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At least 109 records · Page 6Linked to original sources
PubMed1998

Regulating angiogenesis: a new therapeutic strategy.

Angiogenesis is the proliferation of endothelial and smooth muscle cells to form new blood vessels. Largely muted after adolescence, angiogenesis may be reignited by cancerous cells. Neoangiogenesis plays a primary role in tumor growth and metastases. Antiangiogenic therapy to limit and even reverse the growth of tumors are under investigation and showing promise. A derivative of fumagillin, TNP 470, is the first angiogenesis inhibitor to be given to humans. Surprisingly, several potent inhibitors are derived from tumors themselves. Researchers nowc recognize that stimulation of angiogenesis may have a place in the treatment of cardiovascular disease. Reestablishing blood flow to ischemic tissue through angiogenesis may provide a biologic "bypass" for patients with ischemic heart disease. The same applies to the treatment of peripheral vascular disease.

Angiostatins↗
PubMed2006

Comparison of various kinds of bone marrow stem cells for the repair of infarcted myocardium: single clonally purified non-hematopoietic mesenchymal stem cells serve as a superior source.

A variety of adult stem cells have been used to transplant into the infarcted (MI) heart, however, comparative studies are lacking to show more suitable source of cells for transplantation. We have identified a single non-hematopoietic mesenchymal stem cell subpopulation (snMSCs) isolated from human bone marrow and clonally purified, that over 99% of them expressed MSC marker proteins and cardiomyocyte marker proteins when induction in vitro. We also compared the effects of the snMSCs with unpurified MSC (uMSCs), mononuclear cells (BMMNCs), or peripheral blood mononuclear cells (PBMNCs) on myocardial repair after induction of MI in rats. Ninety days later, we observed a better cardiac function assessed by ejection fraction, fraction of shortening and lung wet/dry weight ratios, less remodeling of left ventricle (LV), lower collagen density in the LV, and more vessels in the ischemic wall in the snMSCs transplantation group than in other cell-transplanted groups. Furthermore, the transplanted cells expressing cardiomyocyte specific proteins or vascular endothelial cell marker proteins were more in the snMSCs group than in other ones. We conclude that transplantation with single clonally purified MSCs seems to be more beneficial to the cardiac repair than with other stem cells after MI.

Adult↗
PubMed2001

Endoglin: An accessory component of the TGF-beta-binding receptor-complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies.

Endoglin (CD105) is a cell membrane glycoprotein over-expressed on highly proliferating endothelial cells in culture, and on endothelial cells of angiogenetic blood vessels within benign and malignant tissues. CD105 binds several factors of the Transforming Growth Factor (TGF)-beta superfamily, and its over-expression modulates cellular responses to TGF-beta1. The complex of experimental findings accumulated in the last few years strongly indicate that CD105 is a powerful marker of angiogenesis, and that it might play a critical role in the pathogenesis of vascular diseases and in tumor progression. In this paper, we will review the structural, biological and functional features of CD105, as well as its distribution within normal and neoplastic tissues, emphasizing its foreseeable role as a molecular target for new diagnostic and bioimmunotherapeutic approaches in human malignancies.

Animals↗
PubMed2007

Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy.

Endocannabinoids are now emerging as suppressors of key cell-signaling pathways involved in cancer cell growth, invasion, and metastasis. We have previously observed that the metabolically stable anandamide analog, 2-methyl-2'-F-anandamide (Met-F-AEA) can inhibit the growth of thyroid cancer in vivo. Our hypothesis was that the anti-tumor effect observed could be at least in part ascribed to inhibition of neo-angiogenesis. Therefore, the aim of this study was to assess the anti-angiogenic activity of Met-F-AEA, to investigate the molecular mechanisms underlying this effect and whether Met-F-AEA could antagonize tumor-induced endothelial cell sprouting. We show that Met-F-AEA inhibited bFGF-stimulated endothelial cell proliferation, in a dose-dependent manner, and also induced apoptosis, both effects reliant on cannabinoid CB1 receptor stimulation. Analyzing the signaling pathways implicated in angiogenesis, we observed that the bFGF-induced ERK phosphorylation was antagonized by Met-F-AEA, and we found that p38 MAPK was involved in Met-F-AEA-induced apoptosis. Moreover, Met-F-AEA was able to inhibit bi-dimensional capillary-like tube formation and activity of matrix metalloprotease MMP-2, a major matrix degrading enzyme. Importantly, we demonstrated that Met-F-AEA is also functional in vivo since it inhibited angiogenesis in the chick chorioallantoic neovascularization model. Finally, Met-F-AEA inhibited tumor-induced angiogenesis in a three-dimensional model of endothelial and thyroid tumor cell (KiMol) spheroids co-cultures in different 3-D polymeric matrices that resemble tumor microenvironment and architecture. Thus, our results suggest that anandamide could be involved in the control of cancer growth targeting both tumor cell proliferation and the angiogenic stimulation of the vasculature.

