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The aim of this study was to detect mixed lineage kinase domain-like protein (MLKL) expression in gastric cancer (GC) and to analyze its association with the prognosis of GC patients. Immunohistochemical staining, Western blotting, and quantitative reverse-transcriptase polymerase chain reaction were performed to detect MLKL tissue expression in 117 GC patients. Clinicopathological characteristics and survival data were retrospectively analyzed to discover the clinical importance of MLKL expression. The chi-square test was used to analyze the relationship between MLKL expression and the clinicopathological characteristics. Survival curves were plotted by using the Kaplan-Meier method and compared using the log-rank test. Survival data were evaluated using univariate and multivariate Cox regression analyses. The expression of MLKL mRNA was significantly higher in adjacent normal samples than in the tumor tissues (P = 0.003). Clinicopathological analysis showed that MLKL expression was significantly correlated with age (P = 0.013), histologic type (P = 0.049), differentiation grade (P < 0.001), depth of invasion (P = 0.022), and lymph node metastasis (P = 0.003). Low MLKL expression was significantly associated with decreased overall survival (median 29 months vs. 56 months, P < 0.001). Multivariate analysis suggested that MLKL expression might be an independent prognostic indicator (HR = 0.645, 95 % CI, 0.446-1.165, P = 0.002) for GC patients. In conclusion, our findings provide evidence that MLKL might serve as a candidate tumor suppressor and a potential prognostic biomarker for GC.

Gestational Diabetes Mellitus (GDM) is associated with an increased risk of perinatal morbidity and long term health issues for both the mother and offspring. Previous research has demonstrated associations between maternal diet and GDM development, but evidence in Asian populations is limited. The objective of our study was to examine the cross-sectional relationship between maternal dietary patterns during pregnancy and the risk of GDM in a multi-ethnic Asian cohort. Maternal diet was ascertained using 24-h dietary recalls from participants in the Growing up in Singapore towards healthy outcomes (GUSTO) study-a prospective mother-offspring cohort, and GDM was diagnosed according to 1999 World Health Organisation guidelines. Dietary patterns were identified using factor analysis, and multivariate regression analyses performed to assess the association with GDM. Of 909 participants, 17.6% were diagnosed with GDM. Three dietary patterns were identified: a vegetable-fruit-rice-based-diet, a seafood-noodle-based-diet and a pasta-cheese-processed-meat-diet. After adjusting for confounding variables, the seafood-noodle-based-diet was associated with a lower likelihood of GDM (Odds Ratio (95% Confidence Interval)) = 0.74 (0.59, 0.93). The dietary pattern found to be associated with GDM in our study was substantially different to those reported previously in Western populations., Competing Interests: K.M.G. and Y.-S.C. have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. K.M.G. and Y.-S.C. are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have no financial or personal conflict of interest to declare.

The aim of this study was to detect forkhead box L1 (FOXL1) expression in gastric cancer (GC) and to analyze its association with the prognosis of GC patients. Immunohistochemical staining, Western blotting, and quantitative reverse transcriptase polymerase chain reaction were performed to detect FOXL1 tissue expression in 109 GC patients. Clinicopathological characteristics and survival data were retrospectively analyzed to discover the clinical importance of FOXL1 expression. The chi-square test was used to analyze the relationship between FOXL1 expression and the clinicopathological characteristics. Survival curves were plotted by using the Kaplan-Meier method and compared using the log-rank test. Survival data were evaluated using univariate and multivariate Cox regression analyses. The expression of FOXL1 messenger RNA (mRNA) was significantly higher in adjacent normal samples than in the tumor tissues (P = 0.043). Clinicopathological analysis showed that FOXL1 expression was significantly correlated with depth of invasion (P = 0.017), lymph node metastasis (P = 0.019), and distant metastasis (P = 0.047). FOXL1-negative as opposed to the FOXL1-positive patients had lower 5-year overall survival (14.06 vs. 37.78 %, P < 0.001). Multivariate analysis suggested that FOXL1 expression might be an independent prognostic indicator (hazard ratio = 0.307, 95 % confidence interval, 0.187-0.505; P < 0.001) for GC patients. In conclusion, our findings provide evidence that FOXL1 might serve as a candidate tumor suppressor and a potential prognostic biomarker for GC.

Background: Sonic hedgehog (SHH) plays critical roles in cell growth and development. Tumor cells express SHH, which can promote cell proliferation and epithelial-to-mesenchymal transition. However, the autocrine SHH pathway has not been described in gastric cancer. The aim of this study was to explore molecular mechanisms underlying autocrine SHH signaling in gastric cancer cells., Methods: SHH expression was assessed using immunohistochemistry and the results were compared with clinicopathologic parameters, including survival. Using gastric cancer cell lines, we measured SHH mRNA and protein expression, and studied the effects of SHH signaling on cell proliferation and SHH secretion. We also studied the effects of an inhibitor of PLC-γ1 on phosphorylation of phospholipase Cγ1 and extracellular signal-regulated kinases (ERK)1/2., Results: SHH protein expression in gastric cancer tissue was significantly higher compared with that in normal gastric tissue (P < 0.001), and the increased expression was significantly associated with pT staging (P = 0.004), pN staging (P = 0.018), pM staging (P = 0.006), and pTNM staging (P < 0.001). In multivariate analyses, overall survival in gastric cancer was significantly shorter in cases with high SHH expression (HR = 1.734, 95% CI: 1.109-2.713, P = 0.016). The AGS and SGC-7901 gastric cancer cell lines expressed SHH mRNA and protein. In these cell lines, SHH promoted carcinogenesis through activation of the PLCγ1-ERK1/2 pathway, resulting in increased cell proliferation and survival., Conclusions: Increased SHH expression is associated with shorter survival in gastric cancer patients, and SHH could represent a useful biomarker or therapeutic target for this disease.

