Coopération entre processus guidés par les données et par les modèles pour la segmentation

Parmi les méthodes de segmentation existantes on peut distinguer deux grands types d'approches : les approches guidées par les données, utilisant l'information sur les niveaux de gris, et les approches à base de modèles, exploitant de la connaissance a priori. Cependant, les résultats obtenus par l'une ou l'autre de ces approches ne sont pas suffisamment satisfaisants (cas de mauvais contrastes pour les approches bas-niveau,trop grande variabilité morphologique pour les approches à base de modèles...) . Nous nous intéressons donc à l'étude et à la mise en oeuvre de techniques de coopération dans le but d'améliorer les résultats de la segmentation. Le travail est appliqué à l'IRM du cerveau

Structure-based design, synthesis and characterization of the first irreversible inhibitor of Focal Adhesion Kinase

Focal Adhesion Kinase signaling pathway and its functions have been involved in the development and aggressiveness of tumor malignancy, it then presents a promising cancer therapeutic target. Several reversible FAK inhibitors have been developed and are being conducted in clinical trials. On the other hand, irreversible covalent inhibitors would bring many desirable pharmacological features including high potency and increased duration of action. Herein we report the structure-guided development of the first highly potent and irreversible inhibitor of the FAK kinase. This inhibitor showed a very potent decrease of autophosphorylation of FAK in squamous cell carcinoma. A cocrystal structure of the FAK kinase domain in complex with this compound revealed the inhibitor binding mode within the ATP binding site and confirmed the covalent linkage between the targeted Cys427 of the protein and the inhibitor

Stat3 controls tubolointerstitial communication during CKD

Functional Genomics of Systemic Disorder

180 Real-world treatment patterns and outcomes with first-line maintenance olaparib for BRCAm advanced ovarian cancer: a pan-European study (OVAL-1)

n/

Se-methylselenocysteine inhibits phosphatidylinositol 3-kinase activity of mouse mammary epithelial tumor cells in vitro

INTRODUCTION: Se-methylselenocysteine (MSC), a naturally occurring selenium compound, is a promising chemopreventive agent against in vivo and in vitro models of carcinogen-induced mouse and rat mammary tumorigenesis. We have demonstrated previously that MSC induces apoptosis after a cell growth arrest in S phase in a mouse mammary epithelial tumor cell model (TM6 cells) in vitro. The present study was designed to examine the involvement of the phosphatidylinositol 3-kinase (PI3-K) pathway in TM6 tumor model in vitro after treatment with MSC. METHODS: Synchronized TM6 cells treated with MSC and collected at different time points were examined for PI3-K activity and Akt phosphorylation along with phosphorylations of Raf, MAP kinase/ERK kinase (MEK), extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). The growth inhibition was determined with a [(3)H]thymidine incorporation assay. Immunoblotting and a kinase assay were used to examine the molecules of the survival pathway. RESULTS: PI3-K activity was inhibited by MSC followed by dephosphorylation of Akt. The phosphorylation of p38 MAPK was also downregulated after these cells were treated with MSC. In parallel experiments MSC inhibited the Raf–MEK–ERK signaling pathway. CONCLUSION: These studies suggest that MSC blocks multiple signaling pathways in mouse mammary tumor cells. MSC inhibits cell growth by inhibiting the activity of PI3-K and its downstream effector molecules in mouse mammary tumor cells in vitro