Predictive nomogram for postoperative atrial fibrillation in locally advanced esophageal squamous carcinoma cell with neoadjuvant treatment.

Background: Neoadjuvant therapy following minimally invasive esophagectomy is recommended as the standard treatment for locally advanced esophageal squamous carcinoma cells (ESCC). Postoperative atrial fibrillation (POAF) after esophagectomy is common. We aimed to determine the risk factors and construct a nomogram model to predict the incidence of POAF among patients receiving neoadjuvant therapy. Methods: We retrospectively included patients with ESCC receiving neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), or neoadjuvant immunochemotherapy (nICT) following minimally invasive esophagectomy (MIE) for analysis. Patients without a history of AF who did not have any AF before surgery and who developed new AF after surgery, were defined as having POAF. We applied a LASSO regression analysis to avoid the collinearity of variables and screen the risk factors. We then applied a multivariate regression analysis to select independent risk factors and constructed a nomogram model to predict POAF. We used the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve to evaluate the nomogram model. Results: A total of 202 patients were included for analysis, with 35 patients receiving nCRT, 88 patients receiving nCT, and 79 patients receiving nICT. POAF occurred in 34 (16.83%) patients. There was no significant difference in the distribution of neoadjuvant types between the POAF group and the no POAF group. There was a significant increase in postoperative hospital stay (p = 0.04), hospital expenses (p = 0.01), and comprehensive complication index (p < 0.001). The LASSO analysis screened the following as risk factors: blood loss; ejection fraction (EF); forced expiratory volume in 1 s; preoperative albumin (Alb); postoperative hemoglobin (Hb); preoperative Hb; hypertension; time to surgery; age; and left atrial (LA) diameter. Further, preoperative Alb ≤41.2 g/L (p < 0.001), preoperative Hb >149 g/L (p = 0.01), EF >67.61% (p = 0.008), and LA diameter >32.9 mm (p = 0.03) were determined as independent risk factors of POAF in the multivariate logistic analysis. The nomogram had an area under the curve (AUC) of 0.77. The Briser score of the calibration curve was 0.12. The DCA confirmed good clinical value. Conclusions: Preoperative Alb ≤41.2 g/L, LA diameter >32.9 mm, preoperative Hb >149 g/L, and EF >67.61% were determined as the risk factors for POAF among patients with ESCC. A novel and valuable nomogram was constructed and validated to help clinicians evaluate the risk of POAF and take personalized treatment plans.

Expression of miRNA in 5-FU resistant esophageal cancer.

Fluoropyrimidine plus platinum (FP) are chemotherapeutic drugs that are most frequently used to treat esophageal squamous cell carcinoma (ESCC). However, drug resistance often occurs, and the mechanisms of resistance to 5-FU is yet to be determined. The role of micro (mi)RNAs has been well established in a variety of human cancers. The aim of the present study was to investigate the expression profile of ESCC, revealing the differential expression between ESCC and 5-FU resistant ESCC. The establishment of a 5-FU resistant (5-FUR) cell lines model provides a way of analyzing the expression of miRNAs in drug resistance. The miRNA expression indicated 50 miRNAs that were upregulated in TE10-5-FUR compared with TE10, while 119 miRNAs were downregulated. The TE11-5-FUR demonstrated 140 miRNAs were upregulated compared with TE11, which exhibited 12 downregulated miRNAs. Both cell lines share the 2 candidate upregulated miRNAs (miR-146a and miR-483-5p) and 5 downregulated miRNAs (miR-34a, miR-141, miR-200b, miR-200c and miR-205). Further studies are required to analyze and evaluate the function of the miRNAs.

Inhibitory effect of oridonin on proliferation and migration of human esophageal squamous cancer cell lines KYSE-150 and KYSE-450 / 解剖学报

Objective To explore the effect of oridonin (ORI) on proliferation, apoptosis, cell cycle and migration of esophageal squamous carcinoma cell (ESCC) lines KYSE-150 and KYSE-450. Methods The effect of ORI on the proliferation and clony formation of esophageal cancer cells were detected by MTT and colony formation assays. Flow cytometry was performed to examine the impact of ORI on cell apoptosis and cell cycle. Transwell assay was applied to detect the role of ORI on cell migration. The effect of ORI on the expression of anti-apoptotic protein Bcl-2, cell cycle inhibitory protein p21Cip1/Waf1, epithelial-mesenchymal transition (EMT) related markers were examined by Western blotting. Results ORI had a significant inhibitory effect on the proliferation, migration and clone formation of KYSE-150 and KYSE-450 cells (P<0. 05) in a time and dose-dependent manner. With the increase of ORI concentration, apoptosis rate and the proportion of cells in G2/M phase increased significantly (P<0. 05), and the proportion of cells in G0/G1 phase decreased significantly (P < 0. 0 5). Bcl-2, vimentin and p-catenin were down-regulated and p21Cipl/Wafl, Ecadherin were up-regulated after treatment of ORI on ESCC cells for 48 hours. Conclusion ORI may inhibit ESCC cell proliferation and clony formation by inducing apoptosis and resting cells in G2/M phase, and suppress ESCC cell migration via inhibiting EMT process.

Simvastatin, but not pravastatin, inhibits the proliferation of esophageal adenocarcinoma and squamous cell carcinoma cells: a cell-molecular study.

