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Results for “Angiogenesis”

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At least 91 records · Page 5Linked to original sources
PubMed2000

Contribution of angiogenesis to the progression of colon cancer: possible inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and hepatic metastasis.

The contribution of angiogenesis to tumor growth and hepatic metastasis of colorectal cancer was investigated by means of immunohistochemical study and in vitro and in vivo experiments. Colorectal cancer specimens from 30 patients with hepatic metastasis and 39 patients without hepatic metastasis were studied by staining with antibodies against factor VIII-related antigen. Microvessel count in patients with liver metastasis was significantly higher than in those without liver metastasis (p<0.005). The effect of TNP-470 was evaluated with in vitro and in vivo experiments using human colon cancer cell line, LM and the highly hepatic metastasis cell line, LM-H5. The effect of TNP-470 on the proliferation of the cancer cells and human umbilical vein endothelial cells (HUVECs) was examined. TNP-470 inhibited more sensitively the proliferation of HUVECs than cancer cells in vitro. IC50 was approximately 3 pg/ml in HUVECs and approximately 2 microg/ml in cancer cells. The effect of TNP-470 on the growth of xenografts and liver metastases by LM-H5 in nude mice was examined. TNP-470 (30 mg/kg) was administered by subcutaneous injection every third day for 4 weeks. TNP-470 inhibited both the growth of xenograft and the hepatic metastasis. The number of metastatic foci in the liver was 78.2+/-30.1 in the control group and 20.6+/-16.5 in the treated group. These results suggest that TNP-470 is a potent agent to inhibit tumor growth and hepatic metastasis of colon cancer.

Adult↗
PubMed2001

[Significance of angiogenesis and clinical application of anti-angiogenesis].

Angiogenesis is essential for tumor growth and metastasis and depends upon the production of angiogenic factors by host and/or tumor cells. Increased vascularity may allow not only an increase in tumor growth but also a greater chance for hematogenous metastasis. We have already reported that vessel density and vascular endothelial growth factor (VEGF) expression are higher in metastatic tumors than in nonmetastatic tumors and that VEGF and its receptor, the KDR ligand/receptor system, also correlate with metastasis. Therefore the anti-VEGF antibody and VEGF receptor antagonist are potential targets for antiangiogenesis therapy in colon cancer. Clinical trials of such agents are continuing to phase II/III in the USA and Europe. In this paper, we introduce data on antiangiogenesis agents in the treatment of metastatic colorectal cancer and point out that the strategy for antiangiogenesis is not tumor shrinkage but tumor dormancy.

Angiogenesis Inhibitors↗
PubMed1998

Inhibition of tumor growth and microvascular angiogenesis by the potent angiogenesis inhibitor, TNP-470, in rats.

The antiangiogenic effects of TNP-470 on the neovascularization of tumors were studied by examining ultrastructural alterations in the vasculature and interstitial fluid pressure (IFP) of tumors. Wistar rats were first inoculated subcutaneously (s.c.) with the Walker 256 carcinosarcoma cell line, then either vehicle medium or TNP-470, 30 mg/kg, was injected s.c. on day 1. A tumor growth assay, the necrotic area, and the IFP in the tumor were all measured on day 12. The antiangiogenic effects of TNP-470 were studied by scanning electron microscopic images of tumor vascular casts. TNP-470 was observed to inhibit tumor growth and increase the necrotic area significantly. In the TNP-470-treated group, the IFP in the superficial layer, defined as 2-3 mm from the tumor capsule, and in the deep layer, defined as 8-10 mm from the tumor capsule, were significantly higher than the corresponding values in the control. Moreover, vascular casts showed a significant reduction in the budding of sprouts in the superficial layer, and a decrease in the maximum diameter of the tumor vessels in the deep layer. It is possible that the higher IFP in the TNP-470-treated tumors might have prevented tumor vessel dilation. The findings of this study demonstrated that TNP-470 inhibited the budding of tumor vessel sprouts, and increased the IFP. These processes seem to act synergistically to suppress tumor angiogenesis.

Animals↗
PubMed2006

Hybrid surgical angiogenesis: omentopexy can enhance myocardial angiogenesis induced by cell therapy.

