Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Angiogenesis”

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 667 records · Page 37Linked to original sources
PubMed2002

[Neoplasms and angiogenesis].

Angiogenesis is a process of new blood vessels formation in many physiological and pathological conditions such as wound healing, cancer, ischaemic diseases (of heart or limb) and chronic inflammations. Neoplastic angiogenesis plays an important role in progression of the disease and development of metastases. The angiogenic process may be initiated by hypoxia in cancerous cells, mutations in suppressor genes or oncogenes. Cancer cells activate specific angiogenic factors mainly vasoendothelial growth factor (VEGF) that stimulate migration and division of vascular endothelial cells. The studies of several pro- and antiangiogenic molecules and factors, and mechanism of vessel growth, have revealed that therapeutic interferences with these processes offers a tool for clinical applications in various pathologies. Inhibition of angiogenesis can prevent diseases with excessive vessel growth such as, particularly, cancers. Stimulation of angiogenesis can be beneficial in the treatment of diseases such as coronary disease and limb ischaemia. In this article some aspects are presented of current knowledge of angiogenesis and its regulation.

Angiogenesis Inducing Agents↗
PubMed2001

Orally administered bovine lactoferrin systemically inhibits VEGF(165)-mediated angiogenesis in the rat.

Lactoferrin (Lf) systemically suppresses tumor growth and metastasis by unknown mechanisms. We have studied the effect of orally administered iron-unsaturated bovine Lf on angiogenesis induced by VEGF(165) and IL-1-alpha in adult rats using the mesenteric-window angiogenesis assay. VEGF(165) is a major angiogenic factor in most, if not all, tumors and other angiogenesis diseases of clinical relevance. A number of objective angiogenesis variables were analyzed using microscopic morphometry and image analysis. Lf treatment significantly inhibited the VEGF(165)-mediated response in terms of microvessel spatial extension, overall vascularity and incidence of crossover. The response to IL-1-alpha decreased significantly only in terms of microvessel crossover. In vitro, Lf exerted an antiproliferative effect on endothelial cells. To our knowledge, Lf is the first endogenous protein that has been shown to be antiangiogenic following oral administration. The oral administration of Lf thus appears to be of potential interest as an antiangiogenesis treatment modality in the clinical setting. Since tumor growth is angiogenesis dependent, the extensive therapeutic potential warrants further study to elucidate the mechanisms responsible for the angiostatic effect of Lf.

Administration, Oral↗
PubMed2006

Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis.

OBJECTIVE: Interleukin-4 (IL-4) can modulate neovascularization. In this study, we used a gene therapy approach to investigate the role of IL-4 in angiogenesis in rat adjuvant-induced arthritis (AIA), a model for rheumatoid arthritis. METHODS: Rats received an adenovirus producing IL-4 (AxCAIL-4), a control virus without insert, or control vehicle (phosphate buffered saline) intraarticularly before arthritis onset. At peak onset of arthritis, rats were killed. Vascularization was determined in the synovial tissue, and correlations with inflammation were assessed. Ankle homogenates were used in angiogenesis assays in vitro and in vivo, and protein levels of cytokines and growth factors were assessed by enzyme-linked immunosorbent assay. Synovial tissue expression of alphav integrins was determined by immunohistochemistry. RESULTS: IL-4 induced a reduction in synovial tissue vessel density, which was paralleled by a decrease in inflammation. AxCAIL-4 joint homogenates significantly (P < 0.05) inhibited both endothelial cell (EC) migration and tube formation in vitro. Similarly, AxCAIL-4 inhibited capillary sprouting in the rat aortic ring assay, and vessel growth in the in vivo Matrigel plug assay. The angiostatic effect occurred despite high levels of vascular endothelial growth factor (VEGF), and was associated with down-regulation of the proangiogenic cytokines IL-18, CXCL16, and CXCL5 and up-regulation of the angiogenesis inhibitor endostatin. Of interest, AxCAIL-4 also resulted in decreased EC expression of the alphav and beta3 integrin chains. CONCLUSION: In rat AIA, IL-4 reduces synovial tissue vascularization via angiostatic effects, mediates inhibition of angiogenesis via an association with altered pro- and antiangiogenic cytokines, and may inhibit VEGF-mediated angiogenesis and exert its angiostatic role in part via alphavbeta3 integrin. This knowledge of the specific angiostatic effects of IL-4 may help optimize target-oriented treatment of inflammatory arthritis.

