Project: SARCOMBAT - Cellular and molecular responses induced by combined application of differentiating and antiangiogenic agents in sarcoma cell lines
Person in Charge: Doc. RNDr. Renáta Veselská, PhD., M.Sc
Country of Origin: Slovakia
Country of scientific activity: Germany
Project duration: 24 months
Scientific panel: Life sciences
The main aim of the project is in vitro study of the possibilities to modulate antineoplastic effect of all-trans retinoic acid (ATRA) by combined application of inhibitors of 5-lipoxygenase (LOX) and cyclooxygenase-2 (COX) or of dihydroxyvitamin D3 on sarcoma cell lines. These compounds are used in pediatric oncology as a part of COMBAT metronomic protocol (= combined oral maintenance biodifferentiating and antiangiogenic therapy in patients with relapsed solid tumors. Related in vitro study on cell lines derived from neurogenic tumors demonstrated a synergic effect of combined application of ATRA and LOX/COX inhibitors. The proposed project should continue this research on other type of high-risk solid tumors in children – on sarcomas. Established osteosarcoma and rhabdomyosarcoma cell lines previously derived in the host Laboratory of Tumor Biology and Genetics should be used for this study. The effect of combined application of ATRA and LOX/COX inhibitors or dihydroxyvitamin D3 will be evaluated on both cellular level (differences in the proliferation, migration, cell cycle and apoptosis) and molecular level (changes in gene expression). A special attention should be paid to the intracellular metabolism of ATRA; these changes should be assessed indirectly by detection of the cellular retinoic acid binding proteins (CRABPs).