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https://www.readbyqxmd.com/read/28213941/population-pharmacokinetic-and-exposure-simulation-analysis-for-cediranib-azd2171-in-pooled-phase-i-ii-studies-in-patients-with-cancer
#1
Jianguo Li, Nidal Al-Huniti, Anja Henningsson, Weifeng Tang, Eric Masson
AIMS: A population pharmacokinetic (PPK) model was developed for cediranib to simulate cediranib exposure for different doses, including co-medication with strong UGT/Pgp inducers such as rifampicin, in cancer patients. METHODS: Plasma concentrations and covariates from 625 cancer patients after single or multiple oral cediranib administrations ranging from 0.5 to 90 mg in 19 Phase I and II studies were included in the analysis. Stepwise covariate modelling was used to develop the PPK model...
February 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28213002/a-phase-ii-trial-of-dovitinib-in-previously-treated-advanced-pleural-mesothelioma-the-ontario-clinical-oncology-group
#2
Scott A Laurie, Desiree Hao, Natasha B Leighl, John Goffin, Abderrahim Khomani, Ashish Gupta, Christina L Addison, Anita Bane, Jean Seely, Marc L Filion, Gregory R Pond, Mark N Levine
OBJECTIVES: Following failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM. METHODS: This open-label multicentre phase II trial [NCT01769547] enrolled fit, consenting adult patients with advanced MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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/28193911/eif3i-activity-is-critical-for-endothelial-cells-in-tumor-induced-angiogenesis-through-regulating-vegfr-and-erk-translation
#5
Yaguang Zhang, Ping Wang, Qian Zhang, Xiaomin Yao, Linjie Zhao, Yibin Liu, Xiaowei Liu, Rui Tao, Chuan Yu, Yuhao Li, Xiangrong Song, Shaohua Yao
Translational control is a critical step in the regulation of gene expression. Accumulating evidence shows that translational control of a subgroup of mRNAs tends to be selective. However, our understanding of the function of selective translational control in endothelial cells is still incomplete. We found that a key translational regulator, eIF3i, is highly expressed in endothelial cells during embryonic and tumor angiogenesis. Knockdown of eIF3i restrained cell proliferation and migration in endothelial cells...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28190652/novel-6-methoxycarbonyl-indolinones-bearing-a-pyrrole-mannich-base-moiety-as-angiokinase-inhibitors
#6
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
#7
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/28186980/diet-induced-obesity-links-to-er-positive-breast-cancer-progression-via-lpa-pkd-1-cd36-signaling-mediated-microvascular-remodeling
#8
Liuyi Dong, Ye Yuan, Cynthia Opansky, Yiliang Chen, Irene Aguilera-Barrantes, Shiyong Wu, Rong Yuan, Qi Cao, Yee Chung Cheng, Daisy Sahoo, Roy L Silverstein, Bin Ren
Obesity increases cancer risk including breast cancer (BC). However, the direct regulatory mechanisms by which obesity promotes BC progression remain largely unknown. We show that lysophosphatidic acid/protein kinase D1 (LPA/PKD-1)-CD36 signaling is a bona fide breast cancer promoter via stimulating microvascular remodeling in chronic diet-induced obesity (DIO). We observed that the growth of an estrogen receptor (ER) positive breast cancer was markedly increased when compared to the lean control, and specifically accompanied by increased microvascular remodeling in a syngeneic BC model in female DIO mice...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28183357/proangiogenic-effects-of-soluble-%C3%AE-klotho-on-systemic-sclerosis-dermal-microvascular-endothelial-cells
#9
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/28176910/apatinib-as-post-second-line-therapy-in-egfr-wild-type-and-alk-negative-advanced-lung-adenocarcinoma
#10
Shen-Cun Fang, Hai-Tao Zhang, Ying-Ming Zhang, Wei-Ping Xie
In the absence of a driver mutation, chemotherapy is the standard treatment option as first- and second-line therapy for advanced non-small-cell lung cancer (NSCLC). Though a large number of patients are suitable for post second-line therapies, the quality and quantity of the available drugs in this setting is poor. Apatinib, a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, is a first-generation oral antiangiogenesis drug approved in the People's Republic of China for use as a subsequent line of treatment for advanced gastric cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28165839/targeting-vegfr-2-in-metastatic-gastric-cancer-results-from-a-literature-based-meta-analysis
#11
Giandomenico Roviello, Karol Polom, Franco Roviello, Daniele Marrelli, Andrea Giovanni Multari, Giovanni Paganini, Chiara Pacifico, Daniele Generali
Angiogenesis is a key process in cancer development. We performed a meta-analysis to assess the efficacy and safety of the novel VEGFR-2 inhibitors in patients with metastatic gastric and gastroesophageal junction cancer. A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. The primary outcome was the overall survival. The pooled analysis from RCTs on anti-VEGFR-2 inhibitors revealed a significant increase in overall survival (hazard ratio for death: 0.69, 95% confidence interval: 0...