BACKGROUND: The conditions at the injection site are important in cell transplantation for severe ischemic heart disease. The omentum is both a well-vascularized tissue and a source of angiogenic factors. We examined the effectiveness of autologous bone marrow-derived mononuclear cells (BM-MNCs) with or without omentopexy in a large animal model. METHODS: Myocardial infarction was generated in the lateral wall by ligation of coronary artery branches in miniswine. Animals received BM-MNC injection with or without omentopexy. Controls received saline only. Three weeks after surgery, regional myocardial blood flow and contractility were measured, and density of arterioles was evaluated immunohistologically. Angiography and postmortem examinations were performed to determine collateral communication. RESULTS: Regional myocardial contractility was significantly improved by BM-MNC transplantation both with and without omentopexy (0.29 +/- 0.02 vs 0.11 +/- 0.03, p < 0.01, 0.30 +/- 0.02 vs 0.12 +/- 0.01, p < 0.01, respectively). Relative regional myocardial blood flow in the combined omentopexy group was significantly higher than the controls both at rest (1.05 +/- 0.11 vs 0.57 +/- 0.07, p < 0.01) and under stress (1.09 +/- 0.08 vs 0.40 +/- 0.10, p < 0.01). The number of arterioles (< 50 microm) in both groups were higher than the controls (88.1 +/- 5.00 vs 38.1 +/- 8.99, p < 0.01 and 109.2 +/- 9.91 vs 38.1 +/- 8.99, p < 0.01, respectively). The number of large arterioles (> 50 microm) in the combined omentopexy group was significantly higher than in both BM-MNC alone (26.9 +/- 2.4 vs 17.6 +/- 1.8, p = 0.011) and controls (26.9 +/- 2.4 vs 10.0 +/- 1.3, p < 0.01). Collateral communication between the omentum and myocardium was demonstrated by angiography and postmortem injection. CONCLUSIONS: The BM-MNC transplantation may attenuate cardiac contractile dysfunction, and omentopexy may enhance angiogenesis induced by BM-MNC transplantation.

Angiography↗
PubMed1999

Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: angiogenesis in chronic pancreatitis and in pancreatic cancer.

Recent epidemiologic evidence suggests that patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic carcinoma (PCA). In spite of numerous similarities in both diseases, mechanisms for progression from CP to PCA are poorly understood. We hypothesized that enhanced angiogenesis might play a pivotal role in the etiology and histopathology of both CP and PCA, and thus form a possible link between precancer and carcinoma. In surgical specimens of 18 patients with CP, 10 with PCA, and 18 controls, absolute numbers of blood vessels and relative blood vessel density were assessed after immunostaining of endothelial cells for von Willebrand factor and PECAM-1 (platelet/ endothelial cell adhesion molecule-1). Furthermore, the expression of cell adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) and of VEGF (vascular endothelial growth factor) was investigated in all specimens. Both CP and PCA exhibited areas of high vascular density ("hot spots"). The mean number of blood vessels in these areas in PCA was 132.2+/-16.8 per mm2, and in CP, 99.2+/-7.4 per mm2. The mean vessel count in controls was 25.1+/-5.1. Relative vessel density was increased in both PCA (41.3+/-3.5%) and CP (30.6+/-2.6%) versus controls (8.0+/-0.8%). Both absolute vessel count and relative vessel density were significantly higher (p<0.05) in PCA than in CP. Enhanced expression of ICAM-1 in CP and PCA was seen in ductal cells in CP and cancer cells. In controls, ICAM-1 and VCAM-1 were expressed only at low levels in endothelial cells. VCAM-1 was strongly expressed in acinar cells as well as in ductal cells. In CP and PCA, VEGF was strongly expressed in ductal cells in CP as well as in cancer cells. We show for the first time that angiogenic activity is increased in both CP and PCA. Based on this study, we suggest that antiangiogenesis might be a novel target for prevention or therapy in chronic pancreatic diseases.

Adenocarcinoma↗
PubMed2000

[Angiogenesis in tumors. Part I. Its role in the determination of biological characteristics of tumors; factors controlling the onset and development of angiogenesis].

