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https://www.readbyqxmd.com/read/28220020/randomized-phase-ii-study-of-ramucirumab-or-icrucumab-in-combination-with-capecitabine-in-patients-with-previously-treated-locally-advanced-or-metastatic-breast-cancer
#1
Linda T Vahdat, Rachel Layman, Denise A Yardley, William Gradishar, Mohamad A Salkeni, Anil Abraham Joy, Agustin A Garcia, Patrick Ward, James Khatcheressian, Joseph Sparano, Gladys Rodriguez, Shande Tang, Ling Gao, Rita P Dalal, John Kauh, Kathy Miller
BACKGROUND: Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and -2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced or metastatic breast cancer. METHODS: Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m(2) orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM + CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR + CAP) every 21 days...
February 20, 2017: Oncologist
https://www.readbyqxmd.com/read/28214828/role-for-target-of-rapamycin-mtor-signal-pathway-in-regulating-neuronal-injury-after-intracerebral-hemorrhage
#2
Jie-Ping Wang, Meng-Yu Zhang
BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR signal and its downstream products to brain injuries induced by intracerebral hemorrhage (ICH) in rats. METHODS: Western Blot analysis was employed to examine the protein expression of mTOR and its downstream pathway and Caspase-3...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28212521/angiogenesis-in-the-atherosclerotic-plaque
#3
REVIEW
Caroline Camaré, Mélanie Pucelle, Anne Nègre-Salvayre, Robert Salvayre
Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis...
February 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28194096/morphological-plasticity-of-emerging-purkinje-cells-in-response-to-exogenous-vegf
#4
Leonard Herrfurth, Verena Theis, Veronika Matschke, Caroline May, Katrin Marcus, Carsten Theiss
Vascular endothelial growth factor (VEGF) is well known as the growth factor with wide-ranging functions even in the central nervous system (CNS). Presently, most attention is given to the investigation of its role in neuronal protection, growth and maturation processes, whereby most effects are mediated through VEGF receptor 2 (VEGFR-2). The purpose of our current study is to provide new insights into the impact of VEGF on immature and mature Purkinje cells (PCs) in accordance with maturity and related receptor expression...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28190652/novel-6-methoxycarbonyl-indolinones-bearing-a-pyrrole-mannich-base-moiety-as-angiokinase-inhibitors
#5
Mingze Qin, Shuang Yan, Lei Wang, Haotian Zhang, Ye Tian, Yanfang Zhao, Ping Gong
Inhibition of tumor angiogenesis through simultaneously disturbing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) mediated signaling pathways is a well-established approach in intervention of tumor. A series of 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety were synthesized and evaluated as potent angiokinase inhibitors. Compound 8a demonstrated favorable enzymatic activity against all subtypes of VEGFR and PDGFR. Also, it potently suppressed proliferation of HT-29 cells by inducing apoptosis...
January 25, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28187520/exogenous-vegf-delivery-prior-to-endothelial-precursor-cell-transplantation-in-orthotopic-liver-transplant-induced-hepatic-ischemia-reperfusion-injury
#6
Ding Cao, Menghao Wang, Junhua Gong, Sidong Wei, Jianping Gong, Jinzheng Li
BACKGROUND: Vascular endothelial growth factor (VEGF) promotes angiogenesis in vivo. We hypothesized that exogenous delivery of VEGF prior to bone marrow-derived endothelial precursor cell (EPC) transplantation may improve orthotopic liver transplantation (OLT)-induced hepatic ischemia-reperfusion injury (HIRI). METHODS: OLT between Sprague Dawley donor rats and inbred LEW Wistar recipient rats was performed in six experimental groups to comparatively assess the effects of VEGF gene: an untreated normal control group, a surgical control group, a liposomal control group, a VEGF group receiving only the liposome-encapsulated VEGF plasmid, an EPC group receiving only EPCs, and an EPC+VEGF group receiving the liposome-encapsulated VEGF plasmid followed by EPCs...
