Purpose: Osteosarcoma and Ewing's sarcoma are high-grade neoplasms typically arising in the bones of children and adolescents. Despite improvement in therapy, the five-year survival rate is only 20% for patients not responding to treatment or presenting with metastases. Among new therapeutic strategies, the efficacy of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily with strong antitumoral activity and minimal toxicity to most normal cells and tissues, was investigated by complementary approaches both in vitro and in preclinical models.Experimental design: The sensitivity of osteosarcoma and Ewing's sarcoma cell lines to TRAIL was investigated in vitro by determining TRAIL receptor expression together with TRAIL effects on cell viability and apoptosis. Complementary preclinical studies were carried out in respective tumor models by inoculation of osteosarcoma or Ewing's sarcoma tumor cells in paraosseous location. In addition, a model of lung nodule dissemination was developed by i.v. injection of osteosarcoma cells.Results: In vitro, both osteosarcoma and Ewing's sarcoma cells that express the TRAIL death receptors were highly sensitive to TRAIL-induced caspase-8-mediated apoptosis. TRAIL administered in vivo by nonviral gene therapy inhibited primary bone tumor incidence and growth by 87% and prevented tumorinduced osteolysis, leading to a significant 2-fold increase in animal survival 40 days after tumor induction. Furthermore, TRAIL inhibited tumor nodule dissemination in lungs and increased survival in an osteosarcoma model.Conclusion: These findings suggest that TRAIL is a promising candidate for the development of new therapeutic strategies in the most frequent malignant primary bone tumors.

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Using the lateral malleolus as the cutaneous reference for the distal insertion of the CFL seems to be more reliable than the pure arthroscopic technique. This study describes a percutaneous technique to obtain a calcaneal tunnel for distal insertion of the CFL. The sural nerve is at the greatest risk of injury with this technique and requires careful subcutaneous incision to prevent injury. This new percutaneous technique is less invasive than a purely arthroscopic technique and more accurately identifies the location of the tunnel. It can be used to do calcaneal tunnel in clinical practice during anatomic ligament reconstruction for chronic ankle instability.

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