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https://www.readbyqxmd.com/read/28333941/phenotypically-heterogeneous-podoplanin-expressing-cell-populations-are-associated-with-the-lymphatic-vessel-growth-and-fibrogenic-responses-in-the-acutely-and-chronically-infarcted-myocardium
#1
Maria Cimini, Antonio Cannatá, Gianandrea Pasquinelli, Marcello Rota, Polina Goichberg
Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts...
2017: PloS One
https://www.readbyqxmd.com/read/28332573/discovery-of-multi-target-receptor-tyrosine-kinase-inhibitors-as-novel-anti-angiogenesis-agents
#2
Jinfeng Wang, Lin Zhang, Xiaoyan Pan, Bingling Dai, Ying Sun, Chuansheng Li, Jie Zhang
Recently, we have identified a biphenyl-aryl urea incorporated with salicylaldoxime (BPS-7) as an anti-angiogenesis agent. Herein, we disclosed a series of novel anti-angiogenesis agents with BPS-7 as lead compound through combining diarylureas with N-pyridin-2-ylcyclopropane carboxamide. Several title compounds exhibited simultaneous inhibition effects against three pro-angiogenic RTKs (VEGFR-2, TIE-2 and EphB4). Some of them displayed potent anti-proliferative activity against human vascular endothelial cell (EA...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327934/pazopanib-or-placebo-in-completely-resected-stage-i-nsclc-patients-results-of-the-phase-ii-ifct-0703-trial
#3
B Besse, J Mazières, L Ribassin-Majed, F Barlesi, J Bennouna, R Gervais, L Moreau, H Berard, D Debieuvre, O Molinier, D Moro-Sibilot, P J Souquet, S Jacquot, L Petit, H Lena, J P Pignon, B Lacas, F Morin, B Milleron, G Zalcman, J C Soria
Background: Adjuvant treatment in resected stage I non-small cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population. Patients and methods: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/d (P800) for 6 months with a two-step Fleming design...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28323051/anticancer-and-anti-angiogenic-activities-of-extract-from-actinidia-eriantha-benth-root
#4
Jian-Guo Wu, Li Ma, Shui-Hua Lin, Yan-Bin Wu, Jun Yi, Bin-Jun Yang, Jin-Zhong Wu, Ka-Hing Wong
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Actinidia eriantha Benth (AER) are commonly used traditional folk medicine for the treatment of gastric carcinoma, nasopharyngeal carcinoma, and breast carcinoma. Besides, the anti-proliferative and immunomodulatory effects of AER polysaccharides on tumor-bearing mice have been reported previously. AIM OF THE STUDY: This work was carried out to investigate the anticancer and anti-angiogenic activities of AER. MATERIALS AND METHODS: The growth inhibitory effects of ethanol extracts from the leaves (EEL), stems (EES) and roots (EER) of A...
March 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28322737/the-tead-family-transcription-factor-scalloped-regulates-blood-progenitor-maintenance-and-proliferation-in-drosophila-through-pdgf-vegfr-receptor-pvr-signaling
#5
Gabriel B Ferguson, Julian A Martinez-Agosto
The Drosophila lymph gland is a well-characterized hematopoietic organ in which a population of multipotent stem-like progenitors is maintained by a combination of signals from different cellular populations within the organ. The lymph gland serves as an ideal model both for the interrogation of signaling mechanisms involved in progenitor maintenance as well as a tool for the identification of novel regulatory mechanisms in the highly conserved process of hematopoiesis. Here, we demonstrate a requirement for the TEAD transcription factor Scalloped in the maintenance and proliferation of hematopoietic progenitors...
