Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neovascularization, Pathologic”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2005

Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen.

Several anti-angiogenic factors are derived from proteolytic processing of large molecules including endostatin from type XVIII collagen and angiostatin from plasminogen. In previous studies we showed that neostatin-7, the C-terminal 28kDa endostatin-spanning proteolytic fragment, is generated from the proteolytic action of matrix metalloproteinase matrilysin (MMP)-7 on type XVIII collagen. Now, we report a second member of the neostatin family of proteins, neostatin-14. Given the small quantities of neostatin-7 and -14 generated by the breakdown of naturally occurring collagen XVIII (using MMP-7 and -14, respectively), we used two other approaches to characterize the anti-angiogenic properties of these molecules: murine recombinant neostatin in vitro, and gene therapy. We demonstrate that murine recombinant neostatin-7 inhibits calf pulmonary artery endothelial cell proliferation and that microinjection of neostatin-7 and neostatin-14 naked DNA into the corneal stroma of mice results in significant reduction of basic fibroblast growth factor-induced corneal neovascularization. These results provide supportive evidence of the possible anti-angiogenic effect of neostatins.

Amino Acid Sequence↗
PubMed2005

Inhibition of sphingosine-1-phosphate- and vascular endothelial growth factor-induced endothelial cell chemotaxis by red grape skin polyphenols correlates with a decrease in early platelet-activating factor synthesis.

Vascular endothelial growth factor (VEGF) and platelet-derived lipid sphingosine-1-phosphate (S1P) are two proinflammatory mediators which contribute to angiogenesis, in part through the synthesis of platelet-activating factor (PAF). The red grape skin polyphenolic extract (SGE) both prevents and inhibits angiogenesis in the Matrigel model, decreases the basal motility of endothelial and cancer cells, and reverses the chemotactic effect of S1P and VEGF on bovine aortic endothelial cells (BAECs) as well as the chemotactic effect of conditioned medium on human HT-1080 fibrosarcoma, human U-87 glioblastoma, and human DAOY medulloblastoma cells. Inhibition of VEGF- and S1P-mediated chemotaxis by SGE is associated with a down-regulation of ERK and p38/MAPK phosphorylation and a decreased in acute PAF synthesis. Notably, as do extracellular inhibitors of PAF receptor, SGE prevents S1P-induced PAF synthesis and the resulting activation of the S1P/endothelial differentiation gene-1 cascade. Given the key role of VEGF and S1P in inflammation, angiogenesis, and tumor invasion, SGE may therefore contribute to prevent (or to delay) the development of diseases associated with angiogenesis dysregulation, including cancer. The dual inhibition of S1P- and VEGF-mediated migration of endothelial cell and of serum-stimulated migration of U-87 cells suggests a usefulness of SGE against highly invasive human glioblastoma.

Animals↗
PubMed2003

Troponin I peptide (Glu94-Leu123), a cartilage-derived angiogenesis inhibitor: in vitro and in vivo effects on human endothelial cells and on pancreatic cancer.

Several inhibitors of angiogenesis have been identified in bovine and shark cartilage. One of them is troponin I, which is the molecule responsible for the inhibition of the actomyosin ATPase during muscle contraction. In this study we sought to investigate if the active site of troponin I (peptide Glu94-Leu123; pTnI) is also the one responsible for the antiangiogenic properties of this protein. The effects of pTnI on endothelial cell tube formation and endothelial cell division were investigated using human umbilical vein endothelial cells, Matrigel, light microscopy, carboxyfluorescein diacetate, succinimidyl esterlabeling, and flow cytometry. Its effects on induction of ICAM-1 and production of vascular endothelial growth factor by pancreatic cancer cells (CAPAN-1) were also investigated, as was its efficacy in a mouse model of pancreatic cancer metastases. Our results show that concentrations as low as 1 pg/ml of pTnI significantly inhibit endothelial cell tube formation, and that endothelial cell division was inhibited at 96 hours by 3 microg/ml pTnI (P=0.0001). No effects were seen using troponin peptide 124-181 as a control. pTnI-treated supernatant from the pancreatic cancer cell line CAPAN-1 downregulated ICAM-1 expression on human umbilical vein endothelial cells up to 10 ng/ml pTnI, and a significant reduction in vascular endothelial growth factor production was seen by treating CAPAN-1 cells with up to 1 microg/ml pTnI. After intrasplenic injection of CAPAN-1 cells, mice treated with pTnI had fewer liver metastases compared to control mice (liver/body weight 5.5 vs. 11.1; P=0.03). The active region of troponin I is the one responsible for its antiangiogenic effect. The mechanism of action of this peptide is probably multifactorial.

