Here, we demonstrate pronounced differences in the expression of TF and its interactors factor VII and protease-activated receptor 2 (PAR-2) in nine human glioma cell lines (U87, U251, U343, U373, MZ-18, MZ-54, MZ-256, MZ-304, Hs 683) as detected by RT-PCR and CX-6258 Western blot analysis. Inhibition of TF signaling by a neutralizing monoclonal antibody (mAb TF9-10H10) led to significantly reduced proliferation in high-grade astroglial (MZ-18 and MZ-304) and oligodendroglial (Hs 683) cell lines abundantly expressing TF, but not in U373 cells expressing low amounts of TF. Scratch migration assays and Boyden
chamber assays indicated that mAb TF9-10H10 and lentiviral knockdown of TF significantly reduced cell migration and invasion of MZ-18, MZ-304 and Hs 683 cells, both under normoxic and hypoxic conditions. Of note, all three cell lines displayed increased cell migration and invasion under hypoxic conditions (1% O(2)), which was associated with enhanced
expression of TF and increased phosphorylation of p44/42 mitogen-activated protein kinase (ERK1/2). Silencing of TF blocked activation of the ERK pathway, induction of T expression and the potentiating effect of hypoxia on cell migration and invasion. RNA interference against PAR-2 abrogated the autocrine effects of TF on cell proliferation, Evofosfamide cost migration and invasion, indicating that TF signals via PAR-2 in glioma cells. Our results suggest an important role for the ALOX15 TF/FVIIa/PAR-2/ERK axis in tumor growth and invasion of glioma and suggest that TF may be a suitable target for the development of novel therapies against high-grade glioma. (C) 2010 IBRO. Published by Elsevier
Ltd. All rights reserved.”
“Classical eyeblink conditioning (EBC) has been widely used to probe cerebellar function in humans and non-human mammals. Although die neural pathways governing behavior in this task are well understood and fairly discrete, it remains unclear in the human literature how conditioned stimuli (CSs) of different modalities (e.g., visual and auditory) influence the exhibition of conditioned responses (CRs). In the present study, therefore, CRs to a visual CS and an auditory CS were examined with the single-cue delay EBC procedure. An initial experiment (N = 61) was conducted to identify visual and auditory stimuli that had equal perceived intensities. Using these perceptually equivalent stimuli, a second group of 25 subjects completed auditory and visual EBC procedures in two testing sessions 5-8 days apart. Whereas the acquisition of CRs was similar between the CS modality conditions, the timing of the CRs differed such that earlier CR onset and peak latencies were associated with the visual CS. In addition, CR timing improved across testing sessions, as indicated by the later CR peak latencies exhibited during the second testing session, as compared with the first.”
“Tinnitus is a non-observable phantom sensation.