Adjuvants, Immunologic↗
PubMed2003

Biology of angiogenesis in tumors of the gastrointestinal tract.

The realization that the growth and spread of tumors are dependent on angiogenesis has created new avenues of research designed to help us to better understand cancer biology and to facilitate the development of new therapeutic strategies. However, the process of angiogenesis consists of multiple, sequential, and interdependent steps with a myriad of positive and negative regulators of angiogenesis being involved. The survival of tumors and thus their metastases are dependent upon the balance of endogenous angiogenic and anti-angiogenic factors such that the outcome favors increased angiogenesis. Several growth factors have been identified that regulate angiogenesis in cancers of the gastrointestinal tract. These include pro-angiogenic factors like vascular endothelial growth factor (VEGF) and anti-angiogenic factors, i.e., thrombospondin. The following review provides a brief overview about the most important factors that are involved in the angiogenic process in tumors derived from colon, stomach, and pancreas. A thorough understanding of the role these factors play in the angiogenic process may lead to the development of novel therapeutic antineoplastic strategies.

Angiogenesis Inhibitors↗
PubMed2003

Abnormal angiogenesis in diabetes mellitus.

The adverse long-term effects of diabetes mellitus have been well described and involve many organ systems. While diabetes management has largely focused on control of hyperglycemia, the presence of abnormalities of angiogenesis may cause or contribute to many of the clinical manifestations of diabetes. When compared with non-diabetic subjects, diabetics demonstrate vascular abnormalities of the retina, kidneys, and fetus. Diabetics have impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. In each of these conditions, and possibly in diabetic neuropathy as well, abnormalities of angiogenesis can be implicated in the pathogenesis. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. In this review, the clinical features, molecular mechanisms, and potential therapeutic options of abnormal angiogenesis in diabetes will be reviewed.

Angiogenesis Inhibitors↗
PubMed2001

Peptides encoded by exon 6 of VEGF inhibit endothelial cell biological responses and angiogenesis induced by VEGF.

VEGF induces pathological angiogenesis and is an important target for the development of novel antiangiogenic molecules. In this study, we tested synthetic peptides based on the sequence of VEGF(189) for their ability to inhibit VEGF receptor binding and biological responses. We identified 12-amino acid peptides derived from exon 6 that inhibited VEGF binding to HUVECs, VEGF-stimulated ERK activation, and prostacyclin production. These peptides inhibited VEGF-induced mitogenesis, migration, and VEGF-dependent survival of endothelial cells, but caused no increase in apoptosis in the absence of VEGF. Exon 6-encoded peptides also caused a marked inhibition of VEGF-induced angiogenesis in vitro. Studies of effects of peptides on cross-linking of VEGF to its receptors and on binding of VEGF to porcine aortic endothelial cells expressing either KDR or neuropilin-1 showed that exon 6-encoded peptides effectively blocked the interaction of VEGF with both receptors. Exon 6-derived peptides caused release of bFGF from endothelial cells but inhibited bFGF-dependent ERK activation, cell proliferation and angiogenesis. Our findings indicate that VEGF exon 6-encoded peptides inhibit VEGF-induced angiogenesis, at least in part through inhibition of VEGF binding to KDR. In addition, exon 6-encoded peptides are also effective inhibitors of bFGF-mediated angiogenesis.

