Protective effects of methyl protodioscin against lipid disorders and liver injury in hyperlipidemic gerbils.

Methyl protodioscin (MPD) is the main component of total diosgenin, which was reported to reduce cholesterol and triglyceride levels potentially. This study aimed to investigate the beneficial effects of MPD against lipid disorder in hyperlipidemic gerbils induced by a high-fat diet (HFD). Hyperlipidemia was induced in gerbils by feeding them with HFD for six weeks, and a daily oral dose of MPD solution (25 and 50 mg/kg/day) was administered. This study investigated blood lipid levels and hepatic lipid accumulation in hyperlipidemic gerbils. The potential mechanism of MPD was explored by detecting the expression level of genes, including SREBPs, ACC, FASN, HMGCR, PCSK9, and LDL-R. The results showed that MPD treatment decreased the body weight, the relative weight of the liver, blood lipid, and hepatic lipid levels of gerbils fed with HFD. The administration of MPD alleviates liver steatosis and injury in gerbils fed with an HFD. MPD treatment reduced the expression of HMGCR, increased the expression of LDL-R, and decreased the expression of PCSK9 for cholesterol reduction. Additionally, MPD treatment reduced the expression of hepatic ACC and FASN for triglycerides reduction. The underlying mechanisms for these effects are attributed to MPD-induced inhibition of protein expression of LXR, SREBP1, and SREBP2. This study demonstrates that MPD protects gerbils against lipid disorders and liver injury by suppressing hepatic SREBPs expression.

Increased cancer-specific mortality of very small size in carcinoembryonic antigen-elevated rectal cancer.

BACKGROUND: The present study aimed to investigate the cause-specific survival (CSS) of very small rectal cancer in the context of preoperative serum carcinoembryonic antigen (CEA) elevation. METHODS: Patients diagnosed with node-negative rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database from January 2004 to December 2010 meeting the inclusion criteria were identified for this study. The Cox proportional hazards regression analyses were conducted to identify independent factors associated with CSS. Pearson's chi-squared tests and Kaplan-Meier methods were performed. RESULTS: A total of 8,413 patients were included into our study. Kaplan-Meier analyses showed lower 7-year CSS rate of very small tumors (≤5 mm) compared to those larger than 40 mm (70.4% vs. 76.0%, log-rank P=0.469). Multivariate Cox analyses showed that patients with very small tumor size (≤5 mm) was also associated with a significantly increased risk of cancer-specific mortality compared with those with large tumor size (HR =2.567, 95% CI: 1.285 to 5.130, P=0.008, using ≥41 mm, C+ as a reference). CONCLUSIONS: Very small tumor size in the context of preoperative serum CEA elevation could be a surrogate for biological aggressiveness. Our finding would provide a better understanding of tumor biology for us and elicit more future biological researches.

Prognostic accuracy of different lymph node staging systems in rectal adenocarcinoma with or without preoperative radiation therapy.

BACKGROUND AND OBJECTIVE: A variety of different lymph node (LN) staging systems have been developed to describe the lymph node status accurately. We aim to compare the prognostic accuracy of American Joint Committee on Cancer seventh N stage relative to negative number of lymph node (nLN), lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) in rectal adenocarcinoma (RC). METHODS: A total of 19 167 Stage II-III rectal cancer patients who underwent surgical resection of rectal adenocarcinoma were identified from Surveillance, Epidemiology and End Results database. Akaike's Information Criterion (AIC) and the Harrell's concordance index (c statistic) were used to evaluate the relative discriminative power of the different LN staging systems. RESULTS: Of the 19 167 patients, 10 958 received preoperative radiotherapy (pre-RT cohort) and 8209 patients were treated with surgical resection directly (SURG cohort). When assessed using categorical cutoff values, LNR has a somewhat better prognostic accuracy both in pre-RT (c-index: 0.62; AIC: 2988.6) and SURG groups (c-index: 0.60; AIC: 3359.8). Further analysis based on different total number of lymph node (TNLN) suggested that when less than 10 lymph nodes were retrieved, LNR exhibited significant superiority (pre-RT: c-index: 0.597, AIC: 1006.8; SURG: c-index: 0.560, AIC: 810.5). When analyzed as a continuous variable, the LODDS system performed the best and was not impacted by TNLN. CONCLUSION: When assessed as a categorical variable, LNR was the most powerful method to predict survival for Stage II-III RC patients with limited TNLN. Rather, LODDS was the most accurate staging system regardless of the TNLN when LN status was modeled as continuous variable.

Expression of miR-221 in colon cancer correlates with prognosis.

MicroRNAs are increasingly important in the study of cancer because of their ability to down regulate the expression of tumor suppressors and promote tumorigenesis. Here, miR-221, which is dysregulated in various tumors, was investigated for its expression in colon cancer tissues and its correlation with patient prognosis. Colon cancer tissue samples were obtained from 182 individuals who underwent surgical resection in our hospital from June 2008 to September 2009. Real-time PCR was used to detect the expression of miR-221 in these tissues. Patient survival was determined by telephone interview, and survival curves were plotted by using the Kaplan-Meier method and compared by the Log-rank test. Statistical methods also included X(2) test and Cox proportional hazard regression model. Differences in the expression of miR-221 by gender, pathology, and pathological staging were not statistically significant (P>0.05), but differences in the expression of miR-221 among age groups were statistically significant (P<0.05). A survival analysis indicated that high expression of miR-221 was closely associated with a shorter survival time (P<0.05). Further, later p-TNM (hazard ratio, HR=2.973, 95% confidence interval, CI: 1.329-6.519, P=0.003) and high expression of miR-211 (HR=2.394, 95% CI: 1.210-4.910, P=0.006) were identified as risk factors for colon cancer prognosis. Thus, high miRNA-221 expression might be a prognostic marker of colon cancer patients. The high expression of miRNA-221 was associated with poor prognosis of patients with colon cancer.