February 6, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28162024/immunotherapeutic-strategies-for-the-treatment-of-renal-cell-carcinoma-where-will-we-go
#12
Inês Anselmo da Costa, Steffen Rausch, Stephan Kruck, Tilman Todenhöfer, Arnulf Stenzl, Jens Bedke
Historically, renal cell carcinoma (RCC) is considered a chemotherapy-resistant tumor. The cornerstone of systemic therapy included mammalian target of rapamycin (mTOR) inhibitors, endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Currently, a new era is enteres with promising immunotherapeutic treatments, which are becoming commercially available. Areas covered: We provide a comprehensive review using PubMed and ClinicalTrials.gov about the following immunotherapies in RCC: i) vaccine therapy, ii) adoptive T Cell Transfer and CAR T cells, iii) nonspecific immunotherapy-IL-2 (new formulations), iv) Checkpoint inhibitors, v) other checkpoint-molecules...
February 4, 2017: Expert Review of Anticancer 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
#13
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
#14
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
#15
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
#16
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/28132823/preparation-and-characterisation-of-vandetanib-eluting-radiopaque-beads-for-locoregional-treatment-of-hepatic-malignancies
#17
Alice Hagan, Gary J Phillips, Wendy M Macfarlane, Andrew W Lloyd, Peter Czuczman, Andrew L Lewis
Since their introduction around a decade ago, embolic drug-eluting beads (DEBs) have become a well-established treatment option for the locoregional transarterial treatment of hepatic malignancies. Despite this success, the therapy is seen to be limited by the choice of drug and more effective options are therefore being sought. These include the small molecule multi-tyrosine kinase inhibitors (MTKi), which exert an anti-angiogenic and anti-proliferative effect that could be highly beneficial in combating some of the unwanted downstream consequences of embolization...
January 27, 2017: European Journal of Pharmaceutical Sciences
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
#18
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/28124835/a-pareto-algorithm-for-efficient-de-novo-design-of-multi-functional-molecules
#19
Frits Daeyaert, Micheal W Deem
We have introduced a Pareto sorting algorithm into Synopsis, a de novo design program that generates synthesizable molecules with desirable properties. We give a detailed description of the algorithm and illustrate its working in 2 different de novo design settings: the design of putative dual and selective FGFR and VEGFR inhibitors, and the successful design of organic structure determining agents (OSDAs) for the synthesis of zeolites. We show that the introduction of Pareto sorting not only enables the simultaneous optimization of multiple properties but also greatly improves the performance of the algorithm to generate molecules with hard-to-meet constraints...
January 2017: Molecular Informatics
https://www.readbyqxmd.com/read/28123542/influence-of-vegfr-single-nucleotide-polymorphisms-on-the-efficacy-of-sunitinib-therapy-against-renal-cell-carcinoma
#20
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
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