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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of tumor angiogenesis is a promising therapeutic approach to treat cancer; translation of this concept into clinical practice requires an understanding of the molecular events that are responsible for the development of tumor vasculature. Renal cell carcinoma is characterized by the frequent loss of the von Hippel-Lindau tumor suppressor gene which results in the loss of one of the critical mechanisms for regulating the level of hypoxia inducible factor 1 and leads to the overproduction of vascular endothelial growth factor (VEGF) by the tumor cell. Therapeutic strategies to inhibit the function of these important pathways have been effective in preventing tumor angiogenesis in preclinical models of kidney cancer, and more recently, in the clinical setting. Strategies to treat renal cell carcinoma with agents that are designed to prevent angiogenesis have included interruption of the VEGF signaling pathway, mimics of endogenous angiogenesis inhibitors, prevention of destruction of the basement membrane, and direct inhibition of endothelial cells by a variety of agents with complex, novel, or undetermined mechanisms. Recent clinical studies of bevacizumab, the first anti-VEGF agent to be marketed for the treatment of cancer, have provided proof for the concept that these strategies can lead to tangible benefits for patients who have advanced renal cell carcinoma and likely will be applicable broadly to the treatment of cancer.
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PMID:Renal cell carcinoma: rationale and development of therapeutic inhibitors of angiogenesis. 1547 39

Angiopoietins have been implicated in playing an important role in blood vessel formation, remodeling, maturation, and maintenance. However, the role of angiopoietins in tumor angiogenesis remains uncertain. In this study, expression of human angiopoietin-1 (hAng-1) and angiopoietin (hAng-2) was amplified in the rat glioma cell line GS9L by stable transfection using an inducible tet-off system. Transfected cells were implanted intracerebrally into syngenic Fischer 344 rats. We demonstrated by means of magnetic resonance imaging that increased hAng-1 expression promoted a significant in vivo growth of intracerebral gliomas in rats. Overexpression of hAng-1 resulted in more numerous, more highly branched vessels, which were covered by pericytes. On the other hand, tumors derived from hAng-2-overexpressing cells were smaller than empty-plasmid control tumors. The tumor vasculature in these tumors was composed of aberrant small vascular cords, which were associated with few mural cells. Our results indicate that in the presence of hAng-1, tumors induce a more functional vascular network, which led to better tumor perfusion and growth. On the other hand, overexpression of hAng-2 led to less intact tumor vessels, inhibited capillary sprouting, and impaired tumor growth.
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PMID:Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. 1550 26

The molecular signature that defines tumor microvasculature will likely provide clues as to how vascular-dependent tumor proliferation is regulated. Using purified endothelial cells, we generated a database of gene expression changes accompanying vascular proliferation in invasive breast cancer. In contrast to normal mammary vasculature, invasive breast cancer vasculature expresses extracellular matrix and surface proteins characteristic of proliferating and migrating endothelial cells. We define and validate the up-regulated expression of VE-cadherin and osteonectin in breast tumor vasculature. In contrast to other tumor types, invasive breast cancer vasculature induced a high expression level of specific transcription factors, including SNAIL1 and HEYL, that may drive gene expression changes necessary for breast tumor neovascularization. We demonstrate the expression of HEYL in tumor endothelial cells and additionally establish the ability of HEYL to both induce proliferation and attenuate programmed cell death of primary endothelial cells in vitro. We also establish that an additional intracellular protein and previously defined metastasis-associated gene, PRL3, appears to be expressed predominately in the vasculature of invasive breast cancers and is able to enhance the migration of endothelial cells in vitro. Together, our results provide unique insights into vascular regulation in breast tumors and suggest specific roles for genes in driving tumor angiogenesis.
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PMID:Alterations in vascular gene expression in invasive breast carcinoma. 1552 Jan 92

