Fixed or mobile-bearing total knee arthroplasty

Fixed and mobile-bearing in total knee arthroplasty are still discussed controversially. In this article, biomechanical and clinical aspects in both fixed and mobile-bearing designs were reviewed. In biomechanical aspect, the mobile-bearing design has proved to provide less tibiofemoral contact stresses under tibiofemoral malalignment conditions. It also provides less wear rate in in-vitro simulator test. Patients with posterior stabilized mobile-bearing knees had more axial tibiofemoral rotation than patients with posterior stabilized fixed-bearing knees during gait as well as in a deep knee-bend activity. However, in clinical aspect, the mid-term or long-term survivorship of mobile-bearing knees has no superiority over that of fixed-bearing knees. The theoretical advantages for mobile-bearing design to provide a long-term durability have not been demonstrated by any outcome studies. Finally, the fixed-bearing design with all-polyethylene tibial component is suggested for relatively inactive, elder people. The mobile-bearing design is suggested for younger or higher-demand patients due to the potential for reduced polyethylene wear and more normal kinematics response after joint replacement. For younger surgeon, the fixed-bearing design is suggested due to less demand for surgical technique. For experienced surgeon, one familiar surgical protocol and instrumentation is suggested rather than implant design, either fixed-bearing or mobile-bearing

Inhibition of Mitochondria- and Endoplasmic Reticulum Stress-Mediated Autophagy Augments Temozolomide-Induced Apoptosis in Glioma Cells

Autophagy is a crucial process for cells to maintain homeostasis and survival through degradation of cellular proteins and organelles, including mitochondria and endoplasmic reticula (ER). We previously demonstrated that temozolomide (TMZ), an alkylating agent for brain tumor chemotherapy, induced reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK)-mediated autophagy to protect glioma cells from apoptosis. In this study, we investigated the role of mitochondrial damage and ER stress in TMZ-induced cytotoxicity. Mitochondrial depolarization and mitochondrial permeability transition pore (MPTP) opening were observed as a prelude to TMZ-induced autophagy, and these were followed by the loss of mitochondrial mass. Electron transport chain (ETC) inhibitors, such as rotenone (a complex I inhibitor), sodium azide (a complex IV inhibitor), and oligomycin (a complex V inhibitor), or the MPTP inhibitor, cyclosporine A, decreased mitochondrial damage-mediated autophagy, and therefore increased TMZ-induced apoptosis. TMZ treatment triggered ER stress with increased expression of GADD153 and GRP78 proteins, and deceased pro-caspase 12 protein. ER stress consequently induced autophagy through c-Jun N-terminal kinases (JNK) and Ca2+ signaling pathways. Combination of TMZ with 4-phenylbutyrate (4-PBA), an ER stress inhibitor, augmented TMZ-induced cytotoxicity by inhibiting autophagy. Taken together, our data indicate that TMZ induced autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. This study provides evidence that agents targeting mitochondria or ER may be potential anticancer strategies

Mechanistic Studies on Regioselective Dephosphorylation of Phosphate Prodrugs during a Facile Synthesis of Antitumor Phosphorylated 2-Phenyl-6,7-methylenedioxy-1H-quinolin-4-one

Phosphorylation of 2-(3-hydroxy-5-methoxyphenyl)-6,7-methylenedioxy-1 H-quinolin-4-one ( 1) afforded diphosphate 2. We found that, upon treatment with methanol under mild conditions, 2 can undergo facile and highly regioselective dephosphorylation to give the monophosphate 3, with a phosphate group remaining on the phenyl ring. The details of the dephosphorylation process were postulated and then probed by LC-MS and HPLC analyses. Furthermore, as a preliminary study, the water soluble monophosphate prodrug 4 was tested for antitumor activity against a MCF-7 xenograft nude mice model