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https://www.readbyqxmd.com/read/28516164/engineered-ligand-based-vegfr-antagonists-with-increased-receptor-binding-affinity-more-effectively-inhibit-angiogenesis
#1
Shiven Kapur, Adam P Silverman, Anne Z Ye, Niv Papo, Darren Jindal, Mark S Blumenkranz, Jennifer R Cochran
Pathologic angiogenesis is mediated by the coordinated action of the vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling axis, along with crosstalk contributed by other receptors, notably αvβ3 integrin. We build on earlier work demonstrating that point mutations can be introduced into the homodimeric VEGF ligand to convert it into an antagonist through disruption of binding to one copy of VEGFR2. This inhibitor has limited potency, however, due to loss of avidity effects from bivalent VEGFR2 binding...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28512254/catecholamines-facilitate-vegf-dependent-angiogenesis-via-%C3%AE-2-adrenoceptor-induced-epac1-and-pka-activation
#2
Jaspal Garg, Yu-Xi Feng, Sepp R Jansen, Julian Friedrich, Frank Lezoualc'h, Martina Schmidt, Thomas Wieland
Chronic stress has been associated with the progression of cancer and antagonists for β-adrenoceptors (βAR) are regarded as therapeutic option. As they are also used to treat hemangiomas as well as retinopathy of prematurity, a role of endothelial β2AR in angiogenesis can be envisioned. We therefore investigated the role of β2AR-induced cAMP formation by analyzing the role of the cAMP effector molecules exchange factor directly activated by cAMP 1 (Epac1) and protein kinase A (PKA) in endothelial cells (EC)...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502557/antecedents-and-early-correlates-of-high-and-low-concentrations-of-angiogenic-proteins-in-extremely-preterm-newborns
#3
Alan Leviton, Stanthia Ryan, Elizabeth N Allred, Raina N Fichorova, T Michael O'Shea, Karl Kuban, Olaf Dammann
BACKGROUND: To identify the antecedents and very early correlates of low concentrations of angiogenic proteins in the blood of extremely preterm newborns during the first postnatal month. METHODS: Using multiplex immunoassays we measured the concentrations of vascular endothelial growth factor A (VEGF), VEGF receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), placenta growth factor (PIGF), and angiopoietins 1 and 2 (Ang-1, Ang-2), as well as 21 other proteins in blood spots collected on postnatal days 1 (N=1062), 7 (N=1087), 14 (N=989), 21 (N=940) and 28 (N=880) from infants born before the 28th week of gestation...
May 11, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28501476/endothelial-cells-are-not-required-for-specification-of-respiratory-progenitors
#4
Jamie A Havrilak, Kristin R Melton, John M Shannon
Crosstalk between mesenchymal and epithelial cells influences organogenesis in multiple tissues, such as lung, pancreas, liver, and the nervous system. Lung mesenchyme comprises multiple cell types, however, and precise identification of the mesenchymal cell type(s) that drives early events in lung development remains unknown. Endothelial cells have been shown to be required for some aspects of lung epithelial patterning, lung stem cell differentiation, and regeneration after injury. Furthermore, endothelial cells are involved in early liver and pancreas development...
May 10, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28499383/nintedanib-antiangiogenic-inhibitor-effectiveness-in-delaying-adenocarcinoma-progression-in-transgenic-adenocarcinoma-of-the-mouse-prostate-tramp
#5
Raquel Frenedoso da Silva, Ellen Nogueira-Pangrazi, Larissa Akemi Kido, Fabio Montico, Sarah Arana, Dileep Kumar, Komal Raina, Rajesh Agarwal, Valéria Helena Alves Cagnon
BACKGROUND: In recent times, anti-cancer treatments have focused on Fibroblast Growth Factor (FGF) and Vascular-Endothelial Growth Factor (VEGF) pathway inhibitors so as to target tumor angiogenesis and cellular proliferation. One such drug is Nintedanib; the present study evaluated the effectiveness of Nintedanib treatment against in vitro proliferation of human prostate cancer (PCa) cell lines, and growth and progression of different grades of PCa lesions in pre-clinical PCa transgenic adenocarcinoma for the mouse prostate (TRAMP) model...
