Efficacy and safety of Hou Gu Mi Xi in patients with spleen qi deficiency syndrome who underwent radical gastrectomy for gastric cancer: protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Spleen qi deficiency (SQD), a syndrome based on traditional Chinese medicine (TCM) theory, is common in patients after radical gastrectomy. SQD manifests with chronic gastrointestinal disorders and systemic symptoms and is challenging to manage. Hou Gu Mi Xi (HGMX) is a dietary TCM formula for SQD. This study aims to evaluate the efficacy and safety of HGMX in patients with SQD who have undergone radical gastrectomy for gastric cancer. METHODS AND DESIGN: This study is a multicenter, randomized, double-blind, placebo-controlled trial. One hundred thirty patients with SQD who have undergone radical gastrectomy for gastric cancer will be assigned to receive either HGMX or placebo for 2 years. The main outcome will be changes in SQD symptoms assessed by the Spleen Qi Deficiency Symptoms Grading and Quantifying Scale. The secondary outcomes will be changes in quality of life assessed by the Short Form 36 scale, performance status as assessed by the Eastern Cooperative Oncology Group Performance Status scale, body weight, and body mass index. Progression-free survival will also be assessed as a secondary outcome. Adverse events (AEs), severe AEs, and study withdrawal due to AEs will be recorded to evaluate the safety of HGMX. DISCUSSION: The results of this trial will provide initial evidence for the use of HGMX as an alternative and complementary intervention to manage chronic postoperative complications in patients who have undergone radical gastrectomy for gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03025152 . Registered on 17 January 2017.

Polymorphism in miR-146a associated with clinical characteristics and outcomes in gastric cancer patients treated with adjuvant oxaliplatin and fluoropyrimidines.

PURPOSE: Polymorphism in miR-146a (rs2910164) has been reported to be associated with gastric cancer risk in the Chinese population. We aimed at evaluating the relationship between rs2910164 and the clinical characteristics and outcomes in stage IB-III gastric cancer patients treated with adjuvant chemotherapy after surgery. MATERIALS AND METHODS: Ninety-eight patients with stage IB-III gastric cancer treated with surgical resection followed by adjuvant chemotherapy of oxaliplatin and fluoropyrimidines were included in the analysis. Genomic DNA was extracted from peripheral blood sample of all patients. Polymerase chain reaction-based restriction fragment length polymorphism assay was used to determine the genotypes. RESULTS: The 2-year disease-free survival rate was 63%, and the 3-year overall survival (OS) rate was 73.4%. In dominant model, we found that rs2910164 GC + CC (G: guanine, C: cytosine) genotype carriers were less likely to develop lymph node metastasis (P=0.059). The 3-year OS was significantly different for patients with or without lymph node metastasis (89.3% vs 63.7%, P=0.015) and for patients with stage I-III disease (100.0%, 88.6%, and 56.9%; P=0.018). The 3-year OS for GC + CC carriers was significantly higher than for GG carriers (75.1% vs 66.7%, P=0.041). After the multivariant Cox regression analysis, histological grade (P=0.033, relative risk: 5.116, 95% confidence interval: 1.145-22.865) and lymph node status (P=0.031, relative risk: 6.648, 95% confidence interval: 1.191-37.118) were found to be independent prognostic factors for these patients. CONCLUSION: rs2910164 could be associated with the lymph node metastasis and prognosis of Chinese gastric cancer patients treated with oxaliplatin and fluoropyrimidines after surgical resection.

Antitumor activity of chloroquine in combination with Cisplatin in human gastric cancer xenografts.

PURPOSE: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. MATERIALS AND METHODS: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. RESULTS: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). CONCLUSIONS: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

Changing patterns of Serum CEA and CA199 for Evaluating the Response to First-line Chemotherapy in Patients with Advanced Gastric Adenocarcinoma.