Angiogenesis Inhibitors↗
PubMed2002

Mesenchymal cells potentiate vascular endothelial growth factor-induced angiogenesis in vitro.

The role of soluble factors (including angiogenic cytokines) and extracellular matrix components in the regulation of angiogenesis is clearly established. However, the interrelationship between these factors and perivascular mesenchymal cells is not well understood. Here we have used a three-dimensional collagen gel coculture system to assess the effect of mesenchymal C3H10T1/2 cells on vascular endothelial growth factor-A (VEGF-A)- and fibroblast growth factor-2 (FGF-2)-induced angiogenesis in vitro. We found that coculture markedly potentiated the angiogenic activity of VEGF-A, irrespective of whether or not direct cell-to-cell contact occurred. In contrast, under conditions in which cell-to-cell contact was possible, FGF-2-induced angiogenesis was inhibited by cocultured 10T1/2 cells; this effect was not seen when cell-to-cell contact was prevented. Attempts to identify the molecules responsible for this effect allowed us to exclude FGF-2, transforming growth factorbeta1, platelet derived growth factor-BB, angiopoietin-1, and NO as possible mediators of the potentiating effect of coculture on VEGF-A-induced invasion. In the living organism, angiogenesis occurs in a three-dimensional microenvironment. Contrary to the inhibitory effect of 10T1/2 cells previously reported by others in two-dimensional cultures, our data demonstrate that the paracrine interaction between endothelial and mesenchymal cells potentiates angiogenesis in vitro and that this is cytokine-specific, i.e., it occurs with VEGF-A but not with FGF-2.

Angiogenesis Inducing Agents↗
PubMed2000

Generational analysis reveals that TGF-beta1 inhibits the rate of angiogenesis in vivo by selective decrease in the number of new vessels.

Quantitative analysis of vascular generational branching demonstrated that transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine and angiogenic regulator, strongly inhibited angiogenesis in the arterial tree of the developing quail chorioallantoic membrane (CAM) by inhibition of the normal increase in the number of new, small vessels. The cytokine was applied uniformly in solution at embryonic day 7 (E7) to the CAMs of quail embryos cultured in petri dishes. After 24 h the rate of arterial growth was inhibited by as much as 105% as a function of increasing TGF-beta1 concentration. Inhibition of the rate of angiogenesis in the arterial tree by TGF-beta1 relative to controls was measured in digital images by three well-correlated, computerized methods. The first computerized method, direct measurement by the computer code VESGEN of vascular morphological parameters according to branching generations G(1) through G(>/=5), revealed that TGF-beta1 selectively inhibited the increase in the number density of small vessels, N(v>/=5) (382 +/- 85 cm(-2) for specimens treated with 1 microg TGF-beta1/CAM for 24 h, compared to 583 +/- 99 cm(-2) for controls), but did not significantly affect other parameters such as average vessel length or vessel diameter. The second and third methods, the fractal dimension (D(f)) and grid intersection (rho(v)), are statistical descriptors of spatial pattern and density. According to D(f) and rho(v), arterial density increased in control specimens from 1.382 +/- 0.007 and 662 +/- 52 cm(-2) at E7 (0 h) to 1.439 +/- 0.013 and 884 +/- 55 cm(-2) at E8 (24 h), compared to 1. 379 +/- 0.039 and 650 +/- 111 cm(-2) for specimens treated with 1 microg TGF-beta1/CAM for 24 h. TGF-beta1 therefore regulates vascular pattern and the rate of angiogenesis in a unique "fingerprint" manner, as do other major angiogenic regulators that include VEGF, FGF-2 (bFGF), and angiostatin. TGF-beta1 did not stimulate angiogenesis significantly at low cytokine concentrations, which suggests that this quail CAM model of angiogenesis is not associated with an inflammatory response.

Allantois↗
PubMed2004

Inhibition of angiogenesis as a therapeutic strategy against brain tumors.