Eph receptors are a unique family of receptor tyrosine kinases (RTK) that play critical roles in embryonic patterning, neuronal targeting, and vascular development during embryogenesis. In adults, Eph RTKs and their ligands, the ephrins, are frequently overexpressed in a variety of cancers and tumor cell lines, including breast, prostate, non-small cell lung and colon cancers, melanomas, and neuroblastomas. Unlike traditional oncogenes that often function only in tumor cells, recent data show that Eph receptors mediate cell-cell interaction both in tumor cells and in tumor microenvironment, namely the tumor stroma and tumor vasculature. As such, Eph RTKs represent attractive potential targets for drug design, as targeting these molecules could attack several aspects of tumor progression simultaneously. This review will focus on recent advances in dissecting the role of Eph RTKs in tumor cells, tumor angiogenesis, and possible contribution to trafficking of inflammatory cells in cancer.
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PMID:Eph receptor tyrosine kinases in tumor and tumor microenvironment. 1554 26

Many novel antiangiogenic agents are currently in various phases of clinical testing. These agents tend to be cytostatic, and therefore few responses are observed with conventional imaging by computerized tomography. Furthermore, toxicity with these agents is seen when the maximum-tolerated dose is combined with chemotherapy. Hence, there is a need to develop imaging strategies that can determine the minimum and optimum biologically active doses. There is increasing awareness of the need to obtain evidence of drug activity through the use of surrogate markers of the biologic mechanism of action during early clinical trials, in addition to determining the pharmacokinetics, toxicity profile, and maximum-tolerated dose. One of the major impediments to the rapid development of antiangiogenic agents in the past has been the lack of validated assays capable of measuring an antiangiogenic effect directly in patients. Recently, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has emerged as a useful technique for noninvasive imaging of tumor vasculature in preclinical and clinical models. The problem of tumor heterogeneity remains to be addressed. The major challenge is the standardization of the technique worldwide for the purpose of early clinical studies that are likely to be multicenter. Convincing data on correlations between changes observed through molecular imaging and changes in tumor angiogenesis, and hence tumor biology, are still lacking. Whether this would translate into a survival advantage remains to be seen. The ultimate test of the surrogate biological end points determined by molecular imaging will occur in randomized phase III trials. Results of the first randomized trial that showed a survival advantage in favor of antiangiogenic agents were released at the American Society of Clinical Oncology meeting in 2003. There it was reported that the combination of 5-fluorouracil, leucovorin, and irinotecan (Camptosar; Pfizer Pharmaceuticals; New York, NY) with anti-vascular endothelial growth factor antibody (bevacizumab-Avastin; Genentech, Inc.; South San Francisco, CA) was superior to the chemotherapy regimen alone when used to treat patients with metastatic colorectal cancer. However, until further phase III clinical trials confirm these results, surrogate end points of clinical efficacy of the newer agents are urgently needed so that development of ineffective drugs can be halted early. This review briefly discusses the role of molecular imaging in general, and DCE-MRI in particular, in relation to treatment with antiangiogenic agents and highlights some of the difficulties encountered in this area.
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PMID:Molecular imaging of antiangiogenic agents. 1570 11

Angiogenesis, the formation of new blood vessels, is essential for tumor growth, progression and metastasis. The development of agents that target tumor vasculature is ultimately dependent on the availability of appropriate preclinical screening assays. The chorioallantoic membrane (CAM) assay is well established and widely used as a model to examine angiogenesis, and anti-angiogenesis. This review 1) summarizes the currently used angiogenesis assays and the importance of CAM model among them; 2) summarizes the current knowledge about the development and structure of the CAM's capillary bed; 3) reports findings regarding the role played by molecular signaling pathways in angiogenesis process; 4) discusses the use, advantages and limitations of the CAM as a model for studying tumor angiogenesis and invasiveness, as well as development of angiogenic and/or anti-angiogenic agents; 5) discusses the importance of standardization of the major methodologies for all aspects of the use of the CAM in angiogenesis-related studies; 6) and finally, summarizes major findings regarding the agents developed by the use of CAM model in the study of tumor angiogenesis, invasion and development of anti-angiogenic agents.
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PMID:The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents. 1597 46

