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Angiogenic Properties (angiogenic + property)
Selected AbstractsReduction of TIP30 correlates with poor prognosis of gastric cancer patients and its restoration drastically inhibits tumor growth and metastasisINTERNATIONAL JOURNAL OF CANCER, Issue 3 2009Xiaohua Li Abstract Gastric cancer is an aggressive cancer with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of gastric cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple functions including tumorigenic suppression, apoptosis induction and diminishing angiogenic properties. Here, the level of TIP30 expression was determined in gastric cancer, and the impact of its alteration on cancer biology and clinical outcome was investigated. We found that TIP30 protein was absent or reduced in gastric cancer cell lines. There was also a loss or substantial decrease of TIP30 expression in 106 cases of gastric tumors as compared with that in normal gastric mucosa (p < 0.05), which was significantly associated with inferior survival duration. In a Cox proportional hazards model, TIP30 expression independently predicted better survival (p < 0.05). We also restored TIP30 protein expression in human gastric cancer-derived cells AGS and MKN28 lacking endogenous TIP30 protein to study the effects of TIP30 expression on cell proliferation, cell kinetics, tumorigenicity and metastasis in BALB/c nude mice and found that adenoviral-mediated restoration of TIP30 expression led to downregulation of cyclin D1, Bcl-2, Bcl-xl, but to upregulation of p27, Bax, p53, caspase 3 and 9 expression, cell cycle G0/G1 arrest and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Taken together, the present work revealed a novel function of TIP30, which can possibly be used as an independent prognostic factor and a potential therapeutic target for gastric cancer. © 2008 Wiley-Liss, Inc. [source] Increased VEGFR2 expression during human late endothelial progenitor cells expansion enhances in vitro angiogenesis with up-regulation of integrin ,6JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2007David M. Smadja Abstract In vitro expansion of late endothelial progenitor cells (EPCs) might yield a cell therapy product useful for myocardial and leg ischaemia, but the influence of EPC expansion on the angiogenic properties of these cells is unknown. In the present study, we investigated the effect of in vitro EPC expansion on vascular endothelial growth factor (VEGF) receptor expression. EPCs were obtained from CD34+ cord blood cells and expanded for up to 5 weeks. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that VEGFR2 expression, contrary to VEGFR1 and VEGFR3 expression, was significantly higher on expanded EPCs than on freshly isolated CD34+ cells or on human umbilical vein endothelial cells (HUVECs). Quantitative flow cytometry confirmed that VEGFR2 density on EPCs increased during the expansion process and was significantly higher than on HUVECs. The impact of VEGFR2 increase was studied on the three theoretical steps of angiogenesis, i.e., EPC proliferation, migration and differentiation. VEGFR2 up-regulation had no effect on VEGF-induced cell proliferation, but significantly enhanced EPC migration and pseudotubes formation dependent on integrin ,6 subunit overexpression. In vitro expansion of late EPCs increases the expression of VEGFR2, the main VEGF receptor, with possible implications for EPC-based angiogenic therapy. [source] Antiangiogenic and Immunomodulatory Effects of Rapamycin on Islet Endothelium: Relevance for Islet TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2006V. Cantaluppi Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angionesis-related factors VEGF, ,V,3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation. [source] Human adipose-derived stem cells: isolation, characterization and applications in surgeryANZ JOURNAL OF SURGERY, Issue 4 2009Michelle Locke Abstract The ideal stem cell for use in functional tissue engineering needs to be abundantly available, harvested with minimal morbidity, differentiated reliably down various pathways and able to be transplanted safely and efficaciously. Adult human adipose tissue contains a population of mesenchymal stem cells, termed ,adipose-derived stem cells' (ASC), which seem to fulfil most, if not all, of these criteria. ASC can be harvested readily, safely, and in relative abundance by modern liposuction techniques. They are capable of differentiating into other mesenchymal tissue types, including adipocytes, chondrocytes, myocytes and osteoblasts. They also show angiogenic properties, with recent evidence of a potential role in healing radiotherapy-damaged tissue, possibly due to their secretion of vascular endothelial growth factor. Similarly, they may have a role in healing chronic wounds, and as such are being investigated in phase 1 trials for their ability to aid healing of recurrent Crohn's fistulae. Subsequently they have a wide range of potential clinical uses in all fields of surgery. This article reviews the current and potential clinical applications of ASC in relation to surgery, as well as methods for their isolation, differentiation and molecular characterization. [source] Modulation of the angiogenic phenotype of normal and systemic sclerosis endothelial cells by gain,loss of function of pentraxin 3 and matrix metalloproteinase 12ARTHRITIS & RHEUMATISM, Issue 8 2010Francesca Margheri Objective Studies have shown that in systemic sclerosis (SSc) endothelial cells, overproduction of matrix metalloproteinase 12 (MMP-12) and pentraxin 3 (PTX3) is associated with defective angiogenesis. This study was undertaken