March 18, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28319199/a-computational-analysis-of-in-vivo-vegfr-activation-by-multiple-co-expressed-ligands
#6
Lindsay E Clegg, Feilim Mac Gabhann
The splice isoforms of vascular endothelial growth A (VEGF) each have different affinities for the extracellular matrix (ECM) and the coreceptor NRP1, which leads to distinct vascular phenotypes in model systems expressing only a single VEGF isoform. ECM-immobilized VEGF can bind to and activate VEGF receptor 2 (VEGFR2) directly, with a different pattern of site-specific phosphorylation than diffusible VEGF. To date, the way in which ECM binding alters the distribution of isoforms of VEGF and of the related placental growth factor (PlGF) in the body and resulting angiogenic signaling is not well-understood...
March 20, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28314990/an-apparent-clinical-pharmacokinetic-drug-drug-interaction-between-bevacizumab-and-the-anti-placental-growth-factor-monoclonal-antibody-ro5323441-via-a-target-trapping-mechanism
#7
Ka Wang, Franziska Schaedeli Stark, Tilman Schlothauer, Angelika Lahr, Valerie Cosson, Jianguo Zhi, Kai Habben, Jean Tessier, Eginhard Schick, Roland F Staack, Oliver Krieter
PURPOSE: RO5323441 is a humanized anti-placental growth factor (PlGF) monoclonal antibody that has shown preclinical activity in several cancer models. The objective of this analysis is to examine the pharmacokinetic (PK) results from four Phase I studies that have been conducted with RO5323441 (n = 61) and to report an apparent drug-drug interaction observed when RO5323441 was administered in combination with bevacizumab. METHODS: The four Phase I studies were a multiple-ascending dose study in 23 patients with solid tumors (Study 1), an open-label study in seven patients with colorectal/ovarian cancer (Study 2), a sorafenib combination study in nine patients with hepatocellular carcinoma (Study 3), and a bevacizumab combination study in 22 patients with recurrent glioblastoma (Study 4)...
March 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28314255/anti-metastatic-efficacy-of-traditional-chinese-medicine-tcm-ginsenoside-conjugated-to-a-vefgr-3-antibody-on-human-gastric-cancer-in-an-orthotopic-mouse-model
#8
Xiaojun Dai, Dongmei Liu, Moxiang Liu, Xiaochun Zhang, Weiming Wang, Feng Jin, Yayun Qian, Xuanyi Wang, Jingjing Zhao, Yongjian Wu, Fangfang Xiong, N A Chang, Y U Sun, Zhijian Yang, Robert M Hoffman, Yanqing Liu
Background/Aim: The aim of the present study was to investigate the efficacy of a traditional Chinese medicine (TCM), VEGFR-3 antibody-conjugated ginsenoside Rg3nanoemulsion (VRIN), targeting lymphangiogenesis, on the inhibition of tumor growth and metastasis in an orthotopic mouse model of human gastric cancer. Materials and Methods: An orthotopic nude-mouse model of gastric cancer was established with the red fluorescent protein (RFP)-expressing human gastric cancer cell line NUGC-4-RFP. The tumor-bearing mice were treated with vehicle (0...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28304102/design-synthesis-and-cytotoxic-evaluation-of-certain-7-chloro-4-piperazin-1-yl-quinoline-derivatives-as-vegfr-ii-inhibitors
#9
Mohamed Nabil Aboul-Enein, Aida M Abd El-Sattar El-Azzouny, Fatma Abdel-Fattah Ragab, Mohamed Farouk Hamissa
Signaling pathway inhibition of VEGFR-II is visualized as valuable tool in cancer management. In the current study, the synthesis of novel 1-4-(7-chloroquinolin-4-yl)piperazin-1-yl)-2-(N-substituted-amino)-ethanone derivatives (4a-t) was achieved through the amination of 2-chloro-1-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)ethanone (3) with different secondary amines. The structures of the target compounds were confirmed by IR, (1) H-NMR, (13) C-NMR, HRMS, and microanalysis. Compounds 4a-t were subjected to in vitro anticancer screening against human breast cancer (MCF-7) and prostate cancer (PC3) cell lines...