May 12, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28498441/radiolabeling-of-vegf165-with-99mtc-to-evaluate-vegfr-expression-in-tumor-angiogenesis
#6
Filippo Galli, Marco Artico, Samanta Taurone, Isabella Manni, Enrica Bianchi, Giulia Piaggio, Bruce D Weintraub, Mariusz W Szkudlinski, Enzo Agostinelli, Rudi A J O Dierckx, Alberto Signore
Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic drugs that block the VEGFR pathway. Aim of the present study was to radiolabel the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the expression of VEGFR in both cancer and endothelial cells in the tumor microenvironment...
May 8, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28498260/combined-gene-therapy-using-adsvegfr2-and-adstie2-with-chemotherapy-reduces-the-growth-of-human-ovarian-cancer-and-formation-of-ascites-in-mice
#7
Laura Tuppurainen, Hanna Sallinen, Anni Karvonen, Elina Valkonen, Hanne Laakso, Timo Liimatainen, Elisa Hytönen, Kirsi Hämäläinen, Veli-Matti Kosma, Maarit Anttila, Seppo Ylä-Herttuala
OBJECTIVES: Ovarian cancer is highly dependent on tumor microvessels and angiogenesis regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) and angiopoietins (Ang) and their Tie receptors. We studied the efficacy of adenoviral (Ad) gene therapy with soluble VEGFR2 and Tie2 combined with paclitaxel and carboplatin for the treatment of ovarian cancer. METHODS: An intraperitoneal human ovarian cancer xenograft model in nude mice (n = 44) was used in this study...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28492503/synthetic-receptors-induce-anti-angiogenic-and-stress-signaling-on-human-first-trimester-cytotrophoblast-cells
#8
Ahmed F Pantho, Mason Price, Ahm Zuberi Ashraf, Umaima Wajid, Maryam Emami Khansari, Afsana Jahan, Syeda H Afroze, Md Mhahabubur Rhaman, Corey R Johnson, Thomas J Kuehl, Md Alamgir Hossain, Mohammad Nasir Uddin
The cytotrophoblast (CTB) cells of the human placenta have membrane receptors that bind certain cardiotonic steroids (CTS) found in blood plasma. One of these, marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used synthetic receptors (SR) to study their effectiveness on the angiogenic profile of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. Culture media of CTB cells treated with ≥1 nM SR level revealed sFlt-1 (Soluble fms-like tyrosine kinase-1) was significantly increased while VEGF (vascular endothelial growth factor) was significantly decreased in the culture media (* p < 0...
May 11, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28483438/construction-of-vascularized-pacemaker-tissues-by-seeding-cardiac-progenitor-cells-and-endothelial-progenitor-cells-into-matrigel
#9
Luping Zhang, Xiaotong Li, Xiaolong Yu, Yuquan Li, Aijun Sun, Chao Huang, Feng Xu, Jinping Guo, Yao Sun, Xi Zhang, Xiangqun Yang, Chuansen Zhang
AIMS: Transplantation of a tissue engineered cardiac pacemaker (TECP) may represent a novel therapy for cardiac sinus node dysfunction. We previously reported that cardiac progenitor cells (CPCs) derived from embryonic heart tubes could differentiate into cardiac pacemaking cells after endothelin-1 treatment. We aimed to examine the feasibility of TECP fabricated from CPCs-derived pacemaking cells and vascularization of TECP fabricated from CPCs-derived pacemaking cells and endothelial progenitor cells (EPCs) in vitro and in vivo implantation...
