Inhibitory effect and significance of rapamycin on the mammalian target of rapamycin signaling pathway in osteosarcoma stem cells and osteosarcoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the effect of rapamycin on the MG-63 osteosarcoma cells (OC), osteosarcoma stem cells (OSC) and on mTOR signaling pathway, and explore the feasibility of rapamycin as a novel therapeutic measure in osteosarcoma chemotherapy regimens.</p><p><b>METHODS</b>OC and OSC were cultured in vitro. Immunofluorescence assay was used to detect the expression of Nanog and Oct4 in OC and OSC. OC and OSC were treated with rapamycin in concentrations of 0, 20, 50 and 100 nmol/L. Semi-quantitative PCR and RT-PCR were used to detect the mTOR mRNA and CCK-8 assay was used to detect cell proliferation, and the cell morphology was observed under an inverted microscope.</p><p><b>RESULTS</b>The cores of MG-63 cellular spheres exhibited embryonic stem cell characteristics such as Nanog and Oct4 expession. The mTOR pathway was activated in the OSC and the expression of mTOR mRNA was higher in OSC (0.761 ± 0.080) than that in OS (0.406 ± 0.090, P < 0.05) by semi-quantitative PCR. RT-PCR showed that the expression of mTOR mRNA was lower in OSCs treated with 100 nmol/L rapamycin (0.961 ± 0.060) than that with 0 nmol/L rapamycin (1.654 ± 0.246, P < 0.05). Cell counting kit-8 (CCK-8) assay showed that the proliferation of OC treated with 20, 50 and 100 nmol/L rapamycin was significantly inhibited, compared with that with 0 nmol/L rapamycin (P < 0.05). Compared with 0 nmol/L rapamycin, the proliferation of OSC treated with 20 and 50 nmol/L rapamycin was not significantly inhibited (P > 0.05), but that with 100 nmol/L rapamycin was significantly inhibited (P < 0.05). The invert microscopic observation revealed that rapamycin inhibited the formation of OSC spheres.</p><p><b>CONCLUSIONS</b>Rapamycin can effectively inhibit cell proliferation and the ability of sphere formation of OSCs. It will provide a basis for a novel therapeutic approach in osteosarcoma chemotherapy regimens.</p>

Biomechanical comparison of internal fixations in osteoporotic intertrochanteric fracture. a finite element analysis

To compare the biomechanical characteristics of dynamic hip screw [DHS] and proximal femoral nail anti-rotation [PFNA] for the treatment of 3 types of osteoporotic femoral intertrochanteric fracture [OFIF] by modeling, and virtual reduction with finite element analysis, and to provide some theoretical basis and reference to select the best internal fixation for clinical treatment of OFIF. The experiment was conducted at the Laboratory of Biomechanics, Shanghai Institute of Orthopedics and Traumatology, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China from February to December 2011. The CT scan was performed in 3 cases with different types of OFIF [Evans-Jensen II, III, and IV]. Upon validation, fracture models with different internal fixations were developed to simulate and analyze. Under the conditions of 7 different apparent bone densities and 3 different loads, the Von Mises stresses, and the failure rates were calculated, and the stress distribution patterns were compared. The PFNA internal fixation system has better stress distribution than DHS. The former has smaller maximum Von Mises stress of femur and internal fixation, and the femoral element failure rate, as well. The safety range of osteoporosis in PFNA is wider than the DHS. The experiment verifies, from the view of biomechanics, that PFNA should be taken into consideration firstly for OFIF [Evans-Jensen II, III, and IV]