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Background Preoperative chemoradiation combined with surgery has been of focus recently in order to improve prognosis in esophageal squamous cell carcinoma ( ESCC) patients. Finding biological markers that may assist in predicting the therapeutic effect of chemoradiation may benefit the treatment effect. In this study, the role of RUNX3 in the formation of cisplatin resistance in ESCC was examined. Methods The study enrolled 103 stage IIa-IIIb ESCC patients who had undergone esophagectomy. RUNX3 expression in ESCC tissue was detected. Results A higher expression of RUNX3 in ESCC patients correlated with a more sensitive response to cisplatin-based chemotherapy. A consistently lower expression of RUNX3 was found in the ESCC tissues of patients who agreed to perioperative chemotherapy compared with patients who had undergone no preoperative treatment. A lower RUNX3 expression in cisplatin-resistant ESCC cell lines, Eca109 and TE-1, was observed compared with parental cell lines. Heterologous RUNX3 expression significantly suppressed cisplatin resistance in Eca109 and TE-1, both in vitro and vivo. Meanwhile, heterologous RUNX3 expression could inhibit growth and induce apoptosis in cisplatin resistant Eca109 and TE-1 cell lines in vitro. Remarkable inhibition of the Akt pathway was observed in heterologous RUNX3 expression in Eca109 and TE-1. Silencing Akt1 could reverse cisplatin resistance in Eca109 and TE-1. Conclusion Our results confirmed that a loss of RUNX3 in ESCC may contribute to cisplatin-resistance. RUNX3 could reverse cisplatin resistance via suppression of the Akt pathway in ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (TKIEGFRs) present a new prospect for the treatment of lung cancer. However, in clinical application, the majority of patients become TKI resistant within a year. More and more studies have shown that a loss of phosphatase and tensin homolog (PTEN) expression is associated with TKI resistance. An alternative method of upregulating PTEN expression may reverse TKI resistance. Methods: We designed five candidate small activating ribonucleic acids (saRNAs) to target PTEN, and transfected them into H-157 cells to screen out functional saRNA. We used reverse transcriptase-polymerase chain reaction and Western blot to evaluate the effect of saRNA to PTEN expression. We then analyzed the growth and apoptosis of cells transfected with saRNA under the treatment of TKI to investigate whether saRNAs can reverse TKI resistance by upregulating PTEN expression. Results: The functional saRNA we designed could upregulate PTEN expression. The H-157 cells transfected with saRNA grew slower in the presence of TKI drugs than the cells that were not transfected with saRNA. The apoptosis rate was also obviously higher. Conclusions: Our study proves that loss of PTEN expression is an important mechanism of TKI resistance. It is possible to control TKI resistance by upregulating PTEN expression using RNA activation technology. [ABSTRACT FROM AUTHOR]

Background The poor prognosis of esophageal squamous cell carcinoma ( ESCC) is attributed to a high recurrence rate after surgery. Cyclooxygenase 2 ( COX2) is an important regulator of cell growth, differentiation, apoptosis, and transformation. COX2 overexpression is significantly associated with the tumorigenesis and progression of diverse cancers; however, its expression and significance in ESCC remains unclear. Methods We enrolled 118 patients with ESCC who had undergone Ivor-Lewis esophagectomy. The expression profile of COX2 was examined by immunohistochemistry. Results A high expression of COX2 correlated with a higher T staging ( P = 0.014), lower differentiation degree ( P = 0.002), lymph node metastasis ( P = 0.009), recurrence status ( P = 0.004), and tumor node metastasis ( TNM) stage ( P = 0.001). Cox regression analysis showed that TNM stage ( P = 0.001), differentiation degree ( P = 0.001), and high COX2 expression ( P = 0.004) were independent risk factors of prognosis. Conclusion Our data indicated that COX2 expression level is associated with key clinicopathological features and could be an effective biomarker to predict ESCC prognosis. [ABSTRACT FROM AUTHOR]