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Cartilage Invasion (cartilage + invasion)
Selected AbstractsSupracricoid laryngectomy with cricohyoidoepiglottopexy for advanced glottic cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2006Roberto A. Lima MD Abstract Background. Supracricoid laryngectomy with cri-cohyoidoepiglottopexy (CHEP) is a conservative surgical procedure indicated in selected cases of advanced glottic carcinoma. Methods. This study is a review of our experience with 43 patients with T3/T4 glottic squamous cell carcinoma who underwent CHEP in our institution. All but two patients underwent selective neck dissections. All patients were staged on the basis of the 2002 TNM classification. Rates of recurrence and death were estimated by the Kaplan,Meier method. Results. The 5-year disease-specific survival and 5-year relapse-free survival rates were 78% and 83%, respectively. Neck metastases were found in three patients. Cartilage invasion occurred in 11 cases. The average length of hospital stay was 5.7 days. The mean time of enteral feeding tube was 33.8 days, and the mean time for tracheotomy was 29.6 days. Overall, normal swallowing was achieved in 74.4% of patients. Eleven patients had mild and major complications. Laryngeal stenosis emerged as the most frequent major complication. Three patients (6.9%) had local recurrences. Two patients (4.6%) had neck metastases. Conclusions. On the basis of this study, over a 7-year period with 43 patients with advanced glottic cancer, a successful on-cologic outcome is confirmed. © 2006 Wiley Periodicals, Inc. Head Neck 28: 481,486, 2006 [source] Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2008Cristina P. Rodriguez MD Abstract Background. Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success. Methods. Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure. Results. The 5-year Kaplan,Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control. Conclusion. Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 10 2010Klaus W. Frommer Objective Rheumatoid arthritis (RA) is associated with increased production of adipokines, which are cytokine-like mediators that are produced mainly in adipose tissue but also in synovial cells. Since RA synovial fibroblasts (RASFs), lymphocytes, endothelial cells, and chondrocytes are key players in the pathophysiology of RA, this study was undertaken to analyze the effects of the key adipokine adiponectin on proinflammatory and prodestructive synovial effector cells. Methods Lymphocytes were activated in part prior to stimulation. All cells were stimulated with adiponectin, and changes in gene and protein expression were determined by Affymetrix and protein arrays. Messenger RNA and protein levels were confirmed using semiquantitative reverse transcription,polymerase chain reaction (PCR), real-time PCR, and immunoassays. Intracellular signal transduction was evaluated using chemical signaling inhibitors. Results Adiponectin stimulation of human RASFs predominantly induced the secretion of chemokines, as well as proinflammatory cytokines, prostaglandin synthases, growth factors, and factors of bone metabolism and matrix remodeling. Lymphocytes, endothelial cells, and chondrocytes responded to adiponectin stimulation with enhanced synthesis of cytokines and various chemokines. Additionally, chondrocytes released increased amounts of matrix metalloproteinases. In RASFs, adiponectin-mediated effects were p38 MAPK and protein kinase C dependent. Conclusion Our previous findings indicated that adiponectin was present in inflamed synovium, at sites of cartilage invasion, in lymphocyte infiltrates, and in perivascular areas. The findings of the present study indicate that adiponectin induces gene expression and protein synthesis in human RASFs, lymphocytes, endothelial cells, and chondrocytes, supporting the concept of adiponectin being involved in the pathophysiologic modulation of RA effector cells. Adiponectin promotes inflammation through cytokine synthesis, attraction of inflammatory cells to the synovium, and recruitment of prodestructive cells via chemokines, thus promoting matrix destruction at sites of cartilage invasion. [source] Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial fibroblastsARTHRITIS & RHEUMATISM, Issue 5 2010Caroline Ospelt Objective Since fibroblasts in the synovium of patients with rheumatoid arthritis (RA) express the serine proteases fibroblast activation protein (FAP) and dipeptidylpeptidase 4 (DPP-4)/CD26, we undertook the current study to determine the functional role of both enzymes in the invasion of RA synovial fibroblasts (RASFs) into articular cartilage. Methods Expression of FAP and DPP-4/CD26 by RASFs was analyzed using fluorescence-activated cell sorting and immunocytochemistry. Serine protease activity