In particular, inhibition of protein prenylation and ras signalling
within osteoclasts leads to defects in intracellular vesicle transport. As an example, osteoclasts became defective as concerns ruffled borders which is required for bone resorption. Bisphosphonates induce caspase-dependent apoptosis, inhibit metalloproteinase HMPL-504 price activity and have antiangiogenic properties. Reduction in Vascular Endothelial Growth factor (VEGF) levels was showed during pamidronate treatment in cancer patients . The intense effect exerted within bone microenvironment may have a great result not only for metastatic but also for primitive tumors of bone. Recent reports support a direct antitumor activity by zoledronic acid. This selleck screening library effect was documented in cellular and animal models of osteosarcoma [6–8]. Zoledronic acid, paclitaxel alone or associated were tested in a murine model of Ewing sarcoma . Tumor growth was showed in 78% of rats treated with paclitaxel, 44% of rats treated with zoledronic acid and 22% of rats treated with zoledronic acid plus paclitaxel
. In this study, paclitaxel and zoledronic acid act synergically despite the minimal antitumor activity of paclitaxel in sarcomas. Therefore the activity of some chemotherapeutic agents may improve in association with zoledronic acid. Many reports are in line with this suggestion [6, 8, 10]. Preclinical models of chondrosarcoma confirm the effect of zoledronic acid . Insights into molecular
find more mechanisms have demonstrated DNA-damage S-phase checkpoint and up-regulation of mitochondrial permeability independently of p53 and retinoblastoma status . Therefore, zoledronic acid can inhibit cell proliferation and induce apoptosis in tumors where these mutations frequently Thiamet G occur. Skeletal-related events and bone pain share the same underlying origin. The inhibition of tumor-induced bone resorption by N-BPs produce significant reduction in skeletal morbidity and bone pain . Usually pain is the first symptom of metastatic involvement of bone by tumor. Pain could increase gradually and treatment with opioids or palliative radiation therapy may be required. Typically, bone pain is not adequately managed and 75%–95% of patients with advanced cancer experience severe pain . Treatment with zoledronic acid provides substantial benefit in terms of pain relief in patients with bone metastases by various tumors [14, 15]. Zoledronic acid was currently approved worldwide for the treatment of bone metastases independent of the primary tumor type. However, there is no reported clinical experience concerning chondrosarcoma and/or chordoma until now. Following we report on a 63-year-old man patient with advanced chondrosarcoma and a 66-year-old woman with sacrum chordoma treated with zoledronic acid.