BackgroundThe diagnosis of lymph node metastasis in esophageal cancer by the presence and number of metastatic lymph nodes is an extremely important prognostic factor. In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C) is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic vasculature. In this study, we investigated the expression of VEGF-C and whether it correlated with various clinico-pathologic findings.MethodsKYSE series of esophageal cancer cell lines and 106 patients with primary esophageal squamous cell carcinomas who had undergone radical esophagectomy were analyzed. VEGF-C mRNA expression was determined by quantitative RT-PCR.ResultsHigh expression of VEGF-C was detected in most of the KYSE cell lines, especially KYSE410, yet, in an esophageal normal epithelium cell line, Het-1A, VEGF-C was not detected. In the clinical specimen, the expression of VEGF-C in the cancerous tissue was higher than in the corresponding noncancerous esophageal mucosa (p = 0.026). The expression of VEGF-C was found to be higher in Stage2B-4A tumors than in Stage0-2A tumors (p = 0.049). When the patients were divided into two groups according to their expression levels of VEGF-C (a group of 53 cases with high expression and a group of 53 cases with low expression), the patients with high VEGF-C expression had significantly shorter survival after surgery than the patients with low expression (p = 0.0065). Although univariate analysis showed that high expression of VEGF-C was a statistically significant prognostic factor, this was not shown in multivariate analysis. In the subgroup of patients with Tis and T1 tumors, the expression of VEGF-C was higher in N1 tumors than in N0 tumors (p = 0.029). The survival rate of patients from the high expression group (n = 10) was lower than that in the low expression group (n = 11), and all the patients in the low VEGF-C expression group survived.ConclusionsThe expression of VEGF-C correlates with lymph node metastasis and poor prognosis. In patients with Tis and T1 esophageal tumors, the expression of VEGF-C may be a good diagnostic factor for determining metastasis of the lymph node.

Purpose and MethodsThe translocation of β-catenin/CTNNB1 to the nucleus activates Wnt signaling and cell proliferation; however, the precise mechanism underlying this phenomenon remains unknown. Previous reports have provided evidence that NOTCH1 is involved in the Wnt signaling pathway. Therefore, we sought to determine the mechanism by which NOTCH1 influences the Wnt/β-catenin pathway. We constructed a vector expressing the NOTCH1 intracellular domain (NICD1) and transfected the vector into HCT116 which has low expression of NICD1. Furthermore, inhibition of NOTCH signal pathway in SW480 which has abundant NICD1 expression, was performed by transfection of siNICD1 or DAPT, gamma secretase inhibitor, treatment. In addition, we evaluated NICD1 and β-catenin localization in colon cancer cell lines and in 189 colon cancer tissue samples and analyzed the correlation between the nuclear localization of NICD1 and the clinicopathological features of colon cancer patients.ResultsImmunohistochemical assays demonstrated that NICD1 and β-catenin exhibited a similar localization pattern in colon cancer tissues. In addition, we found that NICD1 induced the translocation of β-catenin to the nucleus and that NICD1 and β-catenin co-localized in the nucleus. Overexpression of NICD1 increased luciferase activity of Wnt signal pathway. On the other hand, reduction of NICD1 reduced luciferase activity of Wnt signaling pathway. In the 189 analyzed colon cancer cases, multivariate COX regression analysis demonstrated the independent prognostic impact of nuclear localization of NICD1(p=0.0376).ConclusionNOTCH1 plays a key role in the Wnt pathway and activation of NOTCH1 is associated with the translocation of β-catenin to the nucleus.

Purpose: The prognosis of patients with esophageal cancer remains poor, and the classification of tumor node metastasis has proven insufficient to predict patient prognosis. Therefore, novel predictive markers of esophageal cancer prognosis are needed. Notch receptors and their ligands have been reported to be upregulated in cervical, lung, colon, renal, and pancreatic cancers, but NOTCH1 expression has not been studied in esophageal cancer. Methods: Expression of NOTCH1 was quantified by real-time reverse transcription-polymerase chain reaction in 55 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We then examined the correlations between NOTCH1 expression, clinicopathological factors, and prognosis in patients with ESCC. Results: The probability of overall survival was significantly lower for patients with high NOTCH1 expression (p = 0.0028; log-rank test). Overexpression of NOTCH1 was identified as a significant and independent prognostic factor (p = 0.0061) in patients who had undergone surgical treatment for ESCCs. The hazard ratio for predicting early death was 4.298 (95% confidence interval 1.515-12.195) for high versus low NOTCH1 expression. Conclusions: Our data indicate that NOTCH1 may be a candidate molecular prognostic marker and a molecular target for the development of an effective therapeutic intervention for patients with ESCC.

Abstract. Esophageal squamous cell carcinoma (ESCC) is a common malignancy and one of the more difficult diseases to diagnose in Japan due to its poor prognosis. MicroRNAs are small non-coding RNAs of 21-23 nucleotides that regulate gene expression. MicroRNA-34b (miR-34b) has been reported to be overexpressed in various types of cancer. However, its role in ESCC has yet to be extensively studied. The present study investigated the expression of miR-34b in 88 ESCC patients. The miR-34b expression in ESCC was significantly higher than that in the corresponding normal esophageal mucosa. It was more highly expressed in tumors with more advanced stages. However, its expression did not correlate with the p53 status. Transfection of anti-miR-34b to the ESCC cells suppressed cell growth in vitro. These results suggest an oncogenic role of miR in ESCC.

AIM:To investigate the use of the V-Loc wound closure device for transabdominal preperitoneal hernia repair. METHODS:We performed conventional transabdominal preperitoneal hernia repair in 19 patients, including one single incisional case using V-Loc. Except for the use of V-Loc for peritoneal closure, the procedures were the same as those used in conventional techniques. RESULTS:Although the operators included 2 residents who have no experience in laparoscopic herniorrhaphy and intracorporeal suture, the operations were completed. We believe that V-Loc is especially suitable for inexperienced surgeons and the use of V-Loc reduces the operative time by a small amount but reduces operator stress significantly. CONCLUSION:We conclude that V-Loc is the ideal peritoneal closure device for transabdominal preperitoneal hernia repair.