Chiaretti A.,Catholic University of Rome |
Ruggiero A.,Catholic University of Rome |
Coccia P.,Catholic University of Rome |
Antonelli A.,Catholic University of Rome |
And 6 more authors.
Leukemia Research | Year: 2011
Brain damage related to intrathecal methotrexate in children with acute lymphoblastic leukemia (ALL) is still unclear. Neuroinflammatory mechanisms and intracerebral production of specific biomarkers, play a key role in determining neuroprotective mechanisms after brain injury. To determine whether the CSF concentrations of neuron-specific enolase (NSE), neurotrophic factors and doublecortin (DCX) are influenced by repeated intrathecal methotrexate administrations, we prospectively collected CSF samples from 10 children with ALL and 10 controls. Our results showed an increased expression of the liquoral markers. This up-regulation could be interpreted as a neuroprotective response of the brain against the neuronal damages induced by MTX. © 2011 Elsevier Ltd. Source
Morosetti R.,University Cattolica |
Gliubizzi C.,University Cattolica |
Sancricca C.,Don Gnocchi Onlus Foundation |
Broccolini A.,University Cattolica |
And 3 more authors.
American Journal of Pathology | Year: 2012
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 exert pleiotropic effects, including regulation of myogenesis. Sporadic inclusion-body myositis (IBM) is the most common muscle disease of the elderly population and leads to severe disability. IBM mesoangioblasts, different from mesoangioblasts in other inflammatory myopathies, display a myogenic differentiation defect. The objective of the present study was to investigate TWEAK-Fn14 expression in IBM and other inflammatory myopathies and explore whether TWEAK modulation affects myogenesis in IBM mesoangioblasts. TWEAK, Fn14, and NF-κB expression was assessed by immunohistochemistry and Western blot in cell samples from both muscle biopsies and primary cultures. Mesoangioblasts isolated from samples of IBM, dermatomyositis, polymyositis, and control muscles were treated with recombinant human TWEAK, Fn14-Fc chimera, and anti-TWEAK antibody. TWEAK-RNA interference was performed in IBM and dermatomyositis mesoangioblasts. TWEAK levels in culture media were determined by enzyme-linked immunosorbent assay. In IBM muscle, we found increased TWEAK-Fn14 expression. Increased levels of TWEAK were found in differentiation medium from IBM mesoangioblasts. Moreover, TWEAK inhibited myogenic differentiation of mesoangioblasts. Consistent with this evidence, TWEAK inhibition by Fn14-Fc chimera or short interfering RNA induced myogenic differentiation of IBM mesoangioblasts. We provide evidence that TWEAK is a negative regulator of human mesoangioblast differentiation. Dysregulation of the TWEAK-Fn14 axis in IBM muscle may induce progressive muscle atrophy and reduce activation and differentiation of muscle precursor cells. © 2012 American Society for Investigative Pathology. Source