Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neovascularization characterizes diabetic retinopathy and choroidal neovascularization associated with age-related macular degeneration, the most common causes of severe visual loss in the developed world. Gene transfer to the eye using adeno-associated viral (AAV) vectors is a promising new treatment for inherited and acquired ocular diseases. We used an AAV vector with rapid onset and high levels of gene expression in the retina to deliver three anti-angiogenic factors (pigment epithelium-derived factor, tissue inhibitor of metalloproteinase-3, and endostatin) to the eyes of mice in a mouse model of retinopathy of prematurity. All three vectors inhibited ischemia-induced neovascularization.
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PMID:Inhibition of retinal neovascularization by intraocular viral-mediated delivery of anti-angiogenic agents. 1237 90

Several interacting and mutually perpetuating biochemical pathways or systems, such as the polyol pathway, nonenzymatic glycation, oxidative stress, protein kinase Cbeta and the reninangiotensin system, may be activated as a result of sustained hyperglycemia in diabetes. These abnormally activated pathways may in turn influence several vasoactive factors and cytokines, such as vascular endothelial growth factor, interleukin-6, pigment epithelium-derived factor and endostatin, which are important in mediating the functional and structural changes of diabetic retinopathy. Intricate and interacting regulatory mechanisms involving these factors may control their ultimate ability to produce biologically significant effects. A better understanding of these factors and their interactions may assist in the development of adjuvant therapies for the treatment of diabetic retinopathy. (c) 2002 Prous Science. All rights reserved.
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PMID:Pathophysiology of Diabetic Retinopathy. 1267 48

A catalogue of proteins in the human vitreous humor may contribute to elucidating the pathogenesis of various diseases in ophthalmology. To improve the recovery of proteins in vitreous, we applied one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D-PAGE). Proteins were extracted from unstained gel strips and digested in gel with trypsin and the peptides were analyzed by capillary-column reversed-phase high-performance liquid chromatography coupled with electrospray ionization-ion trap-mass spectrometry. From a patient with diabetic retinopathy, 84 different proteins were identified. Most of the proteins which we identified in vitreous previously using 2D-PAGE were also identified in the present study. In total, we identified 121 different proteins including five proteins seen at the genomic level only. Four angiogenic factors, insulin-like growth factor, vascular endothelial growth factor, fibroblast growth factor, and placental endothelial cell growth factor, and three anti-angiogenic factors, pigment epithelium-derived factor, endostatin, and thrombospondin, were found, and this may contribute to elucidating the pathological changes in the concentration and the modified structures of these proteins, in diseases of the retina, especially, diabetic retinopathy.
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PMID:Catalogue of soluble proteins in human vitreous humor by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray ionization mass spectrometry including seven angiogenesis-regulating factors. 1282 93

There is no unique formula for angiogenesis. Instead there is a large group of potential participating proteins that interact in complex ways. Depending upon the surrounding cell types and the relative expression levels of angiogenesis-related proteins, the 'angiogenesis cascade' can vary. Therefore, it is valuable to study and compare the role of proteins in several well-characterized vascular beds. The eye provides a useful model system, because it contains several vascular beds sandwiched between avascular tissue. This allows for unequivocal identification and quantitation of new vessels. Retina-specific promoters combined with inducible promoter systems provide a means to regulate the expression of proteins of interest. As a relatively isolated compartment, the eye also provides advantages for gene transfer. By gaining insight regarding the molecular signals involved in various types of ocular angiogenesis, general concepts can emerge that may apply to other settings, including tumor angiogenesis. One concept that has emerged is that despite participation of multiple stimulatory factors for ocular neovascularization, VEGF plays an essential role and interruption of VEGF signaling is an important therapeutic strategy. Another concept is that while most studies have focused on prevention of ocular neovascularization, regression of new vessels is desirable and is achievable with at least three agents, combretastatin A-4 phosphate, pigment epithelium-derived factor, and angiopoietin-2. Finally, endostatin and angiostatin, which have been sources of controversy because of inconsistent results in tumor models, have been shown to have good efficacy when delivered by gene transfer in models of ocular neovascularization. These results provide leads for new ocular treatments and perspective for evaluation of studies of neovascularization in extraocular tissues.
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PMID:Ocular neovascularization: a valuable model system. 1452 78

Angiogenesis is the formation of new blood vessels from pre-existing vessels to form capillary networks, which, among other diseases, such as diabetic retinopathy and macular degeneration, is particularly important for tumor growth and metastasis. Thus, depriving a tumor of its vascular supply by means of anti-angiogenic agents has been of great interest since its proposal in the 1970s. This review looks at the common angiogenic inhibitors (angiostatin, endostatin, maspin, pigment epithelium-derived factor, bevacizumab and other monoclonal antibodies, and zoledronic acid) and their current status in clinical trials.
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PMID:Angiogenesis inhibitors and the need for anti-angiogenic therapeutics. 1789 Jun 68

Angiogenesis, which usually heralds a poor prognosis for patients, is essential for malignancy. However, this same process is useful in providing a direct and systemic route for the delivery of cytotoxics to the actively growing parts of the tumour. In fact, there is even some merit to stabilising (normalising) the tumour vasculature to aid drug delivery to the deeper recesses of a growing tumour. Additionally, natural biological inhibitors of angiogenesis such as pigment epithelium-derived factor (PEDF) are being developed to test whether they have better activity than older ones such as endostatin. The field of cancer angiogenesis, more than 35 years old now, has seen a few drugs reaching the market, such as Avastin. However, there have been a multitude of failed ones, due to lack of activity, especially when tested in vivo and some failing at clinical trials. This review looks at the current state of play in the area of cancer angiogenesis, and development of therapies to target it.
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PMID:Cancer angiogenesis: targeting the heel of Achilles. 1860 57

The review of literature covers the topical aspects of the interaction of proangiogenic cytokines and angiogenic inhibitors, their implication in the pathogenesis of proliferative retinopathies occurring, among other diseases, in the presence of diabetes mellitus. The paper provides the historical facts of development of the angiogenic homeostasis theory that implies that there is a dynamic equilibrium between two antagonistic systems: proangiogenic and antiangiogenic. The major angiogenic inhibitors involved in the maintenance of the normal structure and function of the eye and in the processes linked with abnormal proliferation are enumerated. Particular emphasis is laid on the pigment epithelium-derived factor that is a potent antiangiogenic agent that is directly synthesized by ocular tissues and a vascular endothelial growth factor antagonist. The review of the literature considers the pathogenesis of diabetic retinopathy in the context of interaction of these two growth factors.
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PMID:[Factors influencing ocular angiogenesis]. 1956 51

Cytokine and antiangiogenic gene therapies have proved effective in implanted hepatocellular carcinoma (HCC) models in which small tumor burdens were established in small rodents. These models, however, may not reflect human HCCs, which are frequently detected at a stage when tumors are large and multifocal. In addition, HCC in patients is often associated with viral hepatitis. To investigate the effectiveness of a mixture type of gene therapy strategy on large tumor burdens, we used the woodchuck model in which woodchuck hepatitis virus-induced HCCs are large and multifocal, simulating the conditions in humans. Adenoviruses encoding antiangiogenic factors (pigment epithelium-derived factor and endostatin) or cytokines (GM-CSF and IL-12) were delivered via the hepatic artery separately or in combination into woodchuck livers bearing HCCs. Our results showed that the mixture type of strategy, which contained two cytokines and two antiangiogenic factors, had better antitumor effects on large tumors as compared with monotherapy either with antiangiogenic or cytokine genes. The immunotherapy recruited significant levels of CD3(+) T cells that infiltrated the tumors, whereas the antiangiogenesis-based therapy significantly reduced tumor vasculature. The mixture type of gene therapy achieved both effects. In addition, it induced high levels of natural killer cells and apoptotic cells and reduced the levels of immunosuppressive effectors in the tumor regions. Hence, antiangiogenic therapy may provide the advantage of reducing immune tolerance in large tumors, making them more vulnerable to the immune reactions. Our study implies that in the future, the combination therapy may prove effective for the treatment of patients with advanced HCC.
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PMID:Combining antiangiogenic therapy with immunotherapy exerts better therapeutical effects on large tumors in a woodchuck hepatoma model. 2067 98

Traditional forms of cancer therapy, which include chemotherapy, have largely been overhauled due to the significant degree of toxicity they pose to normal, otherwise healthy tissue. It is hoped that the use of biological agents, most of which are endogenously present in the body, will lead to safer treatment outcomes, without sacrificing efficacy. The finding that pigment epithelium-derived factor (PEDF), a naturally-occurring protein, is a potent angiogenesis inhibitor has become the basis for studying the role of PEDF in tumours that are highly resistant to chemotherapy. The determination of the direct role of PEDF against cancer paves the way for understanding and developing PEDF as a novel drug. This review focuses on the patent applications behind testing the anticancer therapeutic effect of PEDF via its receptors as an antiangiogenic agent and as a direct anticancer agent. The majority of the PEDF patents describe the antiangiogenic ability and usage of recombinant vectors as the mode of treatment delivery. PEDF's therapeutic potential against different diseases and the discovery of its receptors open possibilities for improving PEDF-based peptide design and drug delivery modes.
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PMID:Pigment epithelium-derived factor as an anticancer drug and new treatment methods following the discovery of its receptors: a patent perspective. 2120 26

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In advanced AMD, new vessels from choriocapillaris (CC) invade through the Bruch's membrane (BrM) into the retina, forming choroidal neovascularization (CNV). BrM, an elastic lamina that is located between the retinal pigment epithelium (RPE) and CC, is thought to act as a physical and functional barrier against CNV. The BrM of patients with early AMD are characterized by decreased levels of antiangiogenic factors, including endostatin, thrombospondin-1 (TSP-1), and pigment epithelium-derived factor (PEDF), as well as by degeneration of the elastic layer. Motivated by a previous report that heat increases elastin expression in human skin, we examined the effect of heat on human ARPE-19 cell production of BrM components. Heat treatment stimulated the production of BrM components, including TSP-1, PEDF, and tropoelastin in vitro and increased the antiangiogenic activity of RPE measured in a mouse corneal pocket assay. The effect of heat on experimental CNV was investigated by pretreating the retina with heat via infrared diode laser prior to the induction of CNV. Heat treatment blocked the development of experimental CNV in vivo. These findings suggest that heat treatment may restore BrM integrity and barrier function against new vessel growth.
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PMID:Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity. 2206 81


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