Effects of EpCAM overexpression on human breast cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Recently, EpCAM has attracted major interest as a target for antibody- and vaccine-based cancer immunotherapies. In breast cancer, the EpCAM antigen is overexpressed in 30-40% of all cases and this increased expression correlates with poor prognosis. The use of EpCAM-specific monoclonal antibodies is a promising treatment approach in these patients.</p> <p>Methods</p> <p>In order to explore molecular changes following EpCAM overexpression, we investigated changes of the transcriptome upon EpCAM gene expression in commercially available human breast cancer cells lines Hs578T and MDA-MB-231. To assess cell proliferation, a tetrazolium salt based assay was performed. A TCF/LEF Reporter Kit was used to measure the transcriptional activity of the Wnt/β-catenin pathway. To evaluate the accumulation of β-catenin in the nucleus, a subcellular fractionation assay was performed.</p> <p>Results</p> <p>For the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578T^EpCAMand MDA-MB-231^EpCAMindicate an association of EpCAM overexpression with the downregulation of the Wnt signaling inhibitors SFRP1 and TCF7L2. Confirmation of increased Wnt signaling was provided by a TCF/LEF reporter kit and by the finding of the nuclear accumulation of ß-catenin for MDA-MB-231^EpCAMbut not Hs578T^EpCAMcells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression.</p> <p>Conclusions</p> <p>These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.</p

DNA Methylation in Colorectal cancer—Impact on Screening and Therapy Monitoring Modalities?

Colorectal cancer (CRC) is a common malignancy. It arises from benign neoplasms and evolves into adenocarcinomas through a stepwise histological progression sequence, proceeding from either adenomas or hyperplastic polyps/serrated adenomas. Genetic alterations have been associated with specific steps in this adenoma-carcinoma sequence and are believed to drive the histological progression of CRC. Recently, epigenetic alterations (especially DNA methylation) have been shown to occur in colon polyps and CRC. The aberrant methylation of genes appears to act together with genetic alterations to drive the initiation and progression of colon polyps to CRC

14-3-3 Sigma And p53 Expression in Gastric Cancer and Its Clinical Applications

14-3-3 sigma (σ) induces G2 arrest enabling the repair of damaged DNA. The function of 14-3-3 σ is frequently lost in tumor cells, indicating a potential tumor suppressor function. The purpose of this study was to evaluate the prognostic value of 14-3-3 σ expression in human gastric cancer. 14-3-3 σ expression was analyzed by immunohistochemistry in 157 tumor samples of patients, who underwent resection for gastric cancer. Since 14-3-3 σ is involved in the p53 network, p53 expression was detected in parallel and correlated with 14-3-3 σ. 14-3-3 σ was found to be overexpressed in 75 (47.8%) of 157 cases, the overexpression rate of p53 protein was 27.4%. 14-3-3 σ overexpression was statistically significantly associated with pT-stage (p=0.041) pN-stage (p=0.015) and UICC-stage (p=0.019) and showed a borderline significance with Lauren classification (p=0.057). Univariate survival calculations revealed a coexistent 14-3-3 σ and p53 overexpression as a significant predictor of disease-free survival. Multivariate analysis did not unfold 14-3-3 as an independent prognostic factor for disease-free survival and overall survival. Concomitant 14-3-3 σ and p53 overexpression in tumor cells of patients with gastric cancer identifies a population of patients with relatively unfavorable prognosis

Circulating Cell-Free DNA in Plasma of Locally Advanced Rectal Cancer Patients Undergoing Preoperative Chemoradiation: A Potential Diagnostic Tool for Therapy Monitoring

Circulating cell-free DNA opens up an interesting field for therapy monitoring, in particular during multimodal therapy protocols. The objective of this proof of principle study was to evaluate whether the amount of circulating plasma DNA has the potential to serve as a marker for therapy monitoring during the treatment course of locally advanced rectal cancer patients. We especially focused on kinetics of circulating DNA to assess whether variances in kinetics have the potential to discriminate between therapy responders and nonresponders

Dickkopf-3 as a new potential marker for neoangiogenesis in colorectal cancer : expression in cancer tissue and adjacent non-cancerous tissue

Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P>0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P>0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P>0.0001). All microvessels in normal mucosa samples were negative for Dkk-3. Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies

The world network of scientific collaborations between cities: domestic or international dynamics?