March 17, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28303365/immunoglobulin-like-domain-4-mediated-ligand-independent-dimerization-triggers-vegfr-2-activation-in-huvecs-and-vegfr2-positive-breast-cancer-cells
#10
Sheng Zhang, Xiaoping Gao, Wei Fu, Shengwei Li, Limin Yue
PURPOSE: The extracellular region (EC) of the vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) contains seven immunoglobulin-like (Ig-like) domains that are required for specific ligand binding and receptor dimerization. Studies of domain 4-7 deletions and substitutions provided insights into the interaction between receptors in the absence of VEGF. In this study, we investigated the effect of domain 4 in ligand-independent VEGFR-2 dimerization and activation in human vascular endothelial cells and human breast cancer cells...
March 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28301910/soluble-fms-like-tyrosine-kinase-1-as-a-link-between-angiogenesis-and-endothelial-dysfunction-in-pediatric-patients-with-%C3%AE-thalassemia-intermedia
#11
Azza Abdel Gawad Tantawy, Amira Abdel Moneam Adly, Eman Abdel Rahman Ismail, Omneya Ibrahim Youssef, Mohamed ElSayed Ali
Endothelial damage has been implicated in the pathogenesis of vascular complications in β-thalassemia intermedia (β-TI). Soluble fms-like tyrosine kinase 1 (sFLT-1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. Soluble fms-like tyrosine kinase 1 is an antiangiogenic protein that induces endothelial dysfunction by adhering to and inhibiting VEGF and placenta growth factor. The aim of this study was to assess the level of sFLT-1 in 35 children and adolescents with β-TI, correlating it with markers of hemolysis and iron overload as well as cardiopulmonary complications...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28297758/-role-of-master-transcriptional-factor-prox-1-in-lymphatic-endothelial-differentiation-of-kaposiform-hemangioendothelioma
#12
Z Y Ke, S J Yang
Objective: To analyze the clinical and pathological features of Kaposiform hemangioendothelioma (KHE), and to investigate the role of master transcriptional factor Prox-1 in the regulation of lymphatic differentiation. Methods: Nine cases of KHE (during the period from October 2009 to June 2016) were collected with clinical and pathological data. H&E stained section review and immunohistochemietry using the Dako EnVision method were performed. Results: There were 6 female and 3 male patients with age ranging from 2 months to 8 years (median 3 years and 4 months)...
March 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28294324/blocking-fibrotic-signaling-in-fibroblasts-from-patients-with-carpal-tunnel-syndrome
#13
REVIEW
Yoshiaki Yamanaka, Anne Gingery, Gosuke Oki, Tai-Hua Yang, Chunfeng Zhao, Peter C Amadio
Fibrosis of the subsynovial connective tissue (SSCT) in carpal tunnel syndrome (CTS) patients is increasingly recognized as an important aspect of CTS pathophysiology. In this study, we evaluated the effect of blocking profibrotic pathways in fibroblasts from the SSCT in CTS patients. Fibroblasts were stimulated with transforming growth factor β1 (TGF-β1), and then treated either with a specific fibrosis pathway inhibitor targeting TGF-β receptor type 1 (TβRI), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) or vascular endothelial growth factor receptor (VEGFR)...
March 10, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28292023/green-tea-and-its-anti-angiogenesis-effects
#14
REVIEW
Bahman Rashidi, Mehrnoush Malekzadeh, Mohammad Goodarzi, Aria Masoudifar, Hamed Mirzaei
The development of new blood vessels from a pre-existing vasculature (also known as angiogenesis) is required for many physiological processes including embryogenesis and post-natal growth. However, pathological angiogenesis is also a hallmark of cancer and many ischaemic and inflammatory diseases. The pro-angiogenic members of the VEGF family (vascular endothelial growth factor family), VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor (PlGF), and the related receptors, VEGFR-1, VEGFR-2 and VEGFR-3 have a central and decisive role in angiogenesis...
