Berberine inhibits epithelial-mesenchymal transition and promotes apoptosis of tumour-associated fibroblast-induced colonic epithelial cells through regulation of TGF-ß signalling.

Tumour-associated fibroblasts (TAFs) mediate the differentiation of adjacent stromal cells. Berberine (BBR), a monomer of traditional Chinese herbs, exhibits a potent therapeutic effect against cancer. However, the effects of BBR on the differentiation of normal colonic epithelial cells induced by TAFs have not been determined. In the present study, we selected the TAF-like myofibroblast cell line CCD-18Co. CCD-18Co-derived conditioned medium (CM) and co-culture induced epithelial-mesenchymal transition (EMT) changes in colonic epithelial HCoEpiC cells with decreased E-cadherin and increased vimentin and α-SMA expression. In addition, CCD-18Co stimulated the expression of ZEB1 and Snail and promoted motility. We used LY364947, a TGF-ß receptor kinase type I (TßRI) inhibitor, and BBR. Our results showed that LY364947 and BBR inhibited these phenomena. BBR decreased the expression of ZEB1 and Snail, and this effect was concentration dependent. BBR also downregulated the expression of TßRI, TßRII, Smad2/p-Smad2 and Smad3/p-Smad3. In addition, BBR induced apoptosis in EMT-like HCoEpiC cells in a concentration-dependent manner with upregulation of Bax and downregulation of Bcl-2. However, VX-702, an inhibitor of p38 MAPK, significantly suppressed the apoptosis rate. BBR promoted the expression of p38 MAPK and phosphorylated p38 MAPK. In conclusion, berberine inhibits EMT and promotes apoptosis in TAF-induced colonic epithelial cells through mediation of the Smad-dependent and SMAD-independent TGF-ß signalling pathways.

[Impact of different extents of lymph node dissection on the survival in stage III esophageal cancer patients].

OBJECTIVE: To investigate the safety, feasibility and the impact of different extents of lymph node dissection on the survival in the patients with locally advanced thoracic esophageal carcinoma. METHODS: From January 2001 to December 2006, 122 patients with locally advanced thoracic esophageal carcinoma underwent radical resection through cervical, thoracic, and abdominal incisions, and were randomly divided into two-field lymph node dissection group (Two-FD) and three-field lymph node dissection group (Three-FD). Life-table method was used to compare the difference of survival rates between the two groups. Kaplan-Meier method was used to compare the cumulative survival time and median survival time between the two groups. Multivariate analysis was performed using Cox model to identify the prognostic factors affecting the survival (alpha = 0.05). RESULTS: There was no significant difference between the two groups in age, sex, and disease stage. Postoperative complication rate and perioperative mortality rate were 14.5% and 1.6% in the two-FD group versus 15.0% and 1.7% in the three-FD group, statistically without a significant difference (P > 0.05). The 1-, 3- and 5-year survival rates were 78.2%, 39.6% and 14.5% in the two-FD group, and 83.7%, 42.4% and 18.1% in the three-FD group, respectively. The median survival time was 24.0 months in the two-FD group and 31.0 months in the three-FD group. Log-rank analysis showed that in the patients without preoperative weight loss, in T3N1M0 stage, only single regional lymph node metastasis but < 3 in total, the three field lymph node dissection achieved a better prognosis (P < 0.05). Multivariate analysis using Cox model showed that T and N stages and lymph node dissection extent were still risk factors in patients with stage III locally advanced thoracic esophageal carcinoma. CONCLUSION: Compared with the two field lymph node dissection, the three field lymph node dissection is safe and feasible, and can improve the survival for a part of stage III esophageal cancer patients without increase in operative mortality and complications.

[Two patterns of mediastinal lymph node resection for non-small cell lung cancer of stage IIIA: survival analysis of 219 cases].

BACKGROUND & OBJECTIVE: Correctly dealing with mediastinum lymph nodes during operation is critical to the prognosis of resectable non-small cell lung cancer (NSCLC) of stage IIIA, but the removal extent of mediastinum lymph nodes is controversial. This study was to explore the effects of 2 patterns of mediastinum lymph node resection on long-term survival of stage IIIA NSCLC patients. METHODS: Clinical data of 219 stage IIIA NSCLC patients, underwent complete resection from Jan. 1999 to Jan. 2004 in Xinjiang Tumor Hospital, were reviewed. Of the 219 patients, 109 underwent mediastinal lymph node sampling (LS), and 110 underwent systematic mediastinal lymphadenectomy (SML). Survival statuses of the patients were analyzed by Life table method and Kaplan-Meier method; the prognosis was analyzed with Cox multivariate regression model. RESULTS: The 1-, 3-, and 5-year survival rates were 82%, 28%, 13% in LS group, and 88%, 37%, 16% in SML group. The median survival time was significantly longer in SML group than in LS group (23.5 months vs. 20.0 months, P<0.05). Cox multivariate analysis showed that histopathologic type, metastasis state of mediastinal lymph nodes, mediastinum lymph node resection pattern were prognostic factors of stage IIIA NSCLC patients. CONCLUSION: As compared with LS, SML in radical operation could improve the survival rate of stage IIIA NSCLC patients.