miRNA-766 induces apoptosis of human colon cancer cells through the p53/Bax signaling pathway by MDM4.

miRNAs are closely associated with tumor genesis and development. The present study investigated the role of the expression of miRNA-766 in the survival of patients with colon cancer and the underlying molecular mechanisms. Reverse transcription-quantitative polymerase chain reaction analysis and microarray analysis were used to analyze the expression of miRNA-766. The results revealed that the expression of miRNA-766 was decreased in patients with colon cancer. The overall survival and disease-free survival rates of patients with colon cancer with a high expression of miRNA-766 were prolonged, compared with those with a low expression of miRNA-766. The overexpression of miRNA-766 reduced cell growth and induced apoptosis in colon cancer cells through suppression of the MDM4/p53 pathway. By contrast, the downregulation of miRNA-766 promoted cell growth and reduced apoptosis in colon cancer cells through activation of the MDM4/p53 pathway. The promotion of MDM4 attenuated the anticancer effect of miRNA-766 in colon cancer cells. These results demonstrated that miRNA-766 induced cell apoptosis in human colon cancer through MDM4/p53.

Active lymphangiogenesis is a major risk factor for anastomotic leakage following sphincter-sparing resection of rectal cancer.

OBJECTIVE: Anastomotic leakage is a major complication of rectal surgery and controversy about its risk factors still exists. The aim of present study was to identify risk factors for anastomotic leakage following sphincter-sparing resection of rectal cancer, focusing on the role of tissular lymphatic vessel density (LVD) in tumorous margin and distal clearance margin. METHODS: In a 9-year period, from September 1999 to September 2009, 750 consecutive patients who underwent anterior resection with restoration of the bowel continuity were included. Univariate and multivariate analysis were applied to identify risk factors for anastomotic leakage. RESULTS: The rate of anastomotic leakage was 7.6% (57 of 750 patients). In a multivariate analysis, high LVD in tumorous margin [P=0.0017; odds ratio (OR)=5.93; 95% confidence interval (CI)=2.61-8.514], high LVD in distal clearance margin (P=0.0011; OR=6.05; 95% CI=2.72-10.108) and lower tumor location (P=0.006; OR=4.620; 95% CI=1.76-6.97) were identified as independent factors for anastomotic leakage. A significant LVD correlation was shown by Spearman's rank test between the tumorous and distal clearance margin (r=0.796). CONCLUSIONS: Tissular LVD in tumorous or distal clearance margin and lower tumor location are important risk factors for anastomotic leakage.

Lymphatic vessel density as predictive marker for the local recurrence of rectal cancer.

PURPOSE: This study identified possible factors affecting the frequency of local recurrence of rectal cancer, focusing on lymphangiogenesis as a predictor. METHODS: We examined 352 primary rectal cancer cases and 34 local recurrent specimens by lymphatic hyaluronan receptor. The lymphangiogenesis of all specimens was evaluated by measuring by lymphatic vessel density and other clinicopathologic factors. RESULTS: A multivariate analysis using the Cox proportional hazard model showed that lymphatic vessel density, lymph node metastasis, depth of invasion, and lymphatic invasion were significant independent predictive factors of local recurrence; lymphatic vessel density was the strongest predictor. In addition, a significant correlation was found between the lymphatic vessel density of the primary rectal cancer and the corresponding local recurrent cases. CONCLUSIONS: We suggest that rectal cancers, which have active lymphangiogenesis, also demonstrate a greater potential for local recurrence, and the lymphatic vessel density of surgical specimens is an independent risk factor and a valuable predictive factor for the local recurrence of rectal cancer.

[Clinical significance of lymphatic vessel density in determining the length of distal resection in rectal cancer].

OBJECTIVE: To study the the relationship between lymphatic vessel density (LVD) and distal intramural spread (DIS), and evaluate the value of LVD in determining the length of distal resection in low rectal cancer. METHODS: Ninety-two samples from patients undergone curative resection of low rectal cancer were studied. DIS was detected by HE stain. LVD was examined by immunohisto-chemical LYVE-1 (lymphatic vessel endothelial hyaluronan receptor). The association of LVD with DIS and other clinicopathological factors were examined. RESULTS: DIS (range 0.1-2.4 cm, mean 0.31 cm) was present in 44(47.8%) patients with low rectal cancer, including 23(52.3%) cases with cancer emboli in lymphatic vessels. LVD of peritumoral lesion was significantly higher than that of intratumoral lesion. LVD of DIS subgroup was significantly higher than that of non-DIS subgroup. Positive correlation was found by rank correlation test between the length of DIS and the LVD at peritumor tissue in DIS group (n=44, r=0.755, P<0.01). LVD was also positively correlated with the infiltration extent, lymphatic invasion and lymph node metastasis. CONCLUSIONS: Lymphangiogenesis plays an important role in rectal cancer metastasis and cancer emboli in lymphatic vessels is the most common modality of DIS. The LVD is positively correlated with DIS, which may be helpful to determine the distal clearance length of rectal cancer.