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Zhizhen Dong, Jianrong Chen, Xuli Yang, Wenjie Zheng, Li Wang, Miao Fang, Mengna Wu, Min Yao, Dengfu Yao
Lung cancer is the most common malignant tumor with increasing angiopoietin-2 (Ang-2) and a high rate of metastasis. However, the mechanism of Ang-2 enhancing tumor proliferation and facilitating metastasis remains to be clarified. In this study, Ang-2 expression and its gene transcription on effects of biological behaviors and epithelial-mesenchymal transition (EMT) were investigated in lung cancers. Total incidence of Ang-2 expression in the cancerous tissues was up to 91.8 % (112 of 122) with significantly higher (χ2 =103...
February 27, 2018: Oncotarget
David M Hyman, Naiyer A Rizvi, Ronald B Natale, Deborah K Armstrong, Michael J Birrer, Lawrence Recht, Efrat Dotan, Vicky Makker, Thomas J Kaley, Denison Kuruvilla, Matthew Gribbin, Jennifer McDevitt, Dominic W Lai, Mohammed M Dar
PURPOSE: This first-in-human study aimed to determine the maximum tolerated dose (MTD) and safety of MEDI3617, a selective anti-angiopoietin-2 (Ang2) monoclonal antibody, alone and combined with bevacizumab or cytotoxic chemotherapy. Experimental Design: This phase I/Ib, multicenter, open-label, dose escalation and dose expansion study evaluated patients with advanced solid tumors. Patients received intravenous MEDI3617 as monotherapy (5-1500 mg every 3 weeks [Q3W]) or with bevacizumab every 2 weeks (Q2W) or Q3W, weekly paclitaxel, or carboplatin plus paclitaxel Q3W...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Guo Nan Yin, Hai-Rong Jin, Min-Ji Choi, Anita Limanjaya, Kalyan Ghatak, Nguyen Nhat Minh, Jiyeon Ock, Mi-Hye Kwon, Kang-Moon Song, Heon Joo Park, Ho Min Kim, Young-Guen Kwon, Ji-Kan Ryu, Jun-Kyu Suh
Penile erection requires well-coordinated interactions between vascular and nervous system. Penile neurovascular dysfunction is a major cause of erectile dysfunction (ED) in patients with diabetes, which causes poor response to oral phosphodiesterase-5 inhibitors. Dickkopf2 (DKK2), a Wnt antagonist, is known to promote angiogenesis. Here, using DKK2-Tg mice or DKK2 protein administration, we demonstrate that overexpression of DKK2 in diabetic mice enhances penile angiogenesis and neural regeneration and restores erectile function...
March 20, 2018: Diabetes
Hwi Young Kim, Dong Hyeon Lee, Jeong-Hoon Lee, Young Youn Cho, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
BACKGROUND: Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). METHODS: This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib...
March 20, 2018: BMC Cancer
Wieneke Dijk, Sophie Schutte, Edo O Aarts, Ignace M C Janssen, Lydia Afman, Sander Kersten
BACKGROUND: Elevated plasma triglycerides are increasingly viewed as a causal risk factor for coronary artery disease. One protein that raises plasma triglyceride levels and that has emerged as a modulator of coronary artery disease risk is angiopoietin-like 4 (ANGPTL4). ANGPTL4 raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL), the enzyme that catalyzes the hydrolysis of circulating triglycerides on the capillary endothelium. OBJECTIVE: The objective of the present study was to assess the association between ANGPTL4 and LPL in human adipose tissue, and to examine the influence of nutritional status on ANGPTL4 expression...
