Xiao-Zhong Yang

Dickkopf-1 Expression Is a Novel Prognostic Marker for Gastric Cancer

Aim. To investigate the involvement of Dickkopf-1 expression in gastric cancer. Methods. Dickkopf-1 mRNA and protein expression were determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry in specimens of primary cancer and their adjacent noncancerous tissues in gastric cancer patients. Results. Dickkopf-1 mRNA and protein expression levels were both significantly upregulated in gastric cancer lesions compared with adjacent noncancerous tissues. Its positive expression was correlated with depth of invasion, vessel invasion, lymph node and distant metastasis, and TNM stage of tumors. Additionally, in stages I, II, and III gastric cancers, the 5- year survival rate of patients with a high expression of Dickkopf-1 was significantly lower than that in patients with low expression. In stage IV, Dickkopf-1 expression did not correlate with the 5-year survival rate. Further multivariate analysis suggested that the up-regulation of Dickkopf-1 was an independent prognostic indicator for gastric cancer. Conclusion. A subset of cases with gastric cancer revealed the up-regulation of Dickkopf-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, Dickkopf-1 expression may be predictor for poor prognosis in patients with gastric cancer. This is the first report describing the involvement of Dickkopf-1 in gastric cancer.

Cholecystectomy does not significantly increase the risk of fatty liver disease.

AIM To investigate the relationship between cholecystectomy and fatty liver disease (FLD) in a Chinese population. METHODS A total of 32428 subjects who had voluntarily undergone annual health checkups in the Second Affiliated Hospital of Nanjing Medical University from January 2011 to May 2013 were included in this study. Basic data collection, physical examination, laboratory examination, and abdominal ultrasound examination were performed. RESULTS Subjects undergoing cholecystectomy were associated with greater age, female sex, higher body mass index, and higher levels of systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglycerides. However, no significant differences were found in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, albumin, and serum uric acid. The overall prevalence of FLD diagnosed by ultrasonography was high at 38.4%. The prevalence of FLD was significantly higher for subjects who had undergone cholecystectomy (46.9%) than those who had not undergone cholecystectomy (38.1%; χ(2) test, P < 0.001). Cholecystectomy was positively associated with FLD (OR = 1.433, 95%CI: 1.259-1.631). However, after adjusting for possible factors associated with FLD, multivariate regression analysis showed that the association between cholecystectomy and FLD was not statistically significant (OR = 1.096; 95%CI: 0.939-1.279). CONCLUSION According to our study results, cholecystectomy may not be a significant risk factor for FLD.

BCAT1 expression in hepatocellular carcinoma.

The branched chain amino acids (BCAAs), bearing an aliphatic side chain with a branch, account for up to 40% of the performed amino acid requirements of mammals [1]. Branched chain amino acid transaminase 1 (BCAT1), located at 12p12.1, is one of enzymes catabolizing BCAAs [2]. BCAT1 and its encoded protein have been analyzed in a variety of cancers, including gliomas [3], urothelial carcinoma [4], nasopharyngeal carcinoma [5], colorectal cancer [6], etc. However, limited studies have focused on the relationship between BCAT1 and liver disease. Reportedly, upregulation of BCAT1 was found in nonalcoholic steatohepatitis (NASH) [7], reflecting possible metabolic alterations of damaged hepatocytes. To investigate the relationship of BCAT1 and hepatocellular carcinoma (HCC), we analyzed BCAT1 expression in HCC and paired adjacent non-tumour tissues by immunohistochemistry using tissue microarray, and explored its correction with the survival of HCC patients. We analyzed 51 patients (45 men, age range from 38 to 72 years) who underwent curative resection at hospitals for histologically proven HCC that cooperated with National Engineering Center for Biochip at Shanghai during August 2006 to December 2008. All patients were followed up until September 2013 with an observation time of 4.8 to 7 years. Survival curves were estimated using the Kaplan—Meier method and compared by the log-rank test. A two-tailed P value of less than 0.05 was considered statistically significant. We found that 52.9% (27/51) of HCC samples were positive for BCAT1, which was observed primarily in the cytoplasm. In contrast, 78.4% (40/51) of the adjacent liver tissues expressed BCAT1 (P = 0.012, Fisher’s exact test). Segregation of these patients into the BCAT1-positive and BCAT1-negative groups did not reveal significant correlations with tumour number, maximal size, differentiation, pTNM

Combining TRAIL and liquiritin exerts synergistic effects against human gastric cancer cells and xenograft in nude mice through potentiating apoptosis and ROS generation

Gastric cancer is one of the most factors, leading to cancer-related death worldwide. However, the therapies to prevent gastric cancer are still limited and the emergence of drug resistance leads to development of new anti-cancer drugs and combinational chemotherapy regimens. Our study was aimed to explore the anti-gastric cancer effects of liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, which possesses a variety of pharmacological activities. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially inhibited tumor cells over other normal cells, when used in alone or in combination. The results indicated that LIQ, when applied in single, was moderately effective to suppress proliferation, and migration, as well as to induce apoptosis and reactive oxygen species (ROS) generation of human gastric cancer cell lines, AGS and SNU-216, which are TRAIL-resistant. Significantly, when used in combination, the two drugs functioned synergistically to impede the progression and growth of human gastric cancer cells in vitro and gastric cancer cell xenograft nude mice in vivo. Both intrinsic and extrinsic apoptosis were induced by the two in combination via activating Caspases. And c-Jun N-terminal kinase (JNK) activity was dramatically induced by TRAIL/LIQ. Importantly, TRAIL/LIQ-triggered apoptosis and JNK were dependent on ROS production. The data indicated that application of TRAIL/LIQ in combination had a potential value for clinical use to synergistically prevent human gastric cancer development.

Prognostic value of combined and individual expression of microRNA-1290 and its target gene nuclear factor I/X in human esophageal squamous cell carcinoma

BACKGROUND microRNA (miR)-1290 was previously indicated to promote esophageal squamous cell carcinoma (ESCC) progression via regulating its target gene nuclear factor I/X (NFIX). OBJECTIVE To investigate clinical significance of miR-1290 and NFIX in ESCC. METHODS Quantitative real-time PCR was performed to detect miR-1290 and NFIX mRNA expression in ESCC tissues. Associations of miR-1290 and/or NFIX mRNA expression with various clinicopathological features and prognosis in ESCC patients were statistically evaluated. RESULTS Compared to noncancerous esophageal mucosa, miR-1290 expression was upregulated, while NFIX mRNA expression was downregulated in ESCC tissues. There was a significantly negative correlation between miR-1290 and NFIX expression in ESCC tissues (r=-0.427, P= 0.01). Interestingly, miR-1290-high and/or NFIX-low expression were all significantly associated with positive lymph node metastasis and advanced tumor-node-metastasis stage of ESCC patients (all P< 0.05). Moreover, miR-1290 upregulation and NFIX downregulation both correlated short overall and disease-free survivals of ESCC patients. Importantly, the prognostic value of combined miR-1290 and NFIX expression was more significant than those considered alone. CONCLUSIONS Our data suggest that the dysregulation of miR-1290-NFIX axis may play crucial roles in esophageal carcinogenesis and progression. We also confirmed miR-1290 and its target gene NFIX as independent prognostic factors for ESCC patients.