A pro-inflammatory role for nuclear factor kappa B in childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Childhood obstructive sleep apnea syndrome (OSAS) is associated with an elevation of inflammatory markers such as C-reactive protein (CRP) that correlates with specific morbidities and subsides following intervention. In adults, OSAS is associated with activation of the transcription factor nuclear factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation, based on the hypothesis that specific NF-kB signaling is activated in children with OSAS. DESIGN: Adenoid and tonsillar tissues from children with OSAS and matched controls were immunostained against NF-kB classical (p65 and p50) and alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines: interleukin (IL)- 1α, IL-1ß, tumor necrosis factor-α, and IL-8). Serum CRP levels were measured in all subjects. NF-kB induction was evaluated by a luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and in Jurkat cells with inducible NF-kB expression. p65 translocation to the nucleus, reflecting NF-kB activation, was measured in cells expressing fluorescent NF-kB-p65-GFP (green fluorescent protein). SETTING: Sleep research laboratory. PATIENTS OR PARTICIPANTS: Twenty-five children with OSAS and 24 without OSAS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Higher expression of IL-1α and classical NF-kB subunits p65 and p50 was observed in adenoids and tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured by a luciferase-NF-kB reporter assay and by induction of p65 nuclear translocation in cells permanently transfected with GFP-p65 plasmid. IL-1ß showed increased epithelial expression in OSAS tissues. CONCLUSIONS: Nuclear factor kappa B is locally and systemically activated in children with obstructive sleep apnea syndrome. This observation may motivate the search for new anti-inflammatory strategies for controlling nuclear factor kappa B activation in obstructive sleep apnea syndrome.

Measles virus antigens in breast cancer.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women in Western countries, showing a bimodal age distribution with peaks at 50 and 70 years. Multiple factors are encountered in the etiology of BC, including hereditary and hormonal causes. A few viruses, including MMTV, EBV and HPV have been reported to be associated with BC. This group previously described the presence of the measles virus (MV) in biopsies of patients with Hodgkin's lymphoma. The present study explored MV antigens in BC patients. PATIENTS AND METHODS: A total of 131 patients with invasive BC diagnosed during the years 1998-2005 were studied using immunohistochemistry (IHC) for the presence of MV antigens, hemagglutinin and nucleoprotein. Clinicopathological parameters included age, stage, histological grade and the expression of estrogen and progesterone receptors, HER2/neu, p53, and Ki67. RESULTS: Hormone receptors and HER2/neu were positive in 54% and 18% of the tumors, respectively. Both MV antigens were detected in 64% of the tumors. All biopsies containing a DCIS component showed MV in DCIS in addition to invasive BC. In univariate analysis, MV correlated with estrogen receptor (p=0.018), low Ki67 index (<40%, p=0.029), low or intermediate grade (p=0.037), age under 50 years (p=0.039), progesterone receptor (p=0.043) and overexpression of p53 (p=0.049). In multivariate analysis, only grade (p=0.011), p53 (p=0.03) and age (p=0.041) remained associated with MV. CONCLUSION: This study provides evidence for the presence of MV antigens in a relatively large proportion of BC patients. MV was associated with younger age, lower histological grade and overexpression of p53, suggesting that it may play a role in the development of BC.