FAK/c-Src signaling pathway mediates the expression of cell surface HSP90 in cultured human prostate cancer cells and its association with their invasive capability / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of heat shock protein 90 (HSP90) on the cell surface of highly invasive human prostate cancer cells PC3 and its possible molecular mechanisms of its effect on cell invasion through analyzing FAK/Src signaling pathway.</p><p><b>METHODS</b>The expression of cell surface HSP90 on PC3 cells was studied by immunofluorescence staining and surface biotinylation assay respectively. A specific HSP90 antibody was used to inhibit the cell surface HSP90. In vitro cell invasion was assessed by modified Boyden chambers. Phosphorylated FAK on tyr 397, 576, 577 and 925, and phosphorylated c-Src on tyr 416 were examined by Western blot assay. The association between FAK and c-Src was analyzed by immunoprecipitation. The effects of FAK knockdown by siRNA or Src kinases inhibitor PP2, with or without anti-HSP90 antibody, on PC3 cell invasion were also evaluated.</p><p><b>RESULTS</b>A pool of HSP90 was detected on the cell surface of PC3 cells. A specific HSP90 antibody significantly retarded tumor cell invasion. Concomitant with this finding, targeting cell surface HSP90 significantly inhibited the phosphorylations of FAK and c-Src, and also the interactions between FAK and c-Src. FAK knockdown or PP2 dramatically suppressed cell invasion, however, anti-HSP90 antibody didn't further inhibit cell invasion.</p><p><b>CONCLUSIONS</b>Cell surface HSP90 promotes human prostate cancer cell invasion through a FAK/c-Src signaling, with may be a novel therapeutic target against metastatic tumors.</p>

Prediction of traumatic avascular necrosis of the femoral head by single photon emission computerized tomography and computerized tomography: an experimental study in dogs / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the femoral head perfusion and to predict the traumatic avascular necrosis (AVN) of the femoral head by single photon emission computerized tomography and computerized tomography (SPECT/CT).</p><p><b>METHODS</b>Totally 18 adult beagle dogs were divided randomly into three equal-sized (n equal to 6) groups. Subsequently different degrees of ischemia model were developed by destroying blood vessels of the femoral head. The left hip received sham operation as normal control and the right hip underwent blood interruption. In Group A, the ligamentum teres was cut off. In Group B, the marrow cavity of the right femoral neck was destroyed while in Group C, the soft tissues at the base of the femoral neck were stripped in addition to the resection of the ligamentum teres and destruction of the marrow cavity. Three hours after surgery, SPECT/CT was performed. Laser Doppler Flowmetry (LDF) measurements were also obtained at three different time points (before operation, immediately and three hours after operation) in order to assess the change process of blood supply to the femoral head.</p><p><b>RESULTS</b>SPECT/CT showed no significant difference in the radionuclide uptake between the right and left femoral heads in Group A (t equal to -0.09, P equal to 0.94) and Group B (t equal to 0.52, P equal to 0.62). However, in Group C, it was 261+/-62 for the right femoral head, only 12% of that in the left femoral head. LDF measurements indicated that the femoral head perfusion was decreased from (45.0+/-3.3) PU to (39.1+/-3.7) PU in Group A,from (44.0+/-2.7) PU to (34.3+/-2.6) PU in Group B, and from (47.3+/-2.1) PU to (4.96+/-0.6) PU in Group C immediately after operation. However, the perfusion was restored and returned to normal values three hours after operation except in Group C.</p><p><b>CONCLUSION</b>SPECT/CT could assess the perfusion of the femoral head semiquantitatively, which might be useful in predicting the development of traumatic AVN.</p>

Treatment of osteonecrosis of the femoral head by percutaneous decompression and autologous bone marrow mononuclear cell infusion / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of the treatment of osteonecrosis of the femoral head by percutaneous decompression and autologous bone marrow mononuclear cell (BMCs) infusion.</p><p><b>METHODS</b>44 hips in 28 patients with avascular necrosis at early stage were treated by percutaneous multiple holes decompression followed by autologous BMCs infusion. Autologous BMCs were concentrated from bone marrow that was taken from the posterior iliac crest of the patient. Patients were followed up at least 2 years. The results were determined by the changes in the Harris hip score and the progression in the radiograghic stages.</p><p><b>RESULTS</b>No complications were observed after the operation. Before operation, there were stage I of femoral head necrosis in 8 hips, stage II in 15 hips, stage III in 14 hips, stage IV in 7 hips, and the postoperative stages at the most recent follow-up were stage O in 1 hip, stage I in 6 hips, stage II in 13 hips, stage III in 13 hips, stage IV in 7 hips, stage V in 4 hips. The mean preoperative Harris hip score was 58 (46-89), and improved to 86 (70-94) postoperatively. All the femoral head collapsed preoperatively showed that the necrotic size was at least more than 30%.</p><p><b>CONCLUSIONS</b>Percutaneous multiple holes decompression combined with autologous BMCs is a new way to treat avascular necrosis of the femoral head. The earlier the stage, the better the result. A randomized prospective study needed to compare with routine core decompression in the future.</p>