Elevation of circulating big endothelin-1: an independent prognostic factor for tumor recurrence and survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Endothelin(ET) axis plays a key role in many tumor progression and metastasis via various mechanisms such as angiogenesis, mediating extracellular matrix degradation and inhibition of apoptosis. However, there is limited information regarding the clinical significance of plasma big ET-1 levels in esophageal cancer patients. Circulating plasma big ET-1 levels were measured in patients with esophageal squamous cell carcinoma(ESCC) to evaluate the value of ET-1 as a biomarker for predicting tumor recurrence and patients survival. METHODS: Preoperative plasma big ET-1 concentrations were measured by an enzyme linked immunosorbent assay(ELISA) in 108 ESCC patients before surgery, and then again at 1,2,3,10 and 30 days after curative radical resection for ESCC. The association between preoperative plasma big ET-1 levels and clinicopathological features, tumor recurrence and patient survival, and their changes following surgery were evaluated. RESULTS: The preoperative plasma big ET-1 levels in ESCC patients were significantly higher than those in controls. And there was a significant association between plasma big ET-1 levels and disease stage, as well as invasion depth of the tumor and lymph node status. Furthermore, plasma big ET-1 levels decreased significantly after radical resection of the primary tumor and patients with postoperative recurrence had significantly higher plasma big ET-1 levels than that of patients without recurrence. Finally, the survival rate of patients with higher plasma big ET-1 concentrations (>4.3 pg/ml) was significantly lower than that of patients with lower level (< or = 4.3 pg/ml). Multivariate regression analysis showed that plasma big ET-1 level is an independent prognostic factor for survival in patients with ESCC. CONCLUSION: Plasma big ET-1 level in ESCC patients may reflect malignancy and predict tumor recurrence and patient survival. Therefore, the preoperative plasma big ET-1 levels may be a clinically useful biomarker for choice of multimodality therapy in ESCC patients.

[Promoter methylation status and protein expression of p14ARF gene in squamous cell carcinoma and adenocarcinoma of the lung].

BACKGROUND: Recently, the p14 ARF gene has emerged as a new putative tumor suppressor gene, and the alteration of p14 ARF gene is closely related to development of multiple human tumors. The aberrant promoter methylation as a mechanism of inactivation of p14 ARF gene might participate in tumorigenesis. The aim of this study is to investigate promoter methylation status and protein expression of p14 ARF gene in pulmonary squamous cell carcinoma and adenocarcinoma, and to value the role of p14 ARF promoter methylation in carcinogenesis of non-small cell lung cancer. METHODS: Promoter methylation status and protein expression of p14 ARF gene were analyzed in 40 cases of pulmonary squamous cell carcinoma and adenocarcinoma by methylation specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR) and immunohistochemistry (IHC). RESULTS: The positive rate of p14 ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer was 17.5% (7/40) and 2.5% (1/40) respectively (P= 0.025 ). The results of RE-PCR were consistent with the above. The positive rate of p14 ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer (P=0.003). Promoter methylation and protein expression of p14 ARF gene showed a significantly negative correlation (r=-0.56, P= 0.001 ), and both of them did not correlate statistically with the clinicopathologic characteristics of patients such as histological classification, TNM stages, differentiation grade and lymph node involvement. CONCLUSIONS: Promoter methylation is a crucial mechanism of inactivation of p14 ARF gene. Promoter methylation of p14 ARF gene might be involved in carcinogenesis of non-small cell lung cancer, and it is an early event in development process of non-small cell lung cancer.

[Postoperative Th1 and Th2 type cytokine changes in patients with esophageal squamous cell carcinoma and their clinical significance].

OBJECTIVE: To study the expressions of Th1 and Th2 type cytokines in patients with esophageal squamous cell carcinoma and the influence of operation on such expressions. METHOD: Enzyme-linked immunosorbent assay (ELISA) was used to detect Th1 (IL-2 and INF-gamma) and Th2 type cytokines (IL-4, IL-6 and IL-10) in cultured peripheral blood mononuclear cells (PBMCs, for 48 h) from 30 healthy controls and 46 esophageal squamous cell carcinoma patients (collected before and 8 and 30 d after operation, respectively). RESULTS: Compared with the control group, the expressions of Th1 type cytokines, IL-2 and INF-gamma, were significantly depressed in the PBMCs of the cancer patients (P<0.05), while expression of Th2 type cytokines, IL-6 was significantly enhanced (P<0.05), and IL-4 and IL-10 showed only slight enhancement. Such changes in the expressions of the cytokines showed a correlation with TNM (tumor-node-metastasis)stage of the tumors. After operation, the expressions of Th1 type cytokines increased and Th2 type cytokines decreased. CONCLUSIONS: Th1 cells are suppressed in patients with esophageal squamous cell carcinoma, while the function of Th2 cells is enhanced. Operation may reverse such changes, and dynamic detection of Th1 and Th2 type cytokines may indicate the prognosis, therapeutic effect and risks of relapse and metastasis.