to examine whether overexpression of the relevant molecules could inhibit angiogenesis of normal microvascular endothelial cells (MVECs), and whether silencing of these molecules in SSc MVECs could restore the lost angiogenic properties of the cells in vitro and in vivo. Methods Transient transfection of MVECs with human MMP12 and PTX3 was performed by electroporation. Silencing of MMP12 and PTX3 was obtained by treatment with small interfering RNA, and treatment effects were validated by Western blotting with specific antibodies and a fluorimetric assay. In vitro cell migration and capillary morphogenesis were studied on Matrigel substrates. In vivo angiogenesis was studied using a Matrigel sponge assay in mice. Results Transfection of MMP12 and PTX3 in normal MVECs resulted in loss of proliferation, invasion, and capillary morphogenesis in vitro, attributed to truncation of the urokinase-type plasminogen activator receptor by MMP12 and to the anti,fibroblast growth factor 2/anti,vascular endothelial growth factor activity of PTX3. These effects were particularly evident in mixed populations of transfected normal MVECs (50% transfected with MMP12 and 50% with PTX3). Silencing of the same molecules in SSc MVECs increased their invasion in Matrigel. Single-gene silencing did not increase the capillary morphogenesis of SSc MVECs, whereas double-gene,silenced cells showed a burst of capillary tube formation. Culture medium of silenced SSc MVECs stimulated angiogenesis in assays of Matrigel sponge invasion in mice. Conclusion Overexpression of either MMP12 or PTX3 in normal MVECs blunts their angiogenic properties. Loss of function of MMP12 and PTX3 in SSc MVECs restores the ability of the cells to produce capillaries in vitro and induces vascularization in vivo on a Matrigel sponge. [source] Oestrogen Promotes Coronary Angiogenesis even under Normoxic ConditionsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2008Mehdi Nematbakhsh Oestrogen has angiogenic properties under hypoxic condition, and if oestrogen also induces angiogenesis under normoxic condition, it could be used in combination with other angiogenic therapies in the treatment of ischaemic heart disease. In this study, we evaluated the angiogenic effect of high-dose oestrogen treatment in normoxic rat heart tissue. Fifty-two ovariectomized rats were randomized in oestrogen-treated and control groups. 17,-Oestradiol (1 mg/week) and normal saline (1 mg/week) were administered intramuscularly in the treatment and control groups for 2 months. After that, coronary capillary density and coronary vessel permeability were measured. The serum vascular endothelial growth factor (VEGF) level was also measured before and after the treatment. The results indicate that coronary capillary density (number of capillary per square millimetre) and coronary vessel permeability (fluorescence intensity) were significantly higher in the oestrogen-treated group than in the control group (628 ± 26 per mm2 versus 540 ± 26 per mm2; P < 0.05 and 207 ± 10 versus 147 ± 19 per gram tissue; P < 0.05). Oestrogen treatment increased serum VEGF level in the oestrogen-treated group compared to the control group (52 ± 3 versus 33 ± 6 pg/ml; P < 0.05), but interestingly VEGF was also increased in the control group after placebo treatment. It seems that high-dose oestrogen administration has angiogenic properties even in normoxic conditions. These angiogenic properties may result from oestrogen's direct effect on VEGF or other mechanisms, such as endothelial progenitor cell mobilization. Because of the broad effect of oestrogen on angiogenic growth factors and endothelial cells, more studies are required to clarify angiogenic properties of high-dose oestrogen. [source] Expression of the neutrophil-activating CXC chemokine ENA-78/CXCL5 by human eosinophilsCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2003T. Persson Summary Background Eosinophils are seen at sites of inflammation in diseases such as helminthic infestation, asthma, ulcerative colitis and some neoplastic diseases. They are also associated with connective tissue remodelling, for example in longstanding asthma. In the present study, we investigated whether eosinophils express the CXC chemokine epithelial cell-derived neutrophil activating peptide (ENA-78/CXCL5), a chemokine that can activate neutrophils and in addition possesses angiogenic properties. Immunocytochemistry detected CXCL5 in eosinophils and the peptide was localized in the specific granules by immunoelectron microscopy. Methods and Results In eosinophil lysates, 12 ± 2 pg (mean ± SEM) of CXCL5 was detected per 106 cells by enzyme-linked immunosorbent assay (ELISA). Weak constitutive expression of CXCL5, as well as the related CXC chemokine IL,8/CXCL8, could be detected in freshly isolated eosinophils by RT,PCR. However, during prolonged incubation of eosinophils, a strong increase in both CXCL5 and IL-8/CXCL8 expression was seen, as detected by RT-PCR, and increasing amounts of CXCL5 peptide with time were detected in the incubation medium by ELISA. Addition of TNF-, neutralizing antibodies during prolonged incubation significantly inhibited CXCL5 production, demonstrating involvement of auto- and paracrine effects from TNF-, produced by eosinophils themselves. Addition of IFN-, showed a strong inhibitory effect on CXCL5 synthesis. Conclusion These findings suggest that, through expression of CXCL5, eosinophils can recruit and activate CXC receptor 2 (CXCR2)-bearing cells such as neutrophils at sites of inflammation. Eosinophils may also promote connective tissue remodelling through release of this peptide. [source] | ||||||||||