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>

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>

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>

Three-dimensional conformal radiotherapy combined with stereotactic radiotherapy for locally advanced non-small cell lung cancer: efficacy and complications / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic efficacy of three-dimensional conformal radiotherapy (3DCRT) combined with stereotactic radiotherapy (SRT) and the radiation-induced complications in patients with locally advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Sixty-eight patients with locally advanced NSCLC were randomly divided into two groups. The 33 patients in groups A received 3DCRT at the total dose of 66 to 70 Gy in 33 to 35 fractions, and the 35 patents in group B received stereotactic radiotherapy (SRT) at the dose of 20 Gy in 4 fractions (500 cGy per fraction every other day) after 60 Gy 3DCRT.</p><p><b>RESULTS</b>The total response rates in groups A and B were 56.3% and 80.0%, with the complete remission rates of 9.4% and 28.6%, respectively, both showing significant differences between the two groups (P<0.05). The 1- and 2-year survival rates of the patients in group A were 65.6% and 46.8%, respectively, which were comparable to those in group B (74.3% and 51.4%, respectively, P>0.05). The median survival time in groups A and B were 12.6 and 18.3 months, respectively. The major radiation-induced complications in the two groups included grade I to II acute radiation esophagitis and hematopoietic toxicity. The complications in later stages following the radiation were grade I to II radiation lung fibrosis, occurring at a similar incidence between the two groups.</p><p><b>CONCLUSION</b>The combination of 3DCRT and SRT produces better therapeutic effects than 3DCRT alone in patients with locally advanced NSCLC.</p>