Mechanism of heat shock protein 90 for regulating 26S proteasome in hyperthermia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia.</p><p><b>METHODS</b>Hyperthermic HepG2 cell models established by exposure of the cells to 42 degrees celsius; for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed.</p><p><b>RESULTS</b>ROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001).</p><p><b>CONCLUSION</b>The intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.</p>

Therapeutic effect of combined cisplatin and docetaxel vs fluorouracil regimen with concurrent radiotherapy on advanced esophageal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the therapeutic effect and adverse effects of two regimens, namely cisplatin and docetaxel (DC) regimen and fluorouracil (PF) regimen, both with concurrent radiotherapy, in the treatment of advanced esophageal squamous cancer.</p><p><b>METHODS</b>Forty-eight patients with esophageal squamous cancer were randomly assigned in DC regimen and PF regimen groups. All the patients received conventional radiotherapy at a total dose of 60 Gy (in 30 fractions) for 6 weeks. In DC regimen group, the patients received intravenous infusion of docetaxel (75 mg/m(2)) for 1 h on day 1 and DDP (25 mg/m(2) daily) on days 1-3, with every 28 days as one cycle. PF regimen consisted of cisplatin (25 mg/m(2)) on days 1-3 and continuous intravenous infusion of fluorouracil (500 mg/m(2)) for 5 days, with every 28 days as one cycle. All the patients were suggested to have no less than 2 cycles.</p><p><b>RESULTS</b>The 3-year median survival time in DC regimen was slightly longer than that in PF regimen group (26 vs 23 months, Χ2=3.4041, P=0.065). The same result was also found in the short-term effect and adverse reactions including ?myelosuppression and gastrointestinal reactions. Only the adverse reaction of radiotherapy-induced esophagitis showed a significant difference between the two groups (P=0.049).</p><p><b>CONCLUSION</b>DC regimen with synchronous radiotherapy is effective and safe for treating advanced esophageal squamous cancer.</p>

Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity of the combined chemotherapy with docetaxel, capecitabine and cisplatin (TXP) in the treatment of metastatic nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>This retrospective analysis involved 22 patients with metastatic NPC receiving treatment with the TXP regimen. The patients were given docetaxel at 60 mg/m² on day 1, cisplatin at 20 mg/m² on days 1-3, and capecitabine at 1 250 mg/m² on days 1-14, and the treatment cycle was repeated ever 3 weeks.</p><p><b>RESULTS</b>Of the 22 patients, 14 (63%) achieved partial remission, 2 (9%) had complete remission, and 5 (23%) showed stable disease. The overall clinical response rate of the patients was 72% with a 1-year survival rate of 68%, median progression-free survival of 8 months, and overall survival of 14 months. The main toxicity was myelosuppression; 7 (32%) patients experienced grade 3/4 neutropenia, and 5 (23%) had grade 3/4 anemia. All the other adverse effects were tolerable and reversible.</p><p><b>CONCLUSION</b>The TXP regimen is safe and effective for treatment of metastatic NPC, and the results are comparable with those of the reports in recent literatures.</p>

Preparation of long-circulating nolatrexed dihydrochloride liposomes and its antitumor activity / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare long-circulating liposome (LCL) for sustained release of nolatrexed dihydrochloride and evaluate the effect of this preparation against the growth of hepatocarcinoma cells in mice.</p><p><b>METHODS</b>The long-circulating nolatrexed dihydrochloride liposome was prepared by film dispersion-extrusion combined with ammonium sulphate gradient method. Amphipathic polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) was added to modify the property of the liposome membrane. The drug entrapment efficiency of the nolatrexed dihydrochloride-containing liposome was determined using UV detector with Sephadex G50. Electron microscopy and laser particle analyzer were employed to determine the size of the nolatrexed dihydrochloride liposome. For in vivo evaluation of the effect of the liposomal preparation, H22 mouse hepatoma carcinoma cells were transplanted subcutaneouly in mice in the axillary region of the right hind limb to induce growth of solid tumors, which were evaluated for tumor weight inhibition rate and tumor volume changes after administration of the LCL preparations.</p><p><b>RESULTS</b>The mean diameter of the long-circulating nolatrexed dihydrochloride liposomes was 109 nm, with an entrapment efficiency of 68.5%. In vivo antitumor experiment showed that both the common liposomal and LCL preparations of nolatrexed dihydrochloride produced antitumor effect in vivo, and the latter had weaker antitumor effect than free and common liposomal preparation of nolatrexed dihydrochloride, but in the long term, the LCL preparation showed stronger antitumor effect with a tumor weight inhibition rate of 41.68%.</p><p><b>CONCLUSION</b>LCL allows sustained release of nolatrexed dihydrochloride in vivo, and may effectively lengthen the relatively short half life of this drug after administration.</p>

Protective effect of heat preconditioning on NIH-3T3 fibroblast / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish stress adaptation model of mouse fibroblast cell line NIH-3T3, to provide a group of parallel object for stress adaptation research, and to explore the function and mechanism of HSP90 in stress adaptation.</p><p><b>METHODS</b>A stress-adapted cell model was established by thermal preconditioning (42 degrees C, 20 minutes), and the adaptation result was evaluated by observing the change of the membrane injury and the damage of DNA induced by the heat stress for the second time (44 degrees C, 20 minutes). The HSP90 content was detected by Western blot.</p><p><b>RESULTS</b>According to the membrane injury and HSP90 synthesis induced by the heat stress for the second time, it was primarily confirmed that 6 hours after thermal preconditioning were the optimum stress protection time. When cells underwent heat stress for the second time 6 hours after thermal preconditioning, the membrane injury (15.4% +/- 2.6% vs 41.2% +/- 5.1%), damage of DNA (15.1% vs 26.3%) were decreased compared with the control group in which there was no preconditioning. The OD(HSP90)/OD(control) value indicated that the cellular HSP90 contents was decreased immediately after heat stress (44 degrees C, 40 min). The content of HSP90 was 0.82 +/- 0.18 in the heat stress group, 1.70 +/- 0.52 in the preconditioning group and 1.41 +/- 0.16 in the heat stress after preconditioning group.</p><p><b>CONCLUSION</b>With the preconditioning for the NIH-3T3, the time point for the stress protection is confirmed, the model for the cellular stress adaptation is established and the protective effect of HSP90 is primarily confirmed in this model.</p>