Effects of arsenic and its metabolites on expressions of BCL-2α and BCL-2β transcripts / 环境与职业医学

Background Arsenic is a toxicant that can affect the expressions of the cellular anti-apoptotic gene BCL-2 and its protein, but the effects of arsenic on BCL-2α and BCL-2\begin{document}$\beta $\end{document} transcripts have not been reported. Objective To investigate the potential effects of arsenic and its metabolites, methylarsonic acid (MMA) and dimethylarsonic acid (DMA), on BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T (total of α and \begin{document}$\beta $\end{document} transcripts) in human bronchial epithelial cells (16HBE) and human lung adenocarcinoma cells (A549). Methods 16HBE cells and A549 cells were randomly divided into three categories of exposure after in vitro culture: single-selected arsenic compound exposure groups with isoconcentration (16HBE cells were treated with 4.5 μmol·L−1 of MMA, DMA, and sodium arsenite, respectively, while A549 cells were treated with 60 μmol·L−1 of MMA, DMA, and sodium arsenite, respectively), sodium arsenite exposure groups with different concentrations (16HBE cells were treated with 1.5, 3.0, and 4.5 μmol·L−1 of sodium arsenite respectively, while A549 cells were treated with 20, 40, and 60 μmol·L−1 of sodium arsenite respectively), and combined exposure groups (i.e. MMA+sodium arsenite, and DMA+sodium arsenite; the exposure concentrations of 16HBE cells were both 1.5 μmol·L−1 and both 4.5 μmol·L−1 respectively, and those of A549 cells were both 20 μmol·L−1 and both 60 μmol·L−1 respectively). Meanwhile, a blank control group was also set up in each exposure category. After 48 h of continuous exposure, the relative expressions of BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T in both cells were detected by real-time PCR. Results Regarding the single-selected arsenic compound exposure, in 16HBE cells, the expression levels of BCL-2α and BCL-2T under 4.5 μmol·L−1 MMA treatment were lower than those in their control groups (q=3.27, 2.93, both P<0.05), and the expression levels of BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T under 4.5 μmol·L−1 sodium arsenite were lower than those in their respective control groups (q=11.06, 3.65, 10.70, all P<0.05). In A549 cells, the expression level of BCL-2T treated with 60 μmol·L−1 DMA was lower than that in the control group (q=3.12, P<0.05), and the expression levels of BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T treated with 60 μmol·L−1 sodium arsenite were lower than those in their respective control groups (q=7.59, 7.27, 8.06, all P<0.05). Regarding the sodium arsenite exposure: 16HBE cells treated with 1.5 μmol·L−1 sodium arsenite had a lower expression level of BCL-2α and a higher expression level of BCL-2\begin{document}$\beta $\end{document} than those in their respective control groups (q=6.06, 11.92, both P<0.05); the expression level of BCL-2α under 3.0 μmol·L−1 sodium arsenite was lower than that in the control group (q=12.72, P<0.05); and under 4.5 μmol·L−1 sodium arsenite treatment, the expression levels of BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T were lower than those in their respective control groups (q=15.72, 6.79, 6.62, all P<0.05). The expression levels of BCL-2α gradually decreased with increasing concentrations of sodium arsenite (Fα trend=144.80, P<0.001), while BCL-2\begin{document}$\beta $\end{document} and BCL-2T decreased in a dose-dependent manner in the range of 1.5-4.5 μmol·L−1 (F\begin{document}${}_{\beta } $\end{document} trend=135.40, FT trend=38.24, both P<0.001). In A549 cells, the expression levels of BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T under each concentration of sodium arsenite treatments were lower than those in their respective control groups (all P<0.05); the results of further trend tests showed that their expression levels gradually decreased with increasing concentrations of sodium arsenite (Fα trend =31.97, F\begin{document}${}_{\beta} $\end{document} trend=549.50, FT trend=252.40, all P<0.001). Regarding the combined exposure, under MMA+sodium arsenite treatment at both 60 μmol·L−1, the expression levels of BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T in A549 cells were higher than those in their respective control groups (q=6.37, 14.91, 5.33, all P<0.05); under DMA+sodium arsenite treatment at both 60 μmol·L−1, their expression levels in A549 cells were also higher than those in their respective control group (q=8.60, 17.29, 6.91, all P<0.05). Conclusion Exposure to a high concentration (16HBE: 4.5 μmol·L−1, A549: 60 μmol·L−1) of a single arsenic metabolite has no effect on BCL-2 transcripts in 16HBE cells and A549 cells. Exposure to a low concentration (1.5 μmol·L−1) of sodium arsenite alone would decrease the expression level of BCL-2α and increase the expression level of BCL-2\begin{document}$\beta $\end{document} in 16HBE cells, and exposure to all designed concentrations of sodium arsenite alone would decrease the expressions of all transcripts in A549 cells. The combined exposure to high concentrations (both 60 μmol·L−1) of MMA plus sodium arsenite or high concentrations (both 60 μmol·L−1) of DMA plus sodium arsenite would increase the expressions of BCL-2α, BCL-2\begin{document}$\beta $\end{document}, and BCL-2T in A549 cells, which are different from the effects presented by single exposure.

