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Angiogenic
Terms modified by Angiogenic Selected AbstractsAngiogenic and lymphangiogenic microvessel density in recurrent pleomorphic adenomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2009Andresa B. Soares Background:, Recurrent pleomorphic adenoma (RPA) is an uncommon and challenging disease. The aim of this study was to determine if there is a difference between RPA and the pleomorphic adenoma (PA) without recurrence related to tumor blood and lymphatic vascularization. Moreover, we compared the microvessel density (MVD) between cell-rich areas (predominance of epithelial cells) and cell-poor areas (predominance of myxoid and chondroid areas) of the stroma of PA and RPA. In addition, immunohistochemical staining for the Ki-67 antigen was conducted simultaneously to evaluate cell proliferation in PA and RPA. Methods:, A total of 19 cases of PA and 24 cases of RPA, blood, and lymphatic vessels were analyzed by immunohistochemical technique using the antibodies CD34, CD105, D2-40, and Ki-67. Results:, Comparing no recurrent with recurrent tumor, no significant difference was found in terms of lymphatic vessel density, MVD, and proliferation index. When MVD and proliferation index were compared with different areas in cellular composition (cell-rich and cell-poor areas), there was a significant difference in PA, as well as in RPA. Conclusion:, This study shows that although RPA presents more aggressive clinical behavior than PA, there is no difference between tumor blood and lymphatic vascularization, suggesting that there is no correlation between vascularity and risk of recurrence. Furthermore, vascularized stroma in PA, as well as RPA, depends on the proportion of the cellular composition. [source] VESGEN 2D: Automated, User-Interactive Software for Quantification and Mapping of Angiogenic and Lymphangiogenic Trees and NetworksTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2009Mary B. Vickerman Pseudocolor view of vascular branching generations in the chorioallantoic membrane (CAM) of quail. Vascular architecture was analyzed using the automated, user-interactive software, VESsel GENeration Analysis (VESGEN). See Vickerman, et al., on page 320, in this issue. [source] The Role of Angiogenic and Wound Repair Factors During CMV-Accelerated Transplant Vascular Sclerosis in Rat Cardiac TransplantsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008D. N. Streblow Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21,28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival. [source] The higher they climb: plasma levels of angiogenic and lymphangiogenic factors during ascent to Mount EverestACTA PHYSIOLOGICA, Issue 2 2009Joachim FandreyArticle first published online: 30 APR 200 No abstract is available for this article. [source] Vascular endothelial growth factor prevents G93A-SOD1-induced motor neuron degenerationDEVELOPMENTAL NEUROBIOLOGY, Issue 13 2009J. Simon Lunn Abstract Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by selective loss of motor neurons (MNs). Twenty percent of familial ALS cases are associated with mutations in Cu2+/Zn2+ superoxide dismutase (SOD1). To specifically understand the cellular mechanisms underlying mutant SOD1 toxicity, we have established an in vitro model of ALS using rat primary MN cultures transfected with an adenoviral vector encoding a mutant SOD1, G93A-SOD1. Transfected cells undergo axonal degeneration and alterations in biochemical responses characteristic of cell death such as activation of caspase-3. Vascular endothelial growth factor (VEGF) is an angiogenic and neuroprotective growth factor that can increase axonal outgrowth, block neuronal apoptosis, and promote neurogenesis. Decreased VEGF gene expression in mice results in a phenotype similar to that seen in patients with ALS, thus linking loss of VEGF to the pathogenesis of MN degeneration. Decreased neurotrophic signals prior to and during disease progression may increase MN susceptibility to mutant SOD1-induced toxicity. In this study, we demonstrate a decrease in VEGF and VEGFR2 levels in the spinal cord of G93A-SOD1 ALS mice. Furthermore, in isolated MN cultures, VEGF alleviates the effects of G93A-SOD1 toxicity and neuroprotection involves phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Overall, these studies validate the usefulness of VEGF as a potential therapeutic factor for the treatment of ALS and give valuable insight into the responsible signaling pathways and mechanisms involved. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Vascular regeneration and angiogenic-like sprouting mechanism in a compound ascidian is similar to vertebratesEVOLUTION AND DEVELOPMENT, Issue 5 2008Fabio Gasparini SUMMARY Tunicates are useful models for comparing differing developmental processes such as embryogenesis, asexual reproduction, and regeneration, because they are the closest relatives to vertebrates and are the only chordates to reproduce both sexually and asexually. Among them, the ascidian Botryllus schlosseri displays high regenerative potential of the colonial circulatory system (CCS). The CCS runs in the common tunic, forming an anastomized network of vessels defined by simple epithelia and connected to the open circulatory system of the zooids. During asexual propagation, new vessels form by means of a tubular-sprouting mechanism, resembling that occurring in other metazoans, particularly during vertebrate angiogenesis. We studied the regeneration of experimentally ablated