Expression of lymphoid enhancer factor-1 in pancreatic ductal adenocarcinoma and its effect on prognosis / 国际肿瘤学杂志

Objective:To investigate the expression of lymphoid enhancement factor-1 (LEF-1) in Wnt signaling pathway in pancreatic ductal adenocarcinoma (PDAC) and its significance.Methods:The relative expressions of LEF-1 mRNA in human PDAC cell line PANC-1 and normal pancreatic ductal epithelial cell line HPDE6 were detected by fluorescence quantitative PCR. A total of 45 pancreatic cancer tissue specimens and their corresponding paracancerous tissue specimens were collected from the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University from June 2012 to December 2013. The expressions of LEF-1 in the cancer tissues and paracancerous tissues were detected by immunohistochemistry, and the relationships between LEF-1 expression and clinicopathological characteristics and prognosis of patients were analyzed.Results:Fluorescence quantitative PCR showed that the relative expression level of LEF-1 mRNA in PANC-1 cell line was significantly higher than that in HPDE-6 cell line (2.895±0.485 vs. 1.006±0.126, t=3.056, P<0.001). Immunohistochemical results showed that LEF-1 was highly expressed in 33 cases (73.3%) of cancer tissues, which was higher than that in 12 cases (26.7%) of adjacent tissues, and there was a statistically significant difference ( χ2=14.815, P<0.001). LEF-1 expression was correlated with preoperative carbohydrate antigen (CA) 19-9 level ( P<0.001) and local lymph node metastasis ( P=0.041). Survival analysis showed that the median overall survival (OS) was 22.0 months in patients with PDAC, 19.0 months in patients with high LEF-1 expression ( n=33), 31.0 months in patients with low LEF-1 expression ( n=12), and there was a statistically significant difference ( χ2=5.554, P=0.018). Univariate Cox regression analysis showed that age ( HR=1.962, 95% CI: 1.043-3.692, P=0.037), LEF-1 ( HR=2.253, 95% CI: 1.097-4.630, P=0.027), and CA19-9 ( HR=2.667, 95% CI: 1.258-5.656, P=0.011) were associated with OS. Multivariate Cox regression analysis showed that CA19-9 ( HR=6.431, 95% CI: 1.078-38.382, P=0.041), CA125 ( HR=0.151, 95% CI: 0.027-0.839, P=0.031), primary tumor size ( HR=8.364, 95% CI: 1.925-36.335, P=0.005), LEF-1 ( HR=2.281, 95% CI: 1.025-5.075, P=0.043) were independent risk factors affecting the prognosis of PDAC patients. Conclusion:LEF-1 expression is up-regulated in PDAC tissues, which is positively correlated with preoperative CA19-9 level and local lymph node metastasis, and is an independent prognostic factor in patients with PDAC.

Identification of LEF1 as a Susceptibility Locus for Kawasaki Disease in Patients Younger than 6 Months of Age

Kawasaki disease (KD) is an acute febrile vasculitis predominately affecting infants and children. The dominant incidence age of KD is from 6 months to 5 years of age, and the incidence is unusual in those younger than 6 months and older than 5 years of age. We tried to identify genetic variants specifically associated with KD in patients younger than 6 months or older than 5 years of age. We performed an age-stratified genome-wide association study using the Illumina HumanOmni1-Quad BeadChip data (296 cases vs. 1,000 controls) and a replication study (1,360 cases vs. 3,553 controls) in the Korean population. Among 26 candidate single nucleotide polymorphisms (SNPs) tested in replication study, only a rare nonsynonymous SNP (rs4365796: c.1106C>T, p.Thr369Met) in the lymphoid enhancer binding factor 1 (LEF1) gene was very significantly associated with KD in patients younger than 6 months of age (odds ratio [OR], 3.07; p(combined) = 1.10 × 10⁻⁵), whereas no association of the same SNP was observed in any other age group of KD patients. The same SNP (rs4365796) in the LEF1 gene showed the same direction of risk effect in Japanese KD patients younger than 6 months of age, although the effect was not statistically significant (OR, 1.42; p = 0.397). This result indicates that the LEF1 gene may play an important role as a susceptibility gene specifically affecting KD patients younger than 6 months of age.

Thymosin beta4 increases mouse hair regeneration / 中国组织工程研究

BACKGROUND:Results of recent studies demonstrated the modulation of thymosin β4 on hair cycle and regeneration, but the mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism by which thymosinβ4 increases hair regeneration through Wnt signal pathway. METHODS:After the mouse model of depilation was established using rosin/paraffin mixed agents, the experimental animals were randomly assorted to three different groups, including low-dose, high-dose and control groups, and a dose of 0.3μg/50μL, 3μg/50μL thymosinβ4 and PBS was administered on the depilated backs every 12 hours, respectively. Then photography, hematoxylin-eosin staining, immunohistochemistry and in situ hybridization were applied to observe the growth of hair, and the expressions ofβ-catenin and LEF-1 mRNA in different groups at different time were quantitatively evaluated. RESULTS AND CONCLUSION:The hair growth of the low-dose group was faster than that of the other groups. Hematoxylin-eosin staining demonstrated inflammatory cel s infiltration in the dermis after depilation, and the number of hair fol icles that were in the phase of anagen was much more than the other groups as time went by. Immunohistochemistry ofβ-catenin showed the accumulation of intra-cel ularβ-catenin in the low-dose group at the bulge of fol icles assessed by integrated absorbance analysis (P<0.05), so did the in situ hybridization of LEF-1 mRNA. Low-dose thymosinβ4 accelerates hair growth through Wnt signal pathway by elevating the level ofβ-catenin and LEF-1 mRNA.