Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells by modulating proliferation and apoptosis via targeting MET.

Cisplatin (DDP) based chemotherapy is still the main strategy of human gastric cancer (GC) treatment. However, drug resistance is a major obstacle for DDP chemotherapy. Recent studies indicated that the resistance could be modulated by the regulation of dysregulated microRNAs (miRs). Previous study also found miR-34a was associated with cell proliferation and apoptosis in human GC; however, the relationship between miR-34a and DDP resistance still remains unexplored. The purpose of this study was to investigate whether miR-34a is associated with DDP resistance in human GC cells. Our study found that the expression of miR-34a was significantly decreased in DDP resistance human GC tissues and DDP resistance human GC SGC7901/DDP cells compared with normal GC tissues and cells. Upregulation of miR-34a enhanced the DDP sensitivity of SGC7901/DDP cells to DDP through the inhibition of cell proliferation and induction of cell apoptosis; on the other hand downregulation of miR-34a could weaken the DDP sensitivity of SGC7901 cells to DDP. Further study found that MET was a direct target of miR-34a and the regulation of MET could affect the DDP sensitivity of SGC7901/DDP cells. Moreover, our study also indicated that up-regulation of miR-34a could decrease the expression of MET in SGC7901/DDP cells. Therefore, our findings suggested miR-34a could modulate human gastric cancer cell DDP sensitivity by regulation of cell proliferation and apoptosis via targeting MET, potentially benefiting human GC treatment in the future.

Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer. METHODS: For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate. RESULTS: There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups. CONCLUSIONS: These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.

[Comparison study of three methods of digestive tract reconstruction after radical gastrectomy in gastric cancer patients].

OBJECTIVE: To investigate the ideal digestive tract reconstruction methods among three different surgical methods after radical gastrectomy of gastric cancer patients. METHODS: A total of 123 patients who received elective radical gastrectomy for gastric cancer from February 2010 to August 2011 were prospectively enrolled and randomly divided into radical proximal gastrectomy and jejunal interposition group, radical proximal gastrectomy and esophageal with the posterior of residual-stomach group, and radical total gastrectomy and Roux-en-Y esophagojejunostomy group. Patients were followed up for 12 months. Symptoms of reflux esophagitis were observed, gastric emptying tests were done, liver and kidney function was also monitored. The quality of life was documented before operation, and one and twelve months after operation. RESULTS: No significant differences were found among these three groups in the pH value of lower part of esophagus, the blood regular test results and the functional parameters of kidney and liver before and after operation(all P>0.05). Symptoms of reflux esophagitis was reported in 1(2.4%) patients in the jejunal interposition group, 10(24.4%) in esophageal with the posterial of residual-stomach group, and 7(17.1%) in the Roux-en-Y esophagojejunostomy group(P=0.017). There was 1(2.4%), 10(17.1%), and 8(19.5%) patients presented reflux of barium meal in these three groups, respectively (P=0.046). There were no statistically significant difference in PH at the distal esophagus(6.9±0.2 vs. 6.8±0.1 vs. 6.9±0.1, P=0.196). The quality of life was significantly improved one year after surgery in terms of general status, physical function, emotional function, fatigue, nausea/vomiting, pain, constipation, and diarrhea (all P<0.05), with the jejunal interposition superior than the other two methods. CONCLUSION: Three methods of digestive tract reconstruction in radical gastrectomy of gastric cancer patients can improve the health status and the quality of life in gastric cancer patients. Radical proximal gastrectomy and jejunal interposition is the preferred method.

Functional analysis of B7-H3 in colonic carcinoma cells.

B7-H3 is a newly discovered member of the B7/CD28 superfamily which functions as an important T-cell immune molecule. It has been reported recently that B7-H3 is highly expressed in many cancer cells, the data indicating that it may be a regulation factor contributing to tumor-resistance. In our study, we used bioinformatics to identify differentially expressed genes between colonic cancer cells and normal colonic cells, aiming to analyze mechanisms and identify sub-pathways closely related to progression, with the final aim of finding small molecule drugs which might interfere this progression. We found that ajmaline is one related factor which may enhance self-immunity in colon carcinoma therapy and B7-H3 plays important roles with regard to immunoreactions of colonic cancer cells. All the results indicate that H7-B3 is a favorable prognostic biomarker for colon carcinomas, providing novel information regarding likely targets for intervention.