Angiogenesis Inhibitors↗
PubMed2003

Endothelial cell-matrix interactions.

Dynamic interactions between endothelial cells and components of their surrounding extracellular matrix are necessary for the invasion, migration, and survival of endothelial cells during angiogenesis. These interactions are mediated by matrix receptors that initiate intracellular signaling cascades in response to binding to specific extracellular matrix molecules. The interactions between endothelial cells and their environment are also modulated by enzymes that degrade different matrix components and thus enable endothelial invasion. Recent reports on gene targeting in mice have confirmed the role of two classes of matrix receptors, integrins and cell surface heparan sulfate proteoglycans, and a group of matrix degrading proteolytic enzymes, matrix metalloproteinases, in angiogenesis. The significance of endothelial cell-matrix interactions is further supported by several ongoing clinical trials that analyze the effects of drugs blocking this interaction on angiogenesis-dependent growth of human tumors.

Animals↗
PubMed2003

Hormone regulation of endothelial apoptosis and proliferation in vessel regression and angiogenesis.

Apoptosis and endothelial proliferation represent two adverse events which take place during vessel regression and angiogenesis, respectively. Apoptosis, an intrinsically activated programmed cell death, regulates cell elimination during vessel regression. In contrast, angiogenesis involves endothelial cell proliferation, migration, and vascular formation. Several molecules, including growth factors and cytokines, produced by endothelial cells and by other cells within the vicinity of the capillary network, regulate apoptosis and angiogenesis. Hormones and endocrine peptides acting via specific receptors located on the endothelial and perivascular stromal cells also have been found to be involved in the regulation of these two major antagonistic processes. The need for a better understanding of the mechanisms involved in hormone regulation of endothelial cell during apoptosis and angiogenesis is of great importance. The accumulating knowledge of hormone regulation may contribute to the introduction of new therapeutic strategies targeting the endothelial cells.

Animals↗
PubMed2003

Mast cells and angiogenesis.

There is much evidence that angiogenesis is related to mast cells. Mast cells accumulate in many angiogenesis-dependent situations, including tumor growth, rheumatoid arthritis, ovulation, would healing, and tissue repair. Several mast cell mediators are angiogenic and regulate endothelial cell proliferation and function. Stem cell factor, vascular endothelial growth factor, epidermal growth factor, basic fibroblast growth factor, and platelet-derived growth factor induce chemotactic migration of mast cells to sites of neovascularization. Mast cell products such as tryptase also degrade connective tissue matrix to provide space for neovascular sprouts. Angiogenesis has been proposed as a target for anticancer therapy and for treatment of inflammatory disorders such as rheumatoid arthritis. Future studies on the cascade of angiogenic events, including mast cell-target cell interaction, and various intracellular signaling pathways are indicated to provide a new approach for the treatment of cancer and inflammatory disorders and for tissue repair.

Growth Substances↗
PubMed2003

Role of growth factors and their receptors in proliferation of microvascular endothelial cells.

Investigations over the last decade have established the essential role of growth factors and their receptors during angiogenesis. The biological significance of VEGF, EGF, and bFGF is mediated by their receptors, which belong to the family of tyrosine kinase receptors: Flt-1 (VEGFR-1), KDR (VEGFR-2), EGFR, FGFR-1, FGFR-2, FGFR-3, and FGFR-4. Deeper understanding of the mechanism of activation of these growth factor receptors has allowed the development of a new pharmacological strategy aimed at controlling cancer cell proliferation. The results of a large body of preclinical as well as early clinical studies conducted suggest that targeting the growth factor receptors could represent a significant contribution to cancer therapy.