February 17, 2018: Journal of Clinical Lipidology
Riccardo Rizzo, Maria Alvaro, Norbert Danz, Lucia Napione, Emiliano Descrovi, Stefan Schmieder, Alberto Sinibaldi, Subinoy Rana, Rona Chandrawati, Peter Munzert, Thomas Schubert, Emmanuel Maillart, Aleksei Anopchenko, Paola Rivolo, Alessandro Mascioletti, Erik Förster, Frank Sonntag, Molly M Stevens, Federico Bussolino, Francesco Michelotti
Quantitative detection of angiogenic biomarkers provides a powerful tool to diagnose cancers in early stages and to follow its progression during therapy. Conventional tests require trained personnel, dedicated laboratory equipment and are generally time-consuming. Herein, we propose our developed biosensing platform as a useful tool for a rapid determination of Angiopoietin-2 biomarker directly from patient plasma within 30 minutes, without any sample preparation or dilution. Bloch surface waves supported by one dimensional photonic crystal are exploited to enhance and redirect the fluorescence arising from a sandwich immunoassay that involves Angiopoietin-2...
February 1, 2018: Biomedical Optics Express
Regina Trollmann, Theresa Mühlberger, Mandy Richter, Gudrun Boie, Andreas Feigenspan, Florian Brackmann, Susan Jung
Angiogenesis due to hypoxic-ischemic (HI) injury represents a crucial compensatory mechanism of the developing brain that is mainly regulated by hypoxia-inducible transcription factors (HIF). Pharmacological stimulation of HIF is suggested as a neuroprotective option, however, studies of its effects on vascular development are limited. We analyzed the influence of the prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) on post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in the developing mouse brain (P7) assessed after a regeneration period of 72 h...
March 13, 2018: Brain Research
David S Olshan, Daniel J Rader
The angiopoietin-like proteins are a family of proteins that share structural similarities to the angiopoietins. These proteins have been described to play a key role in the regulation of a myriad of physiologic processes, including serving as essential modulators of lipid and glucose metabolism. Angiopoietin-like protein 4 (ANGPTL4) is a key regulator of lipoprotein lipase, and its modulation has been shown to significantly impact the body's processing and distribution of triglycerides and cholesterol. Although more research remains to elucidate the full range of mechanisms through which ANGPTL4 affects triglyceride and cholesterol homeostasis, current research has associated decreased ANGPTL4 function with a beneficial effect on lipid parameters and overall cardiovascular disease risk, opening the possibility of ANGPTL4 as a new therapeutic target for the treatment of cardiovascular disease...
February 2, 2018: Journal of Clinical Lipidology
Chengqiang Wu, Chun Gui, Lang Li, Yiheng Pang, Zhongli Tang, Jing Wei
Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h...
April 2018: Experimental and Therapeutic Medicine
Ke-Wei Tian, Yuan-Yuan Zhang, Hong Jiang, Shu Han
The placenta has emerged as an attractive source of mesenchymal stem cells (MSCs) because of the absence of ethical issues, non-invasive access, and abundant yield. However, inflammatory cell invasion into grafts negatively impacts the survival and efficacy of transplanted cells. Previous studies have shown that synthetic C16 peptide can competitively block the transmigration of leukocytes into the central nerve system, while angiopoietin-1 (Ang-1) can inhibit inflammation-induced blood vessel leakage and inflammatory cell infiltration in rats with experimental allergic encephalomyelitis (EAE)...
March 15, 2018: Scientific Reports
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Jeffrey Earl Gotts, Lauren F Chun, Jason Abbott, Xiaohui Fang, Naoki Takasaki, Stephen L Nishimura, Matthew L Springer, Suzaynn F Schick, Carolyn S Calfee, Michael A Matthay
Evidence is accumulating that exposure to cigarette smoke (CS) increases the risk of developing Acute Respiratory Distress Syndrome (ARDS). S. pneumoniae is the most common cause of bacterial pneumonia, which in turn is the leading cause of ARDS. Chronic smokers have increased rates of pneumococcal colonization and develop more severe pneumococcal pneumonia than nonsmokers, yet mechanistic connections between CS exposure, bacterial pneumonia, and ARDS pathogenesis remain relatively unexplored. We exposed mice to 3 weeks of moderate whole-body CS or air, followed by intranasal inoculation with an invasive serotype of S...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jun Morinaga, Jiabin Zhao, Motoyoshi Endo, Tsuyoshi Kadomatsu, Keishi Miyata, Taichi Sugizaki, Yusuke Okadome, Zhe Tian, Haruki Horiguchi, Kazuya Miyashita, Nobuhiro Maruyama, Masashi Mukoyama, Yuichi Oike
PURPOSE: Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. METHODS: We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay...