International audienceAn earlier publication (Grossetti et al., 2014) has established that we are attending a decreasing concentration of scientific activities within " world-cities ". Given that more and more cities and countries are contributing to the world production of knowledge, this article analyses the evolution of the world collaboration network both at the domestic and international levels during the 2000s. Using data from the Science Citation Index Expanded, scientific authors' addresses are geo-localized and grouped by urban areas. Our data suggests that interurban collaborations within countries increased together with international linkages. In most countries, domestic collaborations increased faster than international collaborations. Even among the top collaborating cities, sometimes referred to as " world cities " , the share of domestic collaborations has gained momentum. Our results suggest that, contrary to common beliefs about the globalization process, national systems of research have been strengthening during the 2000s

The global geography of scientific visibility: a deconcentration process (1999–2011)

International audienceThis article aims to ascertain whether the territorial redistribution observed in the geography of scientific production between 1999 and 2008 translated into a redistribution of the geography of citations, and therefore of scientific visibility. Are publications from formerly marginal locations able to influence researchers based in “central locations”, or is their impact mostly “provincial”? Because the distribution of citations is extremely asymmetrical, it could very well be that the geographic de-concentration of production activities did not lead to the geographic de-concentration of citations, but instead contributed to creating increasingly asymmetrical flows of information for the benefit of “central” cities and countries. This article aims to verify whether this is the case by analysing the geographic distribution of citations received, using a method for localising the publications indexed in the Web of Science by urban areas. Results show a growing convergence between the geography of scientific production and that of scientific citations. The number of citations received by the world’s 30 top publishing countries and cities tended to edge closer to the global average. While Singapore, China, India and Iran suffered from a deficit of visibility in 2000, their level considerably improved by 2007. Moreover, a decrease in the discrepancy between cities’ scientific visibility is observed in almost all countries of the world, except for three: Sweden, Egypt and Denmark. To finish, our results show that the gap between the share of citations and the share of publications has decreased across all disciplines. A significant asymmetry in favour of English-speaking countries has remained in the distribution of citations in humanities and social sciences (but it is diminishing)

Interroger et comprendre les effets d’échelles de la vulnérabilité

Responsables du numéro : Valérie Morel, Sylvie Coupleu

L'eau à découvert

Indispensable à la régulation du climat, au développement de la vie sur Terre, au maintien des écosystèmes, aux populations, au développement de l'agriculture, de l'industrie comme à la production d'énergie, l'eau est un élément vital. Il convient donc, dans un contexte de changement global, d'analyser dans toute sa diversité la place et le rôle de l'eau et de se donner ainsi les moyens de mieux la préserver. Autour de cet enjeu qui engage toute l'humanité, Agathe Euzen, Catherine Jeandel et Rémy Mosseri ont réuni près de cent cinquante contributions, visant à apporter un éclairage sur chacun des domaines et des approches que couvre cette thématique. Quelle est l'origine de l'eau ? Son rapport avec l'apparition de la vie ? Quel rôle a-t-elle joué dans l'histoire de la planète et dans le développement de la vie végétale, animale et humaine ? Quel est son cycle ? Quelles sont ses propriétés chimiques ? Comment les sociétés se sont-elles emparées de cet élément précieux ? Allons-nous manquer d'eau ? L'eau est-elle source de conflits ? Comment l'eau est-elle gérée ? Comment recycle-t-on une eau polluée ? Quels sont les risques pour la santé mondiale ? Quels sont les grands enjeux liés à l'eau au xxie siècle ? Comprendre et proposer des solutions à ces défis majeurs est l'intention de cet ouvrage