Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence

AIM: To investigate the relationship between cycloo- xygenase-2 (COX-2), and vascular endothelial growth factor (VEGF), and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy (CRT). METHODS: Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma (ESCC) who were undergoing preoperative CRT. RESULTS: Fourteen out of 40 ESCC patients showed a pathological complete response (CR) after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression (P < 0.05). There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement (P = 0.0277 and P = 0.0095, respectively). COX-2 expression and VEGF expression had significant prognostic value for disease-free survival (log-rank test; P = 0.0073 and P = 0.0341, respectively), but not for overall survival, as assessed by univariate analysis. CONCLUSION: Our results suggest that COX-2 expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.

Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer

AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.

Effects of age on survival and morbidity in gastric cancer patients undergoing gastrectomy

AIM To evaluate clinicopathological features and surgical outcomes of gastric cancer in elderly and non-elderly patients after inverse probability of treatment weighting(IPTW) method using propensity score.METHODS We enrolled a total of 448 patients with histologically confirmed primary gastric carcinoma who received gastrectomies. Of these, 115 patients were aged > 80 years old(Group A), and 333 patients were aged < 79 years old(Group B). We compared the surgical outcomes and survival of the two groups after IPTW.RESULTS Postoperative complications, especially respiratory complications and hospital deaths, were significantly more common in Group A than in Group B(P < 0.05). Overall survival(OS) was significantly lower in Group A patients than in Group B patients. Among the subset of patients who had pathological Stage Ⅰ?disease, OS was significantly lower in Group A(P < 0.05) than Group B, whereas cause-specific survival was almost equal in the two groups. In multivariate analysis, pathological stage, histology, and extent of lymph node dissection wereindependent prognostic values for OS.CONCLUSION When the gastrectomy was performed in gastric cancer patients, we should recognized high mortality and comorbidities in that of elderly. More extensive lymph node dissection might improve prognoses of elderly gastric cancer patients.

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

AIM: To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC).METHODS: Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSK-related markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients. RESULTS: ECA39, a direct target of c-Myc, was identi-fied as a candidate protein affected by the anti-metastat-ic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P < 0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, posi-tive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P < 0.05). CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in pa-tients with advanced CRC and that its suppression by PSK might represent a useful application of immuno-therapy as part of a program of integrated medicine.

Causal relationships between survival rates, dietary and lifestyle habits, socioeconomic status and physical, mental and social health in elderly urban dwellers in Japan: A chronological study

Life expectancy was well known to associate with lifestyle habits, socioeconomic condition, and three health-related dimensions (physical, mental and social health status). However, the causal effect relationship among these variables remains unclear. The purpose of this study was to determine the causal relationships among health and life conditions, socioeconomic status, dietary and lifestyle habits and three health-related dimensions in elderly urban dwellers in Tokyo, Japan. Of 16,462 eligible elderly individuals aged 65 years and older, 13,195 participants responded to the questionnaire survey conducted in September 2001 (a response rate of 80.2%). A follow-up survey was conducted in September 2004 and a total of 8162 survivors were followed until the end of August 2007 through the municipal resident's registry. Exploratory factor analysis defined five latent variables based on the 13 observed variables. From a cross-lagged effects variation model using structural equation modeling, causal relationships were analyzed using longitudinal data obtained at the 2001 and 2004 survey and the number of survival days between 2004 and 2007. After estimating a best-fit model, we discovered that health and life conditions were not determined by current dietary and lifestyle habits, which many studies showed. However, the conditions were more directly affected by three health-related dimensions three years earlier, and indirectly affected by educational attainment and previous annual income as well. The current model suggests that it might be of great importance for elderly individuals to emphasize the maintenance of psychological well being, physical activity, social communication and participation, as well as income, rather than focusing on improvements in diet and health-related lifestyles per se.

Effect of Aging and Sex on Circulating MicroRNAs in Humans

MicroRNAs (miRNAs) have been reported as potentially being useful biomarkers for various diseases including cancer, diabetes mellitus, heart disease, neurological disease and age-related diseases. In the present study, we aimed to determine whether the expression levels of circulating miRNAs in serum were changed with aging or sex. Serum samples from seven elderly males (69.86 ± 1.77 years old) and females (72.43 ± 1.49 years old), and six young males (26.17 ± 0.83 years old) and females (23.17 ± 1.52 years old) were obtained from the subject’s forearm at rest. The expression levels of circulating miR-146a and miR-20a in serum were determined by real-time TaqMan PCR. There were no differences in the expression levels of miR-146a between all groups. There was a significant interaction in this main effect where miR-20a levels were significantly lower in elderly male subjects when compared to young male subjects with no difference observed in young or elderly female subjects (p = 0.004 and p = 0.971, respectively). These results suggest that not all the miRNAs in the circulation are influenced by the effect of aging, but only some miRNAs may be selectively changed by the effect of aging.