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

Neovascularization is increasingly recognized as an important factor in the pathogenesis of hematologic malignancies as well as solid tumors. The complex interactions between several cell types and numerous cytokine mediators suggest the involvement of autocrine and paracrine signaling mechanisms. Vascular endothelial growth factor (VEGF) in particular is critical to both stimulation of leukemic growth and proliferation of endothelial cells. Tyrosine kinase receptors specific for certain growth factors represent attractive target molecules for anticancer therapy. SU5416 is a competitive inhibitor of VEGF receptor subtypes VEGFR-1 and VEGFR-2 and stem cell factor receptor c-kit. Preclinical evidence shows that SU5416 effectively inhibits VEGF-induced endothelial cell proliferation and slows growth of subcutaneous solid tumor xenografts. This agent is in late-stage clinical trials in patients with solid tumors, and a Phase 2 study was recently initiated to evaluate its utility in the treatment of acute myeloid leukemia. In this Phase 2 study, investigators are seeking to determine the response rate to the antiangiogenic agent SU5416. Translational research in this study is intended to aid our understanding of the precise mechanisms by which SU5416 affects acute myeloid leukemia cells and the bone marrow microenvironment.
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PMID:Role of angiogenesis inhibitors in acute myeloid leukemia. 1177 83

Antiangiogenic gene therapy offers an attractive approach to the treatment of a variety of malignancies, including those of the hematological system. However, evaluation of this approach has been hampered by the lack of appropriate animal models. We have recently produced transgenic mice expressing P230 bcr/abl that develop myeloproliferative disease (MPD) closely resembling human chronic myelogenous leukemia. Using this MPD murine model, we examined the feasibility of systemic antiangiogenic gene therapy for hematological malignancy. An adenoviral vector containing the secretable endostatin gene was injected into the right quadriceps muscle of the MPD mice. The increased endostatin level was detected for at least 6 months. Hematological parameters including platelet counts, granulocyte counts, and the hemoglobin concentration were improved by this gene therapy. Infiltration of megakaryocytes was also significantly inhibited in treated MPD mice. Reduction of the microvessel density was confirmed by histological examination. These results demonstrated, for the first time, that antiangiogenic gene therapy is effective to inhibit leukemogenesis caused by expression of the chimeric bcr/abl gene.
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PMID:Antiangiogenic gene therapy of myeloproliferative disease developed in transgenic mice expressing P230 bcr/abl. 1561 2