Purpose: To investigate the associations of near work, outdoor activity, and anthropometric risk factors with early-onset myopia in Singaporean preschool children., Methods: Pregnant women who attended their first-trimester clinic at two major maternity units were recruited for the GUSTO birth cohort (n = 1236). Cycloplegic autorefraction and axial length (AL) were obtained in 3-year-old children (n = 572). Parents completed detailed questionnaires on parental myopia, near work, and outdoor activities when the child was 2 years of age. Height and weight were measured in the children at various time points from birth to 3 years of age., Results: Among the cohort of 572 children, 35 children (6.1%) had early-onset myopia. In multivariable regression models, compared to children whose parents were not myopic, those with two myopic parents were more likely to have a more myopic spherical equivalent (SE) (regression coefficient: -0.36; 95% confidence interval [CI]: -0.61 to -0.11) and longer AL (regression coefficient: 0.24; 95% CI: 0.10-0.39) and more likely to have myopia (odds ratio [OR] = 4.8; 95% CI: 1.4-16.6). Neither near work nor outdoor activity was associated with SE, AL, and myopia. Taller children were found to have longer AL at birth and at 12, 24, and 36 months, but there were no associations with SE., Conclusions: Genetic factors may have a greater contribution to early development of refractive error compared to environmental factors.

Purposes: This study aims to compare the clinicopathological features of gastric carcinoma between two different time periods, and to investigate the prognostic factors for gastric carcinoma., Patients and Methods: One thousand sixteen consecutive gastric cancer patients were divided into two groups according to the operation date, period I (1994-1999) and period II (2000-2006). The clinicopathological features and prognosis were compared between the two periods., Results: There were significant differences in the proportions of early gastric carcinoma, different tumor node metastasis (TNM) staged patients, specialized operation and adjuvant chemotherapy between the two periods. The 5-year survival rate after curative resection within period II, were significantly higher than those within period I. Stratification analysis revealed that the survival rates of the patients with curative resection, lymph node metastasis, advanced disease, different TNM stages, specialized operations, without adjuvant chemotherapy within period II, were significantly higher than those within period I. Multivariate regression analysis revealed that Borrmann type, histologic type, depth of invasion, lymph node metastasis, curative resection, adjuvant chemotherapy, and different time periods were independent prognostic factors for gastric carcinoma., Conclusions: The treatment efficacy of gastric carcinoma within the recent period improved highly when compared with that within the early period. It was the elevated diagnostic rate of early gastric cancer, standardized radical operation, and adjuvant chemotherapy that contributed to such improvement.

Background and Aims: There is a discrepancy between the American Joint Committee on Cancer (AJCC) guidelines (7th edition) and the Japanese treatment guidelines (3rd edition) with regard to the extent of D2 lymphadenectomy for gastric cancer. In the AJCC, hepatic artery station (No.12a) lymph node (LN) metastasis is classified as distant metastasis, whereas in the Japanese guidelines, this classified is regional metastasis. This study aimed to evaluate whether it is appropriate to reclassify No.12a LN metastasis as distant metastasis in consideration of survival outcome., Methods: In this retrospective analysis, data from patients with gastric cancer who underwent regular D2 or greater lymphadenectomy between 1996 and 2006 were evaluated to determine any association between the clinicopathological features of hepatic artery LNs and survival prognosis., Results: Among the 247 patients with gastric cancer who underwent No.12 LN harvest, 45 (18.2%) were positive for No.12a LN metastasis. No.12a LN metastasis was significantly associated with poor clinicopathological features, advanced tumor stage, and poor overall survival. The 5-year survival rate of patients with No.12a LN metastasis was significantly better than that of patients with distant metastasis (P < 0.05), but was similar to that of patients with LN involvement in the D2 lymphadenectomy region (P > 0.05). No.12a LN metastasis was shown to significantly influence survival outcome in univariate analysis, but was not identified as a significant independent predictor in multivariate analysis. In logistic multivariate regression analysis, T stage, N stage, and station No.3, 5, and 6 LN metastasis were independent predictors of No.12a LN involvement., Conclusions: It is inappropriate to reclassify No.12a LN metastasis as distant metastasis. We propose that this be considered as regional metastasis and be included in the extent of D2 lymphadenectomy to improve survival outcomes in patients with gastric cancer.