Effect of Raltitrexed on ECA109 Cellular Radiosensitivity and its Mechanism in Esophageal Cancer.

BACKGROUND: To investigate the effect of raltitrexed + X-ray irradiation on esophageal cancer ECA109 cells and analyze the potential action mechanism. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the inhibitory effect of raltitrexed on cell proliferation. The effect of raltitrexed on radiosensitivity was studied through a clone-forming experiment. The scratch assay and invasion test were performed to understand the cell migration and invasion abilities. The apoptosis rate change was measured using a flow cytometer, and Western Blotting was used to determine the expression of B cell lymphoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) in each group. RESULTS: Raltitrexed significantly inhibited ECA109 proliferation in a time-dose-dependent manner; there were significant differences among different concentrations and times of action. The results of the clone-forming experiment showed a sensitization enhancement ratio of 1.65, and this demonstrated a radiosensitization effect. After the combination of raltitrexed with X-ray, the cell migration distance was shortened, and the number of cells penetrating the membrane was reduced. CONCLUSION: Raltitrexed can inhibit the growth of esophageal cancer ECA109 cells and has a radiosensitization effect.

A miRNA-205-based model for prediction of the recurrence of endometrioid endometrial cancer.

AIM: To develop a miRNA-205 based model for prediction of the recurrence of endometrial cancer. METHODS: The FIGO (International Federation of Gynecology and Obstetrics) stage, grading, myometrial infiltration, lymph node status and miRNA-205 expression levels were extracted from 90 endometrioid endometrial cancer patients, recurrence related risk factors were analyzed by Cox regression analysis. A risk model was then developed. RESULTS: A total of 90 endometrial cancer patients were retrospectively included for the analysis. The FIGO stage and expression levels of miRNA 205 were independently associated with the recurrence-free survival of the patients. The FIGO stage and expression levels of miRNA 205 were used for a prognostic model of recurrence-free survival. The c-index of the model reached 0.764, and the output of the model (risk score) could stratify the patients into different groups on the risk of recurrence. CONCLUSION: A miRNA-205 based model could predict the risk of recurrence for endometrioid endometrial cancer, and the model could provide a risk stratification of patients by recurrence risk.

Design, synthesis, and structure-activity relationship of novel RIPK2 inhibitors.

The NOD1/2 (nucleotide-binding oligomerization domain-containing protein 1/2) signaling pathways are involved in innate immune control and host defense. NOD dysfunction can result in a variety of autoimmune disorders. NOD-induced generation of inflammatory cytokines is mediated by receptor-interacting protein kinase 2 (RIPK2), which has been considered as a promising therapeutic target. Herein, we disclose the design, synthesis, and SAR study of a series of RIPK2 inhibitors. The lead compound 17 displayed a high affinity for RIPK2 (Kd = 5.9 nM) and was capable of inhibiting RIPK2 kinase function in an ADP-Glo assay. In vitro DMPK studies showed that compound 17 had good metabolic stability and no CYP inhibition. Compound 17 effectively suppressed inflammatory cytokine production in both cells and animal model.

Value of Nomogram Incorporated Preoperative Tumor Volume and the Number of Postoperative Pathologically Lymph Node Metastasis Regions on Predicting the Prognosis of Thoracic Esophageal Squamous Cell Carcinoma.

BACKGROUND: The aim of this study was to explore the influence of preoperative tumor volume, length, maximum diameter and the number of postoperative pathologically lymph node metastasis (LNM) regions on survival prognosis of esophageal squamous cell carcinoma (ESCC) patients. METHODS: A total of 296 patients with ESCC treated by standard curative esophagectomy were retrospectively analyzed. These patients were grouped for further analysis according to the optimal threshold of preoperative tumor volume, length, maximum diameter and the number of postoperative pathologically LNM regions. Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by Log rank test. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. Nomogram model was established by integrating statistically significant clinicopathological parameters, and the predictive value was further verified by calibration curve, concordance index (C-index) and decision curve. RESULTS: The univariate and multivariate Cox regression analysis all showed that differentiation grade, TNM stage, adjuvant therapy, preoperative tumor volume and the number of post operative pathologically LNM regions were independent prognostic factors for PFS and OS (all P<0.05). The C-indexes of PFS and OS by nomograms were predicted to be 0.747 (95% CI: 0.717-0.777) and 0.732 (95% CI: 0.697-0.767), respectively, which were significantly higher than the 7th AJCC TNM stage, the C-indexes 0.612 (95% CI: 0.574-0.650) and 0.633 (95% CI: 0.595-0.671), separately. In addition, the calibration curves of nomogram models were highly consistent with actual observation for the five-year PFS and OS rate, and the decision curve analysis also showed that nomogram models had higher clinical application potentials than TNM staging model in predicting survival prognosis of thoracic ESCC after surgery. CONCLUSION: The nomograms incorporated preoperative tumor volume and the number of postoperative pathologically LNM areas are of great value in predicting survival prognosis of patients with thoracic ESCC.

The MCP-1 A-2518G polymorphism increases the risk of Alzheimer's disease: A case-control study.

Monocyte chemoattractant protein-1 (MCP-1) is reported to associate with the severity and development of Alzheimer's disease (AD). While a few studies have examined the association between the MCP-1 A-2518 G polymorphism and AD risk, no Chinese study has undertaken a study of this association. Therefore, a case-control study with 212 AD cases and 268 controls was designed in Chinese participants. Logistic regression analysis was utilized to probe the potential link between AD susceptibility and the MCP-1 A-2518 G polymorphism. We observed that the GG or GG + AG genotype was shown to elevate the risk of AD. Subgroup analysis revealed this increased risk effect was also presented in males, smokers, APOE ε4+ and those participants ≥ 65 years old. Notably, cross-over analysis found that this polymorphism interacted with smoking, contributing to the increased risk of AD. In addition, we found that the serum MCP-1 levels of AD patients were evidently higher than in controls. Furthermore, the MCP-1 A-2518 G polymorphism was linked with the serum MCP-1 levels of AD patients, but not controls. In conclusion, the MCP-1 A-2518 G polymorphism correlates with an elevated risk of AD and increased MCP-1 serum levels. The interaction between the MCP-1 A-2518 G polymorphism and smoking contributes to the increased risk for AD in Chinese Han individuals.