The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma

<p>Abstract</p> <p>Objectives</p> <p>This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC) to identify its role in tumor progression.</p> <p>Methods</p> <p>The expression of Snail and Slug mRNA in 52 human tissue samples of EHC was investigated. The mRNA of Snail and Slug were quantified using reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. We then investigated transfection of Slug cDNA in endogenous E-cadherin-positive human EHC FRH0201 cells, selectively induced the loss of E-cadherin protein expression, and then small interfering RNA (siRNA) for inhibition of Slug expression in endogenous Slug-positive human EHC QBC939 cells, selectively induced the loss of Slug protein expression. A Boyden chamber transwell assay was used for invasion.</p> <p>Results</p> <p>Slug mRNA was overexpressed in 18 cases (34.6%) of EHC compared with adjacent noncancerous tissue. E-Cadherin protein expression determined in the same 52 cases by immunohistochemistry was significantly down-regulated in those cases with Slug mRNA overexpression (P = 0.0001). The tumor and nontumor ratio of Slug mRNA was correlated with nodal metastasis(p = 0.0102), distant metastasis (p = 0.0001)and Survival time(p = 0.0443). However, Snail mRNA correlated with neither E-cadherin expression nor tumor invasiveness. By inhibiting Slug expression by RNA interference, we found that reduced Slug levels upregulated E-cadherin and decreased invasion in QBC939 cell. When the QBC939 cells was infected with Slug cDNA,, significant E-cadherin was downregulated and increased invasion in QBC939 cell.</p> <p>Conclusions</p> <p>The results suggested that Slug expression plays an important role in both the regulation of E-cadherin expression and in the acquisition of invasive potential in human EHC. Slug is possibly a potential target for an antitumor therapy blocking the functions of invasion and metastasis in human EHCs.</p

Halmyris: Geoarchaeology of a fluvial harbour on the Danube Delta (Dobrogea, Romania)

In Northern Dobrogea, north of the Dunavăţ promontory, the Roman fortress of Halmyris was founded in the late 1st century AD on a Getic settlement dating to the middle of the 1st millennium BC, probably associated with a Greek emporium of the Classical and Hellenistic periods. At the time of the foundation of Halmyris, the Danube delta had already prograded several kilometres to the east leading to the progressive retreat of the sea and the formation of a deltaic plain characterised by numerous lakes and river channels. Here, we present the results of a multiproxy study combining sedimentology and palaeoecology to (1) understand the evolution of fluvial landscapes around Halmyris since ca. 8000 years BP and (2) identify the fluvial palaeoenvironments close to the city in Getic/Greek and Roman times, in order to locate and characterise the waterfront and the harbour. Our overriding objective was to improve understanding of human–environment relations in river delta settings. We demonstrate that Halmyris, protected by the Danubian floods due to its location on a palaeo-cliff top, had direct access to the river. A secondary channel of the Saint George, flowing north of the site, has been elucidated between the 7th century BC and the 7th century AD and could have been used as a natural harbour