CCS by analyzing the general dynamics of reorganization of vessels and tunic, their ultrastructure, cell proliferation, and the immunohistology of regenerating structures using antibodies against vertebrate angiogenic factors-vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), epidermal growth factor (EGF), and receptors: VEGFR-1, VEGFR-2, and EGFR. Results show that the regenerative process of CCS occurs by a sprouting mechanism, with participation of angiogenic factors. They also show correspondence between the CCS sprouting of B. schlosseri and angiogenic sprouting in vertebrates, during both normal development and regeneration, and support the idea that this morphogenetic mechanism was co-opted during the evolution of various developmental processes in different taxa. [source] Therapeutic angiogenesis and vasculogenesis for tissue regenerationEXPERIMENTAL PHYSIOLOGY, Issue 3 2005Paolo Madeddu Therapeutic angiogenesis/vasculogenesis holds promise for the cure of ischaemic disease. The approach postulates the manipulation of spontaneous healing response by supplementation of growth factors or transplantation of vascular progenitor cells. These supplements are intended to foster the formation of arterial collaterals and promote the regeneration of damaged tissues. Angiogenic factors are generally delivered in the form of recombinant proteins or by gene transfer using viral vectors. In addition, new non-viral methods are gaining importance for their safer profile. The association of growth factors with different biological activity might offer distinct advantages in terms of efficacy, yet combined approaches require further optimization. Alternatively, substances with pleiotropic activity might be considered, by virtue of their ability to target multiple mechanisms. For instance, some angiogenic factors not only stimulate the growth of arterioles and capillaries, but also inhibit vascular destabilization triggered by metabolic and oxidative stress. Transplantation of endothelial progenitor cells was recently proposed for the treatment of peripheral and myocardial ischaemia. Progenitor cells can be transplanted either without any preliminary conditioning or after ex vivo genetic manipulation. Delivery of genetically modified progenitor cells eliminates the drawback of immune response against viral vectors and makes feasible repeating the therapeutic procedure in case of injury recurrence. It is envisioned that these new approaches of regenerative medicine will open unprecedented opportunities for the care of life-threatening diseases. [source] Correlation of hypoxic signalling to histological grade and outcome in cartilage tumoursHISTOPATHOLOGY, Issue 5 2010Stephane Boeuf Boeuf S, Bovée J V M G, Lehner B, Hogendoorn P C W & Richter W (2010) Histopathology56, 641,651 Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours Aims:, The molecular mechanisms underlying the progression of central chondrosarcoma are so far poorly understood. The aim of this study was to identify genes involved in the progression of these tumours by comparison of gene expression and correlation of expression profiles to histological grade and clinical outcome. Methods and results:, Array-based gene expression profiling of 19 chondrosarcoma samples was performed. Beside differences in the expression of cartilage matrix molecules, high-grade chondrosarcoma showed enhanced expression of the matrix metalloproteinase MMP-2 and of the hypoxia-inducible molecule galectin 1. Immunohistochemical analysis of galectin 1 and of further hypoxia-associated proteins was performed on 68 central and peripheral tumour samples. Hypoxia-inducible factor 1, (HIF-1,) activation was significantly elevated in high-grade central chondrosarcoma. A negative correlation of carbonic anhydrase IX expression to metastasis-free survival was independent of histological grade. Conclusions:, The expression patterns identified in this study point towards a substantial role for angiogenic and hypoxic signalling in chondrosarcoma progression. The constitutive activation of the transcription factor HIF-1, in high-grade chondrosarcoma could play a central role in the regulation of cell metabolism and vascularization in these tumours and may, for this reason, represent a potential target for chondrosarcoma therapy. [source] Angiogenesis in the female reproductive organs: pathological implicationsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2002Lawrence P. Reynolds Summary. The female reproductive organs (ovary, uterus, and placenta) are some of the few adult tissues that exhibit regular intervals of rapid growth. They also are highly vascular and have high rates of blood flow. Angiogenesis, or vascular growth, is therefore an important component of the growth and function of these tissues. As with many other tissues, vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs) appear to be major angiogenic factors in the female reproductive organs. A variety of pathologies of the female reproductive organs are associated with disturbances of the angiogenic process, including dysfunctional uterine bleeding, endometrial hyperplasia and carcinoma, endometriosis, failed implantation and subnormal foetal growth, myometrial fibroids (uterine leiomyomas) and adenomyosis, ovarian hyperstimulation syndrome, ovarian carcinoma, and polycystic ovary syndrome. These pathologies are also associated with altered expression of VEGFs and/or FGFs. In the near future, angiogenic or antiangiogenic compounds may prove to be effective