Search

Abstract: Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA) in synovial tissues. We investigated the signaling pathway involved in IL-6 production caused by thrombin in synovial fibroblasts. Thrombin caused concentration- and time-dependent increases in IL-6 production. By using pharmacological inhibitors or activators or genetic inhibition by the protease activated receptor (PAR), siRNA revealed that the PAR1 receptor but not other PAR receptors is involved in thrombin-mediated up-regulation of IL-6. Thrombin-mediated IL-6 production was attenuated by thrombin inhibitor (PPACK), phospholipase C inhibitor (U73122), protein kinase Cα inhibitor (Ro320432), Src inhibitor (PP2), NF-κB inhibitor (PDTC), IκB protease inhibitor (TPCK), or NF-κB inhibitor peptide. Stimulation of synovial fibroblasts with thrombin activated IκB kinase α/β (IKK α/β), IκBα phosphorylation, IκBα degradation, p65 phosphorylation at Ser276, p65 and p50 translocation from the cytosol to the nucleus, and κB-luciferase activity. Thrombin-mediated an increase of IKK α/β activity, κB-luciferase activity and p65 and p50 binding to the NF-κB element was inhibited by PPACK, U73122, Ro320432 and PP2. The binding of p65 and p50 to the NF-κB elements, as well as the recruitment of p300 and the enhancement of p50 acetylation on the IL-6 promoter was enhanced by thrombin. Our results suggest that thrombin increased IL-6 production in synovial fibroblasts via the PAR1 receptor/PI-PLC/PKCα/c-Src/NF-κB and p300 signaling pathway. [Copyright &y& Elsevier]

Study Design: Needle tract seeding after biopsy has been reported by many authors. Since the procedure of needle insertion in vertebroplasty is the same as in biopsy, tumor metastasis along the tract of the needle in vertebroplasty should be possible. Objective: We report local metastases along the needle tract as a rare complication of percutaneous vertebroplasty in treating spinal metastases in a lung cancer patient. Summary Of Background Data: The true incidence of tumor implantation along the needle tract may be underestimated as many patients die before the metastases become clinically significant. Methods: A 76-year-old man diagnosed with adenocarcinoma of lung underwent percutaneous vertebroplasty at L1 and L3 vertebral levels due to painful spinal metastases. His condition worsened 3 months later, however, with recurrent back pain and weakness of both legs. Results: MRI of lumbar spine performed post-percutaneous vertebroplasty revealed new contrast-enhanced lesions at the posterior aspect of L1 vertebral body with extension to the adjacent anterior epidural space of L1 and posterior epidural space along T12 to L3 levels with compression of the adjacent dural sac and additional paraspinal involvement. Conclusion: To our knowledge, local metastasis after vertebroplasty in treating spinal metastases has not been reported in the literature. However, this may be a potential complication of vertebroplasty in treating spinal metastases as improvement in cancer treatments occurs with subsequent longer survival times. [ABSTRACT FROM AUTHOR]