read/28526302/an-important-role-of-vegf-c-in-promoting-lymphedema-development
#1
Epameinondas Gousopoulos, Steven T Proulx, Samia B Bachmann, Lothar C Dieterich, Jeannette Scholl, Sinem Karaman, Roberta Bianchi, Michael Detmar
Secondary lymphedema is a common post-cancer treatment complication but the pathomechanisms underlying the disease remain unclear. Using a mouse-tail lymphedema model, we found an increase in local and systemic levels of the lymphangiogenic factor VEGF-C, and identified CD68+ macrophages as a cellular source. Surprisingly, overexpression of VEGF-C in a transgenic mouse model led to aggravation of lymphedema with increased immune cell infiltration and vascular leakage in comparison to wild-type littermates. Conversely, blockage of VEGF-C by overexpression of soluble VEGFR3 reduced edema development, diminishing inflammation and blood vascular leakage...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28459441/mural-lymphatic-endothelial-cells-regulate-meningeal-angiogenesis-in-the-zebrafish
#2
Neil I Bower, Katarzyna Koltowska, Cathy Pichol-Thievend, Isaac Virshup, Scott Paterson, Anne K Lagendijk, Weili Wang, Benjamin W Lindsey, Stephen J Bent, Sungmin Baek, Maria Rondon-Galeano, Daniel G Hurley, Naoki Mochizuki, Cas Simons, Mathias Francois, Christine A Wells, Jan Kaslin, Benjamin M Hogan
Mural cells of the vertebrate brain maintain vascular integrity and function, play roles in stroke and are involved in maintenance of neural stem cells. However, the origins, diversity and roles of mural cells remain to be fully understood. Using transgenic zebrafish, we identified a population of isolated mural lymphatic endothelial cells surrounding meningeal blood vessels. These meningeal mural lymphatic endothelial cells (muLECs) express lymphatic endothelial cell markers and form by sprouting from blood vessels...
June 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28438786/vegfr2-but-not-vegfr3-governs-integrity-and-remodeling-of-thyroid-angiofollicular-unit-in-normal-state-and-during-goitrogenesis
#3
Jeon Yeob Jang, Sung Yong Choi, Intae Park, Do Young Park, Kibaek Choe, Pilhan Kim, Young Keum Kim, Byung-Joo Lee, Masanori Hirashima, Yoshiaki Kubota, Jeong-Won Park, Sheue-Yann Cheng, Andras Nagy, Young Joo Park, Kari Alitalo, Minho Shong, Gou Young Koh
Thyroid gland vasculature has a distinguishable characteristic of endothelial fenestrae, a critical component for proper molecular transport. However, the signaling pathway that critically governs the maintenance of thyroid vascular integrity, including endothelial fenestrae, is poorly understood. Here, we found profound and distinct expression of follicular epithelial VEGF-A and vascular VEGFR2 that were precisely regulated by circulating thyrotropin, while there were no meaningful expression of angiopoietin-Tie2 system in the thyroid gland...
