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Vincent T Ho, Haesook T Kim, Natalie Bavli, Martin Mihm, Olga Pozdnyakova, Matthias Piesche, Heather Daley, Carol Reynolds, Nicholas C Souders, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Jerome Ritz, Glenn Dranoff, Robert J Soiffer
We report a clinical trial testing vaccination of autologous myeloblasts admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells after allogeneic hematopoietic stem cell transplantation (HSCT). Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with ≥5% marrow blasts underwent myeloblast collection before HSCT. At approximately day +30, 6 vaccines composed of irradiated autologous myeloblasts mixed with GM-K562 were administered. Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was not tapered until vaccine completion (∼day 100)...
November 14, 2017: Blood Advances
Nokuzola Mbhele, Jagidesa Moodley, Thajasvarie Naicker
OBJECTIVE: The factors angiopoeitin-2 (Ang-2), endoglin (Eng), and placental growth factor (PlGF) have been implicated in the pathophysiology of preeclampsia (PE). This study assessed their serum levels in HIV-negative and HIV-positive pregnant normotensive and pre-eclamptic women. METHODS: Participants were recruited at the antenatal clinic, serum samples were evaluated using the Bioplex Human Cancer Biomarker (panel 2). RESULTS: Ang-2 and Eng levels were higher, whilst PlGF levels were lower in the PE compared with the normotensive group...
August 2017: Hypertension in Pregnancy
Hanno Ehlken, Roman Zenouzi, Christoph Schramm
PURPOSE OF REVIEW: Primary sclerosing cholangitis (PSC) is associated with an increased risk of hepatobiliary and extrahepatic malignancy. Particularly the risk of cholangiocarcinoma (CCA) is greatly increased. To provide potentially curative treatments for affected patients an early diagnosis of CCA is crucial. We here review the current advances with respect to CCA diagnosis and surveillance and discuss a rational approach on how to perform surveillance of CCA in PSC patients. RECENT FINDINGS: Given the shortcomings of the current modalities for the surveillance and diagnosis of CCA in PSC, recent studies have focused on novel biomarkers for CCA...
March 2017: Current Opinion in Gastroenterology
Longhai Qiu, Bo He, Jun Hu, Zhaowei Zhu, Xiaolin Liu, Jiakai Zhu
Our group pioneered the study of nerve regeneration in China and has successfully developed human "acellular nerve grafts (ACNGs)". However, our clinical studies revealed that the effects of ACNGs for long and large nerve defects are far from satisfactory. To improve the efficacy of ACNGs, we combined Cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) with ACNGs in rat sciatic nerve injury models and observed the outcomes via angiographic, morphological, and functional analyses. Co-cultures of endothelial cells (ECs) and dorsal root ganglion neurons (DRGs) were also used to characterize the relationship between neovascularization and nerve regeneration...
December 2015: Annals of Biomedical Engineering
Heather Menden, Scott Welak, Stephanie Cossette, Ramani Ramchandran, Venkatesh Sampath
Sepsis-mediated endothelial Angiopoeitin-2 (Ang2) signaling may contribute to microvascular remodeling in the developing lung. The mechanisms by which bacterial cell wall components such as LPS mediate Ang2 signaling in human pulmonary microvascular endothelial cells (HPMECs) remain understudied. In HPMEC, LPS-induced Ang2, Tie2, and VEGF-A protein expression was preceded by increased superoxide formation. NADPH oxidase 2 (Nox2) inhibition, but not Nox4 or Nox1 inhibition, attenuated LPS-induced superoxide formation and Ang2, Tie2, and VEGF-A expression...
February 27, 2015: Journal of Biological Chemistry
Anne Burke-Gaffney, Tatiana Svermova, Sharon Mumby, Simon J Finney, Timothy W Evans
OBJECTIVE: Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure following cardiac surgery requiring cardiopulmonary bypass (CPB). Roundabout protein 4 (Robo4), an endothelial-expressed transmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. We investigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI), after cardiac surgery...