Angiogenesis Inhibitors↗
PubMed2004

The vascular endothelial growth factor family and its receptors.

This article focuses on describing the biology of vascular endothelial growth factor (VEGF) and its receptors as well as the regulation of their expression. A thorough understanding of the VEGF system is paramount in optimizing antiangiogenic therapies as a component of antineoplastic regimens.

Animals↗
PubMed2006

Advances in understanding angiogenesis through molecular studies.

Tumors, in most cases, need angiogenesis for their sustained growth. A great deal of evidence has suggested that the process of angiogenesis is regulated by the balance between proangiogenic and antiangiogenic factors. Thus, the inhibition of tumor angiogenesis has been considered to be one of the key targets in anticancer therapy, and more than 60 antiangiogenic compounds are currently under clinical evaluation in cancer patients. However, the molecular mechanisms responsible for the activity of many of these antiangiogenic compounds are still not well understood. The recent development of microarray technology has allowed us to investigate the mechanism of action of these inhibitors more rapidly and extensively. With the use of microarray technology, novel molecules and pathways are shown to play a role in angiogenesis. This article also reviews new experimental approaches combined with microarray analysis to identify the molecular pathways involved in tumor-host interactions. Elucidation of the pathways that mediate both angiogenic and antiangiogenic responses will help us to develop better anticancer therapies.

Angiogenesis Inhibitors↗
PubMed2006

Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma.

Phyllanthus urinaria, a widely used herb medicine in Asia, was tested for its anti-tumor effect in vivo for the first time. The anti-tumor activity in P. urinaria extract was evaluated by its effect on tumor developed in C57BL/6J mice with implantation of Lewis lung carcinoma cells. The oral administration of P. urinaria to mice caused significant inhibition of tumor development with lower occurrence rate and markedly reduced tumor size. Neither the total body weight of mouse nor the weights of organs including heart, lung, liver, spleen and kidney revealed any difference between two groups, suggesting limited in vivo cytotoxic effect of P. urinaria in mice. TUNEL assay demonstrated the increase of apoptosis in tumor sections prepared from P. urinaria-treated mice compared with control mice. It is worth of note that the neovascularization in tumor was inhibited in P. urinaria-treated mice, which implicated the potential anti-angiogenic effect of P. urinaria. Further study using an in vitro matrix-induced tube formation of HUVECs again confirmed the anti-angiogenic action of P. urinaria. P. urinaria exerted no inhibitory effect on the growth of HUVECs, however, the migration of HUVECs as analyzed using transwell assay was suppressed markedly by P. urinaria in a dose-dependent manner. All together, the present study indicated that P. urinaria extract is an anti-tumor and anti-angiogenic agent, which can be used safely in animals.

Animals↗
PubMed2006

Suppression of VEGF-mediated autocrine and paracrine interactions between prostate cancer cells and vascular endothelial cells by soy isoflavones.

Angiogenesis is an essential process involved in the development and progression of prostate cancer. Vascular endothelial growth factor (VEGF) is hypothesized to be a critical regulator of angiogenesis during prostate carcinogenesis. We have reported that dietary soy products inhibit prostate tumor progression in animal models, in association with a reduction in tumor microvessel density. The goal of the present study is to investigate potential antiangiogenic mechanisms of genistein, the major soy isoflavone, using in vitro systems. Genistein (5-50 muM) significantly inhibited the growth of human umbilical vein endothelial cells (HUVECs) in control media when stimulated by supplemental VEGF or when cultured in hypoxia-exposed PC-3 prostate adenocarcinoma cell conditioned media. These in vitro studies suggest detectable inhibitory effects by 5-10 muM genistein (P<.05) with an IC(50) of approximately 20 muM or less. Genistein (10-50 muM) caused significant inhibition of basal VEGF expression and hypoxia-stimulated VEGF expression in both human prostate cancer PC-3 cells and HUVECs based on semiquantitative reverse transcription-polymerase chain reaction (P<.05). In parallel, VEGF secretion by PC-3 cells quantitated by enzyme-linked immunosorbent assay was significantly (P<.05) reduced by genistein (10-50 muM). Furthermore, genistein (10-50 muM) significantly (P<.05) reduced PC-3 nuclear accumulation of hypoxia-inducible factor-1alpha, the principle transcription factor that regulates VEGF expression in response to hypoxia. Expression of the VEGF receptor fms-like tyrosine kinase-1, but not kinase insert domain-containing kinase, in HUVECs was also reduced (P<.05) by genistein (10-50 muM). These observations support the hypothesis that genistein may inhibit prostate tumor angiogenesis through the suppression of VEGF-mediated autocrine and paracrine signaling pathways between tumor cells and vascular endothelial cells.

Cell Division↗
PubMed2004

The role of thrombospondin-1 in human disease.

