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https://www.readbyqxmd.com/read/28596825/kv1-3-channel-blocker-imktx88-maintains-blood-brain-barrier-in-experimental-autoimmune-encephalomyelitis
#1
Jie Huang, Song Han, Qi Sun, Yipeng Zhao, Junchen Liu, Xiaolu Yuan, Wenqian Mao, Biwen Peng, Wanhong Liu, Jun Yin, Xiaohua He
BACKGROUND: Disruption of blood-brain barrier (BBB) and subsequent infiltration of auto-reactive T lymphocytes are major characteristics of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Kv1.3 channel blockers are demonstrated potential therapeutic effects on MS patients and EAE models, maybe via reducing activation of T cells. However, it remains to be explored whether Kv1.3 channel blockers maintain integrity of BBB in MS model. RESULTS: In this study, ImKTx88, a highly selective Kv1...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28592620/phase-ii-study-of-first-line-trebananib-plus-sorafenib-in-patients-with-advanced-hepatocellular-carcinoma
#2
Ghassan K Abou-Alfa, Jean-Frederic Blanc, Steven Miles, Tom Ganten, Jörg Trojan, Jonathan Cebon, Andre K Liem, Lara Lipton, Charu Gupta, Benjamin Wu, Michael Bass, Ellen Hollywood, Jennifer Ma, Margaret Bradley, Jason Litten, Leonard B Saltz
LESSONS LEARNED: Trebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28586644/endothelial-to-osteoblast-conversion-generates-osteoblastic-metastasis-of-prostate-cancer
#3
Song-Chang Lin, Yu-Chen Lee, Guoyu Yu, Chien-Jui Cheng, Xin Zhou, Khoi Chu, Monzur Murshed, Nhat-Tu Le, Laura Baseler, Jun-Ichi Abe, Keigi Fujiwara, Benoit deCrombrugghe, Christopher J Logothetis, Gary E Gallick, Li-Yuan Yu-Lee, Sankar N Maity, Sue-Hwa Lin
Prostate cancer (PCa) bone metastasis is frequently associated with bone-forming lesions, but the source of the osteoblastic lesions remains unclear. We show that the tumor-induced bone derives partly from tumor-associated endothelial cells that have undergone endothelial-to-osteoblast (EC-to-OSB) conversion. The tumor-associated osteoblasts in PCa bone metastasis specimens and patient-derived xenografts (PDXs) were found to co-express endothelial marker Tie-2. BMP4, identified in PDX-conditioned medium, promoted EC-to-OSB conversion of 2H11 endothelial cells...
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28571880/%C3%AE-tocopherol-especially-%C3%AE-tocopherol-phosphate-exerts-antiapoptotic-and-angiogenic-effects-on-rat-bone-marrow-derived-endothelial-progenitor-cells-under-high-glucose-and-hypoxia-conditions
#4
Ziheng Wu, Xiangtao Zheng, Luyang Meng, Xin Fang, Yangyan He, Donglin Li, Chengfei Zheng, Hongkun Zhang
OBJECTIVE: Considering the poor efficacy of local intramuscular injections with endothelial progenitor cells (EPCs) for critical limb ischemia in patients with diabetes, the study aimed to investigate the effect of α-tocopherol (α-T) and α-tocopherol phosphate (α-TP) on apoptosis and angiogenesis in a rat model under oxidative stress conditions. METHODS: Primary EPCs from Sprague-Dawley rats were harvested and treated with α-T and α-TP for 24 hours. Gene transcription and protein expression were evaluated by real-time polymerase chain reaction and Western blot, respectively...
May 29, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28555943/pro-angiogenic-tie-2-expressing-monocytes-tems-as-a-biomarker-of-the-effect-of-sorafenib-in-patients-with-advanced-hepatocellular-carcinoma
#5
Hirotaka Shoji, Sachiyo Yoshio, Yohei Mano, Hiroyoshi Doi, Masaya Sugiyama, Yosuke Osawa, Kiminori Kimura, Taeang Arai, Norio Itokawa, Masanori Atsukawa, Yoshihiko Aoki, Moto Fukai, Akinobu Taketomi, Masashi Mizokami, Tatsuya Kanto
Sorafenib, a multi-kinase inhibitor, inhibits tumor angiogenesis and is the first-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC). However, due to its limited effects and frequent occurrence of side effects, biomarkers are needed to predict the effects of sorafenib. We considered the possibility of using TIE-2-expressing monocytes (TEMs) to predict the response in sorafenib-treated patients with advanced HCC. TEMs serve as a diagnostic marker of HCC and are related to angiogenesis...
