Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to act specifically on the proliferating endothelial cell compartment of the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but may also provide an important therapeutic strategy for the treatment of cancer and other angiogenesis dependent diseases, including diabetic retinopathy and chronic inflammations. Systemic administration of these angiogenesis inhibitors in animals significantly suppresses the growth of a variety of tumors and their metastases. However, their production as functional recombinant proteins has been proven to be difficult. In addition, high dosages of these inhibitors are required to suppress tumor growth in animal studies. Other disadvantages of the antiangiogenic protein therapy include repeated injections, prolonged treatment, transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative strategies need to be developed in order to improve the clinical settings of antiangiogenic therapy. Developments of these strategies are ongoing and they include identification of more potent inhibitors, antiangiogenic gene therapy, improvement of protein/compound half-lives in the circulation, increase of their concentrations at the disease location, and combinatorial therapies with approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the above-mentioned disadvantages, a few inhibitors have entered into the early stages of clinical trials and they may bring new hopes for the treatment of cancer and other angiogenesis dependent diseases.
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PMID:Endogenous angiogenesis inhibitors and their therapeutic implications. 1131 6

Angiogenesis is critical for several physiologic and pathophysiologic processes, and several angiogenesis inhibitors are now in clinical trials for the treatment of cancer. Antithrombin is a member of the serpin family of proteins and functions as an inhibitor of thrombin and other enzymes involved in the clotting cascade. While studying the inhibition of tumor growth by tumor mass in a human small cell lung cancer model, we discovered that the cleaved conformation of antithrombin has potent antiangiogenic and antitumor activity. The stable locked and latent forms of intact antithrombin, which are substantially similar in conformation to the cleaved form of the molecule, also inhibit angiogenesis and tumor growth in vivo and act selectively upon endothelial cells and the tumor vasculature. The intact native molecule does not have this effect. The discovery of antiangiogenic antithrombin provides further evidence that the clotting and fibrinolytic pathways are directly related to the regulation of angiogenesis. As for other endogenous angiogenesis inhibitors, the precise mechanism of action for antiangiogenic antithrombin has not been defined, but several studies now suggest that it may target the endothelial cell at multiple levels resulting in a profound blockade of the angiogenic cascade. In this paper, an overview of the angiogenesis inhibitor antiangiogenic antithrombin and a summary of the pertinent literature are provided.
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PMID:Antiangiogenic antithrombin. 1800 Jul 92