BACKGROUND: This study was designed to investigate the value of CEA and CA199 in predicting the treatment response to palliative chemotherapy for advanced gastric cancer. MATERIALS AND METHODS: We studied 189 patients with advanced gastric cancer who received first-line chemotherapy, measured the serum CEA and CA199 levels, used RECIST1.1 as the gold standard and analyzed the value of CEA and CA199 levels changes in predicting the treatment efficacy of chemotherapy. RESULTS: Among the 189 patients, 80 and 94 cases had increases of baseline CEA (≥5 ng/ml) and CA199 levels (≥ 27U/ml), respectively. After two cycles of chemotherapy, 42.9% patients showed partial remission, 33.3% stable disease, and 23.8% progressive disease. The area under the ROC curve (AUC) for CEA and CA199 reduction in predicting effective chemotherapy were 0.828 (95%CI 0.740-0.916) and 0.897 (95%CI 0.832-0.961). The AUCs for CEA and CA199 increase in predicting progression after chemotherapy were 0.923 (95%CI 0.865-0.980) and 0.896 (95%CI 0.834-0.959), respectively. Patients who exhibited a CEA decline ≥24% and a CA199 decline ≥29% had significantly longer PFS (log rank p=0.001, p<0.001). With the exception of patients who presented with abnormal levels after chemotherapy, changes of CEA and CA199 levels had limited value for evaluating the chemotherapy efficacy in patients with normal baseline tumor markers. CONCLUSIONS: Changes in serum CEA and CA199 levels can accurately predict the efficacy of first-line chemotherapy in advanced gastric cancer. Patients with levels decreasing beyond the optimal critical values after chemotherapy have longer PFS.

Clinicopathological characteristics and prognosis of gastric cancer with malignant ascites.

Management of gastric cancer with malignant ascites is a challenge, and limited data are available. We evaluated factors affecting survival for this condition to determine factors that predict survival outcome and to develop a rational treatment plan. We retrospectively studied 5,542 patients with gastric adenocarcinoma from January 2007 to December 2012. Among them, 347 patients (6.26%) were associated with malignant ascites. The patients' overall survival was compared among the different features. Three hundred forty-seven patients (153 females and 194 males; median age, 53 years) were enrolled, including 78 (22.5%) young patients and 63 (18.1%) elderly patients. One hundred forty-three (41.2%) patients presented with malignant ascites at the initial diagnosis of gastric cancer, and 211 (60.8%) received chemotherapy. After a median follow-up duration of 10.4 months, the median survival after the diagnosis of malignant ascites was 5.2 months (95% CI, 4.8-5.6 months), and the 1-year survival rate was 16.1 %. An ECOG score greater than 2 (P < 0.001), the presence of ascites with the diagnosis of gastric cancer (P < 0.001), no chemotherapy (P < 0.001), an albumin level less than 30 g/L (P = 0.013), an ascites volume greater than 2,000 mL (P = 0.019), Helicobacter pylori infection (P = 0.010), and metastases to other organs (P = 0.037) were associated with poor prognosis, and they were all independent prognostic factors. The survival of gastric cancer patients with malignant ascites is relatively short, and ECOG score and the presence of ascites with the diagnosis of gastric cancer are the most important prognostic factors. Additionally, chemotherapy could improve the overall survival.

Autophagy inhibition sensitizes cisplatin cytotoxicity in human gastric cancer cell line SGC7901.

We aimed to investigate the mechanism and effects of autophagy on cisplatin (DDP)-induced apoptosis in human gastric cancer cell line SGC7901. After SGC7901 cells were treated with DDP and/or chloroquine, cell proliferation was measured using MTT assay; cell apoptosis was determined by flow cytometry; autophagy and apotosis-related proteins expression were detected by Western blot; and quantitative analysis of autophagy after monodansylcadaverine (MDC) staining was performed using fluorescence microscopy. We found after treatment with 5 mg/L DDP for 24 h, the rates of cell apoptosis were (21.07±2.12)%. Autophagy, characterized by an increase in the number of autophagic vesicles and the level of LC3-II protein was observed in cells treated with DDP. After inhibition of autophagy by chloroquine, the rates of cell apoptosis were increased to (30.16±3.54)%, and the level of Caspase-3 and P53 protein were increased, and Bcl-2 protein was decreased. Therefore, autophagy protects human gastric cancer cell line SGC7901 against DDP-induced apoptosis, inhibition of autophagy can promote apoptosis, and combination therapy with DDP and chloroquine may be a promising therapeutic strategy for gastric cancer.