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)

In recent decades, radiation research has concentrated primarily on the cancer cell compartment. Much less is known about the effect of ionizing radiation on the endothelial cell compartment and the complex interaction between tumor cells and their microenvironment. Here we report that ionizing radiation is a potent antiangiogenic agent that inhibits endothelial cell survival, proliferation, tube formation and invasion. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor were able to reduce the radiosensitivity of endothelial cells. Yet, it is also found that radiation induces angiogenic factor production by tumor cells that can be abrogated by the addition of antiangiogenic agents. Receptor tyrosine kinase inhibitors of Flk-1/KDR/VEGFR2, FGFR1 and PDGFR beta, SU5416, and SU6668 enhanced the antiangiogenic effects of direct radiation of the endothelial cells. In a coculture system of PC3 prostate cancer cells and endothelial cells, isolated irradiation of the PC3 cells enhanced endothelial cell invasiveness through a Matrigel matrix, which was inhibited by SU5416 and SU6668. Furthermore, ionizing radiation up-regulated VEGF and basic fibroblast growth factor in PC3 cells and VEGFR2 in endothelial cells. Together these findings suggest a radiation-inducible protective role for tumor cells in the support of their associated vasculature that may be down-regulated by coadministration of angiogenesis inhibitors. These results rationalize concurrent administration of angiogenesis inhibitors and radiotherapy in cancer treatment.
 ...
PMID:SU5416 and SU6668 attenuate the angiogenic effects of radiation-induced tumor cell growth factor production and amplify the direct anti-endothelial action of radiation in vitro. 1283 71

PURPOSE OF THE STUDY Although the congenital short femur is morphologically well characterized, changes at the molecular level have not been described in the literature so far. The absence of such information, along with the unknown aetiology of the defect, was the motivation for analysing angiogenesis and osteogenesis in the pseudoarthrosis (false joint) tissue in PFFD patients compared to physiological bone. The authors expected differences in gene expression, particularly in the quantity of expressed genes. MATERIAL AND METHODS A piece of bone was removed during an elective surgery procedure, placed in an RNA stabilization reagent, which prevents RNA degradation, and deep frozen. Thereafter, RNA was isolated and the profile of transcription was analysed by biochip analysis (SuperArray Bioscience Corporation). In total, it is possible to detect 113 genes of osteogenesis and angiogenesis. From the end of 2005 until the end of 2008, samples of 7 patients with PFFD and 3 physiological bone samples were examined. Several analyses were repeated to confirm the results; in total 13 chips for osteogenesis and 11 chips for angiogenesis expression were used. RESULTS Differences in the quantity and representation of the genes were noted. Some genes were considered over-expressed in PFFD tissue compared with the control sample (e.g. the gene for calcitonin receptor, collagen XII, I alpha 2, collagen II, IX, FGFR2, fibronectin, integrin) and other genes under-expressed (e.g. the gene for annexin A5, collagen XVIII alpha1, collagen I alpha1, cathepsin K, FGFR1, FGFR3, IGF2, VEGFB). CONCLUSIONS The differences in gene expression confirmed the authors' hypothesis. So far, the results cannot be generalized; this is the first step for follow-up experiments to confirm the suggested information and to integrate it with clinical findings, such as the alternative blood supply of affected extremity in some patients. Key words: proximal femoral focal deficiency, gene expression, microarray analysis, angiogenesis, osteogenesis.
 ...
PMID:Analysis of Gene Expression of Pseudoarthrosis Tissue in Congenital Short Femur, Initial Study and First Exprerience. 3314 99