Extra-pancreatic metastasis is a difficult problem for surgical intervention in pancreatic cancer. CXC chemokine receptor 4 (CXCR4) was considered to have an important role in this process. We hypothesized it may contribute to the pancreatic cancer progression through influencing canonical Wnt pathway. The purpose of this study was to examine the functional role of CXCR4 in the progression of pancreatic cancers and explore the possible mechanism. To this end, the relation between CXCR4 and clinical characteristics was analysed. shRNA against CXCR4 was applied to disrupt the SDF-1/CXCR4 signal transduction pathways in pancreatic cancer cell lines. Our results showed that overall survival in the case of patients positive for CXCR4 expression was significantly lower than that in the case of patients negative for CXCR4 expression. Notably, in vitro studies we observed that the abrogation of CXCR4 could obviously influence the pancreatic cancer cell phenotype including cell proliferation, colony formation, cell invasion and also inhibit the TOPflash activity. In addition, Wnt target genes and mesenchymal markers such as Vimentin and Slug were also inhibited in CXCR4 knockdown cells. Collectively, these data reported here demonstrate CXCR4 could modulate the canonical Wnt pathway and perhaps be a promising therapeutic target for pancreatic cancer progression.
Sodium-lithium countertransport (Na-Li CT) is associated with blood pressure (BP) and in many cross-sectional investigations and some longitudinal studies, essential hypertension has been proposed as a biochemical marker or predictor of hypertension risk in adults. The present study investigated prospectively whether baseline Na-Li CT rate was an index of increased risk of future development of hypertension in children. At baseline visit in 1987 of the Hanzhong Children Hypertension Study comprising 4000 school children aged 5-6 years old, 310 samples were randomly selected for measurement of baseline Na-Li CT rate; we made a 10-year follow-up of them in the same season in 1997. This cohort of children is the sample for analysis in the present report. Baseline Na-Li CT rate was positively correlated to systolic BP (SBP) both in baseline and follow-up (baseline, gamma=0.21, P<0.05; follow-up, gamma=0.32, P<0.01), and positively correlated to diastolic BP (DBP) (gamma=0.20, P<0.05) and body mass index (gamma=0.18, P<0.05) in follow-up examination. Longitudinal analysis of 10-year BP evolution, children in higher baseline Na-Li CT (ie, >260 micromoll RBC/h) had greater BP change than children in lower baseline Na-Li CT (ie, =260 mumol/l RBC/h) (SBP, 15.8+/-12.9 vs 19.3+/-13.1, DBP 8.8+/-11.2 and 11.3+/-10.6, P<0.05). Multiple logistic regression analysis showed that children in the higher Na-Li CT (>260 mumol/l RBC/h) were associated with approximately 1.5 times greater risk of high BP) in comparison to placement in lower Na-Li CT (=260 mumol/l RBC/h). Elevated baeline RBC Na-Li countertransport could be a risk predictor predisposing to the development of hypertension in children.
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