ABSTRACT
We performed revision surgery in 2 patients for stem fracture of a cemented tumor prosthesis that occurred more than 25 years after the initial surgery. For revision, the global modular replacement system (GMRS) was used. However, as bone cement in the bone could not be adequately removed, stems with respective diameters of 11 and 12.5 mm were used. In revision surgery for cemented tumor prostheses, adequate removal of residual bone cement is optimal. However, when there is a risk of fracture, it may be appropriate to insert a thicker stem after reaming the femoral canal as much as possible, and then fix the stem using the cement-in-cement method.
Subject(s)
Bone Cements , Femur/surgery , Knee Prosthesis , Prostheses and Implants , Prosthesis Failure , Reoperation/methods , Adult , Bone Cements/therapeutic use , Bone Neoplasms/surgery , Female , Femoral Neoplasms/surgery , Humans , Male , Middle Aged , Osteosarcoma/surgery , Prosthesis Design/methods , Radiography , Time FactorsABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer treatment, but some cancer cell types are resistant to TRAIL cytotoxicity. Therefore, overcoming this resistance is necessary for effective TRAIL therapy. Mitochondrial morphology is important for the maintenance of cell function and survival, and is regulated by the delicate balance between fission and fusion. However, the role of mitochondrial morphology dynamics in TRAIL-induced apoptosis is unknown. Here we show that mitochondrial division inhibitor-1 (mdivi-1), an inhibitor of dynamin-related protein1 (Drp1), modulates mitochondrial morphology and TRAIL-induced apoptosis in human cancer cells. mdivi-1 treatment (≥12.5 µM) caused dose- and timedependent cell death in malignant melanoma, lung cancer and osteosarcoma cells, while sparing normal cells. mdivi-1 also sensitized cancer cells to TRAIL-induced apoptosis. This potentiation of apoptosis occurred through a caspase-depependent mechanism including the mitochondrial and endoplasmic reticulum (ER) stress pathways. Mdivi-1 potentiated mitochondrial oxidative stress, a major cause of mitochondrial and ER stresses, as evidenced by increases in mitochondrial reactive oxygen species levels, mitochondrial mass, and cardiolipin oxidation. Live cell fluorescence imaging using MitoTracker Red CMXRos revealed that Mdivi-1 caused substantial mitochondrial hyperfusion. Moreover, silencing of Drp1 expression also caused mitochondrial hyperfusion and sensitized cancer cells to TRAIL-induced apoptosis. Our results suggest that cancer cells are more vulnerable than normal cells to a perturbation in mitochondrial morphology dynamics and that this higher susceptibility can be exploited to selectively kill cancer cells and sensitize to TRAIL.
Subject(s)
Endoplasmic Reticulum Stress/genetics , GTP Phosphohydrolases/biosynthesis , Melanoma/genetics , Microtubule-Associated Proteins/biosynthesis , Mitochondria/genetics , Mitochondrial Proteins/biosynthesis , TNF-Related Apoptosis-Inducing Ligand/metabolism , Animals , Apoptosis/genetics , Caspase 3/metabolism , Cell Line, Tumor , Dynamins , Enzyme Activation , GTP Phosphohydrolases/genetics , Gene Silencing , Humans , Melanoma/pathology , Membrane Potential, Mitochondrial/genetics , Mice , Microtubule-Associated Proteins/genetics , Mitochondria/pathology , Mitochondrial Proteins/genetics , Reactive Oxygen Species/metabolism , TNF-Related Apoptosis-Inducing Ligand/geneticsABSTRACT
We designed and developed the original cementless femoral stem (HPF) adapted to femurs of developmental dysplasia of the hip (DDH). Twenty-three arthroplasties using HPF were performed in 22 cases. The average age at the operation was 48.4 years. The average follow-up period was 6 years and 10 months. The average Harris Hip Score improved from 46.3 points preoperatively to 93.4 points postoperatively. All stems were classified as bone-ingrown or stable fibrous fixation. Clinically and radiologically excellent results proved the design concept of the HPF realized good fixation in the proximal femur with deformities of DDH. The surface treatment worked well for biological fixation even in clinically difficult cases with poor bone quality and/or complicated deformity of the femur of DDH.
