Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiogenesis, the formation of new capillaries, is critical for normal physiological processes such as embryonic development and wound repair. However, it also facilitates pathological processes including tumor growth, metastases, proliferative diabetic retinopathy and pannus formation in rheumatoid arthritis. It has been described that the angiogenesis occurs through a series of events that include endothelial cell protease production, migration and proliferation, tubule formation, and basement membrane incorporation. Within the last two decades, with in vivo assay systems, various kinds of growth factors were identified as angiogenic factors that promote endothelial cell proliferation and migration, while an in vitro model for angiogenesis indicated that extracellular matrix (ECM) proteins stimulated endothelial cells to organize into a capillary-like tubular network and suggested that the ECM proteins are involved in the tubule formation process of antiogenesis. Recent papers reported the identification of the specific receptors on endothelial cells involved in the ECM-induced capillary tube formation. This article will focus on papers describing the in vitro analyses of tube formation of endothelial cells.
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PMID:[Extracellular matrix components and angiogenesis]. 872 88

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis associated with tumors and other pathological conditions, including proliferative diabetic retinopathy and age-related macular degeneration. The murine anti-human VEGF monoclonal antibody (muMAb VEGF) A.4.6.1 has been shown to potently suppress angiogenesis and growth in a variety of human tumor cells lines transplanted in nude mice and also to inhibit neovascularization in a primate model of ischemic retinal disease. In this report, we describe the humanization of muMAb VEGF A.4.6.1. by site-directed mutagenesis of a human framework. Not only the residues involved in the six complementarity-determining regions but also several framework residues were changed from human to murine. Humanized anti-VEGF F(ab) and IgG1 variants bind VEGF with affinity very similar to that of the original murine antibody. Furthermore, recombinant humanized MAb VEGF inhibits VEGF-induced proliferation of endothelial cells in vitro and tumor growth in vivo with potency and efficacy very similar to those of muMAb VEGF A.4.6.1. Therefore, recombinant humanized MAb VEGF is suitable to test the hypothesis that inhibition of VEGF-induced angiogenesis is a valid strategy for the treatment of solid tumors and other disorders in humans.
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PMID:Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. 2758 49

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. In this study, we have investigated both the in vitro and in vivo growth characteristics of human malignant melanoma G361 cell lines, stably transfected to overexpress human PEDF. Expression levels of PEDF proteins in melanoma cell lines G361 and A375 were comparable with that of human cultured melanocytes, whereas vascular endothelial growth factor levels in two tumor cell lines were much stronger than that in normal melanocytes. Overexpression of PEDF was found to significantly inhibit tumor growth and vessel formation in G361 nude mice xenografts. Furthermore, in vitro proliferation rates of G361 cells were decreased in PEDF-transfected cells. PEDF proteins showed dose-dependent induced growth retardation and apoptotic cell death in nontransfected G361 cells, which were completely prevented by treatment with antibodies against the Fas ligand. Our present study highlights two beneficial effects of PEDF treatment on melanoma growth and expansion; one is the suppression of tumor angiogenesis, and the other is induction of Fas ligand-dependent apoptosis in tumor cells. PEDF therefore might be a promising novel therapeutic agent for treatment of patients with melanoma.
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PMID:Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. 1503 11

Pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that loss of PEDF is involved in angiogenic eye diseases such as proliferative diabetic retinopathy. Angiogenesis is required for tumor growth and progression as well. We, along with others, have recently found that PEDF could inhibit growth of melanoma and hepatocellular carcinoma in nude mice through its anti-angiogenic effects on tumor endothelial cells. However, the possibility of the direct effect of PEDF on tumor cells has remained. In this study, we investigated the effects of PEDF on growth and vascular endothelial growth factor (VEGF) expression in MG63 human cultured osteosarcoma cells. PEDF decreased viable cell number as well as DNA synthesis in MG63 cells in a dose-dependent manner. Furthermore, PEDF was found to increase caspase-3/7 activity and to subsequently induce apoptotic cell death in MG63 cells. PEDF also inhibited VEGF expression in MG63 cells at both mRNA and protein levels. Our present study provides novel beneficial aspects of PEDF on osteosarcoma cells; one is induction of apoptotic cell death of tumor cells, and the other is the suppression of VEGF expression, which would lead to inhibition of tumor angiogenesis. PEDF therefore might be a promising therapeutic agent for treatment of patients with osteosarcoma.
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PMID:Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells. 1598 68

