PMC:3730145 / 21180-22893 JSONTXT

{"project":"2_test","denotations":[{"id":"23970998-22265717-82904863","span":{"begin":428,"end":430},"obj":"22265717"},{"id":"23970998-20940448-82904864","span":{"begin":432,"end":434},"obj":"20940448"},{"id":"23970998-22265717-82904865","span":{"begin":834,"end":836},"obj":"22265717"},{"id":"23970998-18289304-82904866","span":{"begin":1200,"end":1202},"obj":"18289304"},{"id":"23970998-20959474-82904867","span":{"begin":1320,"end":1322},"obj":"20959474"},{"id":"23970998-18289304-82904868","span":{"begin":1708,"end":1710},"obj":"18289304"},{"id":"T23486","span":{"begin":428,"end":430},"obj":"22265717"},{"id":"T94737","span":{"begin":432,"end":434},"obj":"20940448"},{"id":"T8725","span":{"begin":834,"end":836},"obj":"22265717"},{"id":"T79519","span":{"begin":1200,"end":1202},"obj":"18289304"},{"id":"T91540","span":{"begin":1320,"end":1322},"obj":"20959474"},{"id":"T49928","span":{"begin":1708,"end":1710},"obj":"18289304"}],"text":"2.4.3. Malignant Osteolysis\nBoth HNSCC and FOSCC are highly invasive into surrounding soft tissue structures and frequently characterized by malignant osteolysis of underlying bone. Bone-invasion contributes to clinical morbidity and poorer prognosis for HNSCC patients. In both species, in vitro and in vivo bone resorption and osteoclastogenesis are associated with high levels of parathyroid hormone-related protein (PTHrP) [15, 24]. PTHrP is known to stimulate osteoclastic bone resorption by increasing the expression of RANKL in osteoblasts. RANKL expression results in differentiation and activation of osteoclasts, ultimately resulting in bone resorption. SCC cells (murine, human, and feline) also express increased receptor activator of nuclear factor kappa-B ligand (RANKL) or an altered RANKL:OPG (osteoprotegerin) ratio [15, 52]. Osteoprotegerin is a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL); binding of RANKL by OPG inhibits nuclear kappa B (NF-κB) downstream signaling. In feline SCC cells, the aminobisphosphonate zoledronate, clinically used in people to inhibit malignant osteolysis, induces a dose-dependent reduction in RANKL expression [16, 52]. In a murine xenograft (feline SCC cells), zoledronate treatment reduced tumor growth and prevented osteolysis [64]. Serum carboxy-terminal collagen crosslink (CTx) is a useful marker of bone resorption and turnover in clinical patients with skeletal malignancies. Cats with naturally occurring bone-invasive SCC have greater serum CTx concentrations in comparison with geriatric, healthy controls and in FOSCC-affected cats treatment with zoledronate rapidly decreased circulating serum CTx levels [16].\n"}