May 5, 2017: Life Sciences
https://www.readbyqxmd.com/read/28477033/apatinib-inhibits-vegfr-2-and-angiogenesis-in-an-in-vivo-murine-model-of-nasopharyngeal-carcinoma
#10
Qiu-Xia Peng, Yun-Wei Han, Yan-Ling Zhang, Jie Hu, Juan Fan, Shao-Zhi Fu, Shan Xu, Qiang Wan
Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP)...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28477027/efficacy-and-safety-of-different-molecular-targeted-agents-based-on-chemotherapy-for-gastric-cancer-patients-treatment-a-network-meta-analysis
#11
Zheng Ren, Jinping Sun, Xinfang Sun, Hongtao Hou, Ke Li, Quanxing Ge
Increasing numbers of reports have been published to demonstrate that molecular targeted agents are able to improve the efficacy of chemotherapy in gastric cancer. This network meta-analysis aimed to evaluate the efficacy and safety of different molecular targeted agents, which were divided into six groups based on the targets including hepatocyte growth factor receptor (c-MET), vascular endothelial factor and its receptor (VEGF/VEGFR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR) and tyrosine kinase inhibitor (TKI)...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28469955/molecular-mechanism-underlying-the-pharmacological-interactions-of-the-protein-kinase-c-%C3%AE-inhibitor-enzastaurin-and-erlotinib-in-non-small-cell-lung-cancer-cells
#12
Nele Van Der Steen, Lisette Potze, Elisa Giovannetti, Andrea Cavazzoni, Rob Ruijtenbeek, Christian Rolfo, Patrick Pauwels, Godefridus J Peters
Erlotinib is commonly used as a second line treatment in non-small cell lung cancer patients with sensitizing EGFR mutations. In EGFR-wild type patients, however the results are limited. Therefore we evaluated whether the combination of the Protein kinase C-β inhibitor enzastaurin with erlotinib could enhance the effect in the A549 and H1650 cell lines. Cytotoxicity of erlotinib, enzastaurin and their 72-h simultaneous combination was assessed with the MTT assay. The pharmacologic interaction was studied using the method of Chou and Talalay, cell cycle perturbations were assessed by flow cytometry and modulation of ERK1/2 and AKT phosphorylation was determined with ELISA...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28467484/chromatin-modifying-agents-convert-fibroblasts-to-oct4-and-vegfr-2-capillary-tube-forming-cells
#13
Anita Wary, Neil Wary, Jugajyoti Baruah, Victoria Mastej, Kishore K Wary
RATIONALE: The human epigenome is plastic. The goal of this study was to address if fibroblast cells can be epigenetically modified to promote neovessel formation. METHODS AND RESULTS: Here, we used highly abundant human adult dermal fibroblast cells (hADFCs) that were treated with the chromatin-modifying agents 5-aza-2'-deoxycytidine and trichostatin A, and subsequently subjected to differentiation by activating Wnt signaling. Our results show that these epigenetically modified hADFCs increasingly expressed β-catenin, pluripotency factor octamer-binding transcription factor-4 (OCT4, also known as POU5F1), and endothelial cell (EC) marker called vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Fetal Liver Kinase-1)...
2017: PloS One
https://www.readbyqxmd.com/read/28464908/a-phase-i-study-of-lapatinib-in-combination-with-foretinib-a-c-met-axl-and-vascular-endothelial-growth-factor-receptor-inhibitor-in-human-epidermal-growth-factor-receptor-2-her-2-positive-metastatic-breast-cancer
#14
Stephen K Chia, Susan L Ellard, Mihaela Mates, Stephen Welch, Catalin Mihalcioiu, Wilson H Miller, Karen Gelmon, Caroline Lohrisch, Vikaash Kumar, Sara Taylor, Linda Hagerman, Rachel Goodwin, Tao Wang, Shingo Sakashita, Ming S Tsao, Elizabeth Eisenhauer, Penelope Bradbury
BACKGROUND: The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC)...
May 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28457321/effects-of-trauma-hemorrhagic-shock-and-chronic-stress-on-lung-vascular-endothelial-growth-factor
#15
Tyler J Loftus, Andrew J Thomson, Kolenkode B Kannan, Ines G Alamo, Harry N Ramos, Elizabeth E Whitley, Philip A Efron, Alicia M Mohr
BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) regulate vascular permeability and endothelial cell survival. We hypothesized that hemorrhagic shock (HS) and chronic stress (CS) would increase expression of lung VEGF and its receptors, potentiating pulmonary edema in lung tissue. MATERIALS AND METHODS: Male Sprague-Dawley rats aged 8-9 wk were randomized: naïve control, lung contusion (LC), LC followed by HS (LCHS), and LCHS with CS in a restraint cylinder for 2 h/d (LCHS/CS)...