was measured by cleavage of fluorogenic substrates and inhibited upon treatment with L-glutamyl L-boroproline. The induction and expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in RASFs were detected using real-time polymerase chain reaction. Densitometric measurements of MMPs using immunoblotting confirmed our findings on the messenger RNA level. Stromal cell,derived factor 1 (SDF-1 [CXCL12]), MMP-1, and MMP-3 protein levels were measured using enzyme-linked immunosorbent assay. The impact of FAP and DPP-4/CD26 inhibition on the invasiveness of RASFs was analyzed in the SCID mouse coimplantation model of RA using immunohistochemistry. Results Inhibition of serine protease activity of FAP and DPP-4/CD26 in vitro led to increased levels of SDF-1 in concert with MMP-1 and MMP-3, which are downstream effectors of SDF-1 signaling. Using the SCID mouse coimplantation model, inhibition of enzymatic activity in vivo significantly promoted invasion of xenotransplanted RASFs into cotransplanted human cartilage. Zones of cartilage resorption were infiltrated by FAP-expressing RASFs and marked by a significantly higher accumulation of MMP-1 and MMP-3, when compared with controls. Conclusion Our results indicate a central role for the serine protease activity of FAP and DPP-4/CD26 in protecting articular cartilage against invasion by synovial fibroblasts in RA. [source] Glucocorticoids increase ,5 integrin expression and adhesion of synovial fibroblasts but inhibit ERK signaling, migration, and cartilage invasionARTHRITIS & RHEUMATISM, Issue 12 2009Torsten Lowin Objective In rheumatoid arthritis (RA), integrins mediate cell adhesion, migration, and invasion, and their expression is regulated by cytokines and growth factors. The aim of this study was to investigate whether hormones such as cortisol or other steroids can influence integrin expression and function in the synovial cells of patients with RA. Methods We performed immunofluorescence and fluorescence-activated cell sorting analyses to quantify surface integrin levels. Adhesion and migration assays were performed to study the function of synovial fibroblasts (SFs). ERK activation was measured by cellular activation of a signaling enzyme-linked immunosorbent assay. Invasion of SFs into cartilage was determined in the SCID mouse coimplantation model of RA in vivo. Results In RA, expression of integrin subunits ,5, ,v, and ,1 was higher at the site of invasion compared with the sublining zone. Testosterone and 17,-estradiol had no influence on integrin levels, but cortisol up-regulated expression of the ,5 subunit in a time-dependent and dose-dependent manner. In addition, cortisol increased the adhesion of SFs to fibronectin and inhibited ERK signaling upon integrin activation or upon stimulation with tumor necrosis factor. Small interfering RNA or a neutralizing antibody to ,5 integrin increased SF migration, indicating that up-regulated ,5 integrin is responsible for an immobile phenotype. In addition, in the SCID mouse model, SF invasion into cartilage was attenuated by glucocorticoid treatment in vivo. Conclusion Glucocorticoids increase integrin expression and the adhesion of cells to fibronectin, inhibit ERK signaling, and down-regulate the invasiveness of SFs in vivo. This study demonstrates that an important antiinflammatory aspect of glucocorticoids is regulating the expression and function of ,5 integrin. [source] Membrane type 1 matrix metalloproteinase is a crucial promoter of synovial invasion in human rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 3 2009Mary-Clare Miller Objective A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage, and this process requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane type 1 MMP (MT1-MMP), in synovial pannus invasiveness. Methods The expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemical analysis of RA joint specimens. The functional role of MT1-MMP was analyzed by 3-dimensional (3-D) collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, or GM6001. The effect of adenoviral expression of a dominant-negative MT1-MMP construct lacking a catalytic domain was also examined. Results MT1-MMP was highly expressed at the pannus,cartilage junction in RA joints. Freshly isolated rheumatoid synovial tissue and isolated RA synovial fibroblasts invaded into a 3-D collagen matrix in an MT1-MMP,dependent manner. Invasion was blocked by TIMP-2 and GM6001 but not by TIMP-1. Invasion was also inhibited by the overexpression of a dominant-negative MT1-MMP, which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP,dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. Conclusion MT1-MMP serves as an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP,dependent invasion may represent a novel therapeutic strategy for RA. [source] | ||||||||||