2014: PloS One
Lan T H Dang, Nicole T Feric, Carol Laschinger, Wing Y Chang, Boyang Zhang, Geoffrey A Wood, William L Stanford, Milica Radisic
Adhesion molecule signaling is critical to human pluripotent stem cell (hPSC) survival, self-renewal, and differentiation. Thus, hPSCs are grown as clumps of cells on feeder cell layers or poorly defined extracellular matrices such as Matrigel. We sought to define a small molecule that would initiate adhesion-based signaling to serve as a basis for a defined substrate for hPSC culture. Soluble angiopoeitin-1 (Ang-1)-derived peptide QHREDGS added to defined serum-free media increased hPSC colony cell number and size during long- and short-term culture when grown on feeder cell layers or Matrigel, i...
September 2014: Biomaterials
Rajendra Raghow
The pancreatic β-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus (T2DM). The persistent hyperglycemia of T2DM is often treated with anti-diabetic drugs with or without subcutaneous insulin injections, neither of which mimic the physiological glycemic control seen in individuals with fully functional pancreas. A sought after goal for the treatment of T2DM has been to harness the regenerative potential of pancreatic β-cells that might obviate a need for exogenous insulin injections...
December 15, 2013: World Journal of Diabetes
Dorottya K de Vries, Meriem Khairoun, Jan H N Lindeman, Ingeborg M Bajema, Emile de Heer, Mark Roest, Anton J van Zonneveld, Cees van Kooten, Ton J Rabelink, Alexander F Schaapherder, Marlies E J Reinders
BACKGROUND: Recent insights suggest that endothelial cell (EC) activation plays a major role in renal ischemia-reperfusion (I/R) injury. Interactions between ECs and pericytes via signaling molecules, including angiopoietins, are involved in maintenance of the vascular integrity. Experimental data have shown that enhancement of Angiopoietin (Ang)-1 signaling might be beneficial in renal I/R injury. However, little is known about the role of angiopoietins in human renal I/R injury. METHODS: In this study, EC activation and changes in angiopoeitins are assessed in human living-donor (LD) and deceased-donor (DD) kidney transplantation...
August 15, 2013: Transplantation
Meriem Khairoun, Pieter van der Pol, Dorottya K de Vries, Ellen Lievers, Nicole Schlagwein, Hetty C de Boer, Ingeborg M Bajema, Joris I Rotmans, Anton Jan van Zonneveld, Ton J Rabelink, Cees van Kooten, Marlies E J Reinders
Endothelial cells (ECs) are highly susceptible to hypoxia and easily affected upon ischemia-reperfusion (I/R) during renal transplantation. Pericytes and angiopoeitins play important role in modulating EC function. In the present study, we investigate the effect of renal I/R on the dynamics of angiopoietin expression and its association with pericytes and fibrosis development. Male Lewis rats were subjected to unilateral renal ischemia for 45 min followed by removal of the contralateral kidney. Rats were killed at different time points after reperfusion...
September 15, 2013: American Journal of Physiology. Renal Physiology
Mélanie Morin-Brureau, Frédéric De Bock, Mireille Lerner-Natoli
BACKGROUND: It is now recognized that the neuro-vascular unit (NVU) plays a key role in several neurological diseases including epilepsy, stroke, Alzheimer's disease, multiple sclerosis and the development of gliomas. Most of these disorders are associated with NVU dysfunction, due to overexpression of inflammatory factors such as vascular endothelial growth factor (VEGF). Various in vitro models have been developed previously to study the micro-environment of the blood-brain barrier (BBB)...
