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Macamides are a class of bioactive natural products obtained from Lepidium meyenii (maca), which have been reported to exert inhibitory activity in cancer. However, their role in lung cancer is currently unknown. In the present study, macamide B was shown to inhibit the proliferation and invasion of lung cancer cells, as determined by Cell Counting Kit-8 and Transwell assays, respectively. By contrast, macamide B induced cell apoptosis, as determined by Annexin V-FITC assay. Moreover, combined treatment with macamide B and olaparib, an inhibitor of poly (ADP-ribose) polymerase, further suppressed the proliferation of lung cancer cells. At the molecular level, the expression of ataxia-telangiectasia mutated (ATM), RAD51, p53 and cleaved caspase-3 were significantly increased by macamide B, as determined by western blotting, whereas the expression levels of Bcl-2 were decreased. By contrast, when ATM expression was knocked down by small interfering RNA technology in A549 cells treated with macamide B, the expression levels of ATM, RAD51, p53 and cleaved caspase-3 were reduced, whereas those of Bcl-2 were increased. Consistently, cell proliferation and invasive ability were partially rescued by ATM knockdown. In conclusion, macamide B inhibits lung cancer progression by inhibiting cell proliferation and invasion, and inducing apoptosis. Furthermore, macamide B may participate in regulating the ATM signaling pathway. The present study provides a potential new natural drug for treating patients with lung cancer.

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Lung cancer causes thousands of deaths worldwide every year, and present therapeutics show little benefit for advanced-stage patients. Researchers do not know why and how lung cancer begins. Lactamase ß (LACTB) is a tumor-suppressor in some cancers. However, its role in lung cancer is unknown. By analyzing the TCGA database and Kaplan-Meier Plotter database, LACTB was found to be downregulated in lung cancer tissues but the methylation level was increased. Patients with high LACTB expression exhibited improved survival. Then, in vitro assays demonstrated that LACTB overexpression inhibited cell migration and invasion, and induced apoptosis in H1299 and H1975 cells. Knockdown of LACTB caused the reverse effects. Moreover, a much higher apoptotic rate and more potent inhibitory effects on H1299 and H1975 cells were obtained when LACTB was combined with docetaxel. In addition, members of the epithelial-mesenchymal transition (EMT) signaling pathway were assessed using western blot analysis. The expression of E-cadherin was decreased while levels of N-cadherin and vimentin were increased after knockdown of LACTB in lung cancer cells. By contrast, overexpression of LACTB increased the level of E-cadherin but decreased N-cadherin and vimentin. Therefore, LACTB is a tumor suppressor in lung cancer that inhibits cell migration and invasion and induces cell apoptosis. Meanwhile, LACTB was found to strengthen the anticancer role of docetaxel and to suppress the EMT pathway in lung cancer.

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BACKGROUND: To distinguish early-stage lung cancer from benign disease in pulmonary nodules, especially lesions with ground-glass opacity (GGO), we assessed gene mutations of ctDNA in peripheral blood using targeted next-generation sequencing (NGS). METHODS: Single pulmonary nodule patients without mediastinal lymph nodes and symptoms that were hard to diagnose by chest CT and lung cancer biomarker measurement in multiple medical centers were enrolled into the study. All patients accepted minimally invasive surgery but refused preoperative biopsy. Gene mutations in preoperative blood samples were detected by targeted NGS. Mutations with significant differences between lung tumors and benign lesions, as grouped by postoperative pathology, were screened. Protein expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood. RESULTS: In the training set, the RNF213, KMT2D, CSMD3 and LRP1B genes were mutated more frequently in early-stage lung cancer (27 cases) than in benign nodules (15 cases) (P < 0.05). High expression of the RNF213 gene in lung cancers and low expression in benign diseases were seen by immunohistochemistry. The RNF213 gene was mutated in 25% of lung cancer samples in the validation set of 28 samples and showed high specificity (100%). In GGO patients, RNF213 was mutated more frequently in early-stage lung cancer compared to benign diseases (P < 0.05). CONCLUSIONS: RNF213 gene mutations were observed more frequently in early-stage lung cancer, but not in benign nodules. Mutation of the RNF213 gene in peripheral blood may be a high specificity biomarker for the assisted early diagnosis of lung cancer in pulmonary nodules. KEY POINTS: Significant findings of the study: In peripheral venous blood and tumor tissue, RNF213 gene mutated more frequently in lung cancer than benign pulmonary nodules. WHAT THIS STUDY ADDS: Detection mutation of the RNF213 gene in peripheral blood may be a high specificity method for the assisted early diagnosis of lung cancer in pulmonary nodules.