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. Melanoma is one of the most highly invasive and metastatic tumors. Malignant Melanoma is an increasingly common malignancy and also one the most invasive and metastatic tumors, and its mortality rates have been rapidly increasing above those of any other cancer in recent years. Surgical resection and systemic chemotherapy are the main therapeutic strategies for the treatment of malignant melanoma. However, these approaches are insufficiently effective and may be associated with significant adverse effects. Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade and metastasize. Tumor vessels are genetically stable, and less likely to accumulate mutations that allow them to develop drug resistance in a rapid manner. Therefore, targeting vasculatures that support tumor growth, rather than cancer cells, is currently considered the most promising approach to malignant melanoma therapy. Now, novel anti-angiogenic agents with tolerable side effects are actually desired for the treatment of patients with malignant melanoma. In this paper, we review the current understanding of anti-angiogenic therapy for malignant melanoma, especially focusing on PEDF, which was recently identified as the most potent endogenous inhibitor of angiogenesis in the mammalian eye.
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PMID:Pigment epithelium-derived factor prevents melanoma growth via angiogenesis inhibition. 1912 33

The growth of new capillaries from existing vessels (angiogenesis) is of fundamental importance in wound healing and in pathological situations such as proliferative diabetic retinopathy (1), rheumatoid arthritis (2), and tumor growth. Consequently, considerable interest in vascular cell biology has arisen in apparently disparate clinical and experimental fields. Held in common, however, is the hope that an understanding of the cellular and molecular mechanisms that regulate angiogenesis will lead to novel therapeutic agents and targets.
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PMID:Bovine retinal microvascular pericytes : isolation, propagation, and identification. 2134 Sep 25

The inflammatory cytokine, vascular endothelial growth factor (VEGF), plays a central role in human growth and development, and vascular maintenance. VEGF mediated angiogenesis is essential for tumor growth, as well as exudative age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity, all of which are characterized by abnormal neovascularization. Ischemia and inflammation also lead to VEGF-mediated breakdown of the blood-retinal barrier, which causes vision diminishing macular edema. To combat these effects, anti-VEGF drugs (antibodies, aptamers, and tyrosine kinase inhibitors) have been developed for both systemic and local (intraocular) use. The next drug to receive regulatory approval will probably be aflibercept (VEGF-Trap), a fusion protein with high VEGF affinity attributed to binding sequences from the native receptors VEGFR1 and VEGFR2. Aflibercept monotherapy significantly reduces tumor growth and extends survival in several orthotropic animal models, and has both prevented and reduced the growth of experimental choroidal neovascularization. Ongoing phase III trials are evaluating the effectiveness of aflibercept combined with chemotherapy in patients with advanced carcinomas. The phase III VELOUR trial determined that patients receiving aflibercept with irinotecan/5-FU as second line chemotherapy for metastatic colorectal cancer experienced extended progression free survival and overall survival. Intravitreal aflibercept improved visual acuity in patients with exudative age-related macular degeneration and was non-inferior to standard therapy (ranibizumab). Ongoing phase III trials are investigating the use of aflibercept for retinal vein occlusions and diabetic macular edema. A regulatory approval application for use in exudative macular degeneration has been filed, with a decision expected by late 2011.
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PMID:Aflibercept (VEGF-TRAP): the next anti-VEGF drug. 2199 77

Natural products are characterized by high chemical diversity and biochemical specificity; therefore, they are appealing as lead compounds for drug discovery. Given the importance of angiogenesis to many pathologies, numerous natural products have been explored as potential anti-angiogenic drugs. Ocular angiogenesis underlies blinding eye diseases such as retinopathy of prematurity (ROP) in children, proliferative diabetic retinopathy (DR) in adults of working age, and age-related macular degeneration (AMD) in the elderly. Despite the presence of effective therapy in many cases, these diseases are still a significant health burden. Anti-VEGF biologics are the standard of care, but may cause ocular or systemic side effects after intraocular administration and patients may be refractory. Many anti-angiogenic compounds inhibit tumor growth and metastasis alone or in combination therapy, but a more select subset of them has been tested in the context of ocular neovascular diseases. Here, we review the promise of natural products as anti-angiogenic agents, with a specific focus on retinal and choroidal neovascularization. The multifunctional curcumin and the chalcone isoliquiritigenin have demonstrated promising anti-angiogenic effects in mouse models of DR and choroidal neovascularization (CNV) respectively. The homoisoflavanone cremastranone and the flavonoid deguelin have been shown to inhibit ocular neovascularization in more than one disease model. The isoflavone genistein and the flavone apigenin on the other hand are showing potential in the prevention of retinal and choroidal angiogenesis with long-term administration. Many other products with anti-angiogenic potential in vitro such as the lactone withaferin A, the flavonol quercetin, and the stilbenoid combretastatin A4 are awaiting investigation in different ocular disease-relevant animal models. These natural products may serve as lead compounds for the design of more specific, efficacious, and affordable drugs with minimal side effects.
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PMID:Natural product inhibitors of ocular angiogenesis. 2530 18