Alterations of fecal bacterial communities in patients with lung cancer.

Emerging evidence suggests the microbiome may affect a number of diseases, including lung cancer. However, the direct relationship between gut bacteria and lung cancer remains uncharacterized. In this study, we directly sequenced the hypervariable V1-V2 regions of the 16S rRNA gene in fecal samples from patients with lung cancer and healthy volunteers. Unweighted principal coordinate analysis (PCoA) revealed a clear difference in the bacterial community membership between the lung cancer group and the healthy control group. The lung cancer group had remarkably higher levels of Bacteroidetes, Fusobacteria, Cyanobacteria, Spirochaetes, and Lentisphaerae but dramatically lower levels of Firmicutes and Verrucomicrobia than the healthy control group (P < 0.05). Despite significant interindividual variation, eight predominant genera were significantly different between the two groups. The lung cancer group had higher levels of Bacteroides, Veillonella, and Fusobacterium but lower levels of Escherichia-Shigella, Kluyvera, Fecalibacterium, Enterobacter, and Dialister than the healthy control group (P < 0.05). Most notably, correlations between certain specific bacteria and serum inflammatory biomarkers were identified. Our findings demonstrated an altered bacterial community in patients with lung cancer, providing a significant step in understanding the relationship between gut bacteria and lung cancer. To our knowledge, this is the first study to evaluate the correlations between certain specific bacteria and inflammatory indicators. To better understand this relationship, further studies should investigate the underlying mechanisms of gut bacteria in lung cancer animal models.

Reversal of Chemoresistance in Human Lung Cancer Cell Line A549/Taxol by Synthetic Second Mitochondria-Derived Activator of Caspase Peptide.

BACKGROUND: Chemoresistance is a leading cause of treatment failure in advanced lung cancer, including that with the extensively prescribed taxol. Recently, a series of structurally unique second mitochondria-derived activators of caspase (Smac) that act as antagonists of inhibitor of apoptosis proteins (IAPs) have been discovered, exhibiting the ability of inducing enhanced apoptosis of various cancer cell types when combined with chemotherapy. In the present study, we synthesized the second mitochondria-derived activator of caspase peptide (Smac-N7 for short) and explored its capacity in combination with taxol in vitro. METHODS: The sensitivity assay and reversal ability of Smac-N7 were tested by MTT. Flow cytometry was used to analyze apoptosis of cells with Annexin V/PI double staining technique. Cell cloning ability was performed to reflect its biological behavior in each group. RESULTS: Concentrations with inhibitory rates < 10% were selected as the reversal value of Smac-N7 peptide using MTT. The reversal folds were 2.52, 3.26, 3.67, and 5.4 in taxol + Smac-N7 (0.0390625, 0.078125, 0.15625, 0.3125 µg/mL, respectively), and concentrations of Smac-N7 and reversal folds appeared in an obvious positive correlation (r(s) = 1, p = 0.000). Apoptosis analyzed at 48 hours by flow cytometry showed the apoptotic rates in taxol and 0.0390625, 0.078125, 0.15625, and 0.3125 µg/mL Smac-N7 + taxol groups were 15.4 ± 1.09%, 20.8% ± 2.18%, 28.4% ± 4.17%, 37.64% ± 6.41%, and 46.6% ± 7.76%, respectively. Concentrations of Smac-N7 appeared to have negative correlations with PE and SF (r(s) = -1, p < 0.05), which showed that the cells' cloning ability in 0.3125 µg/mL Smac-N7 + taxol group was worse than that of other groups. CONCLUSIONS: When combined with taxol, 0.3125 µg/mL Smac-N7 peptide may significantly increase taxol-induced apoptosis in chemoresistant A549/taxol lung cells at 48 hours, and is potentially useful as a reversal agent in lung cancer therapy.

[Anti-tumor effects induced by fusion of interleukin-18 gene transfected NCI-H460 lung cancer cell line with dendritic cells].

OBJECTIVE: To explore the anti-tumor effects induced by fusion of interleukin (IL)-18 gene transfected lung cancer cell line NCI-H460 cells with dendritic cells (DC). METHODS: (1) DC were induced from human monocytes and fused with IL-18 transfected NCI-H460 cells. Fusion was selected using MACS microbeads. (2) Four groups (group GT, group PT, group NT and group BC) were set up. T cells activated by IL-18 gene transfected fusion or pcDNA3. 1 + vector transfected fusion and non-transfected fusion were taken as effetor cells. No effector cells was in group BC. Lactic dehydrogenase ( LDH) method was used to evaluate the antitumor effect in vitro. (3) Tumor-bearing nude mice were inoculated with effector cells mentioned above. The tumor size and weight in the 4 groups were compared. RESULTS: The killing rate in vitro of 3 groups were 53. 14% ,30. 10% and 31.49% , respectively. The tumor size and weight in the 3 groups were lower than group BC, among which group GT was the lowest. CONCLUSION: Fusion of IL-18 gene transfected NCI-H460 lung cancer cells with dendritic cells can effectively induce anti-tumor immunity in the host.

[An experimental study on the antitumor effects induced by fusions of dendritic cells with NCI-H460 lung cancer cells].

OBJECTIVE: To study the antitumor effects induced by fusions of dendritic cells (DC) and NCI-H460 cells and compared with antigen pulsed DC. METHODS: (1) DC were induced from human monocytes and were fused with NCI-H460 cells. Three experimental groups were set up, including group fusions cell (FC), group pulsed cell (PC) and group T cell (TC), for which T cells activated by fusions, antigen pulsed DC, and non-activated T cells were used as the effector cells respectively. The killing activity of effector cells to NCI-H460 cells were evaluated by lactate dehydrogenase method. (2) NCI-H460 cells were injected subcutaneously to BALB/c nude mice. Then 18 cancer-bearing mice were divided randomly into 3 groups, group FC, group PC and group TC. Effector cells mentioned above were inoculated subcutaneously. The tumor size and tumor weight were assessed and compared. RESULTS: The killing rates to NCI-H460 cells of group FC, group PC and group TC were 43.54%, 26.57% and 3.25% respectively. Comparison of the killing activity of these 3 groups showed group FC > group PC > group TC (F = 5.47, P < 0.05). The tumor size of group FC was significantly smaller than that of group PC and group TC. The tumor weights of group FC, group PC and group TC were (1,129 +/- 123) mg, (1,709 +/- 160) mg and (3,344 +/- 288) mg respectively (F = 37.05, P < 0.01). CONCLUSION: Fusions of DC and NCI-H460 cells could induce powerful antitumor immunity, which was more effective than antigen pulsed DC.