February 10, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28183357/proangiogenic-effects-of-soluble-%C3%AE-klotho-on-systemic-sclerosis-dermal-microvascular-endothelial-cells
#7
Celestina Mazzotta, Mirko Manetti, Irene Rosa, Eloisa Romano, Jelena Blagojevic, Silvia Bellando-Randone, Cosimo Bruni, Gemma Lepri, Serena Guiducci, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
BACKGROUND: Systemic sclerosis (SSc) is characterized by endothelial cell (EC) apoptosis, impaired angiogenesis and peripheral microvasculopathy. Soluble α-Klotho (sKl) is a pleiotropic molecule with multiple effects on ECs, including antioxidant and vasculoprotective activities. On the EC surface, sKl interacts with vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) and transient receptor potential canonical-1 (TRPC-1) cation channel to control EC homeostasis. Here, we investigated whether sKl might act as a protective factor to improve angiogenesis in dermal microvascular endothelial cells (MVECs) from SSc patients (SSc-MVECs)...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28161830/combined-vegf-and-pdgf-inhibition-for-neovascular-amd-anti-angiogenic-properties-of-axitinib-on-human-endothelial-cells-and-pericytes-in-vitro
#8
Jakob Siedlecki, Christian Wertheimer, Armin Wolf, Raffael Liegl, Claudia Priglinger, Siegfried Priglinger, Kirsten Eibl-Lindner
PURPOSE: Drugs currently approved for neovascular age-related macular degeneration (nAMD) offer anti-VEGF monotherapy only. Platelet-derived growth factor (PDGF) signaling is pivotal to pericyte-induced stabilization of choroidal neovascularizations (CNV), and causes partial anti-VEGF resistance. No combination therapy for VEGF and PDGF has been approved yet. Axitinib is a tyrosine kinase inhibitor interfering with VEGF and PDGF signaling, and has been approved for the treatment of renal cell carcinoma...
February 4, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28161476/markers-of-neuroinflammation-associated-with-alzheimer-s-disease-pathology-in-older-adults
#9
Julius Popp, Aikaterini Oikonomidi, Domilė Tautvydaitė, Loïc Dayon, Michael Bacher, Eugenia Migliavacca, Hugues Henry, Richard Kirkland, India Severin, Jérôme Wojcik, Gene L Bowman
BACKGROUND: In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline. OBJECTIVE: To identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i...
February 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28145862/vegf-mediated-signaling-in-oral-cancer
#10
REVIEW
X Lin, S Khalid, M Z Qureshi, R Attar, I Yaylim, I Ucak, A Yaqub, S Fayyaz, A A Farooqi, M Ismail
Increasingly it is being realized that oral cancer arises from genetic/epigenetic mutations, dysregulations of spatio-temporally controlled signal transduction cascades and loss of apoptosis. Epidemiological studies have provided a stronger association between tobacco use (chewed and smoked) and oral cancer. Nevertheless, alcohol has also gained attention as a significant risk factor, having a multiplicative synergistic cancer promoting effect with tobacco. Vascular Endothelial Growth Factor (VEGF) mediated signaling has gained limelight because of its instrumental role in endothelial cell proliferation, survival, invasion, migration, chemotaxis of bone marrow (BM)-derived progenitor cells, vasodilation and vascular permeability...
December 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28138221/immunotherapy-for-the-treatment-of-colorectal-tumors-focus-on-approved-and-in-clinical-trial-monoclonal-antibodies
#11
REVIEW
Alex Françoso, Patricia Ucelli Simioni
Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28131635/effect-of-combined-therapy-inhibiting-egfr-and-vegfr-pathways-in-non-small-cell-lung-cancer-on-progression-free-and-overall-survival
#12
Tao Jiang, Meng Qiao, Fei Zhou, Shengxiang Ren, Chunxia Su, Caicun Zhou
BACKGROUND: To investigate the effect of combined epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway inhibitors on progression-free survival (PFS) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We included 15 randomized clinical trials that had compared the combination of EGFR tyrosine kinase inhibitors and anti-VEGF/VEGFR therapy with different control groups...
December 29, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28118600/tmem2-regulates-embryonic-vegf-signaling-by-controlling-hyaluronic-acid-turnover
#13
Jessica E De Angelis, Anne K Lagendijk, Huijun Chen, Alisha Tromp, Neil I Bower, Kathryn A Tunny, Andrew J Brooks, Jeroen Bakkers, Mathias Francois, Alpha S Yap, Cas Simons, Carol Wicking, Benjamin M Hogan, Kelly A Smith
Angiogenesis is responsible for tissue vascularization during development, as well as in pathological contexts, including cancer and ischemia. Vascular endothelial growth factors (VEGFs) regulate angiogenesis by acting through VEGF receptors to induce endothelial cell signaling. VEGF is processed in the extracellular matrix (ECM), but the complexity of ECM control of VEGF signaling and angiogenesis remains far from understood. In a forward genetic screen, we identified angiogenesis defects in tmem2 zebrafish mutants that lack both arterial and venous Vegf/Vegfr/Erk signaling...
