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Editorial [Hot Topic: Angiogenesis Agents (Executive Editor: Cezary Marcinkiewicz)]

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Angiogenesis, a process of growing new vasculature from pre-existing vessels, is a phenomenon that is the focus of investigation of many laboratories. The pharmacological research targeting this process is related into two aspects, inhibition of pathological angiogenesis such as in cancer development, and therapeutic angiogenesis promoting a vessel growth during several cardiovascular disorders. Highly advance studies are performed on the angiostatic drugs, which target a variety of factors and biological molecules involved in the progression of neovascularization. Structurally, these pharmaceuticals are humanized monoclonal antibodies, short synthetic or recombinant peptides or peptidomimetics and biologically active chemical molecules. Many of these compounds have been isolated from natural sources. The most effective as angiostatic targets are pro-angiogenic growth factors (e.g. VEGF, FGF), receptors present on the surface of endothelial cells (e.g. integrins, growth factors receptors), and intracellular signaling molecules regulating the survival/death cell process (e.g. PKC-β, HIF-1). This issue of journal presents review articles showing the recent progress in development of anti-angiogenic therapy in cancer treatment as well as perspectives in the application of new targets for this therapy. Other papers will overview the application of biopolymers in tissue repair and stimulation of angiogenesis in this process.

In the first paper [1] the authors overview the current stage of investigation of anti-angiogenic agents in therapy of malignant glioma. This brain tumor is considered as the most vascularized and extremely difficult to treat, because of the limited penetration of pathological tissue by oncostatic drugs. This phenomenon is related to the tight junction of the brain blood barrier, which makes designing an effective pharmaceutical for this tumor a big challenge. The promising clinical trials showed the application of anti-angiogenic therapy in combination with chemo- or radio-therapy. The angiostatic agents are usually well tolerated by the patients and further development of these drugs has good pharmaceutical perspectives.

The next review by Silverstein and Febbraio [2] is devoted to the summary of current knowledge about the importance of thrombospondin in angiogenesis in the context of its interaction with e CD36, a cell membrane anchored receptor expressed on endothelial cells. The authors discuss the mechanisms occurring in endothelial cells following the binding of thrombospondin to CD36, that lead to the blocking of cells proliferation. The regulatory effect on angiogenesis in this system is complemented by the circulating histidine-rich glycoprotein (HRGP), which contains the CD36 homology domain. HRGP, by binding to thrombospondin, blocks its anti-angiogenic activities and in consequence promotes angiogenesis. This is a very interesting system for controlling angiogenesis. Its elements may be targeted for the modulation of pathological vascularization process or therapeutic angiogenesis.

The role of annexin II in angiogenesis is discussed in the paper by Sharma and Sharma [3]. This is a multifunctional molecule appearing on the endothelial cell surface and on a variety of other cell types including cancer. It is receptors for plasminogen and tissue and urokinase plasminogen activators, tPA and uPA, respectively. Interestingly, annexin II also binds angiostatin, a fragment of plasminogen, which was characterized as a potent inhibitor of angiogenesis. Moreover, annexin II participates in the conversion of plasminogen to plasmin. This enzyme increases neovascularization and tumoral cells invasion processes by the degradation of extracellular matrix. Therefore annexin II appears to be an interesting pharmaceutical target for the protection of tissues against pathological angiogenesis. The review paper presented by Thijssen and his colleagues [4] summarizes the approaches for selective identification of target molecules on pathological endothelial cells that are activated during the progression of tumor or other angiogenesis-related disorders such as certain inflammatory diseases.....
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Document Type: Research Article

Affiliations: Temple University, School of Medicine Department of Neuroscience Center for Neurovirology 1900 N.12th Street Philadelphia, PA 19122 USA.

Publication date: December 1, 2007

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  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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