March 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28290152/vascular-endothelial-growth-factor-isoform-b-stimulates-neurovascular-repair-after-ischemic-stroke-by-promoting-the-function-of-pericytes-via-vascular-endothelial-growth-factor-receptor-1
#15
Noëmie Jean LeBlanc, Revathy Guruswamy, Ayman ElAli
Ischemic stroke triggers endogenous angiogenic mechanisms, which correlates with longer survival in patients. As such, promoting angiogenesis appears to be a promising approach. Experimental studies investigated mostly the potent angiogenic factor vascular endothelial growth factor isoform-A (VEGF-A). However, VEGF-A increases the risk of destabilizing the brain microvasculature, thus hindering the translation of its usage in clinics. An attractive alternative VEGF isoform-B (VEGF-B) was recently reported to act as a survival factor rather than a potent angiogenic factor...
March 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28287096/blockade-of-vascular-endothelial-growth-factor-receptors-by-tivozanib-has-potential-anti-tumour-effects-on-human-glioblastoma-cells
#16
Majid Momeny, Farima Moghaddaskho, Narges K Gortany, Hassan Yousefi, Zahra Sabourinejad, Ghazaleh Zarrinrad, Shahab Mirshahvaladi, Haniyeh Eyvani, Farinaz Barghi, Leila Ahmadinia, Mahmoud Ghazi-Khansari, Ahmad R Dehpour, Saeid Amanpour, Seyyed M Tavangar, Leila Dardaei, Amir H Emami, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28285368/risk-of-hypertension-with-ramucirumab-based-therapy-in-solid-tumors-data-from-a-literature-based-meta-analysis
#17
REVIEW
Giandomenico Roviello, Chiara Pacifico, Paola Corona, Daniele Generali
Ramucirumab is a monoclonal antibody against Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) approved for the treatment of several solid tumours. As shown in recent trials results, new-onset hypertension is one of the most frequent adverse events associated with ramucirumab therapy. Recent studies looked at the quantification of the risk of hypertension in patients receiving other anti-angiogenesis medications. We conducted a meta-analysis of randomized clinical trials with the aim to investigate the incidence and quantify the risk of new-onset hypertension of any grade in patients treated with ramucirumab...
March 11, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28282869/inhibition-of-vegf-induced-vegfr-2-activation-and-huvec-migration-by-melatonin-and-other-bioactive-indolic-compounds
#18
Ana B Cerezo, Ruth Hornedo-Ortega, M Antonia Álvarez-Fernández, Ana M Troncoso, M Carmen García-Parrilla
Excessive concentrations of vascular endothelial growth factor (VEGF) trigger angiogenesis, which causes complications such as the destabilization of atherosclerotic plaques and increased growth of tumors. This work focuses on the determination of the inhibitory activity of melatonin and other indolic related compounds on VEGF-induced VEGF receptor-2 (VEGFR-2) activation and an approximation to the molecular mechanism underlying the inhibition. Quantification of phosphorylated VEGFR-2 was measured by ELISA...
March 8, 2017: Nutrients
https://www.readbyqxmd.com/read/28279709/vegf-signaling-promotes-vascular-endothelial-differentiation-by-modulating-etv2-expression
#19
Satish Casie Chetty, Megan S Rost, Jacob Ryan Enriquez, Jennifer A Schumacher, Kristina Baltrunaite, Andrea Rossi, Didier Y R Stainier, Saulius Sumanas
Vasculogenesis involves the differentiation of vascular endothelial progenitors de novo from undifferentiated mesoderm, their migration and coalescence to form the major embryonic vessels and the acquisition of arterial or venous identity. Vascular Endothelial Growth Factor (Vegf) signaling plays multiple roles during vascular development. However, its function during embryonic vasculogenesis has been controversial. Previous studies have implicated Vegf signaling in either regulating arteriovenous specification or overall vascular endothelial differentiation...
March 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#20
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
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