BACKGROUND AND OBJECTIVE: Long-term statin therapy has been shown to protect against several cancers, including esophageal cancer (EC). While the mechanisms underlying this effect are not clear. We investigated the effect of hydrophobic simvastatin and hydrophilic pravastatin on the proliferation of EC cells and sought to explore the underlying mechanisms. METHODS: Esophageal adenocarcinoma OE-19 cells and esophageal squamous cell carcinoma Eca-109 cells were treated with different concentrations of simvastatin or pravastatin for 24 h and 48 h. Cell proliferation was assessed by Cell Counting Kit-8 assay. Malondialdehyde (MDA) levels were measured by thiobarbituric acid (TBA) assay. mRNA and protein expression of COX-2 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively; The expression of prostaglandin E2 (PGE2) was measured by ELISA. RESULTS: Simvastatin, but not pravastatin, significantly inhibited the proliferation of OE-19 and Eca-109 cells in a dose- and time-dependent manner, accompanying with the increasing of the MDA level. Moreover, simvastatin suppressed the expression of COX-2 and PGE2 in both OE-19 and Eca-109 cells in a dose-dependent manner. CONCLUSIONS: Lipophilic simvastatin, but not hydrophilic pravastatin, had significant inhibitory effects on the proliferation of Eca-109 and OE-19 cells. The reduction of COX-2 and PGE2 by simvastatin suggested that the inhibitory effect of simvastatin on the proliferation of EC cells may be independent of its lipid-lowering effect. Simvastatin may be a promising agent for the prevention and treatment of EC.

Plumbagin influences the proliferation and apoptosis of esophageal squamous carcinoma cell lines by down-regulation of FoxM1 expression / 药学学报

Plumbagin (Plumbago zeylanica L.) has a wide spectrum of anticancer activity with a relatively lower toxicity. The molecular mechanisms of proliferation inhibition and apoptosis induction by plumbagin on esophageal squamous carcinoma cell lines may be important for the structure modification and clinical application of plumbagin. After treatment of KYSE-30, KYSE-70 and KYSE-140 cells with 0-20 μmol·L-1 of plumbagin for 24, 48, 72 h, CCK8 was used to examine the proliferation, Annexin V and PI immunofluorescence staining for apoptosis, real-time PCR and Western blot for FoxM1 mRNA and protein expression, dual-luciferase reporter gene assay for the transcriptional activity of FoxM1, respectively. In addition, the relationship between anti- tumor effect of plumbagin and FoxM1 was investigated in vivo. Plumbagin significantly inhibited proliferation and induced apoptosis of esophageal squamous carcinoma cell in vitro and in vivo. Moreover, plumbagin down-regulated the expression of FoxM1 through suppression of its gene transcription. Our findings suggest that plumbagin may inhibit the proliferation of esophageal squamous carcinoma cell in vivo and in vitro through down-regulating the expression of FoxM1.

p63-Mediated activation of the ß-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis.

The development of esophageal squamous carcinomas (ESC) results from numerous genetic alterations. Our previous study demonstrated that p63 is highly expressed in human ESC cells and stimulates their growth; however, the mechanism by which p63 regulates ESC cell adhesion and invasion remains unclear. In the present study, we further elucidated the underlying molecular mechanisms by which p63 regulates metastasis in ESC cells. Knockdown of p63 significantly diminished the invasion of ESC cell lines TE-8 and TE-12, whereas overexpression of p63 significantly increased the migration rates of BE3 and OE33 cells. The mRNA and protein levels of vimentin, twist, SUSD2, and uPA were significantly decreased in p63-knockdown ESC cells, while overexpression of p63 induced an increase in vimentin, SUSD2, and uPA. In addition, knockdown of p63 in ESC cells significantly reduced levels of ß-catenin and c-Myc, while overexpression of p63 increased ß-catenin, but reduced p-ß-catenin level. Therefore, p63 regulates the migration and invasion of ESC cells through activation of the ß-catenin/c-Myc pathway. Our results suggest that targeting p63 may constitute a potential therapeutic strategy for ESC.

Inhibitory effect and mechanisms of betulinc acid on esophageal squamous carcinoma cell / 中国药学杂志

OBJECTIVE: To explore the inhibitory effect of betulinc acid(BA) on esophageal squamous cell carcinoma (ESCC) KYSE170 cells and the mechanisms of the inhibitory effect. METHODS: Different concentrations of BA(0, 5, 10, 20, 40, 60, 80 and 100 μg·mL-1) were used to detect their effects and the inhibitory rate on the cells for 24 to 72 h. The clone formation test was used to detect the long term inhibitory effects of different BA concentration(0, 5, 20 and 40 μg·mL-1) on KYSE170 cells. Different concentrations of BA(10, 60 and 100 (μg·mL-1) for 24 and 48 h were used to detect the apoptosis rate of cells by flow cytometry. Different concentrations of BA(0, 10 and 40 μg·mL-1) for 24 h were used to detect the cell cycle of cells by flow cytometry. RESULTS: BA inhibited the growth of KYSE170 cells in a dose- and time-depentent manner. IC50 at 24, 48 and 72 h were (56.81±2.56), (39.73±2.77) and (29.28±3.05) μg·mL-1, respectively. The clone formation plating efficiencies were (89.56±5.00)%, (61.00±2.03)%, (31.33±3.51)% and (15.33±2.33)% when the drug concentrations were 0, 5, 20 and 40 μg·mL-1, respectively. With the increase of BA concentration and the prolong of BA incubation time the apoptosis rate increased significantly (P<0.05 or 0.01). After 0, 1 and 10 μg·mL-1 BA added for 24 h, the rate of Gl phase cells decreased, while the rate of S phase cells increased(P<0.01). CONCLUSION: BA can inhibit the growth of KYSE170 cell by inducing cell apoptosis and blocking cells to stay in S phase. Copyright 2012 by the Chinese Pharmaceutical Association.