April 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28447504/placental-growth-factor-plgf-as-an-angiogenic-inflammatory-switcher-lesson-from-early-pregnancy-losses
#16
Hamid Reza Nejabati, Zeinab Latifi, Tohid Ghasemnejad, Amir Fattahi, Mohammad Nouri
Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial growth factor (VEGF) family. In addition to the angiogenic function of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it can induce inflammatory reactions which could be accompanied with reduced angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic switching states and understand underlying mechanisms. PlGF is expressed in endometrium, placenta and trophoblast cells and is involved in maturation of uterine NK cells...
April 27, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28436035/nap-counteracts-hyperglycemia-hypoxia-induced-retinal-pigment-epithelial-barrier-breakdown-through-modulation-of-hifs-and-vegf-expression
#17
Agata Grazia D'Amico, Grazia Maugeri, Daniela Maria Rasà, Valentina La Cognata, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Diabetic macular edema (DME) is a common complication leading to a central vision loss in patients with diabetes. In this eye pathology, the hyperglycaemic/hypoxic microenvironment of pigmented epithelium is responsible for outer blood retinal barrier integrity changes. More recently, we have shown that a small peptide derived from the activity-dependent neuroprotective protein (ADNP), known as NAP, counteracts damages occurring during progression of diabetic retinopathy by modulating HIFs/VEGF pathway. Here, we have investigated for the first time the role of this peptide on outer blood retinal barrier (BRB) integrity exposed to hyperglycaemic/hypoxic insult mimicking a model in vitro of DME...
April 24, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28423739/sialyllactose-suppresses-angiogenesis-by-inhibiting-vegfr-2-activation-and-tumor-progression
#18
Tae-Wook Chung, Eun-Young Kim, Seok-Jo Kim, Hee-Jung Choi, Se Bok Jang, Keuk-Jun Kim, Sun-Hyung Ha, Fukushi Abekura, Choong-Hwan Kwak, Cheorl-Ho Kim, Ki-Tae Ha
The oligosaccharides in human milk have various biological functions. However, the molecular mechanism(s) underlying the anti-angiogenic action of sialylated human milk oligosaccharides (HMOs) are still unclear. Here, we show that siallylactose (SL) found in human milk can inhibit the activation of vascular endothelial growth factor (VEGF)-mediated VEGF receptor-2 (VEGFR-2) by binding to its VEGF binding site (second and third IgG-like domains), thus blocking downstream signal activation. SL also inhibits growth of VEGF-stimulated endothelial cells...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421362/selective-imaging-of-vascular-endothelial-growth-factor-receptor-1-and-receptor-2-in-atherosclerotic-lesions-in-diabetic-and-non-diabetic-apoe-mice
#19
Yared Tekabe, Lynne L Johnson, Krissy Rodriquez, Qing Li, Marina Backer, Joseph M Backer
PURPOSE: Plaque vulnerability is associated with inflammation and angiogenesis, processes that rely on vascular endothelial growth factor (VEGF) signaling via two receptors, VEGFR-1 and VEGFR-2. We have recently reported that enhanced uptake of scVEGF-PEG-DOTA/Tc-99m (scV/Tc) single photon emission computed tomography (SPECT) tracer that targets both VEGFR-1 and VEGFR-2, identifies accelerated atherosclerosis in diabetic relative to non-diabetic ApoE(-/-) mice. Since VEGFR-1 and VEGFR-2 may play different roles in atherosclerotic plaques, we reasoned that selective imaging of each receptor can provide more detailed information on plaque biology...
April 18, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28412217/dalbergia-odorifera-extract-promotes-angiogenesis-through-upregulation-of-vegfrs-and-pi3k-mapk-signaling-pathways
#20
Zhu-Ming Fan, Da-Ying Wang, Jian-Mei Yang, Zhi-Xiu Lin, Ai-Lin Yang, Hua Fan, Min Cao, Su-Yun Yuan, Zong-Jun Liu, Xin Zhou, You-Hua Wang
ETHNOPHARMACOLOGICAL RELEVANCE: The heart wood of Dalbergia odorifera is a Chinese herbal medicine commonly used for the treatment of various ischemic diseases in Chinese medicine practice. AIM OF THE STUDY: In this study, therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were investigated on transgenic zebrafish in vivo and human umbilical vein endothelial cells (HUVECs) in vitro. MATERIALS AND METHODS: The pro-angiogenic effects of DOE on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and intersegmental vessels (ISVs) injury assay...
April 12, 2017: Journal of Ethnopharmacology
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