Multidisciplinary treatment strategies for patients with malignant brain tumors have resulted in only small gains in terms of prognosis in spite of the use of aggressive therapy. There is a growing realization that a paradigm shift is needed in the conceptual approaches to glioma therapy. Such approaches will rely on identification and modification of key cellular targets that define the biological behavior of these tumors. Among the targets for such treatment approaches, tumor angiogenesis has captured the attention of not only the medical field but also of the lay public because of its conceptual departure from traditional methods of cancer therapy. Angiogenesis and vascular proliferation are particularly important in the growth and progression of malignant gliomas and are used as indicators of the degree of malignancy. Recent studies have helped us gain a better understanding of the molecular mediators of this process. It is now evident that after the initial formation of malignancy the continued growth of a glioma is critically dependent on its angiogenic potential. Hence, several approaches to control angiogenesis are being developed and tested. Preliminary results from clinical studies have shown that angiogenesis inhibition is a valid approach as a therapeutic strategy against gliomas but it is also becoming evident that inhibition of individual modulators of this process may not yield the expected impact on prognosis. To fully realize the potential of antiangiogenic therapy, a deeper understanding of the interplay between the tumor vasculature and its environment is needed. Angiogenesis inhibitors have made the transition from preclinical studies to the clinical arena; it remains for ongoing human trials of such agents to fully explore the feasibility and efficacy of these agents in order to exploit the potential of this approach.

Angiogenesis Inhibitors↗
PubMed1985

Tumor-derived angiogenesis factors from rat Walker 256 carcinoma: an experimental investigation and review.

Angiogenesis, the process of developing a hemovascular network, is an essential feature of the growth of solid tumors, and is induced by factors secreted by tumor cells. Assay procedures suitable for the investigation of angiogenesis, and for the screening of angiogenesis factors during purification are reviewed; and a number of reports describing the purification of angiogenesis factors, primarily from the rat Walker 256 carcinoma as starting material, are discussed. Work from the authors' laboratory is also presented. Walker 256 cells grown in large-scale culture were the source of a reproducible and homogeneous source of angiogenic material. Factors secreted by these cells were isolated by a series of chromatographic steps. Ion exchange chromatography on carboxymethyl-Sephadex produced two active fractions, one of which was fractionated into several macromolecular species by lectin affinity and hydrophobic adsorption chromatography. The other gave a high mol.wt, active fraction that was resolved into a low mol.wt, active component and a non-angiogenic but possibly carrier molecule with a mol.wt of 140,000. While none of the angiogenic factors were identified chemically, the results demonstrate the existence of both high and low mol.wt tumor-secreted angiogenic substances, confirming the hypothesis for tumor-induced angiogenesis and predicting potential means to interfere with the process of tumor growth.

Amnion↗
PubMed2001

Angiogenesis in hematologic malignancies.

Angiogenesis, defined as the blood vessel generation from preexisting blood vessels, was found to play an important role in the progression of solid tumors. In addition, bone marrow-derived endothelial precursor cells may contribute to tumor angiogenesis. Recently angiogenesis induction was described in several hematologic neoplasms as leukemia, lymphoma, myelodysplastic syndrome and multiple myeloma (MM). Clinical angiogenesis research also termed as angiodiagnosis has established the prognostic relevance of markers of angiogenesis e.g., microvessel density and circulating levels of angiogenic peptides. Development of antiangiogenic treatment for hematologic neoplasms has recently been sparked by the success of Thalidomide (Thal) which has antiangiogenic properties in MM. Antiangiogenic treatment strategies are now being tested in clinical trials on several types of hematologic neoplasms.

Angiogenesis Inhibitors↗
PubMed2006

Neridronate inhibits angiogenesis in vitro and in vivo.