Cell Division↗
PubMed2003

Angiogenesis in normal and neoplastic pituitary tissues.

Angiogenesis, or the formation of new blood vessels, is a dynamic process needed for embryogenesis, post-natal growth, morphogenesis, tumorigenesis, and for other biological processes. Angiogenesis is very important for tumor development and progression. This review examines the activators and inhibitors of angiogenesis with emphasis on the pituitary gland and pituitary neoplasms. Some of the proteins regulating angiogenesis in pituitary tumors such as vascular endothelial growth factor (VEGF) and VEGF receptors, fibroblasts growth factors (FGF), transforming growth factor beta (TGFB), interleukins, interferons, and matrix metalloproteinases (MMPs) and inhibitors of MMPs have been examined in animal and human pituitary tumor models. However, many other significant regulators of angiogenesis including angiopoietins, angiostatin, and thrombospondins have not been studied extensively in pituitary tumors to date. Newer concepts and developments in angiogenesis such as vasculogenic mimicry and gene therapy approaches to angiogenesis in cancer treatment are also discussed.

Angiogenesis Inhibitors↗
PubMed2003

Human uterine vascular structures in normal and diseased states.

Menstrual bleeding disorders are one of the most common problems presenting to the gynaecologist. There is increasing evidence that alterations in human uterine vascular structures are associated with spontaneous and sex steroid-induced changes in menstrual bleeding patterns. This article will discuss the normal anatomy and physiology of uterine vascular growth, breakdown, and repair and will indicate where altered anatomy and function may contribute to menstrual disorder. In particular, impact of low-dose progestogens on the endometrial vasculature and endometrial vascular fragility will be discussed. Disturbances of myometrial vascular growth and remodeling, including fibroids, adenomyosis, implantation, and arterio-venous malformations will also be addressed.

Endometrium↗
PubMed1995

Effects of hormones on the prostate in adult and aging men and animals.

Literature on the effect of steroid hormones (androgens, estrogens, and other steroids), of peptide hormones (e.g., prolactin), and growth factors (e.g., EGF, FGF, TGF-beta), on the effect of castration and of experimental hormone application on the prostate is reviewed. Androgens have inductive, repressive, and interactive effects. They counterbalance an agonistic effect on proliferation and an antagonistic effect on cell death; they may influence DNA synthesis and induce the synthesis of substances with mitogenic effects on the prostate. Estrogens exert direct and indirect effects on the prostate. They suppress the secretion of gonatropins, thus repressing testicular androgen secretion. They stimulate the fibromuscular stroma and induce squamous metaplasia of the epithelium. Estrogens may also be involved in the onset of benign prostatic hyperplasia. Prolactin is preferentially bound in the diseased human prostate. An abundance of information has been gained on EGF, FGF, TGF-beta, and other growth factors. They may be involved in the development of prostatic hyperplasia. Castration leads to a striking reduction in prostatic size in a short period of time due to autophagic and heterophagic processes. In castrated individuals, the prostate is enriched in androgen-independent cells. Experimental hormone application involves the substitution of androgens as well as anti-androgens, long-term application of different hormones, and application of combinations of drugs. The results of several studies are described. Further directions in the field of prostate research should concentrate on the role of growth factors in prostate development and pathology and on the effect of certain lectins on prostate diseases. We think that the investigation of interactions between steroid hormones and growth factors in normal and pathological neovascularization of the prostate is important.

Adult↗
PubMed2001

Lymphangiogenesis and lymphangiodysplasia: from molecular to clinical lymphology.