therapeutic agents for treating these pathologies. In addition, monitoring of angiogenesis or angiogenic factor expression may provide a means of assessing the efficacy of these therapies. [source] Gorham-Stout Syndrome: A Monocyte-Mediated Cytokine Propelled Disease,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006Silvia Colucci Abstract We studied the biological features and the immunophenotype of a cell culture established from the lesion of soft tissues of a woman affected by Gorham-Stout syndrome. We found that these cells belonged to a monocytic lineage with some characteristics of immature osteoclasts and were able to release large amounts of osteoclastogenic and angiogenic molecules that may contribute to disease progression. Introduction: Gorham-Stout syndrome is a rare disease characterized by osteolysis and proliferation of vascular or lymphatic vessels, with a severe outcome. Its etiology and the identification of the cell types involved are completely unknown. Materials and Methods: A cell culture from a lesion of soft tissues was established, and its behavior in vitro and in immunodeficient mice was studied. We analyzed (1) the cell phenotype by flow cytometry; (2) the adhesive and migratory properties on different substrates; (3) the ability to differentiate into mature osteoclasts; (4) the production of osteclastogenic and angiogenic molecules; (5) the in vivo angiogenic activity of the cells subcutaneously implanted in mouse in a Matrigel plug; and (6) the ability to recapitulate the disease when transplanted in nude mice. Results and Conclusions: The established culture consisted of a morphologically homogeneous cell population belonging to a monocytic lineage having some features of an osteoclast-like cell type. Cells had an invasive phenotype, were angiogenic, and produced osteoclastogenic (IL-6, TGF-,1, IL-1,) and angiogenic (vascular endothelial growth factor-A {VEGF-A}, CXCL-8) molecules when challenged with inflammatory cytokines. Immunodeficient mice injected with these cells did not show any bone lesions or vascular alteration, but had high amounts of circulating human IL-6 and VEGF-A. Cells isolated from a cutaneous lymphangiomatosis did not show any of these findings. These data suggest that cells of monocyte-macrophage lineage play an essential role in the pathogenesis of Gorham-Stout disease, whose progression is propelled by cytokine circuits that accelerate angiogenesis and osteoclastogenesis. [source] Is Leptin the Link Between Fat and Bone Mass?,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2002Thierry Thomas Ph.D. Abstract Recently, leptin has emerged as a potential candidate responsible for protective effects of fat on bone tissue. However, it remains difficult to draw a clear picture of leptin effects on bone metabolism because published data are sometimes conflicting or apparently contradictory. Beyond differences in models or experimental procedures, it is tempting to hypothesize that leptin exerts dual effects depending on bone tissue, skeletal maturity, and/or signaling pathway. Early in life, leptin could stimulate bone growth and bone size through direct angiogenic and osteogenic effects on stromal precursor cells. Later, it may decrease bone remodeling in the mature skeleton, when trabecular bone turnover is high, by stimulating osteoprotegerin (OPG) expression. Leptin negative effects on bone formation effected through central nervous system pathway could counterbalance these peripheral and positive effects, the latter being predominant when the blood-brain barrier permeability decreases or the serum leptin level rises above a certain threshold. Thus, the sex-dependent specificity of the relationship between leptin and bone mineral density (BMD) in human studies could be, at least in part, caused by serum leptin levels that are two- to threefold higher in women than in men, independent of adiposity. Although these hypotheses remain highly speculative and require further investigations, existing studies consistently support the role of leptin as a link between fat and bone. [source] Induction of Angiogenesis and Inhibition of Apoptosis by Hepatocyte Growth Factor Effectively Treats Postischemic Heart FailureJOURNAL OF CARDIAC SURGERY, Issue 1 2005Vasant Jayasankar M.D. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI. Methods: The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure,volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot. Results: Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 ± 3 vs. control 64 ± 5 mmHg, p < 0.05), maximum dP/dt (3024 ± 266 vs. 1907 ± 360 mmHg/sec, p < 0.05), maximum dV/dt (133 ± 20 vs. 84 ± 6 ,L/sec, p < 0.05), and LV border zone wall thickness (1.98 ± 0.06 vs. 1.53 ± 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 ± 10.0 vs. 90 ± 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 ± 0.3 vs. 8.2 ± 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group. Conclusions: Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure. [source] Involvement of vascular endothelial growth factor, CD44 and CD133 in periodontal disease and diabetes: an immunohistochemical studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2009Guendalina Lucarini Abstract Aim: The aim of this study was to investigate the relationship between expression of angiogenic and regeneration markers and periodontal disease in subjects with/without diabetes mellitus. Material and Methods: Immunohistochemical detection of vascular endothelial growth factor (VEGF), CD44 and CD133 