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Background and purpose: The expression of programmed death ligand-1 (PD-L1) in lung cancer not only is the most important biomarker for predicting the efficacy of programmed death-1 (PD-1)/PD-L1 inhibitors, but also may affect the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) targeted therapy. However, there are currently few reports in the relevant literature on whether the expression of PD-L1 in lung cancer can affect the efficacy of chemotherapy in patients with lung adenocarcinoma. This study mainly explored the effect of PD-L1 expression in lung adenocarcinoma on the efficacy of pemetrexed-based chemotherapy and its underlying mechanism. Methods: From Oct. 2015 to Dec. 2018, 185 eligible lung adenocarcinoma patients treated in Department of Pathology, The General Hospital of Western Theater Command PLA were enrolled. The expressions of PD-L1 and thymidylate synthase (TS), a molecule predicting the efficacy of pemetrexed-based chemotherapy, were detected by immunohistochemistry. The survival curve of patients was drawn by Kaplan-Meier method. The log-rank test and COX regression model were used to analyze the clinicopathological factors affecting the patients’ progression-free survival (PFS) and overall survival (OS). The log-rank test was used to analyze the effects of PD-L1 and TS expressions on the patients’ PFS and OS. Spearman rank correlation test was used to analyze the correlation between PD-L1 expression and TS expression in lung cancer tissues. Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) were used to detect the protein and mRNA expressions of PD-L1 and TS in 6 types of lung adenocarcinoma cell lines. The Pearson correlation test was used to analyze the correlation between PD-L1 and TS at protein expression level and mRNA expression level. Results: Among 51 patients with advanced lung adenocarcinoma who received pemetrexed-based chemotherapy as first-line treatment, the objective response rate (ORR) of the PD-L1 positive group was 20.0%, and the disease control rate (DCR) was 60.0%. There was no significant difference compared with the PD-L1 negative group (ORR: 20.0% vs 35.5%, χ 2 =1.404, P=0.236; DCR: 60.0% vs 80.6%, χ 2 =2.602, P=0.107). The median PFS (mPFS) of patients with negative expression of PD-L1 was significantly better than that of patients with positive expression of PD-L1 (mPFS: 5.6 months vs 4.1 months, log-rank=5.406, P=0.020), and there was no significant difference in median OS (mOS) between them (mOS: 15.9 months vs 12.7 months, log-rank=0.525, P=0.469). Univariate analysis found that the positive expressions of PD-L1 and TS were risk factors for PFS ［PD-L1 negative vs positive: HR=2.002 (1.100-3.645), P=0.023; TS negative vs positive: HR=2.205 (1.367-4.587), P=0.003］. Multivariate analysis found that TS positive expression was an independent risk factor for PFS ［TS negative vs positive: HR=3.245 (1.091-9.652), P=0.034］. Among the 51 patients with advanced lung adenocarcinoma who received pemetrexed-based chemotherapy as the first-line treatment, the expression of PD-L1 in cancer tissues was significantly positively correlated with the expression of TS (r s =0.691, P

Sorafenib, the first‐line agent for treatment of advanced hepatocellular carcinoma (HCC), improves median overall survival by approximately 3 months. In the present study, we investigated whether sorafenib combined with cucurbitacin B (CuB), a natural tetracyclic triterpenoid isolated from Cucurbitaceae, exerts enhanced antitumor effects against HCC. Cell viability and colony formation ability were detected by cell‐counting kit‐8 and colony formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression was detected by western blotting. HepG2 xenografts in nude mice were used to evaluate in vivo antitumor effects. We report that sorafenib and CuB exhibited synergistic effects on cellular proliferation inhibition and cell apoptosis induction, but not on cell cycle arrest. Furthermore, combination treatment enhanced levels of cleaved caspase 3 and cleaved caspase 9, but suppressed phosphorylation of STAT3. Epidermal growth factor, a potent stimulator of signal transducer and activator of transcription‐3 (STAT3), promoted cell viability and colony formation ability, whereas combination treatment exerted inhibitory effects on epidermal growth factor‐induced STAT3 phosphorylation. Finally, HepG2 xenograft mice cotreated with sorafenib and CuB exhibited reduced tumor progression without notable weight loss. In conclusion, sorafenib and CuB exert synergistic antitumor effects through a pathway that may involve STAT3 phosphorylation, and this may represent a promising therapeutic approach for treatment of HCC. [ABSTRACT FROM AUTHOR]

Background/Aims: Tobacco smoking is a major risk factor for the occurrence and progression of periodontitis. We previously demonstrated that nicotine could induce the expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in human and rat periodontal tissues. To further examine the signal pathways mediated by α7 nAChR in periodontal ligament (PDL) cells, we investigated whether nicotine affects interleukin-1β (IL-1β) and interleukin-8 (IL-8) via the α7 nAChR/NF-κB pathway in human PDL cells. Methods: Human PDL cells were pre-incubated with alpha-bungarotoxin (α-BTX) or pyrrolidine dithiocarbamate (PDTC), then cultured with nicotine. Then, we used western blotting, a dual-luciferase reporter, real-time quantitative PCR and an enzyme-linked immunoassay to assess expression of the NF-κB p65 subunit, NF-κB activity and production of IL-1β and IL-8 in human PDL cells. Results: Compared with the control group, nicotine could significantly induce production of IL-1β and IL-8 in human PDL cells and cause the similar effects on the expression of the NF-κB p65 subunit and NF-κB activity. Conclusion: This study demonstrates that nicotine could induce production of IL-1β and IL-8 via the α7 nAChR/NF-κB pathway in human PDL cells, providing data for a better understanding of the relationships among smoking, nicotine, and periodontitis. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]