ABSTRACT
The tumor suppressor LKB1 gene encodes a serine-threonine kinase that regulates cell proliferation and polarity. Inactivation of LKB1 by mutations in LKB1 or loss of its expression is highly correlated with lung, ovarian, and pancreatic cancers, and WNT/ß-catenin pathway is also known to be involved in many human malignancies. However, the relationship between LKB1 and WNT signaling pathway in esophageal carcinoma remains unknown. The expression of LKB1 in 62 cases of esophageal cancer patients was determined by quantitative real-time PCR. It was found that LKB1 mRNA level was significantly lower than the adjacent normal epithelium and that the LKB1 downregulation was correlating with TNM stages. Moreover, the expression of WNT target genes such as Cyclin D1, C-MYC, MMP2, and FZD2 was significantly upregulated in esophageal cancer tissues. LKB1 overexpression in TE10 cells inhibited TOPFlash luciferase reporter activity and WNT target gene expression even in the presence of WNT3A. Conversely, LKB1 knockdown enhanced WNT signaling activity in esophageal cancer cells. It was also found that LKB1 antagonized WNT signaling pathway through interaction with GSK3ß to downregulate ß-catenin expression level. Functional investigation revealed that LKB1 suppressed the promotion effects of WNT3A on the cell growth of TE10 cells. The LKB1 functions in regulating cell growth and WNT target genes expression were impaired by GSK3ß inhibition, suggesting that LKB1 antagonized WNT-induced cell proliferation through enhancement of GSK3ß activity. Together, the interaction between LKB1 and GSK3ß upregulates GSK3ß activity to suppress WNT-induced cell proliferation in esophageal carcinoma cells. Loss of LKB1 expression may result in the deregulation of WNT/ß-catenin pathway to promote malignant progression of esophageal cancer.
Subject(s)
Esophageal Neoplasms/genetics , Glycogen Synthase Kinase 3/genetics , Protein Serine-Threonine Kinases/metabolism , Wnt Signaling Pathway/genetics , AMP-Activated Protein Kinase Kinases , Cell Line, Tumor , Cell Proliferation , Cyclin D1/genetics , Cyclin D1/metabolism , Esophageal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Glycogen Synthase Kinase 3/biosynthesis , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Humans , Male , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/biosynthesis , beta Catenin/biosynthesis , beta Catenin/metabolismABSTRACT
NAD(P)H: quinone oxidoreductase 1 (NQO1) is an important enzyme which can catalyze the two-electron reduction of quinoid compounds into hydroquinones. NQO1 Pro187Ser polymorphism can change the enzymatic activity of NQO1, and it has been proposed to be associated with risk of esophageal cancer. We performed a meta-analysis to examine the association between NQO1 Pro187Ser polymorphism and esophageal cancer. Odds ratio (OR) with a 95% confidence interval (95% CI) was used to assess the association. Twelve case-control studies with 1,725 cases with esophageal cancer and 2,341 controls were finally included in the meta-analysis. Overall, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer (allele model: OR = 1.24, 95% CI 1.06-1.46, P OR = 0.009; homozygote model: OR = 1.59, 1195% CI 1.10-2.30, P OR = 0.013; dominant model: OR = 1.31, 95% CI 1.05-1.64, P OR = 0.018). In the subgroup analysis by ethnicity, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer in Asians but not in Caucasians. Therefore, the meta-analysis suggests that NQO1 Pro187Ser polymorphism is associated with esophageal cancer risk.
Subject(s)
Esophageal Neoplasms/genetics , Genetic Predisposition to Disease/genetics , NAD(P)H Dehydrogenase (Quinone)/genetics , Polymorphism, Single Nucleotide/genetics , Asian People/genetics , Case-Control Studies , Humans , Odds Ratio , White People/geneticsABSTRACT
OBJECTIVE: The objective of this study is to assess the use of a novel, double-lumen electrocautery tube (DLET) device for ablating the sympathetic nerve chain in patients with primary palmar hyperhidrosis (PPH). METHODS: Forty-six patients with severe PPH were recruited into the study between November 2010 and February 2012. All patients underwent single port, bilateral video-assisted thoracoscopic sympathicotomy. Twenty-four patients were randomized to receive sympathicotomy using a conventional 5-mm electrocautery hook (hook group) and 22 patients were randomized to the DLET group. RESULTS: The mean postoperative follow-up period was 8.1 months (range: 1 to 15 months). After surgery the hands of all patients became dry and warm. Mean incision size was 10.6 ± 1.0 in the hook group and 6.5 ± 0.5 mm in the DLET group (p = 0.001). The mean pain score was 1.4 ± 0.6 with hook surgery and 0.9 ± 0.6 with the DLET device (p = 0.016). The mean operative time was longer in the hook group (36.8 ± 3.4 min) than in the DLET group (30.5 ± 3.9 min; p = 0.001). There were no significant differences between the two procedures in terms of hospital stay and compensatory sweating, or patient satisfaction. Pneumothorax occurred in two (8.3%) patients in the hook group and in one (4.5%) patient in the DLET group. None of the patients required chest drainage and none developed Horner syndrome. CONCLUSIONS: Single-port video-assisted thoracoscopic sympathicotomy using hook or DLET procedures is effective, safe, and minimally invasive method for palmar hyperhidrosis. The DLET device allows a shorter operation time, smaller incision, better cosmetic results, less pain, and better clarity of video, making it suitable for single-port thoracoscopic sympathicotomy.
