Microenvironmental regulation of metastasis

Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues

Estudo da hiper-responsividade brônquica em pacientes portadores de refluxo gastroesofágico Bronchial hyperreactivity in patients with gastroesophageal reflux disease

OBJETIVO: O intuito deste trabalho foi evidenciar a existência desse reflexo vagal, através de uma broncoprovocação, em pacientes portadores de refluxo gastroesofágico. MÉTODOS: Onze pacientes com endoscopia sem evidências de refluxo gastroesofágico ou hérnia hiatal (grupo controle) e dez pacientes com hérnia hiatal ou refluxo gastroesofágico foram submetidos à broncoprovocação com carbacol. RESULTADOS: O teste foi positivo em 5 dos pacientes com hérnia hiatal ou refluxo gastroesofágico (50%), e em 3 do grupo controle (27%) (p = 0,64). CONCLUSÃO: A hipótese de que as vias aéreas de pacientes com refluxo gastroesofágico sem sintomas asmatiformes anteriores possam ser mais responsivas do que as de pacientes sem refluxo gastroesofágico permanece não comprovada.<br>OBJECTIVE: To identify this vagal reflex using bronchial provocation tests in patients with gastroesophageal reflux disease. METHODS: The study group was composed of 10 patients presenting endoscopic evidence of hiatal hernia or gastroesophageal reflux disease, and the control group consisted of 11 patients presenting no evidence of either condition. All subjects were submitted to bronchial provocation with carbachol. RESULTS: The provocation test was positive in 5 (50%) of the study group patients and 3 (27%) of the control group patients (p = 0.64). CONCLUSION: The hypothesis that the airways of patients with gastroesophageal reflux disease (and no history of asthma-like respiratory symptoms) might be more responsive than those of individuals without the disease remains unproven

Characteristics of joint involvement and relationship with systemic inflammation in systemic sclerosis: result from the EULAR scleroderma trial and research (EUSTAR) database.

To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc). METHODS: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs. RESULTS: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable. CONCLUSION: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation

Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database

OBJECTIVE: To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc). METHODS: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs. RESULTS: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable. CONCLUSION: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation