The efficacy and safety of nivolumab in the treatment of advanced melanoma: a meta-analysis of clinical trials.

BACKGROUND: Nivolumab has become a therapeutic regimen for the treatment of patients with advanced melanoma. The goal of this study was to assess the efficacy and safety of nivolumab in patients with advanced melanoma. METHODS: A systematic search from January 2008 to August 2015 with "nivolumab" and "advanced melanoma" as search terms was performed for possible clinical trials. According to the hazard ratio and the 95% confidence interval (CI) for progression-free survival (PFS), rates of objective response, complete response, partial response, rates of toxic effects, and the efficacy and safety of nivolumab were assessed. Using the software Review Manager (version 5.3) a meta-analysis was performed. RESULTS: There were four trials with 1,910 patients included. Based on the four trials, the pooled hazard ratio of PFS was 0.53 (95% CI, 0.43-0.66; P<0.001). The pooled risk ratio for the objective response rate, complete response, and partial response was 2.98% (95% CI, 2.38%-3.73%; P<0.001), 3.71% (95% CI, 2.67%-5.14%; P<0.001), and 2.51% (95% CI, 2.12%-2.99%; P<0.001), respectively. Nivolumab plus ipilimumab therapy significantly increased the risk of grade 3/4 rash and fatigue. CONCLUSION: Nivolumab-based therapy prolonged PFS in treatment of advanced melanoma, with less adverse effects. Nivolumab appears to be a favorable treatment option as a novel, targeted anticancer agent, for patients with advanced melanoma.

Fenofibrate enhances radiosensitivity of esophageal squamous cell carcinoma by suppressing hypoxia-inducible factor-1α expression.

Radiation therapy is widely used in esophageal squamous cell carcinoma (ESCC). Promoting radiation sensitivity is important. Recent studies have shown that fenofibrate can inhibit the growth of several cancer lines and hypoxia-inducible factor-1α (HIF-1α) expression in MCF-7 cells. However, few studies on the radiosensitive effect of fenofibrate on ESCCs under hypoxic condition have been conducted. In this study, we assessed the radiosensitive effects of fenofibrate on human ESCC cells. In vitro experiments showed the inhibition of cytotoxic effects after ionizing irradiation. We measured cell viability and clonogenic survival rate. Flow cytometry showed that fenofibrate pretreatment promoted apoptosis. The in vivo data also suggest that fenofibrate had radiosensitizing effects in ECA-109 cells xenografted into nude mice. Western blot and immunohistochemical analyses revealed that the HIF-1α and vascular endothelial growth factor (VEGF) protein content decreased by fenofibrate. Thus, the inhibition of HIF-1α and VEGF expression in ESCC cells contributed to the radiosensitive effect. These data suggest that fenofibrate may be a potential radiosensitive drug.

NEDD9 overexpression correlates with poor prognosis in gastric cancer.

In this study, the expression of neural precursor cell expressed developmentally downregulated 9 (NEDD9) in benign and malignant gastric tissues was investigated, and the significance of NEDD9 in gastric cancer prognosis was explored. Immunohistochemistry was used to detect NEDD9 expression in gastric cancer, nontumor gastric, and normal gastric tissues. The relationship between NEDD9 expression in gastric cancer tissues and the clinicopathologic factors was examined using the Mann-Whitney U test. The two factors between NEDD9 expression and tumor node metastasis (TNM) stage in gastric cancer patients were analyzed by Spearman rank correlation analysis. The Kaplan-Meier method and log-rank test were used to compare the overall survival of NEDD9 negative, weak positive expression, and strong positive expression group. NEDD9 expression rates were significantly higher (P < 0.001) in gastric cancer tissues (162 out of 187, 86.6 %) compared with normal (2 out of 11, 18.2 %) and nontumor (11 out of 58, 19.0 %) gastric tissues. The upregulated NEDD9 expression in gastric cancer tissue was significantly correlated with high preoperative CEA level (P = 0.044), poor differentiation (P = 0.007), tissue invasion (P = 0.015), present lymph node metastasis (P < 0.001), and high TNM stage (P < 0.001). NEDD9 expression was positively correlated with clinical TNM stage. Advancing clinical TNM stage corresponded with higher NEDD9 expression (r s = 0.289, P < 0.001). The overall 5-year survival of gastric cancer patients with strong positive NEDD9 expression was significantly shorter compared with the survival of NEDD9 negative and weakly positive expression group. NEDD9 may be used as a biomarker in the clinical setting to predict the prognosis of gastric cancer patients.

Resveratrol attenuates radiation-induced salivary gland dysfunction in mice.

OBJECTIVES/HYPOTHESIS: In our study we investigated the radioprotective effect of resveratrol (RES) in a murine model of radiation-induced salivary gland dysfunction. STUDY DESIGN: Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent (group I), RES treated (group II; 20 mg/kg/d), 15 Gy irradiation with solvent treatment (group III), and 15 Gy irradiation with RES treatment (group IV; 15 Gy and 20 mg/kg/d RES). RES (group II and IV) was administered intraperitoneally 3 days prior to irradiation through the conclusion of the experiment. METHODS: Saliva and submandibular gland tissues were obtained for biochemical, morphological, immunohistochemical, and Western blot analyses at 8 hours, 24 hours, and 30 days after localized irradiation. RESULTS: Radiation caused a reduction of saliva secretion, salivary amylase activity, superoxide dismutase, and an elevation of malondialdehyde. Administration of RES reversed the reduction of saliva secretion induced by irradiation and restored salivary amylase and superoxide dismutase activity. In addition, RES could inhibit increases in transforming growth factor-ß1 expression induced by radiation. CONCLUSIONS: RES can protect salivary glands against the negative effects of irradiation and has great potential as a treatment for successful radiotherapy in clinical practice.