MDT Treatment of Small Cell Lung Cancer Complicated with Adenocarcinoma: A Case Report and Literature Review / 中国肺癌杂志

Small cell lung cancer (SCLC) is the most malignant lung cancer with the highest mortality. At present, the first-line standard treatment is still based on Etoposide and Platinum chemotherapy. However, for SCLC that progresses after first-line therapy, the treatment options are still very limited. Since the molecular mechanism of first-line drug resistance of SCLC is still unclear, and the precision medicine strategy after first-line drug resistance is still in the pre-clinical stage. The proportion of secondary biopsy and genetic testing is very low after the progress of first-line treatment of SCLC. In this study, we report a case of a middle-aged woman who was first diagnosed with SCLC. Adenocarcinoma with sensitive gene mutations and repeated changes of small cell carcinoma were detected by multiple biopsies during the course of the disease, suggesting that the patient may be a special subtype of SCLC - mixed SCLC (M-SCLC). In this case, the patient has been treated with radiotherapy and chemotherapy, immunotherapy and targeted therapy successively, and the survival time has reached 2 years and 8 months. Through the case report and literature review retrospectively, this study aimed to explore the part patients may start to present hybrid histopathologic types or tissue type change after treatment of SCLC. Biopsy pathologic histology and genetic testing is necessary after disease progression to look for potential therapeutic targets, so as to give precise treatment based on molecular markers detection results and provide the patient with the benefit of survival for as long as possible.
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A Meta-Analysis of Efficacy and Adverse Effects of Lobaplatin and Cisplatin in the Treatment of Malignant Pleural Effusion / 中国肺癌杂志

BACKGROUND@#The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion.@*METHODS@#The databases of Medline (PubMed), Embase, Web of Science, Cochrane, Wanfang, CNKI and VIP were retrieved so as to search the studies about the randomized controlled clinical trials (RCT) that compared the Lobaplatin and Cisplatin for malignant pleural effusion. The main outcome indicators include objective response rate, complete response, partial response, nephrotoxicity, chest pain, gastrointestinal reaction, myelosuppression, fever response and hepatotoxicity. Relative risk was used as the effect size, which was expressed as 95% confidence interval. The meta-analysis was performed using Stata 14.0 statistical software.@*RESULTS@#A total of 12 RCTs and 720 MPE patients were included. The results showed that the ORR (RR=1.27, 95%CI: 1.15-1.40, P<0.001), CR (RR=1.39, 95%CI: 1.09-1.78, P=0.007), PR (RR=1.21, 95%CI: 1.02-1.42, P=0.026) in LBP thoracic perfusion chemotherapy were significantly higher than those in DDP thoracic perfusion chemotherapy. The incidence of nephrotoxicity (RR=0.31, 95%CI: 0.13-0.71, P=0.005) and gastrointestinal reactions (RR=0.44, 95%CI: 0.31-0.62, P<0.001) in the LBP group were significantly lower than those in DDP group.@*CONCLUSIONS@#Compared with DDP pleural perfusion chemotherapy, the ORR, CR and PR of LBP pleural perfusion chemotherapy for MPE are significantly better than DDP, and its nephrotoxicity and gastrointestinal reactions are remarkably lower than DDP.