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At least 721 records · Page 40Linked to original sources
PubMed2003

Angiotherapeutics from natural products: from bench to clinics?

Angiogenesis offers an enormous potentials for therapeutic intervention of many disorders afflicting mankind at present. With the identification of the major molecular players involved in the sequence of events leading to the formation of new blood vessels from pre-existing capillaries, inhibition or induction of the process may now be regulated. Bioactive compounds from natural sources may be used as regulatory agents. Inhibition of angiogenesis can control diseases characterized with excessive blood vessel growth like cancer, arthritis, psoriasis and diabetes retinopathy. Stimulation of angiogenesis would be favorable in the treatment of ischemic disorders and tissue engineering. An increasing number of bioactive compounds from natural sources and whose chemical structures have already been elucidated are reported as either potential inhibitors or inducers of angiogenesis. Drug development from natural products is a fast-emerging field that needs to be supported to provide people with more readily available and affordable healthcare.

Angiogenesis Inducing Agents↗
PubMed2004

Delayed angiogenesis in aging rats and therapeutic effect of adenoviral gene transfer of VEGF.

We have studied an age-related impairment in angiogenesis and evaluated the effect of overexpressing VEGF in this situation. Polyvinyl alcohol sponges were implanted subcutaneously into aged (24-month), adult (12-month), and young (2-month) rats. Blood vessel ingrowth and proliferative activity in the sponges were assessed by histology with immunostaining for von Willebrand's factor and proliferating cell nuclear antigen (PCNA), respectively. The percentage of total sponge area filled with ingrowing fibrovascular tissue was minimal in aged rats, intermediate in adult rats and highest in young rats. A similar pattern was observed for the total blood vessel numbers in the sponges from old to young animals. The percentage of total sponge endothelial cells (ECs) showing proliferative activity (PCNA positive) was lowest in the aged animals, intermediate in the adult rats and highest in the young rats. To further explore the mechanism of impaired angiogenesis in aged animals, we investigated and found a reduced level of endogenous VEGF protein expression in 12-month-old rats compared to that in 2-month-old rats. VEGF121 gene transfer significantly enhanced blood vessel and fibrovascular tissue ingrowth in adult/aged rats. Adenoviral-VEGF gene transfer also significantly stimulated EC proliferation in aged and adult rats. However, identical treatment failed to further stimulate the already more robust angiogenesis in young animals. The different angiogenic response in adult vs. young rats was not due to differences in gene transfer efficiency, since similar levels of human VEGF121 protein was detected in adult and young rats. Our results indicate that the decreased angiogenic response with aging is associated with reduced EC proliferation and reduced endogenous VEGF production. Adenoviral-VEGF121 gene transfer is effective in augmenting angiogenesis, particularly in older animals.

Adenoviridae↗
PubMed2003

[Mechanism of angiogenesis. Ocular involvement].

Over the past several years, there has been important progress in the field of intrinsec mechanisms of ocular neovascularization. Immunohistological studies succeeded a better systematization of the factors that stimulates and inhibits this process. Their presence in different ocular normal structures, without any angiogenic activity, suggests a physiological balance between VEGF (vascular endothelial growth factor) with stimulatory effect on angiogenesis and PEDF (pigment epithelium derived factor) with inhibitory effect. It has been discussing the possibility of modification of physiological balance between VEGF and PEDF to induce the neovascularization process. The understanding of the physiopathological mechanisms of the substances implicated in inhibition of chorioretinal neovascularization makes to be real the expectations for the development of new treatments.

Cornea↗
PubMedDate not supplied

[The similarities and the differences of embryogenesis and carcinogenesis].

The main similarities and embryonic and tumor cells, as well as the mechanisms preventing the malignant transformation of embryonic cells, are presented in this review. Special attention is paid to the role of specific polypeptide growth factors in reciprocally excluding processes: embryogenesis and carcinogenesis. Based on the presented analysis, new potential targets for antitumor drugs are considered.

Animals↗
PubMed2004

[Neovascularization in ocular tissues: mechanisms and role of proangiogenic and antiangiogenic factors].

Blood vessel growth and stability are under precise control of an array of pro- and anti-angiogenic factors. Under physiological conditions, actions of particular regulatory factors, as well as their mutual interactions are harmonized and balanced. Disruption of the balance between these pro- and anti-angiogenic factors is characteristic of many vascular diseases, including those occurring within the eye. Functional dominancy of proangiogenic factors (e.g., vascular endothelial growth factor, VEGF) over antiangiogenic ones (e.g., pigment epithelium-derived growth factor, PEDF), which may occur under ischemic conditions, may initiate the process of retinal or choroidal neovascularization, representing a major threat to the eyesight. This article presents and discusses current ideas concerning molecular and cellular processes underlying aberrant growth on new blood vessels in ocular tissues, in relation to microvascular ocular complications associated mainly (but not only), with diabetes mellitus, age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). This review also surveys latest achievements in the field of clinically more effective future therapeutic strategies, including gene therapy applicable to the neovascular eye diseases.