April 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28410190/dietary-oleuropein-inhibits-tumor-angiogenesis-and-lymphangiogenesis-in-the-b16f10-melanoma-allograft-model-a-mechanism-for-the-suppression-of-high-fat-diet-induced-solid-tumor-growth-and-lymph-node-metastasis
#4
Hyerim Song, Do Young Lim, Jae In Jung, Han Jin Cho, So Young Park, Gyoo Taik Kwon, Young-Hee Kang, Ki Won Lee, Myung-Sook Choi, Jung Han Yoon Park
Previously, we reported that high-fat-diet (HFD)-induced obesity stimulates melanoma progression in the B16F10 allograft model. In this study, we examined whether oleuropein (OL), the most abundant phenolic compound in olives, inhibits HFD-induced melanoma progression. Four-week-old male C57BL/6N mice were fed a HFD-diet with or without OL. After 16 weeks of feeding, B16F10-luc cells were subcutaneously injected and the primary tumor was resected 3 weeks later. OL suppressed HFD-induced solid tumor growth. In the tumor tissues, OL reduced HFD-induced expression of angiogenesis (CD31, VE-cadherin, VEGF-A, and VEGFR2), lymphangiogenesis (LYVE-1, VEGF-C, VEGF-D, and VEGFR3), and hypoxia (HIF-1α and GLUT-1) markers as well as HFD-induced increases in lipid vacuoles and M2 macrophages (MΦs)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376864/antiangiogenic-effects-of-oridonin
#5
Lili Tian, Kangjie Xie, Donglai Sheng, Xiaoqing Wan, Guofu Zhu
BACKGROUND: Oridonin, the major terpene found in Rabdosia rubescens (Henmsl.) Hara, is widely used as a dietary supplement and therapeutic drug. Oridonin has been proven to possess good anti-tumour activity, but little is known about its effect on angiogenesis. The aim of this study was to investigate the antiangiogenic effects of oridonin in vivo and in vitro and prove that oridonin anti-tumour activity is based on suppressing angiogenesis. METHODS: In vitro, the antiangiogenesis effect was studied by proliferation, apoptosis, migration, invasion, and tube formation experiments on human umbilical vascular endothelial cells (HUVECs)...
April 4, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28356442/modulation-of-endothelial-bmpr2-activity-by-vegfr3-in-pulmonary-arterial-hypertension
#6
Cheol Hwangbo, Heon-Woo Lee, Hyeseon Kang, Hyekyung Ju, David S Wiley, Irinna Papangeli, Jinah Han, Jun-Dae Kim, William P Dunworth, Xiaoyue Hu, Seyoung Lee, Omar El-Hely, Avraham Sofer, Boryeong Pak, Laura Peterson, Suzy Comhair, Eun Mi Hwang, Jae-Yong Park, Jean-Léon Thomas, Victoria L Bautch, Serpil C Erzurum, Hyung J Chun, Suk-Won Jin
Background -Bone Morphogenetic Protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP type 2 receptors (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with BMPR2 mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH. Methods -We utilized a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of Vegfr3 to determine the interaction between VEGFR3 and BMPR2...
March 29, 2017: Circulation
https://www.readbyqxmd.com/read/28349940/adventitial-lymphatic-capillary-expansion-impacts-on-plaque-t-cell-accumulation-in-atherosclerosis
#7
Timo Rademakers, Emiel P C van der Vorst, Isabelle T M N Daissormont, Jeroen J T Otten, Kosta Theodorou, Thomas L Theelen, Marion Gijbels, Andrey Anisimov, Harri Nurmi, Jan H N Lindeman, Andreas Schober, Sylvia Heeneman, Kari Alitalo, Erik A L Biessen
During plaque progression, inflammatory cells progressively accumulate in the adventitia, paralleled by an increased presence of leaky vasa vasorum. We here show that next to vasa vasorum, also the adventitial lymphatic capillary bed is expanding during plaque development in humans and mouse models of atherosclerosis. Furthermore, we investigated the role of lymphatics in atherosclerosis progression. Dissection of plaque draining lymph node and lymphatic vessel in atherosclerotic ApoE(-/-) mice aggravated plaque formation, which was accompanied by increased intimal and adventitial CD3(+) T cell numbers...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#8
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28298294/vegfr3-modulates-vascular-permeability-by-controlling-vegf-vegfr2-signaling
#9
