Evaluation of Osteogenic Potentials of Avian Demineralized Bone Matrix in the Healing of Osseous Defects in Pigeons.

OBJECTIVES: To evaluate avian allogeneic demineralized bone matrix (DBM) in the healing of long bone defects as a function of geometry and time in a pigeon model. STUDY DESIGN: Experimental. ANIMALS: Adult rock pigeons (n = 60). METHODS: Midshaft ulnar osseous defects were grafted with 2 geometric forms of DBM (tubular vs. chipped) and stabilized with a hybrid fixator. Autologous chips of sternal keel were used in a third group as control. Outcomes were evaluated by radiography and histology/histomorphometry at 4, 8, 12, and 24 weeks postoperatively. RESULTS: Despite an early rapid healing response, autografts plateaued (histologic score and new bone area) by 8 weeks with no significant improvement afterwards. Conversely, allogeneic DBM implants demonstrated continuous temporal improvement in bone healing, and tubular DBM finally outpaced autograft implants after week 12 with values for metrics achieving statistical significance by week 24. Chip DBM was inferior to tubular DBM and autograft. CONCLUSIONS: Avian DBM is osteogenic, biocompatible, and safe in orthotopic sites with potential usefulness in avian bone grafting. Implant geometry (shape and size) affects such osteogenic potentials.

MLH1 expression sensitises ovarian cancer cells to cell death mediated by XIAP inhibition.

BACKGROUND: The X-linked inhibitor of apoptosis protein (XIAP), an endogenous apoptosis suppressor, can determine the level of caspase accumulation and the resultant response to apoptosis-inducing agents such as cisplatin in epithelial ovarian cancer (EOC). In addition, the mismatch repair protein, hMLH1, has been linked to DNA damage-induced apoptosis by cisplatin by both p53-dependent and -independent mechanisms. METHODS: In this study, hMLH1 expression was correlated with clinical response to platinum drugs and survival in advanced stage (III-IV) EOC patients. We then investigated whether MLH1 loss was a determinant in anti-apoptosis response to cisplatin mediated by XIAP in isogenic and established EOC cell lines with differential p53 status. RESULTS: The percentage of cells undergoing cisplatin-induced cell killing was higher in MLH1-proficient cells than in MLH1-defective cells. In addition, the presence of wild-type hMLH1 or hMLH1 re-expression significantly increased sensitivity to 6-thioguanine, a MMR-dependent agent. Cell-death response to 6-thioguanine and cisplatin was associated with significant proteolysis of MLH1, with XIAP destabilisation and increased caspase-3 activity. The siRNA-mediated inhibition of XIAP increased MLH1 proteolysis and cell death in MLH1-proficient cells but not in MLH1-defective cells. CONCLUSION: These data suggest that XIAP inhibitors may prove to be an effective means of sensitising EOC to MLH1-dependent apoptosis.