Choroid↗
PubMed2004

[Regulation of the Hypoxia-Inducible Factor-1alpha (HIF-1alpha): a breath of fresh air in hypoxia research].

Angiogenesis, a process that leads to the formation of new blood vessels, from a existing network of vessels is tightly regulated. The understanding of mechanisms that control its activity should lead to progress in the treatment of diseases such as cancer and ischemic disorders. In the case of cancer, the rapid growth of tumor cells results in a decrease in the concentration of oxygen, or hypoxia, in the center of the tumor. This stress is the signal that induces angiogenesis. Blood vessels bring nutrients and oxygen to the tumor, allowing it to grow and to metastase. The Hypoxia-Inducible Factor 1, HIF-1, plays a crucial role in this process. HIF-1 is a heterodimer composed of two subunits, alpha and beta. Under hypoxic conditions, HIF-1alpha is stabilized and enters the nucleus, to form a dimer with HIF-1beta, where it induces the expression of its target genes. Among these genes is vegf (vascular endothelial growth factor), a key player in blood vessel formation. The protein HIF-1alpha is subjected to post-translational modifications that are the molecular basis of the hypoxic response although the mechanisms are not completely understood. In this review, we will discuss in particular the multiple post-translational modifications regulating HIF-1alpha activity.

Animals↗
PubMed2004

Anti-angiogenic effect of pyridoxal 5'-phosphate, pyridoxal and pyridoxamine on embryoid bodies derived from mouse embryonic stem cells.

We previously demonstrated anti-angiogenic activity of pyridoxal 5'-phosphate (PLP) and pyridoxal (PL) using in vitro and ex vivo angiogenesis models and anti-colon tumor effect of vitamin B(6) in mice. There is growing evidence that endothelial progenitor cells (EPCs) in circulation contribute to tumor-induced angiogenesis. It is of importance to clarify whether EPC differentiation is involved in the mechanism of anti-angiogenic effect of vitamin B(6). In this study, we investigated the effect of vitamin B(6) on angiogenesis in embryonic stem cell-derived embryoid bodies (EBs). PLP suppressed angiogenesis in EBs at >or=100 microM. Among the vitamin B(6) compounds at the concentration of 200 microM, PL, as well as PLP, was the most effective suppressor of vasculogenesis, while pyridoxine was inactive. These results were consistent with their effects in rat aorta and endothelial cell assays. Interestingly, pyridoxamine (PM), which had no effect in rat aorta and endothelial cell assays, also exerted a significant suppressive effect in this model. This study demonstrated an inhibitory effect of PM on vasculogenesis in this EB model as well as PLP and PL, and suggests that suppression of EPC differentiation is at least in part responsible for the mechanism of the anti-angiogenesis effect of vitamin B(6).

Angiogenesis Inhibitors↗
PubMed2005

Androgens repress the expression of the angiogenesis inhibitor thrombospondin-1 in normal and neoplastic prostate.

In order to understand why the angiogenesis inhibitor thrombospondin-1 (TSP1) is often, although not always, associated with prostatic tumors, we have investigated its relationship with the testosterone and the vasculature on which both normal and tumorigenic prostatic epithelia depend. In vivo, androgen withdrawal led to increased TSP1 production and decreased vascularization in the normal rat prostate which was reversed by androgen replacement. Androgen repression of TSP1 production occurred at the transcriptional level and was dependent on the presence of the first intron of the TSP1 gene. In an experimental model of prostate tumorigenesis, TSP1, when delivered by admixed stromal fibroblasts, markedly delayed LNCaP tumor growth and limited tumor vascularization. However, prolonged exposure to TSP1 resulted in the growth of tumors secreting high levels of vascular endothelial growth factor in the bloodstream of tumor-bearing animals and tumor growth was no longer sensitive to TSP1 inhibitory effects. Clinical evidence also suggested that prostate carcinomas are able to adapt to escape the antiangiogenic effects of TSP1. In human androgen-dependent localized prostate carcinomas, TSP1 expression was inversely correlated with blood vessel density. Androgen deprivation in patients with hormone-responsive tumors led to increased TSP1 expression and vascular regression. In contrast, despite a sustained expression in the tumor bed, TSP1 was no longer associated with decreased vascularization in hormone-refractory prostate tumors. Overall, these results suggest that the high in situ TSP1 exposure triggered by androgen deprivation in patients with prostate cancer could lead to early tumor resistance. Such patients could benefit from a combination of androgen deprivation and antiangiogenic therapy in order to minimize the induction of such tumor escape.