Thrombospondin-1 (TSP-1) is a large matricellular glycoprotein secreted by many cell types. It is a component of the extracellular matrix during active and subacute processes. Due to TSP-1's ability to interact with a variety of matrix proteins and cell-surface receptors, controversy exists about its conflicting functions. In this review, we will discuss the role of TSP-1 in human disease.

Disease↗
PubMed2004

Critical conditions for pattern formation and in vitro tubulogenesis driven by cellular traction fields.

In vitro angiogenesis assays have shown that tubulogenesis of endothelial cells within biogels, like collagen or fibrin gels, only appears for a critical range of experimental parameter values. These experiments have enabled us to develop and validate a theoretical model in which mechanical interactions of endothelial cells with extracellular matrix influence both active cell migration--haptotaxis--and cellular traction forces. Depending on the number of cells, cell motility and biogel rheological properties, various 2D endothelial patterns can be generated, from non-connected stripe patterns to fully connected networks, which mimic the spatial organization of capillary structures. The model quantitatively and qualitatively reproduces the range of critical values of cell densities and fibrin concentrations for which these cell networks are experimentally observed. We illustrate how cell motility is associated to the self-enhancement of the local traction fields exerted within the biogel in order to produce a pre-patterning of this matrix and subsequent formation of tubular structures, above critical thresholds corresponding to bifurcation points of the mathematical model. The dynamics of this morphogenetic process is discussed in the light of videomicroscopy time lapse sequences of endothelial cells (EAhy926 line) in fibrin gels. Our modeling approach also explains how the progressive appearance and morphology of the cellular networks are modified by gradients of extracellular matrix thickness.

Biomechanical Phenomena↗
PubMed2004

Computational model of flow-tissue interactions in intussusceptive angiogenesis.

Angiogenesis, the growth of vascular structures, is a complex biological process which has long puzzled scientists. Better physiological understanding of this phenomenon could result in many useful medical applications such as the development of new methods for cancer therapy. We report on the development of a simple computational model of micro-vascular structure formation in intussusceptive angiogenesis observed in vivo. The tissue is represented by a discrete set of basic structural entities and flow conditions within the resulting domain are obtained by solving the Navier-Stokes equations. The tissue is then remodelled according to the tangential shear stress while approximating advection by means of simple non-diffusive heuristics. The updated tissue geometry then becomes the input for the next remodelling step. The model, consisting of steady-state flow and a simple mechanistic tissue response, successfully predicts bifurcation formation and micro-vessel separation in a porous cellular medium. This opens new modelling possibilities in computational studies of the cellular transport involved in micro-vascular growth.

Capillaries↗
PubMed2004

Angiogenesis and anti-angiogenesis activity of Chinese medicinal herbal extracts.

The aqueous extracts of 24 herbs traditionally used as curing ischemic heart disease in clinic in China were screened for their in vitro angiogenic activity, another twenty-four traditionally used as anti-tumor or anti-inflammatory remedies in China were screened for their in vitro anti-angiogenic activity. The activity of angiogenesis was determined by quantitation of vessels on chick embryo chorioallantoic membrane (CAM) model and cell proliferation of cultured bovine aortic endothelial cells (BAECs). Among the herbal extracts examined, the aqueous extracts of Epimedium sagittatum, Trichosanthes kirilowii and Dalbergia odorifera showed the strong angiogenetic activity both in CAM and BAECs models; and the aqueous extracts of Berberis paraspecta, Catharanthus roseus, Coptis chinensis, Taxus chinensis, Scutellaria baicalensis, Polygonum cuspidatum and Scrophularia ningpoensis elicited significant inhibition at a concentration of 1g dry herb /ml.

Allantois↗
PubMed2005

Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood.

BACKGROUND: Due to a dismal prognosis of advanced lung cancer, novel screening tools and more effective treatments are clearly needed. Lately, an increasing number of tumour-released angiogenic cytokines which affect vessel formation, tumour growth, invasion, and metastasis have been identified. Vascular endothelial growth factors (VEGFs) and basic fibroblast growth factor (bFGF) are among the most important angiogenic factors. Based on available literature, we have explored the mechanisms of angiogenesis and its prognostic significance in non-small cell lung cancer, estimated by microvessel density (MVD) and the presence of VEGF and bFGF in the tumour and blood from NSCLC patients. METHODS: Several comprehensive Pubmed searches for the period January 1993 to May 2005 were performed using strategic combinations of the terms non-small cell lung cancer, angiogenesis, vascular endothelial growth factor, basic fibroblast growth factor, tumour expression, microvessel density, circulating, and serum. RESULTS: NSCLC neoangiogenesis, as measured by MVD, and tumour expression of VEGF are poor prognostic factors for survival (MVD, HR 1.8-2.0; VEGF, HR 1.5). bFGF tumour expression is also associated with poor survival and more aggressive disease. When evaluating the prognostic impact of elevated VEGF levels in blood, 10 of 16 studies (63%) indicated a negative prognostic impact. Of five studies on the prognostic value of circulating bFGF, three studies reported a negative prognostic impact, while one indicated bFGF as a good prognostic factor and one was inconclusive. CONCLUSION: Angiogenic factors are poor prognostic indicators for tumour aggressiveness and survival in NSCLC. Assessments of circulating levels of VEGF and possibly bFGF may be valuable future tools for treatment planning and monitoring of treatment effect and relapse. First, however, these blood tests need to be standardised and validated in large-scale prospective clinical trials.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Hyaluronan-mediated angiogenesis in vascular disease: uncovering RHAMM and CD44 receptor signaling pathways.

