7 research outputs found
Tissue Factor Regulation by Epidermal Growth Factor Receptor and Epithelial-to-Mesenchymal Transitions: Effect on Tumor Initiation and Angiogenesis
ErbB oncogenes drive the progression of several human cancers. Our study shows that in human carcinoma (A431) and glioma (U373) cells, the oncogenic forms of epidermal growth factor receptor (EGFR; including EGFRvIII) trigger the up-regulation of tissue factor (TF), the transmembrane protein responsible for initiating blood coagulation and signaling through interaction with coagulation factor VIIa. We show that A431 cancer cells in culture exhibit a uniform TF expression profile; however, these same cells in vivo exhibit a heterogeneous TF expression and show signs of E-cadherin inactivation, which is coupled with multilineage (epithelial and mesenchymal) differentiation. Blockade of E-cadherin in vitro, leads to the acquisition of spindle morphology and de novo expression of vimentin, features consistent with epithelial-to-mesenchymal transition. These changes were associated with an increase in EGFR-dependent TF expression, and with enhanced stimulation of vascular endothelial growth factor production, particularly following cancer cell treatment with coagulation factor VIIa. In vivo, cells undergoing epithelial-to-mesenchymal transition exhibited an increased metastatic potential. Furthermore, injections of the TF-blocking antibody (CNTO 859) delayed the initiation of A431 tumors in immunodeficient mice, and reduced tumor growth, vascularization, and vascular endothelial growth factor expression. Collectively, our data suggest that TF is regulated by both oncogenic and differentiation pathways, and that it functions in tumor initiation, tumor growth, angiogenesis, and metastasis. Thus, TF could serve as a therapeutic target in EGFR-dependent malignancies
Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme
In glioblastoma multiforme, the most common adult primary brain tumor, the glycolytic enzyme hexokinase 2 facilitates growth and therapeutic resistance
Applying mass spectrometry based proteomic technology to advance the understanding of multiple myeloma
Abstract
Multiple myeloma (MM) is the second most common hematological malignancy in adults. It is characterized by clonal proliferation of terminally differentiated B lymphocytes and over-production of monoclonal immunoglobulins. Recurrent genomic aberrations have been identified to contribute to the aggressiveness of this cancer. Despite a wealth of knowledge describing the molecular biology of MM as well as significant advances in therapeutics, this disease remains fatal. The identification of biomarkers, especially through the use of mass spectrometry, however, holds great promise to increasing our understanding of this disease. In particular, novel biomarkers will help in the diagnosis, prognosis and therapeutic stratification of MM. To date, results from mass spectrometry studies of MM have provided valuable information with regards to MM diagnosis and response to therapy. In addition, mass spectrometry was employed to study relevant signaling pathways activated in MM. This review will focus on how mass spectrometry has been applied to increase our understanding of MM
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RNAseq analysis for the diagnosis of muscular dystrophy
Abstract The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of wholeâexome sequencing and nextâgeneration sequencingâbased gene panels. In this study, we identify a deep intronic mutation in the DMD gene in a patient with muscular dystrophy using both conventional and RNAseqâbased transcriptome analyses. The implications of our data are that noncoding mutations likely comprise an important source of unresolved genetic disease and that RNAseq is a powerful platform for detecting such mutations
La violence
Quâelle soit verbale. gestuelle ou intellectuelle, la violence interpelle. Hier comme aujourd'hui, elle reste un enjeu majeur et une prĂ©occupation quotidienne de l'ensemble des acteurs sociaux et politiques tout comme des professionnels du droit. Pourtant, ce paradigme de violence, polysĂ©mique. d'une dĂ©finition souvent floue, s'avĂšre d'une analyse difficile et nĂ©cessite une approche plurielle, capable d'interroger Ă la fois la sociĂ©tĂ©, la religion, le droit et la politique, en Europe et dans le reste du monde, du Moyen Ăge au xxe siĂšcle. En adoptant cette mĂ©thode, qui autorise une lecture Ă variable multiple des formes de la violence, les vingt-neuf chercheurs ici rĂ©unis proposent des interprĂ©tations, des hypothĂšses et des rĂ©sultats stimulants et fructueux, dans des champs aussi divers que ceux de l'histoire, de l'histoire de l'art, de la gender history, de la littĂ©rature, de l'histoire des idĂ©es et de l'anthropologie. Les Ă©tudes rassemblĂ©es dans ce volume prĂȘtent une attention toute particuliĂšre aux cas singuliers et collectifs, ainsi qu'Ă l'acteur face au « systĂšme » existant (social, politique, religieux, Ă©conomique), en mesure de saisir rĂ©ellement ce phĂ©nomĂšne pluriel sur un plan Ă la fois diachronique et synchronique. Aussi la violence, dans ses configurations multiples, dĂ©voile-t-elle les rĂ©ponses donnĂ©es par les autoritĂ©s - religieuses et laĂŻques -. la famille, la parentĂ©, le voisinage, la communautĂ©, les intellectuels, les artistes, les compositeurs entre le Moyen Age et lâĂ©poque contemporaine