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        2,5-Dimethyl-Celecoxib Inhibits Cell Cycle Progression and Induces Apoptosis in Human Leukemia Cells.

        Sobolewski, Cyril,Rhim, Jiyun,Legrand, Noé,mie,Muller, Florian,Cerella, Claudia,Mack, Fabienne,Chateauvieux, Sé,bastien,Kim, Jeoung-Gyun,Yoon, Ah-Young,Kim, Kyu-Won,Dicato, Mario,Diederich American Society for Pharmacology and Experimental 2015 The Journal of Pharmacology and Experimental Thera Vol.355 No.2

        <P>Cyclooxygenase-2 (COX-2) is an essential regulator of cancer promotion and progression. Extensive efforts to target this enzyme have been developed to reduce growth of cancer cells for chemopreventive and therapeutic reasons. In this context, cyclooxygenase-2 inhibitors present interesting antitumor effects. However, inhibition of COX-2 by anti-COX-2 compounds such as celecoxib was recently associated with detrimental cardiovascular side effects limiting their clinical use. As many anticancer effects of celecoxib are COX-2 independent, analogs such as 2,5-dimethyl-celecoxib (DMC), which lacks COX-2-inhibitory activity, represent a promising alternative strategy. In this study, we investigated the effect of this molecule on growth of hematologic cancer cell lines (U937, Jurkat, Hel, Raji, and K562). We found that this molecule is able to reduce the growth and induces apoptosis more efficiently than celecoxib in all the leukemic cell lines tested. Cell death was associated with downregulation of Mcl-1 protein expression. We also found that DMC induces endoplasmic reticulum stress, which is associated with a decreased of GRP78 protein expression and an alteration of cell cycle progression at the G1/S transition in U937 cells. Accordingly, typical downregulation of c-Myc and cyclin D1 and an upregulation of p27 were observed. Interestingly, for shorter time points, an alteration of mitotic progression, associated with the downregulation of survivin protein expression was observed. Altogether, our data provide new evidence about the mode of action of this compound on hematologic malignancies.</P>

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        Fracture load and survival of anatomically representative monolithic lithium disilicate crowns with reduced tooth preparation and ceramic thickness

        Noor A Nawafleh,Muhanad M Hatamleh,Andreas Öchsner,Florian Mack 대한치과보철학회 2017 The Journal of Advanced Prosthodontics Vol.9 No.6

        PURPOSE. To investigate the effect of reducing tooth preparation and ceramic thickness on fracture resistance of lithium disilicate crowns. MATERIALS AND METHODS. Specimen preparation included a standard complete crown preparation of a typodont mandibular left first molar with an occlusal reduction of 2 mm, proximal/axial wall reduction of 1.5 mm, and 1.0 mm deep chamfer (Group A). Another typodont mandibular first molar was prepared with less tooth reduction: 1 mm occlusal and proximal/axial wall reduction and 0.8 mm chamfer (Group B). Twenty crowns were milled from each preparation corresponding to control group (n=5) and conditioned group of simultaneous thermal and mechanical loading in aqueous environment (n=15). All crowns were then loaded until fracture to determine the fracture load. RESULTS. The mean (SD) fracture load values (in Newton) for Group A were 2340 (83) and 2149 (649), and for Group B, 1752 (134) and 1054 (249) without and with fatigue, respectively. Reducing tooth preparation thickness significantly decreased fracture load of the crowns at baseline and after fatigue application. After fatigue, the mean fracture load statistically significantly decreased (P<.001) in Group B; however, it was not affected (P>.05) in Group A. CONCLUSION. Reducing the amount of tooth preparation by 0.5 mm on the occlusal and proximal/axial wall with a 0.8 mm chamfer significantly reduced fracture load of the restoration. Tooth reduction required for lithium disilicate crowns is a crucial factor for a long-term successful application of this all-ceramic system.

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