Krista Heinolainen, Sinem Karaman, Gabriela D'Amico, Tuomas Tammela, Raija Sormunen, Lauri Eklund, Kari Alitalo, Georgia Zarkada
Rationale: Vascular endothelial growth factor (VEGF) is the main driver of angiogenesis and vascular permeability via VEGF receptor 2 (VEGFR2), while lymphangiogenesis signals are transduced by VEGFC/D via VEGFR3. VEGFR3 also regulates sprouting angiogenesis and blood vessel growth, but to what extent VEGFR3 signaling controls blood vessel permeability remains unknown. Objective: To investigate the role of VEGFR3 in the regulation of VEGF-induced vascular permeability. Methods and Results: Long-term global Vegfr3 gene deletion in adult mice resulted in increased fibrinogen deposition in lungs and kidneys, indicating enhanced vascular leakage at the steady state...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28163024/vascular-endothelial-growth-factor-c-induces-osteogenic-differentiation-of-human-mesenchymal-stem-cells-through-the-erk-and-runx2-pathway
#10
Juri Murakami, Masakazu Ishii, Fumio Suehiro, Kiyohide Ishihata, Norifumi Nakamura, Masahiro Nishimura
Vascular endothelial cell growth factor C (VEGF-C) is a member of the VEGF family and plays a role in a variety of biological activities including lymphangiogenesis, angiogenesis, and neurogenesis through VEGF receptor 2 (VEGFR2) and 3 (VEGFR3). However, it has not been elucidated whether VEGF-C promotes osteogenic differentiation. Herein, we investigated the effects of VEGF-C on osteogenic differentiation in human mesenchymal stem cells (MSCs) and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly increased RUNX2 expression, and led to the promotion of osteogenic marker gene expression and mineralization of MSCs...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28123542/influence-of-vegfr-single-nucleotide-polymorphisms-on-the-efficacy-of-sunitinib-therapy-against-renal-cell-carcinoma
#11
Rui Liu, Xiaojie Wang, Wei Li, Tao Shou, Likun Zhou, Yunfen Li, Ming Bai, Qiang Pei
Single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor receptor (VEGFR) may have effects on the MAPK/ERK/STAT3 signaling pathway, and the resulting phenotypes may influence the response to sunitinib-targeted therapy for renal cell carcinoma. In order to test this hypothesis patients with advanced renal cell carcinoma treated with sunitinib, were enrolled in our study. Peripheral blood samples were used to run a polymerase chain reaction-restriction fragment length polymorphism protocol to type candidate nucleotide polymorphism loci (VEGFR1, VEGFR2 and VEGFR3)...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28102887/clinical-trial-of-nintedanib-in-patients-with-recurrent-or-metastatic-salivary-gland-cancer-of-the-head-and-neck-a-multicenter-phase-2-study-korean-cancer-study-group-hn14-01
#12
Youjin Kim, Su Jin Lee, Ji Yun Lee, Se-Hoon Lee, Jong-Mu Sun, Keunchil Park, Ho Jung An, Jae Yong Cho, Eun Joo Kang, Ha-Young Lee, Jinsoo Kim, Bhumsuk Keam, Hye Ryun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung-Ju Ahn
BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß)...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28087639/vegfd-modulates-both-angiogenesis-and-lymphangiogenesis-during-zebrafish-embryonic-development
#13
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/28055225/overexpression-of-prox1-induces-the-differentiation-of-human-adipose-derived-stem-cells-into-lymphatic-endothelial-like-cells-in-vitro
#14
Jingcheng Deng, Tingting Dai, Yiyu Sun, Qi Zhang, Zhaohua Jiang, Shengli Li, Weigang Cao
Constant levels of homeobox transcription factor Prox1 expression are required throughout the life of lymphatic endothelial cells (LECs) to maintain their differentiated identity. Recent studies have demonstrated that using human LECs for cell transplantation therapy may improve secondary lymphedema in a nude rat model. However, the application is currently limited by the low yield of LECs. In this study, Prox1 was overexpressed in human adipose tissue-derived stem cells (hADSCs) by using the transfection of lentiviral vectors to induce the differentiation of hADSCs to LECs...
