Showing papers by "Jing Liu published in 2018"

Fibronectin Promotes the Malignancy of Glioma Stem-Like Cells Via Modulation of Cell Adhesion, Differentiation, Proliferation and Chemoresistance.

Abstract: Glioma stem-like cells (GSCs) are regarded as the sources of oncogenesis, recurrence, invasion and chemoresistance in malignant gliomas. Growing evidence suggests that the microenvironment surrounding GSCs interacts with tumor cells to influence biological behavior; however, the functional mechanisms involved are still unclear. In the present study, we investigated the modulation of GSCs triggered by fibronectin (FN), a main component of the extracellular matrix (ECM), in terms of cell adhesion, differentiation, proliferation and chemoresistance. We demonstrated that pre-coated FN prompted increased adherence by GSCs, with increased matrix metallopeptidases (MMPs)-2 and -9 expression, in a concentration-dependent manner. Decreases in sox-2 and nestin levels, and increased levels of glial fibrillary acidic protein (GFAP) and β-tubulin were also found in GSCs, indicating cell differentiation driven by FN. Further investigation revealed that FN promoted cell growth, as demonstrated by the elevation of Ki-67, with the activation of p-ERK1/2 and cyclin D1 also evident. In addition, FN suppressed p53-mediated apoptosis and upregulated P-glycoprotein expression, making GSCs more chemoresistant to alkylating agents such as carmustine. In contrast, this effect was reversed by an integrin inhibitor, cilengitide. Activation of the focal adhesion kinase/paxillin/AKT signaling pathway was involved in the modulation of GSCs by FN. Focusing on the interactions between tumor cells and the ECM may be an encouraging aspect of research on novel chemotherapeutic therapies in future.

Pretreatment platelet-to-lymphocyte ratio is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer.

Abstract: Background Several studies have shown that platelet-to-lymphocyte ratio (PLR) is a prognostic factor for various cancers. However, there is no study about the role of PLR in predicting response to first-line chemotherapy of metastatic gastric cancer. Therefore, this study aimed to establish whether PLR is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer. Methods We enrolled 273 patients diagnosed with metastatic gastric cancer. The best cut-off value of PLR to predict chemotherapeutic response was chosen by receiver operating characteristic (ROC) curve analysis. Prognostic significance was determined using the log-rank test and multivariate Cox regression analysis. Results Based on the cut-off value of PLR, patients were divided into a low PLR group and high PLR group. In logistic regression analysis, the low PLR group had a significantly higher disease control rate than the high PLR group had (91.3 vs 76.1%, P=.002), and PLR was an independent risk factor for response to first-line chemotherapy (odds ratio [OR]: 3.256; 95% confidence interval [CI]: 1.521-6.969; P=.002). The low PLR group had significantly longer overall survival (OS) than the high PLR group had (13.4 vs 9.2 months; P=.020). Multivariate survival analysis showed that PLR was significantly associated with OS [hazard ratio (HR): 1.002; 95% CI: 1.000-1.003; P=.020]. Conclusions Pre-treatment PLR is associated with the response rate to first-line chemotherapy and survival outcomes in patients with metastatic gastric cancer.

MiR-429 Regulated by Endothelial Monocyte Activating Polypeptide-II (EMAP-II) Influences Blood-Tumor Barrier Permeability by Inhibiting the Expressions of ZO-1, Occludin and Claudin-5.

Abstract: The blood-tumor barrier (BTB) hinders delivery of chemotherapeutic drugs to tumors in the brain; previous studies have shown that the BTB can be selectively opened by endothelial monocyte activating polypeptide-II (EMAP-II), but the specific mechanism involved remains elusive. In this study, we found that microRNA-429 (miR-429) expression in glioma vascular endothelial cells (GECs) was far lower than in human brain microvascular endothelial cells (ECs). miR-429 had lower expression in GECs and glioma tissues compared to ECs or normal tissues of the brain. Furthermore, miR-429 had lower expression in high grade glioma (HGG) than in low grade glioma (LGG). In in vitro BTB models, we also found that EMAP-II significantly increased BTB permeability, decreased expression of ZO-1, occludin and claudin-5 in GECs, in a time- and dose-dependent manner. EMAP-II greatly increased miR-429 expression in GECs of the BTB models in vitro. Overexpression of miR-429 in GECs significantly decreased the transepithelial electric resistance (TEER) values in BTB models, and led to enhanced horseradish peroxidase (HRP) flux. Overexpression of miR-429 in GECs significantly decreased the expression of tight junction (TJ)-associated proteins (ZO-1, occludin and claudin-5), and decreased the distribution continuity. Silencing of miR-429 in GECs increased the expression of TJ-associated proteins and the distribution continuity. The dual-luciferase reporter assay revealed that ZO-1 and occludin were target genes of miR-429, and we demonstrated that miR-429 overexpression markedly down-regulated protein expression of p70S6K, as well as its phosphorylation levels. The dual-luciferase reporter assay also showed that p70S6K was a target gene of miR-429; miR-429 overexpression down-regulated expression and phosphorylation levels of p70S6K, and also decreased phosphorylation levels of S6 and increased BTB permeability. Conversely, silencing of miR-429 increased the expression and phosphorylation levels of p70S6K, and increased phosphorylation levels of S6, while decreasing BTB permeability. In conclusion, the results indicated that EMAP-II caused an increase in miR-429 expression that directly targeted TJ-associated proteins, which were negatively regulated; on the other hand, miR-429 down-regulated the expression of TJ-associated proteins by targeting p70S6K, also negatively regulated. As a result, the BTB permeability increased.