was performed in 16 samples each of (1) healthy gingiva from non-diabetic subjects (controls), (2) gingiva from non-diabetic subjects with periodontitis, (3) gingiva from subjects with type 1 diabetes and periodontitis, (4) gingiva from subjects with type 2 diabetes and periodontitis. Results: Diseased gingivae from patients with diabetes and periodontitis had greater clinical measures of periodontal disease than those with periodontitis only. VEGF expression was significantly enhanced in epithelial and endothelial cells from patients with periodontitis compared with controls (p<0.05). Epithelial CD44 expression was strong in all groups, while CD44 was significantly enhanced (p<0.05) in connective tissue cells from both diabetic groups. Epithelial and endothelial CD133 expression was comparable in all patients except those with type 2 diabetes and periodontitis, where it was not detected. Stromal CD133 expression was significantly lower in patients with type 2 diabetes and periodontitis and was increased in periodontitis patients (p<0.05). Conclusions: The involvement and high expression of VEGF, CD44 and CD133 in periodontal disease may predict a greater regeneration capacity of gingival tissue. [source] Differences in multidrug resistance phenotype and matrix metalloproteinases activity between endothelial cells from normal brain and gliomaJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Anthony Régina Abstract Endothelial cells (ECs) are new targets for tumor therapy. In this work, we purified endothelial cells from intracerebral and subcutaneous experimental gliomas as well as from normal brain in order to define some of the phenotypical differences between angiogenic and quiescent brain vasculature. We show that the multidrug resistance genes encoding drug efflux pumps at the brain endothelium are expressed differently in normal and tumoral vasculature. We also show that ECs from gliomas present increased activity of gelatinase B (MMP9), key enzyme in the angiogenic process. Importantly, we observe a different phenotype between ECs in the intracerebral and subcutaneous models. Our results provide molecular evidence of phenotypic distinction between tumoral and normal brain vasculature and indicate that the EC phenotype depends on interactions both with tumor cells and also with the microenvironment. [source] Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomasJOURNAL OF NEUROCHEMISTRY, Issue 4 2002Rolf Mentlein Abstract Pleiotrophin (PTN) is a mitogenic/angiogenic, 15.3 kDa heparin-binding peptide that is found in embryonic or early postnatal, but rarely in adult, tissues. Since developmentally regulated factors often re-appear in malignant cells, we examined PTN expression in human glioma cell lines, cell cultures derived from solid gliomas and glioma sections. PTN mRNA or protein was detected by reverse transcriptase-polymerase chain reaction, immunohistochemistry, western blot or enzyme-linked immunoassay in all WHO III and IV grade gliomas and cells analyzed in vitro or in situ. One WHO II grade glioma investigated was PTN negative. In vitro, PTN was synthesized in perinuclear regions of glioma cells, secreted into the cultivation medium, but its production varied considerably between glioma cells cultivated from different solid gliomas or glioma cell lines. In situ, PTN expression was restricted to distinct parts/cells of the tumour. PTN did not influence the proliferation of glioma cells themselves, but stimulated [3H]thymidine incorporation into DNA of microglial cells. Furthermore, in Boyden chamber assays, PTN showed a strong chemotactic effect on murine BV-2 microglial cells. PTN is supposed to be a paracrine growth/angiogenic factor that is produced by gliomas and contributes to their malignancy by targeting endothelial and microglial cells. [source] Effect of cell-based VEGF gene therapy on healing of a segmental bone defectJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2009Ru Li Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0,×,106 fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n,=,9); control groups were treated with fibroblasts (Group 2) (n,=,7), or saline (Group 3) (n,=,7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p,<,0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:8,14, 2009 [source] Role of fibroblasts and fibroblast-derived growth factors in periprosthetic angiogenesisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2007Miklos Tunyogi-Csapo Abstract The periprosthetic granulomatous soft tissue [designated iterfacial membrane (IFM) in this study] exhibits heterogeneous histopathological features, in which highly vascularized areas with dense cellularity alternate with fibrotic and pseudocapsule-like tissue structures. Although macrophage/monocyte activation is a prominent event in the periprosthetic environment, fibroblasts also phagocytose particulate wear debris both in vivo and in vitro. Particulate wear debris and/or cytokines/growth factors alone or in combination (e.g., in conditioned media of explant cultures of IFMs) stimulated normal synovial and IFM fibroblasts to express inflammatory mediators and growth factors such as interleukin (IL)-1,, IL-6, IL-8, three isoforms of vascular endothelial growth factor (VEGF), monocyte/macrophage chemoattractant protein-1 (MCP-1), macrophage-colony-stimulating factor (M-CSF), cycloxygenases (Cox-1 and Cox-2), acid- and basic-fibroblast growth factors (FGF-1 and FGF-2), leukemia inhibitory factor-1 (LIF-1), transforming growth factor ,-1 (TGF-,1), receptor activator of nuclear factor-kappa B ligand (RANKL), and osteoprotegerin (OPG). Thus, the fibroblast is capable of expressing a wide array of angiogenic and osteoclastogenic factors which are involved in the detrimental processes of the periprosthetic osteolysis. