Variants of Osteoprotegerin Lacking TRAIL Binding for Therapeutic Bone Remodeling in Osteolytic Malignancies Running title: Modified osteoprotegerin for osteolytic malignancies Key words: Osteoprotegerin, TRAIL, RANKL, osteoclast, bone
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Variants of Osteoprotegerin Lacking TRAIL Binding for Therapeutic Bone Remodeling in Osteolytic Malignancies.
UNLABELLED Osteolytic bone damage is a major cause of morbidity in several metastatic pathologies. Current therapies using bisphosphonates provide modest improvement, but cytotoxic side effects still occur prompting the need to develop more effective therapies to target aggressive osteoclastogenesis. Increased levels of receptor activator of NF-κB ligand (TNFSF11/RANKL), leading to RANKL-RANK s...
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Osteolytic bone damage is amajor cause ofmorbidity in several metastatic pathologies. Current therapies using bisphosphonates providemodest improvement, but cytotoxic side effects still occur prompting the need to develop more effective therapies to target aggressive osteoclastogenesis. Increased levels of receptor activator ofNF–kB ligand (TNFSF11/RANKL), leading to RANKL-RANK signaling, remai...
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Multiple myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the bone marrow and the development of osteolytic bone disease. Myeloma cells express the receptor activator of nuclear factor kappaB ligand (RANKL), induce RANKL expression in the bone marrow, and down-regulate expression of the decoy receptor osteoprotegerin, thereby promoting bone resorption. ...
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Osteosarcoma is the most frequent primary bone malignant tumor that develops mainly in children and adolescents. Despite recent improvements in chemotherapy and surgery, survival rate is approximately 50% after 5 years. Osteoprotegerin (OPG) is a potent inhibitor of osteoclast differentiation and activation, but its use as therapeutic agent in cancer-associated osteolysis remains controversial ...
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Osteoprotegerin (OPG) binds the ligand for receptor activator of nuclear factor kappa B (RANKL) to prevent association with its receptor RANK and inhibit osteoclast-mediated bone resorption. OPG has been reported, recently, to inhibit TNF-related apoptosisinduced ligand (TRAIL)-induced tumor cell apoptosis. This raises the possibility that OPG may play a unique role in regulating these two sign...
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