The tumor stroma gains increasing attention in recent years. Angiogenesis (AG) is defined as formation of new vessels from the endothelium of the preexisting vasculature. The vascular bed does not only provide supply of nutrition factors and oxygen as well as elimination of metabolic waste, but the neo-formed vessels represent also a gate for lymphogenous and hematogenous metastatic spread of the tumor. For tumor growth beyond the size of several mm, AG must be started to form vascular supply of tumor cells. After the switch to angiogenic phenotype, the tumor starts to exhibit rapid, almost exponential growth. AG is a complex process, involving degradation of the basement membrane of preexisting vessel, proliferation of endothelial buds or solid strands towards the angiogenic stimulus, maturation of endothelial cells with formation of a luminized capillary, connection of such capillaries with creation of vascular loops, and finally formation of a functional vessel, surrounded by basement membrane and pericytes. The most intensive AG is observed at the periphery of the tumor. AG is regulated by numerous angiogenic and anti-angiogenic factors, which can be synthesized and released by tumor cells themselves, stromal elements, as well as inflammatory cells, namely macrophages. The issues of regulation of AG and importance of AG for tumor growth, progression and metastasis are discussed.

Animals↗
PubMed2000

[Angiogenesis in tumors. Part II. Methods and significance of quantification; angiogenesis as a prognostic indicator and the target of therapeutic approaches].

The efforts to quantify tumor angiogenesis (AG) have been limited by the methods available. Only since introduction of immunohistochemistry, detection of early stages of capillary vessel formation is enabled. There were reports showing strong correlation between AG and behavior of the tumor (namely formation of metastases, disease free interval, and overall survival) particularly in carcinomas of the breast, prostate, esophagus, stomach and colon. However, significance of these studies is strongly dependent on the methodological aspects, e.g. the choice of visualized endothelial antigen, microscopic magnification and selection of areas with highest angiogenic activity (so called "hot spots"). We present a review of studies focused on AG and discuss pitfalls, which could bias the results. Current clinical applications as well as perspectives of future antiangiogenic treatment are also discussed.

Breast Neoplasms↗
PubMed2006

Overview of anti-VEGF therapy and angiogenesis. Part 1: Angiogenesis inhibition in solid tumor malignancies.

Several new agents that target the vascular endothelial growth factor (VEGF) pathway and inhibit angiogenesis are emerging as promising therapies in multiple cancer types. Bevacizumab, a humanized monoclonal antibody to VEGF-A, is currently approved in combination with intravenous 5-fluorouracil-containing regimens for the first-line treatment of metastatic colorectal cancer and recently demonstrated clinically important results in combination with chemotherapy in patients with non-small cell lung cancer and metastatic breast cancer. Other anti-VEGF agents that have shown benefit in various cancer types will be discussed in this monograph. Despite the often striking results observed with anti-VEGF agents, several unanswered questions remain, such as the optimal duration of therapy and patient selection criteria. These other issues, including the biologic rationale for anti-VEGF therapy, as well as recent clinical trial data with anti-VEGF agents in colorectal, pancreatic, lung, kidney, and brease cancers, are discussed.

Antibodies, Monoclonal↗
PubMed2005

Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization.

BACKGROUND: Bronchopulmonary dysplasia (BPD) and pulmonary emphysema, both significant global health problems, are characterized by a loss of alveoli. Vascular endothelial growth factor (VEGF) is a trophic factor required for endothelial cell survival and is abundantly expressed in the lung. METHODS AND RESULTS: We report that VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries, mimicking BPD. In hyperoxia-induced BPD in newborn rats, air space enlargement and loss of lung capillaries are associated with decreased lung VEGF and VEGFR-2 expression. Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development in this model of irreversible lung injury. Combined VEGF and angiopoietin-1 gene transfer matures the new vasculature, reducing the vascular leakage seen in VEGF-induced capillaries. CONCLUSIONS: These findings underscore the importance of the vasculature in what is traditionally thought of as an airway disease and open new therapeutic avenues for lung diseases characterized by irreversible loss of alveoli through the modulation of angiogenic growth factors.

Adenoviridae↗