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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
Xiao-Jun Wu, Nathalie Dinguirard, Grzegorz Sabat, Hong-di Lui, Laura Gonzalez, Michael Gehring, Utibe Bickham-Wright, Timothy P Yoshino
Interactions between early developing Schistosoma mansoni larval stages and the hemolymph of its snail intermediate host represent the first molecular encounter with the snail's immune system. To gain a more comprehensive understanding of this early parasite-host interaction, biotinylated sporocyst tegumental membrane (Mem) proteins and larval transformation proteins (LTP) were affixed to streptavidin-agarose beads and used as affinity matrices to enrich for larval-reactive plasma proteins from susceptible (NMRI) and resistant (BS-90) strains of the snail Biomphalaria glabrata...
May 2017: PLoS Pathogens
Davide Valentini, Martin Rao, Lalit Rane, Sayma Rahman, Rebecca Axelsson-Robertson, Rainer Heuchel, Matthias Löhr, Daniel Hoft, Susanna Brighenti, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Bacille Calmette-Guérin (BCG) is the world's most widely distributed vaccine, used against tuberculosis (TB), in cancer immunotherapy, and in autoimmune diseases due to its immunomodulatory properties. To date, the effect of BCG vaccination on antibody responses to host proteins has not been reported. High-content peptide microarrays (HCPM) offer a unique opportunity to gauge specific humoral immune responses. METHODS: The sera of BCG-vaccinated healthy adults were tested on a human HCPM platform (4953 randomly selected epitopes of human proteins) to detect specific immunoglobulin gamma (IgG) responses...
March 2017: International Journal of Infectious Diseases: IJID
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
G Holleran, B Hall, P Crotty, S Smith, D McNamara
INTRODUCTION: Angiodysplasias account for over 50% of small bowel causes of obscure gastrointestinal bleeding. Angiodysplasias are thought to develop as a result of an imbalance in the angiogenic cascade, although the exact mechanism remains elusive. Previous research we have undertaken has associated elevated serum angiopoietin-2 (Ang-2) levels with angiodysplasia. Ang-1 and Ang-2 are ligands of the endothelial receptor tyrosine kinase Tie-2. Ang-1 regulates endothelial cell survival and blood vessel maturation and plays a key role in maintaining vascular integrity...
June 2014: Gut
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
Yu-I Shen, Hasan E Abaci, Yoni Krupsi, Lien-Chun Weng, Jason A Burdick, Sharon Gerecht
Three-dimensional (3D) tissue culture models may recapitulate aspects of the tumorigenic microenvironment in vivo, enabling the study of cancer progression in vitro. Both hypoxia and matrix stiffness are known to regulate tumor growth. Using a modular culture system employing an acrylated hyaluronic acid (AHA) hydrogel, three hydrogel matrices with distinctive degrees of viscoelasticity - soft (78±16 Pa), medium (309± 57 Pa), and stiff (596± 73 Pa) - were generated using the same concentration of adhesion ligands...
May 1, 2014: Biomaterials Science
Robert L Satcher, Tianhong Pan, Chien-Jui Cheng, Yu-Chen Lee, Song-Chang Lin, Guoyu Yu, Xiaoxia Li, Anh G Hoang, Pheroze Tamboli, Eric Jonasch, Gary E Gallick, Sue-Hwa Lin
Bone is one of the common sites of metastases from renal cell carcinoma (RCC), however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected...
2014: PloS One
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
Ashley E Frith, Angela C Hirbe, Brian A Van Tine
Sarcomas collectively represent over 100 different subtypes of bone and soft tissue tumors of mesenchymal origin. The low response rate to cytotoxic chemotherapies has necessitated the need for development of either histologically driven or pathway-specific targeted therapies. As our understanding of the molecular mechanisms driving certain subtypes is rapidly advancing, the number of targeted therapies is also increasing. Recently identified novel druggable targets include the MDM2 amplifications in well-differentiated and dedifferentiated liposarcomas, the new translocation NAB2:STAT6 of solitary fibrous tumors, the angiopoeitin-TIE2 pathway in angiosarcoma, the suppression of Mcl1 in X:18/synovial sarcomas, the mTOR pathway in malignant peripheral nerve sheath tumors, CDK4 in alveolar rhabdomyosarcoma, cMET regulation in alveolar soft parts sarcoma, the metabolic abnormalities in wild-type/SHD GIST, and the lack of argininosuccinate synthetase 1 expression seen in most sarcomas...
August 2013: Current Oncology Reports
Laurie Elit, Hal Hirte
OBJECTIVES: To review the available systemic treatments for women with recurrent ovarian cancer. METHODS: A literature review was conducted for recurrent ovarian cancer articles in English, including randomized trials, Phase II trials, or reviews. RESULTS: We discuss the efficacy and toxicity outcomes associated with systemic therapy for platinum-sensitive and platinum-resistant ovarian cancer. Clearly, platinum-based combination systemic therapy shows a prolonged progression-free interval compared with single-agent chemotherapy with a low toxicity profile...
2013: OncoTargets and Therapy
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
Lena Serghides, Hani Kim, Ziyue Lu, Dylan C Kain, Chris Miller, Roland C Francis, W Conrad Liles, Warren M Zapol, Kevin C Kain
The host immune response contributes to the onset and progression of severe malaria syndromes, such as cerebral malaria. Adjunctive immunomodulatory strategies for severe malaria may improve clinical outcome beyond that achievable with artemisinin-based therapy alone. Here, we report that prophylaxis with inhaled nitric oxide significantly reduced systemic inflammation (lower TNF, IFNγ and MCP-1 in peripheral blood) and endothelial activation (decreased sICAM-1 and vWF, and increased angiopoeitin-1 levels in peripheral blood) in an experimental cerebral malaria model...
2011: PloS One
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