Lung cancer is the most common and fatal malignant tumor in the world. The tumor microenvironment (TME) is closely related to the occurrence and development of lung cancer, in which the inflammatory microenvironment plays an important role. Inflammatory cells and inflammatory factors in the tumor inflammatory microenvironment promote the activation of the NF-κB and STAT3 inflammatory pathways and the occurrence, development, and metastasis of lung cancer by promoting immune escape, tumor angiogenesis, epithelial–mesenchymal transition, apoptosis, and other mechanisms. Clinical and epidemiological studies have also shown a strong relationship among chronic infection, inflammation, inflammatory microenvironment, and lung cancer. The relationship between inflammation and lung cancer can be better understood through the gradual understanding of the tumor inflammatory microenvironment, which is advantageous to find more therapeutic targets for lung cancer.
Objective: To evaluate the potential anti-prostate cancer effects of Paris polyphylla ethanol extract (PPEE) and its underlying mechanisms. Materials and Methods: The anti-proliferation activity of PPEE was tested on PC3 and DU145 cells using Cell Counting Kit-8 assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by flow cytometry. Apoptosis of prostate cancer cells was induced by PPEE through endogenous and exogenous pathways. A mouse xenograft model was used to examine its anti-prostate cancer effects in vivo. Results: We found that the IC50 of PPEE on PC3 cells was 3.98 µg/ml and the IC50 of PPEE on DU145 cells was 8 µg/ml. PPEE induced prostate cancer cell apoptosis in a concentration dependent manner, through endogenous and exogenous pathways. PPEE induced PC3 cell cycle arrest in G0/G1 and G2/M phases, while in DU145cell it induced cell arrest in the G0/G1 phase. PPEE inhibited the growth of prostate cancer cells in vivo. Conclusion: PPEE could inhibit prostate cancer growth in vitro and in vivo, induce apoptosis of prostate cancer cells, and cause cell cycle arrest, which laid the foundation for further research on the anti-tumor mechanism of PPEE.
Objectives: Paris polyphylla var. yunnanensis (PPVY), a Chinese herb, has long been used for cancer treatment, and its steroidal saponins are suggested to exert an anti-tumor activity, however, the underlying mechanism is incompletely understood and their effect on bladder cancer (BC) remains unknown. The present study is thus designed to address these issues. Material and Methods: Total steroidal saponins were extracted with ethanol from PPVY and used to treat BC cells (HT1197 and J82 carrying mutant p53). Gene expression was determined using qPCR and immunoblotting and cell cycle analyzed using flow cytometry. DNA damage response activation was assessed using immunofluorescence staining. Results: PPVY saponins treatment led to dose-dependent declines in the number of both HT1197 and J82 cells with IC50 approximately 1.2 μg/ml, which was coupled with strong growth arrest at G2/M phase and the activation of DNA damage response pathway. Moreover, the clonogenic potential of these cells was severely impaired even in the presence of low concentrations of PPVY saponins. Mechanistically, PPVY saponins induced the degradation of mutant p53 while stimulated CDKN1A gene transcription. Phosphorylated AKT was diminished in PPVY saponin-treated cells, but its specific inhibitor LY294002 exhibited significantly weaker efficacy in inducing CDKN1A expression than did PPVY saponins. Conclusion: PPVY saponins activate DNA damage response pathway, degrade mutant p53 and stimulate CDKN1A expression, thereby inhibiting BC cell growth. Given their poor absorption via oral administration, PPVY saponins may be applicable for intravesical instillations in BC treatment.