The effects of the amino-bisphosphonate neridronate on endothelial cell functions involved in angiogenesis, namely, proliferation and morphogenesis on Matrigel were tested in vitro, whereas its effects on angiogenesis were studied in vivo, by using the chick embryo chorioallantoic membrane (CAM) assay. In vitro, neridronate inhibited endothelial cell proliferation in a dose-dependent fashion, peaking at 30 microM. At the same concentration, neridronate inhibited fibroblast growth factor-2 (FGF-2)-induced capillary-like tube formation in the morphogenesis assay on Matrigel. In vivo, when tested in the CAM assay, neridronate again displayed the capability to inhibit FGF-2-induced angiogenesis. Overall, these results suggest that anti-angiogenesis by neridronate could be used to treat a wide spectrum of angiogenesis-dependent diseases, including certain chronic inflammatory diseases and cancer.

Angiogenesis Inhibitors↗
PubMed2006

Current status and perspective of angiogenesis and antivascular therapeutic strategy: non-small cell lung cancer.

Lung cancer is the leading cause of cancer death worldwide, and most patients die of metastatic disease. Angiogenesis, namely, neovascularization from preexisting vasculature, is necessary for tumor growth in both primary and distant organs to supply oxygen and nutrition. Angiogenesis consists of sprouting and nonsprouting (the enlargement, splitting, and fusion of preexisting vessels) processes, and both can occur concurrently. The growth of non-small cell lung cancer (NSCLC), which accounts for more than 80% of all lung cancers, is usually dependent on angiogenesis, which is regulated by complex mechanisms in the presence of various angiogenesis-related molecules. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is one of the most potent angiogenic molecules, while also regulating both angiogenesis and vascular permeability and hence promoting tumor progression and the development of malignant pleural effusions in NSCLC. Recent clinical trials showed that the anti-VEGF antibody bevacizumab, combined with standard first-line chemotherapy, provided a statistically and clinically significant survival advantage with tolerable toxicity. In addition, the combined use of the anti-VEGF antibody with an inhibitor of epidermal growth factor receptor (EGFR) has also shown favorable antitumor efficiency. These successes proved the validity of an antivasculature strategy for NSCLC. Furthermore, a large number of antivasculature agents have been shown to be effective against multiple targets. The efficiency of these compounds is currently being investigated in clinical trials for NSCLC.

Angiogenesis Inhibitors↗
PubMed2001

Plaque angiogenesis and atherosclerosis.

Therapeutic angiogenesis trials refer to the stimulation of collateral arterioles and new vascular conduits to perfuse ischemic myocardium and limbs. Atherosclerotic lesions responsible for vascular occlusions themselves are associated with angiogenesis within the vessel wall. Plaque neovascularization is comprised of a network of capillaries that arise from the adventitial vasa vasorum and extend into the intimal layer of atherosclerotic lesions and other types of vascular injury. The functions of these plaque capillaries are proposed to be important regulators of plaque growth and lesion instability. The development of agents that are positive and negative regulators of angiogenesis may have potential therapeutic implications in the progression and acute manifestations of atherosclerosis. This review focuses on the role of plaque angiogenesis in atherosclerosis and discusses the potential therapeutic applications of angiogenesis inhibitors in this disease.

Angiogenesis Inhibitors↗
PubMed1988

Multiple forms of an angiogenesis factor: basic fibroblast growth factor.

An angiogenesis factor has been isolated from human placenta and human hepatoma cells on the basis of its ability to stimulate protease production in cultured capillary endothelial cells. The purified angiogenesis factor also stimulated DNA synthesis and motility in capillary endothelial cells and induced angiogenesis in vivo. Amino acid sequence data revealed that the angiogenesis factor was human basic fibroblast growth factor (bFGF). Other angiogenesis factors isolated on the basis of their ability to stimulate endothelial cell proliferation have also been identified as bFGFs. The bFGFs that have been sequenced show variability in their N-termini. These different forms of bFGF may be naturally occurring processed forms or may be generated by proteases released during the isolation procedure. Recently a bFGF with a large N-terminal extension has been identified. This Mr 25,000 bFGF has the same biological activity and the same affinity for the bFGF receptor as the typical Mr 18,000 bFGFs. The Mr 25,000 bFGF can be converted into an Mr 18,000 form by treatment with low concentrations of trypsin, suggesting that it may be a precursor to the Mr 18,000 bFGF.