May 27, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28549617/hematopathological-alterations-of-major-tumor-suppressor-cascade-vital-cell-cycle-inhibitors-and-hematopoietic-niche-components-in-experimental-myelodysplasia
#6
Ritam Chatterjee, Shubhangi Gupta, Sujata Law
Myelodysplastic syndrome (MDS) is a poorly understood dreadful hematopoietic disorder that involves maturational defect and abnormalities in blood cell production leading to dysplastic changes and peripheral blood pancytopenia. The present work aims in establishing the mechanistic relationship of the expressional alterations of major tumor suppressor cascade, vital cell cycle inhibitors and hematopoietic microenvironmental components with the disease pathophysiologies. The study involves the development of N-N' Ethylnitrosourea (ENU) induced mouse model of MDS, characterization of the disease with blood film and bone marrow smear studies, scanning electron microscopic observation, mitochondrial membrane potential determination, flowcytometric analysis of osteoblastic and vascular niche components along with the expressional study of cleaved caspase-3, PCNA, Chk-2, p53, Ndn, Gfi-1, Tie-2, Sdf-1, Gsk-3β, p18 and Myt-1 in the bone marrow compartment...
May 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28545512/tie2-as-a-novel-key-factor-of-microangiopathy-in-systemic-sclerosis
#7
Falk Moritz, Janine Schniering, Jörg H W Distler, Renate E Gay, Steffen Gay, Oliver Distler, Britta Maurer
BACKGROUND: The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28538018/low-serum-angiopoietin-1-high-serum-angiopoietin-2-and-high-ang-2-ang-1-protein-ratio-are-associated-with-early-onset-sepsis-in-surinamese-newborns
#8
Rens Zonneveld, Rianne Jongman, Amadu Juliana, Wilco Zijlmans, Frans Plötz, Grietje Molema, Matijs van Meurs
PURPOSE: Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and -2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. Levels of Ang-2 change in adults and children during sepsis, which is associated with severity of sepsis. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 hours after birth. METHODS: A prospective cohort study was performed amongst 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns...
May 22, 2017: Shock
https://www.readbyqxmd.com/read/28513999/microparticles-of-healthy-origins-improve-endothelial-progenitor-cell-dysfunction-via-microrna-transfer-in-an-atherosclerotic-hamster-model
#9
Nicoleta Alexandru, Eugen Andrei, Loredan Niculescu, Emanuel Dragan, Violeta Ristoiu, Adriana Georgescu
AIM: In this study we aimed: (1) to obtain and functionally characterize the cultures of late endothelial progenitor cells (EPCs) from the animal blood; (2) to investigate the potential beneficial effects of circulating microparticles (MPs) of healthy origins on EPC dysfunctionality in atherosclerosis as well as involved mechanisms. METHODS: Late EPCs were obtained and expanded in culture from peripheral blood isolated from two animal groups: hypertensive-hyperlipidemic (HH) and control (C) hamsters...
May 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28513569/intravenous-arginine-administration-promotes-proangiogenic-cells-mobilization-and-attenuates-lung-injury-in-mice-with-polymicrobial-sepsis
#10
Chiu-Li Yeh, Man-Hui Pai, Yao-Ming Shih, Juey-Ming Shih, Sung-Ling Yeh
This study investigated the influence of intravenous arginine (Arg) administration on alteration of circulating proangiogenic cells and remote lung injury in a model of polymicrobial sepsis. Mice were assigned to one normal control group (NC) and two sepsis groups that were induced by cecal ligation and puncture (CLP). One of the sepsis groups was injected with saline (SS), whereas the other (SA) was administered with a single bolus of 300 mg Arg/kg body weight via the tail vein 1 h after CLP. Septic mice were sacrificed at either 24 or 48 h after CLP, with their blood and lung tissues collected for analysis...
May 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28507810/tie-2-expressing-monocytes-in-human-cancers
#11
Riccardo Turrini, Angélique Pabois, Ioannis Xenarios, George Coukos, Jean-François Delaloye, Marie-Agnès Doucey
Tumor-associated macrophages (TAM) are well known as a key player in the tumor microenvironment, which support cancer progression. More recently, a lineage of monocytes characterized by the expression of the TIE-2/Tek angiopoietin receptor identified a subset of circulating and tumor-associated monocytes endowed with proangiogenic activity. TIE-2 expressing monocytes (TEM) were found both in humans and mice. Here, we review the phenotypes and functions of TEM reported so far in human cancer and their potential use as markers of cancer progression and metastasis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28474375/angiopoietin-2-and-soluble-tie-2-receptor-plasma-levels-in-children-with-obstructive-sleep-apnea-and-obesity
#12
David Gozal, Abdelnaby Khalyfa, Zhuanghong Qiao, Dale L Smith, Mona F Philby, Dorit Koren, Leila Kheirandish-Gozal
OBJECTIVE: Obstructive sleep apnea (OSA) is a prevalent condition, especially in children with obesity, and is associated with increased risk for metabolic syndrome (MetS). Angiopoietins have been identified as potential biomarkers of endothelial dysfunction and MetS. In adults, angiopoietin-2 (Ang-2) and its soluble receptor (sTie-2) are associated with diabetes, hypertension, and obesity and could be increased in children with OSA and obesity, particularly those with evidence of cardiometabolic alterations...