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1378,1388, 2007 [source] Decreased expressions of thrombospondin 2 in cyclosporin A-induced gingival overgrowthJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2004Jeong Tae Koh Objectives:, Cyclosporin A (CsA) is known to elicit fibrous gingival overgrowth with changes of blood vessel profiles. In this study, we examined the expression of several angiogenic and angiostatic genes during the development of CsA-induced gingival overgrowth. Methods:, For the development of gingival overgrowth, Sprague-Dawley rats received subcutaneous injections of CsA in daily doses of 5, 10, 15 mg/kg body weight for 6 weeks, and another group received 10 mg/kg of CsA for 3, 6, and 12 weeks. Human gingival tissues were obtained from three CsA-treated patients following the gingivectomy procedure and from three healthy patients following the crown-lengthening procedure as a control. Gingival fibroblasts were isolated from the healthy gingival tissues of the rat or the human, and cultured with 250,1000 ng/ml of CsA. Results:, Reverse transcription,polymerase chain reaction (RT,PCR) analyses showed that expressions of some angiogenic genes such as angiopoietin 1, basic fibroblast growth factor, and vascular endothelial growth factor, and angiostatic genes such as angiopoietin 2, brain-specific angiogenesis inhibitor 1 and 2, and thrombospondin 1 were not changed significantly in both gingival tissues and cultured fibroblast cells under the CsA treatments. However, expression of thrombospondin 2 (TSP2) decreased dose- and time-dependently in rat and human gingival tissues. Western blot analyses showed that the expression of TSP2 protein was dose-dependently reduced by the CsA treatments in human cultured gingival fibroblasts. Conclusions:, These results indicate that the decrease in angiostatic TSP2 expression may be attributed to the CsA-induced gingival vascularization rather than to the increased expression of angiogenic genes. It suggests that TSP2 is involved in the development of CsA-induced gingival overgrowth with the gingival vascularization. [source] Hemostatic and hematological abnormalities in gain-of-function fps/fes transgenic mice are associated with the angiogenic phenotypeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2004W. Sangrar Summary. The Fps/Fes tyrosine kinase has been implicated in the regulation of hematopoiesis and inflammation. Mice expressing an activated variant of Fps/Fes (MFps) encoded by a gain-of-function mutant transgenic fps/fes allele (fpsMF) exhibited hematological phenotypes, which suggested that Fps/Fes can direct hematopoietic lineage output. These mice also displayed marked hypervascularity and multifocal-hemangiomas which implicated this kinase in the regulation of angiogenesis. Here we explored the potential involvement of Fps/Fes in the regulation of hemostasis through effects on blood cells and the vascular endothelium. Hematological parameters of fpsMF mice were characterized by peripheral blood analysis, histology, and transmission electron microscopy. Hemostasis parameters and platelet functions were assessed by flow cytometry and measurements of activated partial thromboplastin time, prothrombin time, thrombin clot time, platelet aggregation, bleeding times and in vitro fibrinolytic assays. Hematological and morphological analyses showed that fpsMF mice displayed mild thrombocytopenia, anemia, red cell abnormalities and numerous hemostatic defects, including hypofibrinogenemia, hyper-fibrinolysis, impaired whole blood aggregation and a mild bleeding diathesis. fpsMF mice displayed a complex array of hemostatic perturbations which are reminiscent of hemostatic disorders such as disseminated intravascular coagulation (DIC) and of hemangioma-associated pathologies such as Kasabach,Merritt phenomenon (KMS). These studies suggest that Fps/Fes influences both angiogenic and hemostatic function through regulatory effects on the endothelium. [source] Angiogenesis and lymphangiogenesis in bronchial asthmaALLERGY, Issue 8 2010A. Detoraki To cite this article: Detoraki A, Granata F, Staibano S, Rossi FW, Marone G, Genovese A. Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy 2010; 65: 946,958. Abstract Neovascularization plays a prominent role in inflammation and tissue remodeling in several chronic inflammatory disorders. Vessel number and size, vascular surface area and vascular leakage are all increased in biopsies from patients with asthma. High levels of VEGF and other angiogenic factors have been detected in tissues and biological samples of patients with asthma and correlate with disease activity and inversely with airway hyper-responsiveness. Inflammation in the lung stimulates the growth of new blood vessels and these contribute to the airway obstruction or airway hyper-responsiveness, or both. Effector cells of inflammation (human lung mast cells, basophils, eosinophils, macrophages, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. Inhaled corticosteroids reduce vascularity and growth factor expression and might modulate bronchial vascular remodeling in asthma. Specific antagonists to VEGF and other angiogenic factors and their receptors might help to control chronic airway inflammation