Amino Acid Sequence↗
PubMed2005

Regulation of tumor angiogenesis by thrombospondin-1.

Angiogenesis plays a critical role in the growth and metastasis of tumors. Thrombospondin-1 (TSP-1) is a potent angiogenesis inhibitor, and down-regulation of TSP-1 has been suggested to alter tumor growth by modulating angiogenesis in a variety of tumor types. Expression of TSP-1 is up-regulated by the tumor suppressor gene, p53, and down-regulated by oncogenes such as Myc and Ras. TSP-1 inhibits angiogenesis by inhibiting endothelial cell migration and proliferation and by inducing apoptosis. In addition, activation of transforming growth factor beta (TGF-beta) by TSP-1 plays a crucial role in the regulation of tumor progression. An understanding of the molecular basis of TSP-1-mediated inhibition of angiogenesis and tumor progression will aid in the development of novel therapeutics for the treatment of cancer.

Angiogenesis Inhibitors↗
PubMed2004

The novel targets for anti-angiogenesis of genistein on human cancer cells.

Genistein has been reported to be a natural chemopreventive in several types of human cancer. In our prior study, soy isoflavones were shown to induce cell cycle arrest and apoptosis of bladder cancer cells in the range of human urine excretion. This study was designed to identify the novel molecular basis underlying anti-angiogenic activities of soy isoflavones. An immortalized E6 and five human bladder cancer cell lines were studied by immunoassay, flow cytometry, functional activity, reverse transcription-polymerase chain reaction, immunoblotting, and transwell co-culture in vitro. The efficacy of soy isoflavones on angiogenesis inhibition in vivo was examined by nude mice xenograft and chick chorioallantoic membrane bioassay. Factors analyzed included angiogenic factors, matrix-degrading enzymes, and angiogenesis inhibitors. Genistein was the most potent inhibitor of angiogenesis in vitro and in vivo among the isoflavone compounds tested. It may also account for most of the reduced microvessel density of xenografts observed and the suppressed endothelial migration by soy isoflavones. Genistein exhibited a dose-dependent inhibition of expression/excretion of vascular endothelial growth factor165, platelet-derived growth factor, tissue factor, urokinase plasminogen activator, and matrix metalloprotease-2 and 9, respectively. On the other hand, there was an up-regulation of angiogenesis inhibitors-plasminogen activator inhibitor-1, endostatin, angiostatin, and thrombospondin-1. In addition, a differential inhibitory effect between immortalized uroepithelial cells and most cancer cell lines was also observed. Altogether, we discovered that tissue factor, endostatin, and angiostatin are novel molecular targets of genistein. The current investigation provides further evidence in support of soy-based foods as natural dietary inhibitors of tumor angiogenesis.

Angiogenesis Inhibitors↗
PubMed2005

CXC chemokines in angiogenesis.

CXC chemokines display pleiotropic effects in immunity, regulating angiogenesis, and mediating organ-specific metastases of cancer. In the context of angiogenesis, CXC chemokines are a unique family of cytokines, known for their ability to behave in a disparate manner in the regulation of angiogenesis. Members that contain the 'ELR' motif are potent promoters of angiogenesis, and mediate their angiogenic activity via binding and activating CXCR2 on endothelium. In contrast, members, in general, those are inducible by interferons and lack the ELR motif (ELR-) are potent inhibitors of angiogenesis, and bind to CXCR3 on endothelium. This review will discuss the biology of these angiogenic and angiostatic CXC chemokines and discuss their disparate angiogenic activity in the context of a variety of disorders.

Angiogenesis Modulating Agents↗