The correct formation of new blood vessels from existing vasculature (angiogenesis) is essential for embryogenesis and the effective repair of damaged or wounded tissues. However, excessive and detrimental vascularization also occurs in neoplasia, promoting tumour growth and metastasis, as well as in proliferative diabetic retinopathy and atherosclerosis. Greater understanding of the mechanisms controlling the angiogenic process will allow optimization of wound healing, and provide mechanisms to inhibit vascularization in tumours and other diseases. Evidence supports a cascade of events in which the perturbation of one of the steps is sufficient to significantly inhibit neovascularization. The extracellular macromolecules, notably glycosaminoglycans (GAGs), are important mediators of angiogenesis. Hyaluronan (HA), a large, non-sulphated GAG, was first discovered in the vitreous of the eye [.], and is ubiquitously expressed in the extracellular matrix (ECM) of tissues. Native high molecular weight HA (n-HA) is anti-angiogenic, whereas HA degradation products (o-HA; 3-10 disaccharides) stimulate endothelial cell (EC) proliferation, migration and tube formation following activation of specific HA receptors in particular, CD44 and Receptor for HA-Mediated Motility (RHAMM, CD168). The involvement of HA in the regulation of angiogenesis makes it an attractive therapeutic target. We review the role of o-HA in modulation of angiogenesis during tissue injury, and vascular disease, focusing on receptor-mediated signal transduction pathways that have been evaluated.

Animals↗
PubMed2005

Changing the logic of therapeutic angiogenesis for ischemic disease.

The worldwide epidemic of ischemic disease urgently requires innovative treatments. Recently, therapeutic angiogenesis has emerged as a noninvasive supply-side approach, aimed at promoting neovascularization in underperfused tissues through the local delivery of angiogenic growth factors. Successful preclinical studies paved the way for the first clinical trials, with single growth factors given as recombinant proteins or genes. However, clinical results have not matched the initial promises. Our opinion is that the logic of therapeutic angiogenesis needs profound revision. Here, we introduce the concept that pleiotropic agents can stimulate the healing of all the components of ischemic tissue. We also propose prophylactic interventions to delay vascular senescence. The optimization of therapeutic angiogenesis will open unprecedented opportunities for the care of life-threatening ischemic disease.

Angiogenesis Inducing Agents↗
PubMed2004

A murine model of ex vivo angiogenesis using aortic disks grown in fibrin clot.

The rat aortic ring model is well utilized for evaluation of angiogenesis. We report here an alternative assay employing an ex vivo mouse aorta angiogenesis model that can be extensively manipulated and serially evaluated using digital-assisted image analysis. Mouse aortas were harvested, cut into 2-mm disks, and cultured in fibrin matrix with growth media. Radial vascular outgrowths arose from the cut edge of the aortic disk and were digitally photographed and serially quantified. A variety of culture conditions were evaluated to determine their ability to alter angiogenesis in this model. Vessel outgrowth became apparent on day 3 and continued through day 10 with linear growth occurring between days 3 and 6. Increasing concentrations of serum from 0% to 40% resulted in stimulation of angiogenesis after day 3. Suramin and endostatin dramatically inhibited angiogenesis, which was more profound when applied at day 0 than when linear growth could be identified (day 3). Cells isolated from vessel outgrowths were predominantly endothelial in origin by immunocytochemistry and FACS analysis. We demonstrate that angiogenesis in an ex vivo murine model can be easily quantified using digital image analysis, responds appropriately to stimulation and inhibition, and exhibits differential results based on time of inhibitor administration. Antiangiogenic agents may be most effective if administered before development of accelerated vessel growth.

Animals↗
PubMedDate not supplied

Imaging of angiogenesis.

Explore the source record for details and available documents.

Angiogenesis Inducing Agents↗