and vascular remodeling and offer a novel approach for the treatment of chronic inflammatory lung disorders. [source] Cytokines, matrix metalloproteases, angiogenic and growth factors in tears of normal subjects and vernal keratoconjunctivitis patientsALLERGY, Issue 5 2009A. Leonardi Background:, To detect the presence of multiple mediators and growth factors in tears of vernal keratoconjunctivitis (VKC) patients with active disease using stationary phase antibody arrays. Methods:, Tears were collected from 12 normal subjects (CT) and 24 active VKC patients. Tears were centrifuged and successively probed using three microwell plate arrays specific for: (i) cytokines: interleukin (IL)-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, interferon-, and tumour necrosis factor-,; (ii) growth factors: basic fibroblast growth factor (bFGF), platelet-derived growth factor, thrombopoietin, angiopoietin-2, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), keratocyte growth factor, tissue inhibitor of metalloprotease (TIMP)-1 and heparin-binding epithelial growth factor (HB-EGF) and (iii) matrix metalloprotease (MMP)-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1 and TIMP-2. Results:, Interleukin-8 signals were detected in all CT and highly detected in all VKC samples. The Th2-type cytokines, IL-4, IL-5 and IL-10 were detected only in tears of VKC patients. Signals for bFGF, HB-EGF, VEGF and HGF were detected in 41,87% of VKC samples and in few CT samples. Only TIMP-1 and TIMP-2 were found in all normal and patient tear samples, whereas MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10 were highly present in all VKC samples. Conclusions:, Stationary phase antibody array methodology was useful for the screening of various cytokines, growth factors and MMPs in tears. These analyses identified in tears of VKC patients previously unreported factors including MMP-3 and MMP-10 and multiple proteases, growth factors and cytokines, which may all play an important role in the pathogenesis of conjunctival inflammation. [source] Platelet-activating factor and human meningiomasNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2006Y. Denizot Meningiomas are common primary intracranial tumours. Platelet-activating factor (PAF) is an inflammatory and angiogenic lipid mediator involved in several types of cancer. The presence of PAF receptor (PAF-R) transcripts, the levels of PAF, the phospholipase A2 activity (PLA2, the enzymatic activity implicated in PAF formation) and the PAF acetylhydrolase activity (AHA, the PAF degrading enzyme) were investigated in 49 human meningiomas. PAF-R transcripts, PAF, PLA2 and AHA were detected in meningiomas. However, their levels did not correlate with biological parameters such as the tumour grade, the presence of associated oedema, necrosis, mitotic index as well as intensity of the neovascularization and chronic inflammatory response. In conclusion, PAF is present in meningiomas where it might act on tumour growth by altering the local angiogenic and/or cytokine networks as previously suggested for human breast and colorectal cancer. [source] Cyclooxygenase-2 Expression Induced by Photofrin Photodynamic Therapy Involves the p38 MAPK Pathway,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2008Marian Luna Photodynamic therapy (PDT), using the porphyrin photosensitizer Photofrin (PH), is approved for the clinical treatment of solid tumors. In addition to the direct cytotoxic responses of PH,PDT-mediated oxidative stress, this procedure also induces expression of angiogenic and prosurvival molecules including cyclooxygenase-2 (COX-2). In vivo treatment efficacy is improved when PH-PDT is combined with inhibitors of COX-2. In the current study we evaluated the signaling pathways involved with PH,PDT-mediated COX-2 expression in a mouse fibrosarcoma cell line. COX-2 promoter reporter constructs with mutated transcription elements documented that the nuclear factor kappa B (NF,B) element, cyclic-AMP response element 2 (CRE-2), CCAAT/enhancer binding protein (C/EBP) element and activator binding protein-1 (AP-1) element were responsive to PH-PDT. Transcription factor binding assays demonstrated that nuclear protein binding to NF,B, CRE-2, c-fos and c-jun elements were elevated following PH-PDT. Kinase phosphorylation upstream of COX-2 expression was also examined following PH-PDT. Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and c-Jun were phosphorylated following PH-PDT but the SAPK/JNK inhibitor SP600125 failed to attenuate COX-2 expression. In contrast, p38 mitogen-activated protein kinase (MAPK), which activates CRE-2 binding, was phosphorylated following PH-PDT and inhibitors of p38 MAPK, SB203580 and SB202190, decreased PH,PDT-induced COX-2 expression at both the mRNA and protein levels. Extracellular signal-regulated kinase (ERK1/2) phosphorylation, which also increases CRE-2 binding activity, was initially high in untreated cells, decreased immediately following PH-PDT and then rapidly increased. MEK1/2 is immediately upstream of ERK1/2 and the MEK1 inhibitor PD98059 failed to attenuate COX-2 expression while the MEK1/2 inhibitor U0126 induced a slight decrease in COX-2 expression. The NF,B inhibitor SN50 failed to reduce COX-2 expression. These results demonstrate that multiple protein kinase cascades can be activated by oxidative stress and that the p38 MAPK signaling pathway and CRE-2 binding are involved in COX-2 expression following PH-PDT. [source] Modeling the proteome of a Marek's disease transformed