The lymph vascular system parallels the blood vasculature and as one of its key functions returns liquid and solutes to the bloodstream, including macromolecules that have escaped from blood capillaries and entered the interstitium. In conjunction with interspersed lymph nodes and lymphoid organs, the lymphatic vasculature also acts as a conduit for trafficking immune cell populations. Echoing the explosion of knowledge about blood vessel angiogenesis (properly termed "hemangiogenesis"), the past two decades have also witnessed a series of significant, yet less-noticed discoveries bearing on "lymphangiogenesis," along with delineation of the spectrum of lymphedema-angiodysplasia syndromes. Failure of lymph transport promotes a brawny proteinaceous edema of the affected limb, organ, or serous space that is disfiguring, disabling, and on occasion even life-threatening. Key members of the vascular endothelial growth factor (VEGF) and angiopoietin families of vascular growth factors (and their corresponding tyrosine kinase endothelial receptors) have been identified which preferentially influence lymphatic growth and, when manipulated in genetically engineered murine models, produce aberrant "lymphatic phenotypes." Moreover, mutations in VEGF receptor and forkhead family developmental genes have now been linked and implicated in the pathogenesis of two familial lymphedema-angiodysplasia syndromes. Thus, recent advances in "molecular lymphology" are elucidating the poorly understood development, physiology, and pathophysiology of the neglected lymphatic vasculature. In combination with fresh insights and refined tools in "clinical lymphology," these advances should lead not only to earlier detection and more rational classification of lymphatic disease but also to better therapeutic approaches, including designer drugs for lymphangiostimulation and lymphangioinhibition and gene therapy to modulate lymphatic growth.

Angiodysplasia↗
PubMed2002

The integrin family of cell adhesion molecules has multiple functions within the CNS.

Integrins comprise a large family of cell adhesion molecules that mediate interactions between the extracellular environment and the cytoplasm. During the last decade, analysis of the expression and function of these molecules has revealed that integrins regulate many aspects of cell behavior including cell death, proliferation, migration, and differentiation. Within the central nervous system (CNS), most of the early studies focused on the role of integrins in mediating adhesive and migratory events in two distinct processes: neural development and CNS inflammation. Interestingly, recent analysis of transgenic mice has provided some surprising results regarding the role of integrins in neural development. Furthermore, a large body of evidence now supports the idea that in addition to these well-described functions, integrins play multiple roles in the CNS, both during development and in the adult in areas as diverse as synaptogenesis, activation of microglia, and stabilization of the endothelium and blood-brain barrier. Many excellent reviews have addressed the contribution of integrins in mediating leukocyte extravasation during CNS inflammation. This review will focus on recently emerging evidence of novel and diverse roles of integrins and their ligands in the CNS during development and in the adult, in health and disease.

Animals↗
PubMed2007

Mobilization of endothelial precursor cells: systemic vascular response to musculoskeletal trauma.

Postnatal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells (EPC) migrate, differentiate, and incorporate into the nacent endothelium contributing to physiological and pathological neovascularization, has stimulated much interest. Its contribution to tumor nonvascularization, wound healing, and revascularization associated with skeletal and cardiac muscles ischaemia is established. We evaluated the mobilization of EPCs in response to musculoskeletal trauma. Blood from patients (n = 15) following AO type 42a1 closed diaphyseal tibial fractures was analyzed for CD34 and AC133 cell surface marker expression. Immunomagnetically enriched CD34+ mononuclear cell (MNC(CD34+)) populations were cultured and examined for phenotypic and functional vascular endothelial differentiation. Circulating MNC(CD34+) levels increased sevenfold by day 3 postinjury. Circulating MNC(AC133+) increased 2.5-fold. Enriched MNC(CD34+) populations from day 3 samples in culture exhibited cell cluster formation with sprouting spindles. These cells bound UEA-1 and incorporated fluorescent DiI-Ac-LDL intracellularily. Our findings suggest a systemic provascular response is initiated in response to musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of fracture healing.

Adult↗
PubMed1998

Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance imaging.

The goal of this study was to develop an experimental method for noninvasive analysis of angiogenesis, namely the sprouting of capillaries from existing blood vessels. Angiogenesis was assayed in the subcutaneous vasculature of nude mice in a region of 3 x 3 cm that included in its center a defined angiogenic stimulus. Angiogenic stimuli included agarose beads containing angiogenic growth factors, multicellular tumor spheroids, and dermal incisions. Highly significant correlation (r = 0.905, P = 0.0001) was found between the apparent vessel density determined by gradient echo MRI and the density of blood-containing vessels determined postmortem. The functionality of the neovasculature was demonstrated in mice breathing alternatingly carbogen or 95% air/5% CO2. Large signal enhancement with carbogen breathing corresponded to regions of high vessel density. The assay reported here can be applied for the study of dermal wound healing, primary vascularization of subcutaneous implants, and for measuring the activity of angiogenic and antiangiogenic agents.