January 23, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28116460/enhanced-vegf-signalling-mediates-cerebral-neovascularisation-via-downregulation-of-guidance-protein-robo4-in-a-rat-model-of-diabetes
#14
Mohammed Abdelsaid, Maha Coucha, Sherif Hafez, Abdul Yasir, Maribeth H Johnson, Adviye Ergul
AIMS/HYPOTHESIS: Diabetes promotes cerebral neovascularisation via increased vascular endothelial growth factor (VEGF) angiogenic signalling. Roundabout-4 (ROBO4) protein is an endogenous inhibitor of VEGF signalling that stabilises the vasculature. Yet, how diabetes affects ROBO4 function remains unknown. We hypothesised that increased VEGF signalling in diabetes decreases ROBO4 expression and function via binding of ROBO4 with VEGF-activated β3 integrin and that restoration of ROBO4 expression prevents/repairs cerebral neovascularisation in diabetes...
January 23, 2017: Diabetologia
https://www.readbyqxmd.com/read/28111021/structure-of-the-full-length-vegfr-1-extracellular-domain-in-complex-with-vegf-a
#15
Sandra Markovic-Mueller, Edward Stuttfeld, Mayanka Asthana, Tobias Weinert, Spencer Bliven, Kenneth N Goldie, Kaisa Kisko, Guido Capitani, Kurt Ballmer-Hofer
Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel development upon activation of three receptor tyrosine kinases: VEGFR-1, -2, and -3. Partial structures of VEGFR/VEGF complexes based on single-particle electron microscopy, small-angle X-ray scattering, and X-ray crystallography revealed the location of VEGF binding and domain arrangement of individual receptor subdomains. Here, we describe the structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A at 4 Å resolution...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/28103447/pharmacotherapy-for-treating-metastatic-clear-cell-renal-cell-carcinoma
#16
Camillo Porta, Silvia Chiellino, Alessandra Ferrari, Sara Mariucci, Wanda Liguigli
Over the past decade metastatic renal cell carcinoma (RCC) treatment landscape has dramatically evolved from the era of cytokines-based immunotherapy (which benefited very few patients, at the expenses of high toxicities) to the present era of targeted agents and novel immunotherapeutics, greatly improving the prognosis of our patients. Areas covered: Here we have reviewed the present status of the medical treatment of metastatic RCC. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for the relevant trials coducted so far...
February 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28098802/penduliflaworosin-a-diterpenoid-from-croton-crassifolius-exerts-anti-angiogenic-effect-via-vegf-receptor-2-signaling-pathway
#17
Yeyin Liang, Yubo Zhang, Guocai Wang, Yaolan Li, Weihuan Huang
Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2) has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel formation in zebrafish. This study was conducted to further investigate the anti-angiogenic activity and mechanism of penduliflaworosin. Results revealed that penduliflaworosin significantly inhibited VEGF-induced angiogenesis processes including proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs)...
January 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28097238/quantitative-measurement-of-lymphatic-function-in-mice-by-noninvasive-near-infrared-imaging-of-a-peripheral-vein
#18
Steven T Proulx, Qiaoli Ma, Diana Andina, Jean-Christophe Leroux, Michael Detmar
Optical imaging methods have been developed to measure lymphatic function in skin; however, the lymphatic system of many organs is not accessible to this technology. Since lymphatic transport of macromolecules from any organ proceeds to the blood circulation, we aimed to develop a method that can measure lymphatic function by monitoring the fluorescence in a superficial vein of an interstitially injected tracer. We selected a 40-kDa PEGylated near-infrared dye conjugate, as it showed lymphatic system-specific uptake and extended circulation in blood...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28081499/screening-active-compounds-from-corydalis-yanhusuo-by-combining-high-expression-vegf-receptor-hek293-cell-membrane-chromatography-with-hplc-esi-it-tof-msn-method
#19
Fen Wei, Qi Hu, Jing Huang, Shengli Han, Sicen Wang
Corydalis Thizoma,or Yuanhu in China, is a common herbal drug used for thousands of years as analgesic in Chinese medicine that has been reported to have potential anti-angiogenic effects. In this study, a VEGFR/cell membrane chromatography (VEGFR/CMC) coupled with HPLC- ESI-IT-TOF-MSn system was developed and successfully applied for identifying active components from YuanHu extract acting on VEGFR. We identified tetrahydropalmatine and corydaline as bioactive components with VEGFR activity, thus confirming their inhibitory activity on VEGFR engineered HEK293 cell growth by MTT assay...
March 20, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28070992/molecular-signal-networks-and-regulating-mechanisms-of-the-unfolded-protein-response
#20
Jing Gong, Xing-Zhi Wang, Tao Wang, Jiao-Jiao Chen, Xiao-Yuan Xie, Hui Hu, Fang Yu, Hui-Lin Liu, Xing-Yan Jiang, Han-Dong Fan
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum (ER). One of the primary mechanisms is the unfolded protein response (UPR). In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein (BiP) interacts with the three sensors (protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1α (IRE1α))...
2017: Journal of Zhejiang University. Science. B
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