cell line: a natural animal model for CD30 overexpressing lymphomasPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 8 2007Joram J. Buza Dr. Abstract Marek's disease (MD) in the chicken, caused by the highly infectious MD ,-herpesvirus (MDV), is both commercially important and a unique, naturally occurring model for human T-cell lymphomas overexpressing the Hodgkin's disease antigen, CD30. Here, we used proteomics as a basis for modeling the molecular functions and biological processes involved in MDV-induced lymphomagenesis. Proteins were extracted from an MDV-transformed cell line and were then identified using 2-D LC-ESI-MS/MS. From the resulting 3870 cellular and 21 MDV proteins we confirm the existence of 3150 "predicted" and 12 "hypothetical" chicken proteins. The UA-01 proteome is proliferative, differentiated, angiogenic, pro-metastatic and pro-immune-escape but anti-programmed cell death, -anergy, -quiescence and -senescence and is consistent with a cancer phenotype. In particular, the pro-metastatic integrin signaling pathway and the ERK/MAPK signaling pathways were the two predominant signaling pathways represented. The cytokines, cytokine receptors, and their related proteins suggest that UA-01 has a regulatory T-cell phenotype. [source] The Role of Platelet-activating Factor in the Mammalian Female Reproductive TractREPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2008U Tiemann Contents Platelet-activating factor (PAF) is a potent lipid mediator produced by various cell types of mammals and is involved in an inflammatory-like process with increased vascular permeability. Platelet-activating factor exerts its actions through the activation of specific PAF receptors (PAF-R) found in cells and tissues of the female reproductive tract. The aim of this article was summarized briefly in the current research on the role of PAF in female reproductive functions. Platelet-activating factor has been implicated in processes of ovulation, implantation and parturition because of its angiogenic and growth factor properties. This factor is influenced by ovarian steroid hormones in bringing about changes in the uterus and is a candidate molecule for initial embryo,maternal dialogue. Tissue concentrations of PAF are regulated by the equilibrium between biosynthesis and degradation by PAF-acetylhydrolase (PAF-AH). Antagonists of PAF interfere with ovulation and implantation. Platelet-activating factor, its receptor, and PAF-AH activity play an important role in the maintenance of pregnancy. [source] Critical overexpression of thrombospondin 1 in chronic leg ischaemiaTHE JOURNAL OF PATHOLOGY, Issue 3 2005Judith Favier Abstract The aim of this study was to identify gene expression governing the balance of angiogenic and angiostatic factors in human ischaemic leg tissues. In situ hybridization was used to screen for the expression of angiogenesis-related genes in tissues from 13 amputated limbs from patients suffering from critical leg ischaemia. The authors tested for mRNA of hypoxia-inducible transcription factors 1, and 2,, vascular endothelial growth factor, and its receptors VEGFR-1 and -2, the angiopoietin receptor Tie2, and the anti-angiogenic molecule thrombospondin 1. The expression levels of the genes in proximal, healthy muscles were compared with those in the distal, ischaemic counterparts. Surprisingly, only thrombospondin 1 was overexpressed in the ischaemic part of the leg of all patients studied. Thrombospondin 1 mRNA was assayed by real-time RT-PCR and the gene was overexpressed 20-fold. The presence of its encoded protein was confirmed by western blotting. The overproduction of this anti-angiogenic molecule was associated with a decrease in capillary density in the affected muscles. Thrombospondin 1 is thus a marker of chronic ischaemia and may affect angiogenesis in ischaemic tissues. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] A Review of Molecular Contrasts Between Arresting and Viable Porcine Attachment SitesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2007Jocelyn M. Wessels Significant spontaneous fetal loss of unknown cause occurs in North American commercial swine. About 30% of conceptuses, thought to be genetically normal, are lost during the peri-attachment period. An additional 20% are lost at mid-pregnancy. Littermate endometrial and trophoblast biopsies were studied by quantitative real-time PCR for gene expression, and immunohistochemistry for protein expression at gestation day (gd)15,23 and 50. RNA analyses were also conducted on endometrial lymphocytes and arterial endothelial cells removed from biopsies by laser capture microdissection. Genes were selected for study from human literature and cloned as required. As in humans, angiogenic, cytokine, chemokine and chemokine decoy receptor gene expression occurs at the porcine maternal,fetal interface. In each tissue studied, distinct patterns of expression are found between early and mid-pregnancy, as well as between viable and arresting conceptus attachment sites. These changes involve both endometrial lymphocytes and dendritic cells. Restriction in endometrial angiogenesis, reduction in expression of the chemokine decoy receptor D6, and reduction in dendritic cell numbers contribute to fetal arrest. In peri-attachment loss, interferon-, is more abundantly transcribed than tumor necrosis factor-,, but this ratio is reversed during midgestation failure. Further characterization of spontaneous fetal loss in pigs will identify targets for modification by hog