Animals↗
PubMed2006

Role of the ephrin and Eph receptor tyrosine kinase families in angiogenesis and development of the cardiovascular system.

Angiogenesis is a highly complex orchestrated process that plays a critical role in normal development and in the pathophysiology of multiple disease processes, including tumour neovascularization, ischaemic recovery, and wound healing. In recent years there has been a resurgence of interest in Eph receptors and their ligands, ephrins, as their participation in vasculogenesis and angiogenesis has become apparent. The Eph receptor family is the largest family of receptor tyrosine kinases identified to date. The Eph receptors and their membrane-anchored ligands, ephrins, are unique in that they mediate bi-directional signalling. This is concomitant with activation of the Eph receptor tyrosine kinase domain and transduction of the typical forward signal into the receptor-bearing cell. The ligand-receptor interaction also leads to transduction of a reverse signal into the ephrin-bearing cell. The Eph/ephrin signalling mechanism is responsible for diverse and complex biological functions mediated by Eph receptors and ephrin ligands. These include vascular development, tissue-border formation, cell migration, axon guidance, and synaptic plasticity. The role of Eph receptors and ephrins in the processes of development of the cardiovascular system, angiogenesis, and vascular remodelling has been the subject of intense investigation since they were first identified in 1987. This review addresses the role of this new growth factor receptor tyrosine kinase family in those processes and provides new insights into the way in which Eph receptors and ephrin ligands modulate the angiogenic response and participate in vascular remodelling and vascular boundary formation during development of the cardiovascular system and vascularization of cancer.

Animals↗
PubMed2001

Thrombospondin-1, vascular endothelial growth factor and fibroblast growth factor-2 are key functional regulators of angiogenesis in the prostate.

BACKGROUND: Prostate cells secrete many molecules capable of regulating angiogenesis; however, which of these actually function as essential regulators of neovascularization is not yet clear. METHODS: Functional angiogenic mediators secreted by normal and diseased prostate cells were identified using an in vitro angiogenesis assay. These factors were quantified by immunoblot or ELISA and localized in tissue by immunohistochemistry. RESULTS: Normal prostate epithelial cell secretions were anti-angiogenic due to inhibitory thrombospondin-1 (TSP-1) whereas this inhibitor was decreased in the pro-angiogenic secretions derived from benign prostatic hyperplasia (BPH) and cancer cells. This pro-angiogenic activity depended primarily on fibroblast growth factor-2 (FGF-2) and/or vascular endothelial growth factor (VEGF) whose secretion was increased. Immunolocalization studies confirmed that the changes detected in vitro also occurred in vivo. CONCLUSIONS: During disease progression in the prostate, production of TSP-1, the major inhibitor, is down-regulated while that of stimulatory FGF-2 and/or VEGF rise, leading to the induction of the new vessels necessary to support tumor growth.

Adolescent↗
PubMed2001

Inhibition of angiogenesis by humulone, a bitter acid from beer hop.

On the basis of our previous finding that humulone, a bitter acid from beer hop extract, was a potent inhibitor of bone resorption and inhibited the catalytic activity of cyclooxygenase-2 (COX-2) and more potently the transcription of the COX-2 gene, we examined the effect of humulone on angiogenesis, using chick embryo chorioallantoic membranes (CAMs) and vascular endothelial and tumor cells. Humulone significantly prevented in vivo angiogenesis in CAM in a dose-dependent manner with an ED(50) of 1.5 microg/CAM. Humulone also inhibited in vitro tube formation of vascular endothelial cells. Moreover, it suppressed the proliferation of endothelial cells and the production of vascular endothelial growth factor (VEGF), an angiogenic growth factor, in endothelial and tumor cells. Thus, humulone is a potent angiogenic inhibitor, and may be a novel powerful tool for the therapy of various angiogenic diseases involving solid tumor growth and metastasis.

Allantois↗