Identification of plasma SAA2 as a candidate biomarker for the detection and surveillance of non-small cell lung cancer.

This study aimed to measure the expression of SAA2 in plasma and to assess its diagnostic efficacy as a biomarker for non-small cell lung cancer (NSCLC). The gene expression of SAA2 in NSCLC was analyzed based on a database. Then, SAA2 expression was detected by immunohistochemistry in lung tissue and by enzyme-linked immunosorbent assay in 90 patients with NSCLC and 61 normal controls. Finally, the diagnostic performance was assessed in terms of accuracy, sensitivity, and specificity. At the gene and protein levels, the SAA2 expression was significantly higher in the NSCLC group than in the control group (p<0.01). It was higher in lung squamous carcinoma than in lung adenocarcinoma and in males than in females, and this trend was also observed in the lung squamous carcinoma group. Of note, the expression of SAA2 increased with increasing disease stage. Receiver operating characteristic (ROC) curve analysis revealed that the sensitivity of SAA2 was 83.61%, the specificity was 91.11%, and the area under the curve (AUC) was 0.9252. Its accuracy was 68.89%, which was higher than that of other conventional diagnostic biomarkers, and the combined application can effectively improve the diagnostic efficiency. Based on the results, SAA2 expression was positively correlated with the disease stage of NSCLC. Notably, SAA2 is more concerning in male patients with lung squamous carcinoma, and it can help in the screening and diagnosis of NSCLC. SAA2 may represent a novel diagnostic biomarker in NSCLC.

CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model.

Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8+ T cells, and cytokines (tumor growth factor (TGF)-ß, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.

The Apoptosis Mechanism of Epirubicin Combined with BCG on Human Bladder Cancer Cells.

AIMS: The purpose of our study was to explore the combination effect of epirubicin and Bacillus Calmette Guerin (BCG) and its mechanism. BACKGROUND: Bladder cancer is a threat to human health worldwide. Commonly used chemotherapy drugs and biotherapy have significant therapeutic effects on bladder cancer, but the mechanism and combined effects are still unclear. OBJECTIVE: To evaluate the anti-cancer effect of epirubicin combined with BCG on human bladder cancer cells, our studies were carried out. METHODS: The viability of human bladder cancer cells with epirubicin and/or BCG treatments was examined by Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma 2 (Bcl-2) were detected by western blot. RESULTS: The viability of human bladder cancer with epirubicin or BCG treatment was decreased and the viability with epirubicin combined with BCG treatment was decreased more, which were determined by CCK-8 assay. Both epirubicin and BCG increased the apoptosis rate of human bladder cancer and arrested more cells into G0/G1 phase, which were tested by flow cytometry. The expression of caspase-3, p53 and Bax was increased and the expression of Bcl-2 was decreased with epirubicin treatment on human bladder cells, which were analyzed by western blot. The expression of caspase-3 and p53 was increased with BCG treatment, which was examined by western blot. CONCLUSION: Epirubicin induced apoptosis in human bladder cancer cells by up-regulating the expression of proapoptotic factors (caspase-3, p53 and Bax) and down-regulating the expression of anti-apoptotic factor (Bcl-2). BCG promoted apoptosis of human bladder cancer cells by up-regulating the expression of caspase-3 and p53. BCG plays a potential role at the time of the combination of epirubicin and BCG on bladder cancer cells in early stage. Both epirubicin and BCG affected cell cycle distribution via arresting more bladder cancer cells at G0/G1 phase, which ultimately led bladder cancer proliferation in vitro and promoted apoptosis.

CpG Oligodeoxynucleotides Induces Apoptosis of Human Bladder Cancer Cells via Caspase-3-Bax/Bcl-2-p53 Axis.

OBJECTIVE: To evaluate the anti-cancer effect of unmethylated cytosine-phosphorothioate-guanine (CpG)-containing oligodeoxynucleotides (ODNs) on human bladder cancer UM-UC-3 cells, our study was carried out. METHODS: The viability of cells (UM-UC-3, T24 and SV-HUC-1) with CpG ODN treatments was examined by cell counting kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma 2 (Bcl-2) were detected by western blot. RESULTS: Experimental results showed that the viability of human bladder cancer cells (UM-UC-3 and T24) with CpG ODN treatment was decreased and the viability of human normal urothelial cells (SV-HUC-1) with CpG ODN treatment was increased with time-dependance manner. Moreover, CpG ODN increased the apoptosis rate of UM-UC-3 cells and arrested more cells in G0G1 phase. Furthermore, the expression of caspase-3, p53 and Bax were increased and the expression of Bcl-2 was decreased with CpG ODN treatment on UM-UC-3 cells. CONCLUSION: CpG ODN promoted the proliferation of normal urinary transitional epithelial cells (SV-HUC-1) and inhibited the cell viability of human bladder cancer cells (UM-UC-3 and T24) in vitro. CpG ODN induced the apoptosis of human bladder cancer (UM-UC-3) cells in a cascade progress via enhancing the expression of caspase-3, p53 and Bax, and inhibiting the expression of Bcl-2 with significant time-dependancy. CpG ODN inhibited cell cycle distribution of human bladder cancer (UM-UC-3) cells with more cells were arrested in G0G1 phase. This study suggested that the CpG ODN is the potential candidate on human bladder cancer.