producers and may provide a model for identification of antecedents to fetal loss in humans. [source] Upregulation of Interleukin-8 by Hypoxia in Human OvariesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2003Osamu Yoshino Problem: To evaluate the effect of hypoxia on interleukin (IL)-8 expression in human ovarian follicles. Method of study: Follicular fluid (FF) from each follicle was separately collected from women undergoing in vitro fertilization and embryo transfer. Concentrations of oxygen, progesterone, estradiol, IL-1,/,, IL-8, and tumor necrosis factor (TNF)- , in FF were measured. Isolated granulosa-lutein cells (GLC) from obtained FF were cultured under normoxic or hypoxic conditions, and concentrations of IL-8 in culture media were measured. Results: Simple regression analysis demonstrated a significant negative correlation between the concentrations of IL-8 and oxygen in FF (r = 0.50, P < 0.0001). However, none of the concentrations of progesterone, estradiol, IL-1,, and TNF- , in FF showed a significant correlation with IL-8 concentrations. Hypoxia stimulated the secretion of IL-8 by cultured GLC over twofolds compared with a normoxic control (P < 0.05). Conclusions: These findings suggest that IL-8, like other angiogenic factors, is upregulated under hypoxic condition, which argues that hypoxia in the ovarian follicles comes into play in ovarian functions by inducing a range of proangiogenic and chemoattractive substances. [source] Mapping pro- and antiangiogenic factors on the surface of prostasomes of normal and malignant cell originTHE PROSTATE, Issue 8 2010Adil A. Babiker Abstract BACKGROUND Angiogenesis is the formation of new blood vessels by capillary sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and the formation of new blood vessels is associated with the increased expression of angiogenic factors. Prostasomes are secretory granules produced, stored and released by the glandular epithelial cells of the prostate. We investigated the expression of selected angiogenic and anti-angiogenic factors on the surface of prostasomes of different origins as well as the direct effect of prostasomes on angiogenesis. METHODS VEGF, endothelin-1, endostatin, and thrombospondin-1 were determined on prostasomes from seminal fluid and human prostate cancer cell lines (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal microvascular endothelial cells were incubated with seminal and DU145 cell-prostasomes and with radioactive thymidine. The effect of prostasomes on angiogenesis was judged by measuring the uptake of labeled thymidine. The presence of any deleterious effects of prostasomes on the endothelial cells was investigated using thymidine assay and confocal laser microscopy. RESULTS VEGF and endothelin-1 were determined on malignant cell-prostasomes (no difference between cell lines) but not determined on seminal prostasomes. The same applies for the expression of endostatin but with much higher expression on malignant cell-prostasomes with obvious differences between them. Seminal and DU145 cell-prostasomes were found to have anti-angiogenic effect which was more expressed by DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial function was detected using either thymidine assay or microscopy. CONCLUSIONS Prostasomes contain pro- and anti-angiogenic factors that function to counteract each other unless the impact from one side exceeds the other to bring about dysequilibrium. Prostate 70: 834,847, 2010. © 2010 Wiley-Liss, Inc. [source] Bcl-2 mediated modulation of vascularization in prostate cancer xenografts,THE PROSTATE, Issue 5 2009Yoshihisa Sakai Abstract PURPOSE We previously demonstrated that Bcl-2 overexpression enhances the radiation resistance of PC-3 human prostate cancer cells and xenografts by inhibiting apoptosis, increasing proliferation, and promoting angiogenesis. To further elucidate the relationship between Bcl-2 expression and the angiogenic potential of PC-3-Bcl-2 cells, tumorigenicity, angiogenesis, and lymphangiogenesis were evaluated and compared in a Bcl-2 overexpressing clone in vitro and in vivo. EXPERIMENTAL DESIGN Human prostate cancer cells over expressing Bcl-2 were studied in vitro and in vivo to determine the angiogenic and lymphangiogenic properties of these cells. RESULTS Increased Bcl-2 expression enhanced the tumorigenicity of prostate cancer xenografts. It also enhanced the expression and secretion of key angiogenic and lymphangiogenic factors that stimulated the synthesis of CD31-positive blood vessels and LYVE-1 positive lymphatics. Specifically, the increased angiogenic and lymphangiogenic potential correlated with increased serum levels of basic fibroblast growth factor (bFGF), interleukin 8 (CXCL8), and matrix metalloproteinase (MMP 9). In vitro analysis demonstrated that Bcl-2 expressing tumor cells secreted bFGF and vascular endothelial growth factor (VEGF) into culture supernatants. Microarray analysis of Bcl-2 expressing PC-3 cells demonstrated increased transcription of genes involved in metabolism, such as interleukins, growth factors, tumor necrosis factors (TNF) family members, and peptidases. CONCLUSIONS Together, these results demonstrate that Bcl-2 can regulate tumoral angiogenesis and lymphangiogenesis and suggest that therapy targeted at Bcl-2 expression, angiogenesis, and lymphangiogenesis may synergistically modulate tumor growth and confirm that Bcl-2 is a pivotal target for cancer therapy. Prostate 69:459,470, 2009. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||