The dynamic monitoring of CEA in response to chemotherapy and prognosis of mCRC patients

Abstract: The role of carcinoembryonic antigen (CEA) change patterns in tumor response and long-term outcome is unclear. This study aimed to investigate the correlation between changes in CEA levels and tumor response as a potential prognostic model. CEA levels were determined from baseline to progression. A χ2 test was used to assess the correlation between CEA changes and tumor response. Univariate and multivariate COX models were used to explore the correlation of CEA changes to progression-free survival (PFS) and overall survival (OS). All 114 patients were divided into five groups according to CEA change pattern (A: patients had an initial fast CEA decrease that then turned into a slow increase; B: patients had an initial slow CEA decrease that then turned to a slow increase; C: patients had a continually slow CEA increase; D: patients had a continually fast CEA increase; E: patients had an initial fast CEA decrease that then turned into a fast increase). Patients in Group A had the longest OS and PFS while Group E patients had the shortest OS. Baseline to week 12 and week 12 to week 18 change rates were consistent with tumor response and progression, respectively. An increase in CEA level by ≥2.7% from week 12 to 18 was an independent negative prognostic factor of OS. CEA changes mirror the tumor response to first-line chemotherapy and are associated with prognosis. CEA monitoring may be a substitute for computed tomography during the CEA stable period of treatment.

A Clinical Prognostic Score to Predict Survival of Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Patients Receiving First-Line Chemotherapy: A Retrospective Analysis.

Abstract: BACKGROUND Although several complicated models have been built to evaluate the prognosis of NSCLC patients receiving chemotherapy, simple economic models are still needed to give a preliminary survival assessment of these patients. MATERIAL AND METHODS This study retrospectively assessed the clinical and biological parameters of 223 patients with advanced NSCLC. Univariate and multivariate analyses of overall survival (OS) and progression-free survival (PFS) for the parameters and the prognostic score were assessed. RESULTS Performance status (PS) score=1, smoking history, fibrinogenemia, thrombocytosis, increased lactate dehydrogenase (LDH) level, and anemia were independent predictors of poor prognosis in the univariate analysis of OS and were assessed in multivariate analysis. There was a significant difference in PS=1 (HR=2.134, p<0.0001), increased LDH level (HR=1.508, p=0.014), thrombocytosis (HR=1.547, p=0.012), and smoking history (HR=1.491, p=0.008), based on which the patients were classified into 3 risk groups: low risk (0-1 points), moderate risk (2 points), and high risk (3-5 points). At p values of <0.0001, the median OS was 565, 340, and 273 days and the median progression-free survival was 250, 209, and 135 days, respectively in these 3 risk groups. CONCLUSIONS We established a new prognostic score model using PS, LDH level, PLT count, and smoking history to predict the survival of patients receiving first-line chemotherapy for advanced NSCLC, which might be useful in clinical practice.

Respiratory syncytial virus prevents the subsequent development of ovalbumin-induced allergic responses by inhibiting ILC2 via the IL-33/ST2 pathway.

Abstract: Aim How respiratory syncytial virus (RSV) influences the development of ovalbumin (OVA)-induced asthma remains elusive. As potent T helper (Th)2 cytokine producers, group 2 innate lymphoid cells (ILC2s) are known to serve important functions in the pathogenesis of allergic inflammation. However, how RSV infection affects innate immunity, especially with regard to the function of ILC2s in OVA-induced allergic airway inflammation, is largely unknown. Materials & methods RSV was used to infect adult BALB/c mice intranasally prior to sensitization and subsequent challenge with OVA. ILC2 frequencies and Th2 cytokine production by ILC2s were assessed by flow cytometry. Cytokine levels were detected both by real-time PCR and ELISA. Results Previous infection with RSV attenuated airway inflammation and decreased Th2 cytokine production in mice sensitized and challenged with OVA. Furthermore, previous infection with RSV inhibited the influx of ILC2s into the lung, and constrained their Th2 cytokine production. Adoptive transfer of ILC2s increased asthma-associated airway inflammation in mice previously infected with RSV. These results indicate that previous infection with RSV prevents OVA-induced asthma development via inhibition of ILC2s. Previous infection with RSV attenuated IL-33 production in lung tissue and reduced relative ST2L expression in lung ILC2s, meaning that previous infection with RSV may alter ILC2 function via the IL-33/ST2 signaling pathway. Conclusion These results demonstrate that previous infection with RSV attenuates OVA-induced airway inflammation by inhibiting the recruitment and Th2 cytokine production of ILC2s via the IL-33/ST2 pathway.