February 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28049091/taspine-derivative-12k-suppressed-a549-cell-migration-through-the-wnt-%C3%AE-catenin-and-ephrinb2-signaling-pathway
#15
Bingling Dai, Yujiao Ma, Tianfeng Yang, Wenjie Wang, Yanmin Zhang
12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28004478/cs2164-a-novel-multi-target-inhibitor-against-tumor-angiogenesis-mitosis-and-chronic-inflammation-with-anti-tumor-potency
#16
You Zhou, Song Shan, Zhi-Bin Li, Li-Jun Xin, De-Si Pan, Qian-Jiao Yang, Ying-Ping Liu, Xu-Peng Yue, Xiao-Rong Liu, Ji-Zhou Gao, Jin-Wen Zhang, Zhi-Qiang Ning, Xian-Ping Lu
Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range...
March 2017: Cancer Science
https://www.readbyqxmd.com/read/27901498/targeting-the-vegf-c-vegfr3-axis-suppresses-slug-mediated-cancer-metastasis-and-stemness-via-inhibition-of-kras-yap1-signaling
#17
REVIEW
Yu-Wen Yeh, Ching-Chia Cheng, Shu-Ting Yang, Chi-Feng Tseng, Ting-Yu Chang, Sin-Ying Tsai, Earl Fu, Chien-Ping Chiang, Li-Chuan Liao, Pei-Wen Tsai, Yung-Luen Yu, Jen-Liang Su
Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27896475/an-exploratory-association-of-polymorphisms-in-angiogenesis-related-genes-with-susceptibility-clinical-response-and-toxicity-in-gastrointestinal-stromal-tumors-receiving-sunitinib-after-imatinib-failure
#18
Gloria Ravegnini, Margherita Nannini, Corrado Zenesini, Vittorio Simeon, Giulia Sammarini, Milena Urbini, Lidia Gatto, Maristella Saponara, Guido Biasco, Maria A Pantaleo, Nicola Venturoli, Patrizia Hrelia, Sabrina Angelini
The angiogenic pathway plays a pivotal role in tumor growth, invasiveness and metastasis. The most important actors in the angiogenic pathway are VEGFA and its receptors VEGFR1, 2 and 3. These genes are polymorphic, and the presence of single nucleotide polymorphisms may result in angiogenic deregulation. Herein, we hypothesized that germline variants may affect sunitinib efficacy (TTP and OS) and/or toxicity. Therefore, we investigated 19 polymorphisms, in four genes, in 54 GIST patients, treated with second-line sunitinib and 147 healthy controls...
November 28, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27861873/notch-signaling-pathway-regulates-angiogenesis-via-endothelial-cell-in-3d-co-culture-model
#19
Dan Zhao, Changyue Xue, Shiyu Lin, Sirong Shi, Qianshun Li, Mengting Liu, Xiaoxiao Cai, Yunfeng Lin
This study aimed to investigate the role of Notch signaling pathway for angiogenesis in a three-dimensional (3D) collagen gel model with co-culture of adipose-derived stromal cells (ASCs) and endothelial cells (ECs). A 3D collagen gel model was established in vitro by implanting both ASCs from green fluorescent protein-labeled mouse and ECs from red fluorescent protein-labeled mouse, and the phenomena of angiogenesis with Notch signaling inducer Jagged1, inhibitor DAPT and PBS, respectively were observed by confocal laser scanning microscopy...
June 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27787629/lymphangiogenesis-in-rat-asthma-model
#20
Aigul Moldobaeva, John Jenkins, Qiong Zhong, Elizabeth M Wagner
Although bronchial angiogenesis has been well documented in allergic asthma, lymphangiogenesis has not been widely studied. Therefore, we evaluated changes in lung lymphatics in a rat model of allergen-induced asthma using house dust mite (Der p 1; 100 μg/challenge). Additionally, properties of isolated lung lymphatic endothelial cells (CD45(-), CD141(+), LYVE-1(+), Prox-1(+)) were studied in vitro. Three weeks after the onset of intranasal allergen exposure (twice-weekly), an increase in the number of lung lymphatic vessels was measured (34% increase) by lung morphometry...
February 2017: Angiogenesis
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