Inhibition of autophagy enhances the radiosensitivity of nasopharyngeal carcinoma by reducing Rad51 expression.

Radiotherapy has long been considered as the mainstay of treatment for nasopharyngeal carcinoma (NPC). However, locoregional recurrence or distant metastasis may occur in some patients due to the radiation resistance of cancer cells. Autophagy plays a vital role in protecting cells against radiation. However, the mechanism of autophagy in radiation therapy remains obscure. In the present study, we demonstrated that suppression of autophagy related 5 (Atg5) aggravated ionizing radiation (IR)-induced DNA damage and apoptosis in human NPC cells without accelerating the cell cycle, whereas regulation of the cell cycle has been widely regarded as the most important determinant of IR sensitivity. Further study showed that inhibition of autophagy suppressed the mRNA expression of Rad51, a key protein of homologous recombination that has been demonstrated to play a critical role in the repair of DNA double-strand breaks induced by radiation. Moreover, suppression of Atg5 had no impact on the radiosensitivity when cells were pre-treated by the Rad51 inhibitor, and the enhanced radiosensitivity by Atg5 suppression was reversed by overexpression of Rad51 in human NPC cells. Our results suggest that inhibition of autophagy enhances the susceptibility of NPC cells to radiation by reducing Rad51 expression. Therefore, Rad51 targeted therapy may be investigated as a potential novel agent for the adjuvant treatment of traditional radiation of NPC.

[Phase II clinical trial of home-produced Nedaplatin in treating advanced esophageal carcinoma].

BACKGROUND & OBJECTIVE: Nedaplatin is a second-generation anticancer drug containing organic platinum. Clinical researches in overseas showed that Nedaplatin is an anticancer drug with broad spectrum and high efficiency, especially in treating esophageal carcinoma. But the therapeutic efficacy and toxicity of home-produced Nedaplatin in China are unclear. This study was to evaluate the efficacy of home-produced Nedaplatin in China on esophageal carcinoma, and observe its toxicity. METHODS: A multi-center, phase II, prospective clinical trial was conducted. Naive patients with esophageal carcinoma were enrolled and randomized into trial group and control group. The patients in trial group were treated with home-produced Nedaplatin plus 5-fluorouracil (5-FU); the patients in control group were treated with cisplatin (DDP) plus 5-FU. RESULTS: A total of 52 patients were enrolled: 30 in trial group, and 22 in control group. For trial group, therapeutic efficacy was evaluable in 27 cases, and toxicity was evaluable in all cases; for control group, therapeutic efficacy and toxicity were evaluable in all cases. The response rate was significantly higher in trial group than in control group (29.62% vs. 22.72%, P<0.05). The complete remission (CR) rates were 18.51% in trial group and 4.55% in control group. When considering myelosuppression, the occurrence rate of anemia was similar in the 2 groups; but the occurrence rates of neutropenia and thrombocytopenia were higher in trial group than in control group, especially for grade III-IV thrombocytopenia (20.68% vs. 0%, P<0.01). The occurrence rate of gastrointestinal reaction was lower in trial group than in control group. There were no significant differences in hepatotoxicity, renal toxicity, heart toxicity, peripheral nerve toxicity, and alopecia between the 2 groups. CONCLUSIONS: Nedaplatin is an effective platinum drug for esophageal carcinoma. The treatment efficacy of Nedaplatin plus 5-FU regimen is better than that of DDP plus 5-FU regimen. It has a good clinical tolerance. The main toxicity is myelosuppression, and thrombocytopenia is predominant.

[Treatment of mix gas containing butyl acetate, n-butyl alcohol and phenylacetic acid from pharmaceutical factory by bio-trickling filter].

The bio-trickling filter packed with ZX02 stuffing is used to treat the mix gases containing butyl acetate, n-butyl alcohol and phenylacetic acid(BBP), which are discharged from Penicillin workshop of Pharmaceutical Factory. The reactor was operated for 110 days to investigate the effect of influent load, retention time and spray water on the removal of BBP and the biodegradation characteristics. The reactor displayed preferential utilization of BBP, when the maximum influent load of BBP were 229.5g/(m3 x h), 275.4 g/(m3 x h) and 42.5g/(m3 x h), the removal efficiencies were 96%, 95% and 100% respectively. The results show that the bio-trickling filter can effectively treat the mix gases and the optimum parameters were as followed: retention time was 31.2 s, the volume of spray water was 4 L/(L x d). The bio- trickling reactor has strong ability to resist shock of high influent load and resistance is maintained at low value, what's more, it doesn't need to carry out back washing frequently. With all these advantages it can be operated steadily for long time.

[Phase II clinical trial of nedaplatin in advanced non-small cell lung cancer].

BACKGROUND & OBJECTIVE: The aim of this study was to observe the efficacy and the side effects of nedaplatin in treatment of non-small cell lung cancer (NSCLC). METHODS: This is a multi-center phase II clinical trial. The previously chemotherapy treated patients with NSCLC were administrated nedaplatin alone. Nedaplatin was given at 100 mg/m2, i.v., repeated every 3 weeks. The chemonaive patients with NSCLC were randomized to two groups. The combination trial group was given with nedaplatin + vindesine regimen, and the combination control group with cisplatin + vindesine. RESULTS: Of 138 patients, 16 were in the nedaplatin single drug group; 60 were in the combination trial group; and 62 were in the combination control group. All of the 16 cases in the single drug group, which were treated with platinum previously, achieved 12.5% of response rate. And the combination trial group and control group had a very similar response rate, which were 26.7% versus 25.8%, respectively. The incidence rates of neutropenia and anemia were similar in the two groups. But the incidence rate of thrombocytopenia was higher in the trial group than that in the control group. Nedaplatin has a possibility to result in mild nausea/vomiting. CONCLUSION: Nedaplatin is an effective platinum drug in the treatment of NSCLC, not only for no previously chemotherapy patients, but also for those patients resistant to cisplatin/carboplatin. Nedaplatin has a good clinical tolerance. And the main adverse reaction was myelosuppression, especially thrombocytopenia.