2013: Fluids and Barriers of the CNS
Rongsong Li, David Mittelstein, Karen Fang, Tyler Beebe, Katherine Quigley, Judith Berliner, Tzung K Hsiai
Angiopoeitin-2 (Ang-2) antagonizes Angiopeitin-1 (Ang-1)-mediated Tie-2 signaling. Ang-1 is reported to up-regulate anti-apoptotic Survivin expression. Here, we investigated the interplay between Ang-2 and Survivin in response to oxidized low density lipoprotein (OxLDL)-induced apoptosis. We demonstrate that treatment of human aortic endothelial cells (HAEC) with 100 μg/ml of OxLDL down-regulated Ang-2 expression as early as 4h after treatment and persisted up to 24h (p<0.05, n=3), but did not down-regulate Survivin until the 24h point...
January 6, 2012: Biochemical and Biophysical Research Communications
Christina Coleman, Danielle Levine, Raj Kishore, Gangjian Qin, Tina Thorne, Erin Lambers, Sharath P Sasi, Mina Yaar, Barbara A Gilchrest, David A Goukassian
Telomere homolog oligonucleotides (T-oligos) activate an innate telomere-based program that leads to multiple anticancer effects. T-oligos act at telomeres to initiate signaling through the Werner protein and ATM kinase. We wanted to determine if T-oligos have antiangiogenic effects. We found that T-oligo-treated human melanoma (MM-AN) cells had decreased expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, angiopoeitin-1 and -2 and decreased VEGF secretion. T-oligos activated the transcription factor E2F1 and inhibited the activity of the angiogenic transcription factor, HIF-1alpha...
2010: Journal of Oncology
Shefalee K Bhavsar, Satinder Singh, Suresh Giri, Mukul R Jain, Dev D Santani
ETHNOPHARMACOLOGICAL RELEVANCE: We characterized saponins as active constituents from traditionally used antidiabetic plant Helicteres isora. AIM OF THE STUDY: To evaluate the changes in the gene expression of the glucose and lipid metabolism regulating genes in C57BL/KsJ-db/db mice. MATERIALS AND METHODS: C57BL/KsJ-db/db mice were divided into four different groups; one diabetic control, the mice in other three groups were treated with methanol extract (100 mg/kg), saponins (100 mg/kg) and pioglitazone (30 mg/kg) for 14 days...
July 30, 2009: Journal of Ethnopharmacology
Maria Florian, Livia Florianova, Sabah Hussain, Sheldon Magder
The role of estrogen replacement therapy in postmenopausal women remains controversial. The authors hypothesized that contradictory results with estrogen therapy may be explained by estrogen's potent proangiogenic property, which could be protective in women without atherosclerotic disease but in the presence of chronic inflammation, could lead to destabilization of atherosclerotic plaques. The authors thus examined the interaction between 17beta-estradiol (E2) and the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) in an early stage of angiogenesis...
September 2008: Endothelium: Journal of Endothelial Cell Research
Kory J Lavine, Fanxin Long, Kyunghee Choi, Craig Smith, David M Ornitz
Vascular development begins with formation of a primary capillary plexus that is later remodeled to give rise to the definitive vasculature. Although the mechanism by which arterial and venous fates are acquired is well understood, little is known about when during vascular development arterial and venous vessels emerge and how their growth is regulated. Previously, we have demonstrated that a hedgehog (HH)/vascular endothelial growth factor (VEGF) and angiopoeitin 2 (ANG2) signaling pathway is essential for the development of the coronary vasculature...
September 2008: Development
Zoya Gluzman, Belly Koren, Meir Preis, Tzafra Cohen, Adili Tsaba, Francois-Loic Cosset, Rona Shofti, Basil S Lewis, Renu Virmani, Moshe Y Flugelman
RATIONAL AND OBJECTIVES: Activation of fully differentiated vascular cells using angiogenic genes can lead to phenotypic changes resulting in formation of new blood vessels. We tested whether Ang-1 gene transfer to endothelial cells (EC) activates these cells. METHODS AND RESULTS: EC and SMC were transduced using retroviral or adenoviral vectors to produce Ang-1 or vascular endothelial growth factor (VEGF). EC Tie-2 receptor was phosphorilated by autologous secretion of Ang-1...
July 27, 2007: Biochemical and Biophysical Research Communications
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