angiogenin and Bone-Neoplasms

It is proven that angiogenesis and cartilage resorption processes involving vascular endothelial growth factor (VEGF) and its receptors play an important role in bone tissue regeneration and bone tumor development. A comparative analysis of VEGE VEGF-R1, VEGF-R2 and angiogenin content in blood serum of healthy persons, and patients with primary malignant, benign and borderline bone tumors was performed. 366 bone tumor patients aged 14-76 years were examined; 223 (60,9%) male and 143 (39,1%) -female. Control group included 48 practically healthy subjects aged 15-69 years; 25 (52,1%) male and 23 (47,9%) female. Serum VEGE VEGF-R1, VEGF-R2 and angiogenin concentrations measured using standard ELISA kits produced by "R&D Systems Inc. ", USA. It was shown that long-term treatment outcome (3-years overall survival) of typical osteosarcoma patients depended on tumor malignancy grade (determined by the criterion G). Baseline serum VEGF, its soluble receptors and angiogenin concentrations had no predictive value.

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Case-Control Studies; Female; Humans; Male; Middle Aged; Osteosarcoma; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

Angiogenin (ANG) is a secreted ribonuclease that cleaves tRNA to initiate a stress-response program in mammalian cells. Here we show that ANG inhibits protein synthesis and promotes arsenite- and pateamine A-induced assembly of stress granules (SGs). These effects are abrogated in cells transfected with the ANG inhibitor RNH1. Transfection of natural or synthetic 5'- but not 3'-tRNA fragments (tRNA-derived stress-induced RNAs; tiRNAs) induces the phospho-eukaryotic translation initiation factor 2alpha-independent assembly of SGs. Natural 5'-tiRNAs but not 3'-tiRNAs are capped with a 5'-monophosphate that is required for optimal SG assembly. These findings reveal that SG assembly is a component of the ANG- and tiRNA-induced stress response program.

Topics: Arsenites; Blotting, Western; Bone Neoplasms; Carrier Proteins; Cells, Cultured; Cytoplasmic Granules; Enzyme Inhibitors; Epoxy Compounds; Eukaryotic Initiation Factor-2; Fluorescent Antibody Technique; Humans; Macrolides; Osteosarcoma; Oxidative Stress; Phosphorylation; Protein Biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease, Pancreatic; RNA, Messenger; RNA, Small Interfering; RNA, Transfer; Teratogens; Thiazoles; Tumor Cells, Cultured

The concentrations of vascular endothelium growth factor and angiogenin were measured by enzyme immunoassay in the sera of healthy subjects and patients with osteosarcoma and Ewing's tumor with consideration for the main clinical and morphological characteristics of the diseases. The studied angiogenic factors were characterized by high individual variability in both healthy subjects and age- and sex-matched patients with primary bone sarcomas. The level of endothelial growth factor was higher in control women than in men. The highest concentration of endothelial growth factor was detected in male patients with Ewing's tumor. Possible involvement of vascular endothelium growth factor and angiogenin in the pathogenesis of osteosarcoma and Ewing's tumor is discussed.

Topics: Adolescent; Adult; Bone Neoplasms; Case-Control Studies; Endothelial Growth Factors; Female; Humans; Lymphokines; Male; Osteosarcoma; Ribonuclease, Pancreatic; Sarcoma, Ewing; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors