BackgroundTo compare the efficacy and toxicity of anti-programmed cell death receptor 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) versus docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC).Materials and methodsPhase III randomised clinical trials (RCTs) were identified after systematic review of databases and conference proceedings. A random-effect model was used to determine the pooled HR for overall survival (OS), progression-free survival (PFS) and duration of response. The pooled OR for overall response and treatment-related side effects were calculated using the inverse-variance method. Heterogeneity was measured using the τ2 and I2 statistics.ResultsAfter the systematic review, we included four phase III RCTs (n=2737) in this meta-analysis. The use of anti-PD-1/anti-PD-L1 agents (atezolizumab, nivolumab and pembrolizumab) was associated with better OS in comparison with docetaxel alone (HR: 0.69; 95% CI 0.63 to 0.75; p<0.00001). Similarly, the PFS and duration of response was significantly longer for patients receiving immunotherapy (HR: 0.85; 95% CI 0.75 to 0.96; p=0.007 and HR:0.32; 95% CI 0.24 to 0.43; p<0.00001, respectively) versus single agent chemotherapy. The overall response rate was also higher for patients who received any anti-PD-1/anti-PD-L1 therapy in comparison with docetaxel (OR: 1.77; 95% CI 1.26 to 2.50; p=0.001). Regarding treatment-related side effects grade 3 or higher, patients who received immunotherapy experienced less events than patients allocated to docetaxel (OR: 0.19; 95% CI 0.12 to 0.30; p<0.00001)ConclusionThe use of anti-PD-1/anti-PD-L1 therapy in patients with progressive advanced NSCLC is significantly better than the use of docetaxel in terms of OS, PFS, duration of response and overall response rate.
Background: Diets rich in polyphenols are well-known to reduce lung cancer risk among high-risk populations. We analyzed the efficacy of polyphenols-rich Haskap (Lonicera caerulea L.) fruit extracts in preventing tobacco specific nitrosamine (TSNA)-induced DNA damage in BEAS-2B lung epithelial cells. Methods: Monomeric polyphenols of Haskap fruits were extracted in ethanol and water, and profiled. TSNA, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-[(acetoxymethyl) nitrosamino]-1-(3-pyridyl)-1butanone (NNKOAc) were used (at sub-lethal concentrations) independently to induce the carcinogenesis process in BEAS-2B cells. Cell viability assay was confirmed that the tested concentrations of Haskap extracts were not cytotoxic to BEAS-2B cells. Results: The Haskap extracts contain diversity of polyphenols including phenolic acids and flavonoids, however, cyanidin-3-O-glucoside was the most predominant. Pre-treatment of cells with the Haskap extracts could significantly reduce the NNK-and NNKOAc-induced DNA double strand breaks, DNA fragmentation and intracellular reactive oxygen species, compared to non-treated cells. Immunocytochemistry for H2AX-phosphorylation (Serine 139, red) A. NNKOAc 100 mM, 3 h; B. Haskap ethanol extract (50 mg/mL, 3 h)+NNKOAc (100 mM, 3 h). DNA counterstaining was performed with 4,6-diamino-2-phenylindole (blue).
Conclusion:The polyphenols-rich Haskap extracts could prevent TSNA-induced DNA damage in lung epithelial cells in vitro. Protective effects of Haskap polyphenols against DNA damage are being investigated in vivo using A/J mice.
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