While significant progress has been made in understanding the induction of tumor vasculature by secreted angiogenic factors, little is known regarding contact-dependent signals that promote tumor angiogenesis. Here, we report that the Notch ligand Jagged1 induced by growth factors via mitogen-activating protein kinase (MAPK) in head and neck squamous cell carcinoma (HNSCC) cells triggered Notch activation in neighboring endothelial cells (ECs) and promoted capillary-like sprout formation. Jagged1-expressing HNSCC cells significantly enhanced neovascularization and tumor growth in vivo. Moreover, the level of Jagged1 was significantly correlated with tumor blood vessel content and associated with HNSCC development. Our results elucidate a novel mechanism by which the direct interplay between tumor cells and ECs promotes angiogenesis through MAPK and Notch signaling pathways.
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PMID:Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. 1602 95

We previously reported that during mouse embryogenesis, plexin D1 (plxnD1) is expressed on neuronal and endothelial cells. Endothelial cells gradually loose plxnD1 expression during development. Here we describe, using in situ hybridization, that endothelial plxnD1 expression is regained during tumor angiogenesis in a mouse model of brain metastasis. Importantly, we found PLXND1 expression also in a number of human brain tumors, both of primary and metastatic origin. Apart from the tumor vasculature, abundant expression was also found on tumor cells. Via panning of a phage display library, we isolated two phages that carry single-domain antibodies with specific affinity towards a PLXND1-specific peptide. Immunohistochemistry with these single-domain antibodies on the same tumors that were used for in situ hybridization confirmed PLXND1 expression on the protein level. Furthermore, both these phages and the derived antibodies specifically homed to vessels in brain lesions of angiogenic melanoma in mice after i.v. injection. These results show that PLXND1 is a clinically relevant marker of tumor vasculature that can be targeted via i.v. injections.
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PMID:Plexin D1 expression is induced on tumor vasculature and tumor cells: a novel target for diagnosis and therapy? 1616 8

The last decade has seen enormous progress in understanding the development of cancer. It is now recognized that tumor growth is a multistep process that may take years to become clinically relevant. Angiogenesis is an absolute requirement for tumors to become clinically detectable. The importance of angiogenesis for tumor growth is supported by several clinical studies that showed a positive correlation between tumor angiogenesis and tumor stage. In animal studies, inhibition of angiogenesis caused impressive reduction of tumor growth. The aim of antivascular therapy in the treatment of cancer is to attack the tumor through its vasculature. Antivascular therapy can be divided in two different areas: (1) inhibition of angiogenesis with the aim to prevent formation of new blood vessels and (2) vascular targeting agents with the goal to destroy the existing tumor vasculature. Vascular endothelial growth factor (VEGF) has been recognized as one of the most important factors involved in tumor angiogenesis and has become an important target for anticancer treatment. This review focuses mainly on the inhibition of angiogenesis in gastrointestinal tumors by blocking the VEGF receptor/ligand signaling. We will discuss the biology of the VEGF receptor/ligand signaling system and give an overview of the current approaches for therapy in gastrointestinal cancer targeting the VEGF signaling pathway.
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PMID:VEGF as a target of therapy in gastrointestinal oncology. 1617 85

Angiogenesis is a very important process for tumor growth and proliferation. Given its high temporal and spatial resolution, magnetic resonance (MR) imaging is well suited for use in the assessment of angiogenesis. MR angiography can be used clinically and experimentally for identification of tumor feeding and draining vessels, for tumor characterization, and for treatment planning. The morphologic structure of tumor vessels can be investigated in relation to tumor vessel permeability with use of specific contrast agents. To gain insight into tumor angiogenesis in vivo, the authors compared images obtained with digital photography, high-resolution MR angiography, and intravital microscopy through a dorsal skin-fold window in a rodent model. The close correlation between images obtained with these various modalities, with regard to the depiction of the developing tumor vasculature, indicates that noninvasive quantification of angiogenesis may be possible with MR imaging. Future directions in tumor imaging may include so-called four-dimensional MR angiography, in which high-resolution three-dimensional MR angiography is combined with dynamic contrast-enhanced MR imaging.
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PMID:MR angiography of tumor-related vasculature: from the clinic to the micro-environment. 1622 99


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