Androgens↗
PubMed2005

[The similarities between the mechanism of wound healing and tumor development--literature review on the occasion of a patient with colonic adenocarcinoma metastasis in a dog-bite wound].

For more than a century, the role of wound healing in the growth of tumours has been implied based on observations in experimental and clinical studies. In the recent 10-15 years processes such as cell adhesion, angiogenesis, metastatic cascade and growth factors (fe: EGF, TGF-alpha, TGF-beta, IGF-1, IGF-II, PDGF) have been identified to play key roles in different stages of wound healing as well as in tumor progression. Experimental and clinical studies have established that wound healing creates a suitable environment favouring tumour growth and metastatic potential. Based on these observations, the clinical relevance of surgical procedures comes up, may playing a role in tumor recurrence after primary resection for cancer. This makes the opportunity of the development of completely new targeted approaches (antiangiogenic therapy, dormancy therapy) for the treatment of cancer. This review article is based on a case report of a 63-year-old female patient who had colonic adenocarcinoma metastasis of the hand after biting by a dog.

Adenocarcinoma↗
PubMed2005

Effects of plant extracts on angiogenic activities of endothelial cells and keratinocytes.

Numerous bioactive chemical compounds of plant origin may influence the angiogenic activity of various cell types and may thus affect the formation of blood vessels. Here we present the angiogenic effects of extracts of edible plants collected in Crete, Southern Italy and Southern Spain. Extracts have been applied to cultured human microvascular endothelial cells (HMEC-1), human umbilical vein endothelial cells (HUVEC) and human keratinocytes (HaCaT). About half out of 96 extracts exerted an inhibitory effect on HMEC-1 proliferation. Additionally, we have noted the inhibitory effects of extracts on HUVEC differentiation on a Matrigel layer. None of the extracts showed a stimulatory activity. The extract of Thymus piperella exerted moderate inhibitory effect on cobalt-chloride induced VEGF synthesis, however, CoCl(2)-induced activation of hypoxia responsive element of VEGF promoter was significantly attenuated only by extract of Origanum heracleoticum. Our study indicates that extracts of local food plants, of potential value as nutraceuticals, contain chemical compounds which may inhibit angiogenesis. Demonstration of their real influence on human health requires, however, extensive animal studies and controlled clinical investigations.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Roxithromycin inhibits angiogenesis of human hepatoma cells in vivo by suppressing VEGF production.

BACKGROUND: Recently, 14-member macrolide antibiotics such as Clarithromycin and Roxithromycin (RXM) have been shown to have anti-cancer and anti-angiogeneic effects. However, it is not fully understood whether and how RXM suppresses angiogenesis in human hepatoma, which is a well-known hypervascular tumor. MATERIALS AND METHODS: In the present study, we examined the effects of RXM on tumor angiogenesis in the human hepatoma cell line, HepG2. In vivo, angiogenesis was examined using a mouse dorsal air sac model. RESULTS: The inhibitory effect of RXM was dose-dependent and the angiogenesis index of 100mg/kg/day of RXM administered intraperitoneally twice a day was significantly lower than the control. Next, we examined the effect of RXM on vascular endothelial growth factor (VEGF) mRNA expression and its protein level in HepG2 cells. When 100 microM of RXM were added, VEGF mRNA expression in HepG cells was inhibited and its protein level reduced. CONCLUSION: These results suggest that RXM inhibits tumor angiogenesis in human hepatoma, and that VEGF alteration may be involved in the mechanism of this inhibitory effect. Because RXM is widely used in clinical practice, it may represent an effective new strategy for human hepatoma therapy.

Air Sacs↗
PubMed2004

Vascular endothelial growth factor receptors: expression and function in solid tumors.

Vascular endothelial growth factor (VEGF) and its family members are important mediators of tumor angiogenesis. The multiple functions of the VEGF are mediated through complex and selective interactions between the ligands, their high-affinity tyrosine kinase receptors, and co-receptors (neuropilins). While these receptors are historically described as being exclusively expressed on endothelial cells, emerging evidence has documented expression of these receptors on a number of nonendothelial cells, including tumor cells. The VEGF receptors (VEGFR) have also been shown to be functional in a number of nonendothelial systems, where they may be targets for anti-VEGF therapy. This article will review the basic effects and interactions of the VEGFRs on endothelial cells and the evidence for their expression and function on tumor cells. The novel expression of VEGFRs on tumor cells contributes to the understanding of the complex roles of VEGF within the tumor microenvironment, potentially affecting both endothelial cells and tumor cells expressing the VEGFRs. This elucidation of VEGF activity may further refine antineoplastic regimens for solid malignancies.

Angiogenesis Inhibitors↗