June 2017: Obesity
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
#13
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/28423009/correction-circulating-angiopoietin-2-and-its-soluble-receptor-tie-2-concentrations-are-related-to-renal-function-in-two-population-based-cohorts
#14
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0166492.].
2017: PloS One
https://www.readbyqxmd.com/read/28415910/transfer-of-training-in-simple-addition
#15
Yalin Chen, Jamie I D Campbell
In recent years several researchers have proposed that skilled adults may solve single-digit addition problems (e.g. 3 + 1 = 4, 4 + 3 = 7) using a fast counting procedure. Practicing a procedure, often leads to transfer of learning and faster performance of unpracticed items. Such transfer has been demonstrated using a counting-based alphabet arithmetic task (e.g., B + 4 = C D E F) that indicated robust generalization of practice (i.e., RT gains) when untrained transfer problems at test had been implicitly practiced (e...
April 18, 2017: Quarterly Journal of Experimental Psychology: QJEP
https://www.readbyqxmd.com/read/28369068/all-trans-retinoic-acid-suppresses-the-angiopoietin-tie2-pathway-and-inhibits-angiogenesis-and-metastasis-in-esophageal-squamous-cell-carcinoma
#16
Na Li, Yanjuan Lu, Daoming Li, Xiangyu Zheng, Jingyao Lian, Shanshan Li, Huijuan Cui, Linda Zhang, Luqian Sang, Ying Wang, Jane J Yu, Taiying Lu
Esophageal squamous cell carcinoma (ESCC) is the second common cancer in Henan province and is well-known for aggressiveness and dismal prognosis. Adjuvant therapies, chemotherapy, radiotherapy and endoscopic treatment have not improved survival rates in patients with late stage esophageal carcinoma. All-trans retinoic acid (ATRA) is the active ingredient of Vitamin A and affects a wide spectrum of biological processes including development, growth, neural function, immune function, reproduction, and vision...
2017: PloS One
https://www.readbyqxmd.com/read/28351775/nox2-nox4-and-mitochondrial-derived-reactive-oxygen-species-contribute-to-angiopoietin-1-signaling-and-angiogenic-responses-in-endothelial-cells
#17
Sharon Harel, Dominique Mayaki, Veronica Sanchez, Sabah N A Hussain
Angiopoietin-1 (Ang-1) is a ligand of Tie-2 receptors that promotes survival, migration, and differentiation of endothelial cells. Several studies have linked reactive oxygen species (ROS) to Ang-1 signaling and distinct angiogenic responses, but the molecular sources of these ROS have never been clearly identified. In this study, we have identified source-specific contributions of ROS to Ang-1/Tie 2 signaling and angiogenic responses in human umbilical vein endothelial cells (HUVECs), specifically the differential contributions of mitochondrial ROS (mtROS) and ROS from two isoforms of NADPH oxidase (NOX2, NOX4)...
March 27, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28345548/polyglycolic-acid-fibrous-scaffold-improving-endothelial-cell-coating-and-vascularization-of-islet
#18
Yang Li, Ping Fan, Xiao-Ming Ding, Xiao-Hui Tian, Xin-Shun Feng, Hang Yan, Xiao-Ming Pan, Pu-Xun Tian, Jin Zheng, Chen-Guang Ding, Wu-Jun Xue
BACKGROUND: Improving islet graft revascularization has become a crucial task for prolonging islet graft survival. Endothelial cells (ECs) are the basis of new microvessels in an isolated islet, and EC coating has been demonstrated to improve the vascularization and survival of an islet. However, the traditional method of EC coating of islets has low efficiency in vitro. This study was conducted to evaluate the effect of a polyglycolic acid (PGA) scaffold on the efficiency of islet coating by ECs and the angiogenesis in the coated islet graft...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28332573/discovery-of-multi-target-receptor-tyrosine-kinase-inhibitors-as-novel-anti-angiogenesis-agents
#19
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/28289658/expressions-and-clinical-significances-of-angiopoietin-1-angiopoietin-2-and-tie-2-receptor-in-patients-with-colorectal-cancer
#20
Sunghoon Hong, Hae Il Jung, Tae Sung Ahn, Han-Jo Kim, Kyu-Taek Lee, Moo-Jun Baek, Sang-Byung Bae
PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients...
February 2017: Annals of Coloproctology
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