Background. The prognosis of non-small-cell lung cancer (NSCLC) has not been significantly improved. In the past several years, research on epigenetics is in full swing. There is a focus on the gene EZH2; however, its role as a predictor of the prognosis of NSCLC is in the debate. Objective. To clarify if the expression level of EZH2 can influence the prognosis of NSCLC and explain its prognostic value. Methods. We have systematically searched PubMed, Web of Science, and Cochrane library, screened relevant articles, and conducted a meta-analysis on the expression level of EZH2 in NSCLC. We collected the hazard ratio (HR) and the 95% confidence interval (CI) and used STATA 12.0 to calculate the combined result of EZH2 overall survival. In addition, we conducted subgroup analyses, a sensitivity analysis, and a funnel plot to test the reliability of the results. We further validated these meta-analysis results using the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) database. In addition, we have investigated the correlation between EZH2 expression and EGFR expression, KRAS expression, BRAF expression, and smoking in TCGA database to further explore the mechanism behind the influence of high EZH2 expression on lung cancer prognosis. Results. 13 studies including 2180 participants were included in the meta-analysis. We found that high expression of EZH2 indicates a poor prognosis of NSCLC ( HR = 1.65 and 95% CI 1.16-2.35; p ≤ 0.001 ). Subgroup analyses showed high heterogeneity in stages I-IV ( I 2 = 85.1 % and p ≤ 0.001 ) and stages I-III ( I 2 = 66.9 % and p = 0.029 ) but not in stage I ( I 2 = 0.00 % and p = 0.589 ). In the Kaplan-Meier plotter database, there was a high expression in 963 cases and low expression in 964 cases ( HR = 1.31 and 95% CI 1.15-1.48; p < 0.05 ). Further analysis found that the high expression of EZH2 was statistically significant in lung adenocarcinoma ( HR = 1.27 and 95% CI 1.01−1.6; p = 0.045 ), but not in lung squamous cell carcinoma ( HR = 1.03 and 95% CI 0.81−1.3; p = 0.820 ). The results of the TCGA database showed that the expression of EZH2 in normal tissues was lower than that in lung cancer tissues ( p < 0.05 ). Smoking was associated with high expression of EZH2 ( p < 0.001 ). EZH2 was also highly expressed in lung cancers with positive KRAS expression, and the correlation was positive in lung adenocarcinoma ( r = 0.3129 and p < 0.001 ). The correlation was also positive in lung squamous cell carcinoma ( r = 0.3567 and p < 0.001 ). EZH2 expression was positively correlated with BRAF expression ( r = 0.2397 and p < 0.001 ), especially in lung squamous cell carcinoma ( r = 0.3662 and p < 0.001 ). In lung squamous cell carcinoma, a positive yet weak correlation was observed between EZH2 expression and EGFR expression ( r = 0.1122 and p < 0.001 ). Conclusions. The high expression of EZH2 indicates a poor prognosis of NSCLC, which may be related to tumor stage or cancer type. EZH2 may be an independent prognostic factor for NSCLC. EZH2 high expression or its synergistic action with KRAS and BRAF mutations affects the prognosis of non-small-cell lung cancer.
Background. Emerging evidences have shown that long noncoding RNA SPRY4-IT1 can be aberrantly expressed in human cancers, and it could be an unfavorable prognostic factor in cancer patients. However, the prognostic mechanism of SPRY4-IT1 is still unclear. This study is aimed at evaluating its potential predictive value for cancer prognosis. Methods. We thoroughly searched PubMed, Embase, Web of Science, and MEDLINE databases so as to explore the relationship between SPRY4-IT1 expression and cancer prognosis value. Then, TCGA datasets were used to validate the results of our meta-analysis. Results. In all, seventeen studies involving 1650 patients were included in this meta-analysis. Pooled results showed that high expression of SPRY4-IT1 was significantly correlated with poor OS ( HR = 1.96 , 95% confidence interval CI = 1.47 ‐ 2.62 , P < 0.001 ) in cancer patients. Furthermore, exploration of TCGA dataset further validated that SPRY4-IT1 was aberrantly expressed in various cancers, which partially confirmed our results in this meta-analysis. Conclusions. The present systematic review and meta-analysis implicated that the aberrant expressions of lncRNA SPRY4-IT1 were strongly associated with clinical survival outcomes in various cancers and therefore might serve as a promising biomarker for predicting prognosis of human cancers.
Objective: To observe the effects and mechanisms of nanocrystallized realgar for the treatment of skin cancer. Methods: The clinical part was observing the therapeutic effect for the skin ulceration by externally using the nanocrystallized realgar. The experimental part was culturing the human squamous cell carcinoma A431 cells (A431) in vitro environment, estimating the effects of proliferation and apoptosis of A431 by MTT method and flow cytometry, and observing the effects on the expression of Survivin, Caspase-3 by RT-PCR method. Results: External treatment with nanocrystallized realgar had a therapeutic effect for the skin ulceration; it can promote the ulcers of skin cancer and skin metastasis healing. The experiments confirmed that nanocrystallized realgar can inhibit the A431 proliferation, induce the cells apoptosis, promote the expression of Caspase-3 and reduce the expression of Survivin. And the experiments also found that the effects were in a concentration-dependent manner, and they have a synergistic effect with cis-Dichlorodiamineplatinum (DDP). Conclusions: External treatment with nanocrystallized realgar for the patients of skin cancer or skin metastasis achieved satisfactory therapeutic effects by inhibiting A431 proliferation and inducing these cells apoptosis. The mechanism might be associated with promoting the expression of Caspase-3 and reducing the expression of Survivin.
Randomized controlled trials regarding efficacy and safety of TCM in the treatment of TNBC. I: TCM or TCM combined with other treatments (including surgery, radiotherapy, chemotherapy, Chinese medicine, etc.).
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