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An increasing number of studies have suggested the dysbiosis of salivary microbiome has been linked to the advancement of multiple diseases and proved to be helpful for the diagnosis of them. Although epidemiological studies of salivary microbiota in carcinogenesis are mounting, no systemic study exists regarding the oral microbiota of non-small cell lung cancer (NSCLC) patients. In this study, we presented the characteristics of the salivary microbiota in patients from NSCLC and healthy controls by sequencing of the 16S rRNA microbial genes. Our result revealed distinct salivary microbiota composition in patients from NSCLC compared to the healthy controls. As principal co-ordinates analysis (PCoA) showed, saliva samples clearly differed between the two groups, considering the weighted (p = 0.001, R2 = 0.17), and unweighted (p = 0.001, R2 = 0.25) UniFrac distance. Phylum Firmicutes (31.69% vs 24.25%, p < 0.05) and its two genera Veillonella (15.51%% vs 9.35%, p < 0.05) and Streptococcus (9.96% vs 6.83%, p < 0.05) were strongly increased in NSCLC group compared to the controls. Additionally, the relative abundances of Fusobacterium (3.06% vs 4.92%, p = 0.08), Prevotella (1.45% vs 3.52%, p < 0.001), Bacteroides (0.56% vs 2.24%, p < 0.001), and Faecalibacterium (0.21% vs 1.00%, p < 0.001) in NSCLC group were generally decreased. Furthermore, we investigated the correlations between systemic inflammation markers and salivary microbiota. Neutrophil-lymphocyte ratio (NLR) positively correlated with the Veillonella (r =0.350, p = 0.007) and lymphocyte-monocyte ratio (LMR) negatively correlated with Streptococcus (r =-0.340, p = 0.008). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways inferred by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed that pathways related to xenobiotics biodegradation and metabolism (p < 0.05) and amino acid metabolism (p < 0.05) were enriched in the NSCLC group. Folate biosynthesis (p < 0.05) significantly decreased in NSCLC group. The specific correlations of clinical systemic inflammation markers and predicted KEGG pathways also could pronounce a broad understanding of salivary microbiota in patients with NSCLC. Moreover, our study extended the new sight into salivary microbiota-targeted interventions to clinically improve the therapeutic strategies for salivary dysbiosis in NSCLC patients. Further investigations of the potential mechanism of salivary microbiota in the progression of NSCLC are still in demand.

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OBJECTIVE: The objective of this study was to investigate the molecular mechanisms involved in rapamycin-induced inhibition of tumor growth. MATERIALS AND METHODS: Murine S180 sarcoma cells were subcutaneously injected into mice, and the tumor-bearing mice were randomly divided into three groups (vehicle control, 2 mg/kg rapamycin, and 4 mg/kg rapamycin). The effect of rapamycin on tumor growth was determined by measuring tumor volume. Mammalian target of rapamycin (mTOR), Beclin1, ULK1, LC3, Notch1, CD133, and CD90 expressions was confirmed using confocal microscopy and Western blotting. RESULTS: The tumor growth inhibition rates induced by high-dose and low-dose rapamycin were 48.8% and 30.1%, respectively. Beclin1 and ULK1 expressions and the LC3-II/LC3-I ratio in tumor tissues were altered by rapamycin, whereas mTOR, Notch1, CD133, and CD90 expressions were significantly inhibited by rapamycin in immunofluorescence assays. Western blotting also showed similar results. CONCLUSION: Tumor growth delay induced by rapamycin may be associated with the suppression of the cancer stem cell phenotype (Notch1, CD133, and CD90) and promotion of autophagy (mTOR, Beclin1, ULK1, and LC3-II/LC3-I ratio) in the murine S180 sarcoma model.

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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.

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Armillaria mellea is a famous traditional Chinese medicinal and edible fungus. In this study, we purified a water-soluble polysaccharide (AMP) from the fruiting bodies of this fungus. AMP contained 94.8% carbohydrate, 2.3% uronic acid and 0.5% protein. Its molecular weight was determined as 4.6 × 105 Da, as determined by high-performance gel-permeation chromatography (HPGPC). Gas chromatography (GC) analysis indicated that AMP was mainly composed of d-glucose. In vitro assay, AMP exhibited a potent tumor growth inhibitory effect on A549 cells, and induced cell cycle disruption in the G0/G1 phase, accompanied by an increment of apoptotic cells. Furthermore, AMP induced the disruption of mitochondrial membrane potential, thus leading to cytochrome c release from mitochondria and activation of caspase-3 and -9. Taken together, our results demonstrate that AMP possesses strong antitumor activities through the mitochondria dependent pathway and activation of caspase cascade through cytochrome c release.

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