Cell death induced by N-methyl-N-nitrosourea, a model SN1 methylating agent, in two lung cancer cell lines of human origin

New therapeutic approaches are needed for lung cancer, the leading cause of cancer death. Methylating agents constitute a widely used class of anticancer drugs, the effect of which on human non small cell lung cancer (NSCLC) has not been adequately studied. N-methyl-N-nitrosourea (MNU), a model SN1 methylating agent, induced cell death through a distinct mechanism in two human NSCLC cell lines studied, A549(p53wt) and H157(p53null). In A549(p53wt), MNU induced G2/M arrest, accompanied by cdc25A degradation, hnRNP B1 induction, hnRNP C1/C2 downregulation. Non-apoptotic cell death was confirmed by the lack of increase in the sub-G1 DNA content, Poly (ADP-ribose) polymerase cleavage and caspase-3, -7 activation. In H157(p53 null), MNU induced apoptotic cell death, confirmed by cytofluorometry of DNA content and immunodetection of apoptotic markers, accompanied by overexpression of hnRNP B1 and C1/C2. Thus, the mechanism of the cell death induced by SN1 methylating agents is cell type-dependent and must be assessed prior treatment. © 2009 Springer Science+Business Media, LLC

Uveitis in der Kindheit: eine epidemiologische Studie über 20 Jahre [Epidemiology of Childhood Uveitis in a Tertiary Care Center: A 20-Year Study]

To investigate demographics and causes of pediatric uveitis in a Swiss tertiary reference center over a 20-year period. Retrospective cohort study on patients with uveitis aged less than 16 years seen at Jules-Gonin Eye Hospital between 1 January 2000 and 31 December 2019. Out of 2846 patients with uveitis seen in the Jules-Gonin Eye Hospital Ocular Immune-Infectiology Department, 317 (11.1%) were under 16 years of age and were included in this study. Median age at onset of the uveitis was 8.9 years (range 0 - 16). Anterior uveitis was the most frequent presentation (45.1%) followed by posterior uveitis in 26.2%, intermediate uveitis in 23.3%, and panuveitis in 5.4%. The inflammation was most frequently bilateral and non-granulomatous. A systemic inflammatory disease was found in 34% of the cases and an infectious cause in 24%. The repartition of the location of the uveitis was similar to previous reports from Western countries. Uveitis in juvenile idiopathic arthritis is the most frequent etiology related to a systemic disease in children. An infectious cause was found in 24% of our patients, which is a greater proportion than in adult cohorts

Disease evolution in systemic juvenile idiopathic arthritis: an international, observational cohort study through JIRcohort

Abstract Background Systemic juvenile idiopathic arthritis (systemic JIA) is a severe disease with both systemic and joint inflammation. This study aims to identify predictors of disease evolution within the systemic JIA population enrolled in the Juvenile Inflammatory Rheumatism cohort (JIRcohort). Methods Observational patient cohort study with 201 recruited children from 4 countries (3 European, 1 North Africa) from 2005 until 2019, using retrospectively (2005–2015) and prospectively (2015–2019) routine care collected data. Results Sixty-five patients with complete follow-up data for 24 months after first diagnosis were classified as monophasic (n = 23), polyphasic (n = 6) or persistent group (n = 36) corresponding to their evolution (unique flare, recurrent flares, or persistent disease activity respectively). The patients of the persistent group were more likely to have an earlier disease onset, before the age of 6 (OR 2.57, 95%-CI 0.70–9.46), persistence of arthritis at 12-months post-diagnosis (OR 4.45, 95%-CI 0.58–34.20) and higher use of synthetic DMARD (sDMARD, OR 5.28, 95%-CI 1.39–20.01). Other variables like global assessment by physician and by patient and C Reactive Protein levels at 12-months post-diagnosis were assessed but without any predictive value after adjusting for confounding factors. Conclusions Our results suggest that the earlier disease onset, the persistence of arthritis throughout the first year of disease evolution and the need of sDMARD might predict a persistent disease course

Additional file 1 of Disease evolution in systemic juvenile idiopathic arthritis: an international, observational cohort study through JIRcohort

Additional file 1: Supplementary Table 1. Clinical and laboratory features of patients with persistent vs non persistent disease evolution