Showing papers by "Saby George published in 2010"

RANK Ligand: Effects of Inhibition

Abstract: Receptor activator of nuclear factor κ-light-chain-enhancer of activated B-cells (RANK) and its ligand (RANKL) belong to the tumor necrosis factor (TNF) superfamily. RANK mRNA is expressed widely in bone and bone marrow. It has a significant role in stimulating osteoclast differentiation and maturation, and also in preventing apoptosis. Because osteoclast activity is an important aspect of bone resorption in malignancy, targeting these cells is a good rationale for preventing skeletal-related events in malignancies. Preclinical studies have demonstrated the efficacy of denosumab in preventing bone loss in mice and improving bone mineral density. Denosumab is a fully human monoclonal antibody against RANKL, which has been shown to be effective in reducing signaling via RANK and thus osteoclast activity. It has been demonstrated in large, randomized, phase 3 studies to be effective in preventing fractures and bone loss, and improving the bone mineral density in various cancerous and noncancerous settings. This article reviews the latest evidence of RANKL inhibition and its clinical implications.

Stable disease in renal cell carcinoma after using signal transduction inhibitors.

Abstract: Malignant solid tumors have been traditionally treated utilizing cytotoxic chemotherapies, which work against rapidly multiplying tumors. The current response evaluation in solid tumor is based on the Response Evaluation Criteria in Solid Tumors (RECIST). This method relies mainly on computerized tomography (CT scans) and other imaging modalities by which the diameter of tumors is taken into consideration to assess response to therapy. Recent years have witnessed the introduction of a series of new signal transduction inhibitors in the management of metastatic RCC. Stable disease (SD) is more frequently seen with morphologic lesion changes such as, change in attenuation, pattern of intratumoral enhancement / necrosis and cavitation, all of which pose a challenge for the investigator in the accurate assessment of response to therapy. This article attempts to introduce the reader to various alternate concepts of monitoring response following biologic therapy and offers a detailed analysis of a few lesions.