2018: PloS One
Silvia Barja-Fernandez, José María Moreno-Navarrete, Cintia Folgueira, Gemma Xifra, Mònica Sabater, Cecilia Castelao, Johan FernØ, Rosaura Leis, Carlos Diéguez, Felipe F Casanueva, Wifredo Ricart, Luisa M Seoane, José Manuel Fernandez-Real, Rubén Nogueiras
SCOPE: Angiopoietin-like protein 4 (ANGPTL-4) regulates plasma lipoprotein levels but its relevance in human obesity and type 2 diabetes is largely unknown. We aimed to investigate the regulation of circulating ANGPTL-4 levels in obesity, type 2 diabetes and after changes in body weight. METHODS AND RESULTS: Circulating ANGPTL-4 levels were measured in two different cohorts. First, in a cross-sectional study, we evaluated ANGPTL-4 levels in lean and obese patients with normoglycemia or with altered glucose tolerance (n = 282)...
March 14, 2018: Molecular Nutrition & Food Research
Antoni Torres
No abstract text is available yet for this article.
March 12, 2018: American Journal of Respiratory and Critical Care Medicine
Meng Hou, Jinjin Cui, Jingjin Liu, Fang Liu, Rui Jiang, Kai Liu, Yongshun Wang, Li Yin, Wenhua Liu, Bo Yu
No abstract text is available yet for this article.
2018: PloS One
Dorien Reijnders, Chin-Chi Liu, Xinjing Xu, Anna Zhao, Kelsey Olson, Scott D Butler, Nataki C Douglas, Jenny L Sones
Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface...
March 9, 2018: Physiological Genomics
Dai Fukumura, Jonas Kloepper, Zohreh Amoozgar, Dan G Duda, Rakesh K Jain
Immunotherapy has emerged as a major therapeutic modality in oncology. Currently, however, the majority of patients with cancer do not derive benefit from these treatments. Vascular abnormalities are a hallmark of most solid tumours and facilitate immune evasion. These abnormalities stem from elevated levels of proangiogenic factors, such as VEGF and angiopoietin 2 (ANG2); judicious use of drugs targeting these molecules can improve therapeutic responsiveness, partially owing to normalization of the abnormal tumour vasculature that can, in turn, increase the infiltration of immune effector cells into tumours and convert the intrinsically immunosuppressive tumour microenvironment (TME) to an immunosupportive one...
March 6, 2018: Nature Reviews. Clinical Oncology
T D Tremaine, A A Fouladi-Nashta
The vascular changes associated with endometrial maturation in preparation for embryo implantation depend on numerous growth factors, known to regulate key angiogenic events. Primarily, the vascular endothelial growth factor (VEGF) family promotes vascular growth, whilst the angiopoietins maintain blood vessel integrity. The aim was to analyse protein levels of VEGFA ligand and receptors, Angiopoietin-1 and 2 (ANG1/2) and endothelial cell receptor tyrosine kinase (TIE-2) in the ovine endometrium in the follicular and luteal phases of the oestrus cycle and in response to ovarian steroids...
March 5, 2018: Reproduction in Domestic Animals, Zuchthygiene
C Y Lan, B Ling, W W Guo, W Yin, X G Zhong, Y M Han, X F Dong
Objective: To detect the possible molecular mechanisms of the formation of vessels that encapsulated tumor clusters (VETC) and identify the relationship between vimentin protein expression in endothelial cells and contrast-enhanced ultrasound characters in VETC (+ ) hepatocellular carcinoma (HCC). Methods: A total of 64 paraffin embedded HCC tissue samples were collected, all of which the tumor diameters were between 2 cm and 5 cm measured by the preoperative ultrasound. Immunohistochemistry staining for CD34 was used to detect the formation of VETC and the expressions of angiopoietin-2 (Ang-2) and vimentin were also determined...
February 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
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