Simultaneous CXCL12 and ESR1 CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer

<p>Abstract</p> <p>Background</p> <p>CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. <it>CXCL12 </it>promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (<it>ESR1</it>) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the <it>CXCL12 </it>promoter and <it>ESR1 </it>in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data.</p> <p>Methods</p> <p>First, we analysed <it>CXCL12 </it>expression in breast tumour cell lines by RT-PCR. We also used 5-aza-2'-deoxycytidine (5-aza-CdR) treatment and DNA bisulphite sequencing to study the promoter methylation for a specific region of <it>CXCL12 </it>in breast tumour cell lines. We evaluated <it>CXCL12 </it>and <it>ESR1 </it>methylation in primary tumour samples by methylation-specific PCR (MSP). Finally, promoter hypermethylation of these genes was analysed using Fisher's exact test and correlated with clinicopathological data using the Chi square test, Kaplan-Meier survival analysis and Cox regression analysis.</p> <p>Results</p> <p><it>CXCL12 </it>promoter hypermethylation in the first region (island 2) and second region (island 4) was correlated with lack of expression of the gene in tumour cell lines. In the primary tumours, island 2 was hypermethylated in 14.5% of the samples and island 4 was hypermethylated in 54% of the samples. The <it>ESR1 </it>promoter was hypermethylated in 41% of breast tumour samples. In addition, the levels of ERα protein expression diminished with increased frequency of <it>ESR1 </it>methylation (p < 0.0001). This study also demonstrated that <it>CXCL12 </it>island 4 and <it>ESR1 </it>methylation occur simultaneously at a high frequency (p = 0.0220).</p> <p>Conclusions</p> <p>This is the first study showing a simultaneous involvement of epigenetic regulation for both <it>CXCL12 </it>and <it>ESR1 </it>genes in Brazilian women. The methylation status of both genes was significantly correlated with histologically advanced disease, the presence of metastases and death. Therefore, the methylation pattern of these genes could be used as a molecular marker for the prediction of breast cancer outcome.</p

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Influences of Domestication and Island Evolution on Dental Growth in Sheep

Funder: Department of Zoology, University of CambridgeFunder: Leverhulme Trust; doi: http://dx.doi.org/10.13039/501100000275Abstract: Domestication and island evolution can lead to changes of life history along the slow-fast gradient. Shifts of life history patterns, in turn, are potentially related to alterations of patterns and timing of tooth eruption. Schultz’s rule predicts an earlier eruption of molars relative to premolars as fecundity increases during the domestication process. On the other hand, evolution on a predator-free, resource limited island might lead to a generally slow life history and delayed tooth eruption, as in the Plio-Pleistocene Balearic caprine Myotragus. In this study, we investigate tooth eruption and its relation to life history in a unique sheep population that is an example of both domestication and island evolution: the ancient and feral Soay sheep (Ovis aries) of the St. Kilda archipelago, Scotland. Tooth eruption timing and sequence is investigated in a comparative framework featuring new data on other domestic sheep (O. aries), including European mouflon (O. a. musimon), as well as wild sheep (O. vignei, O. cycloceros, O. arkal, O. orientalis, O. ammon). These data indicate that the order of eruption is similar in wild and domestic sheep, despite the fundamental life history changes that came about with domestication. However, in contrast to other domestic sheep breeds, Soay sheep erupt their teeth at an absolute older age and also tend to grow more slowly, which resembles the evolutionary trend in island-adapted Myotragus. Despite these similarities, Soay sheep do not share the slow life history pattern inferred for Myotragus, highlighting the distinctive nature of tooth eruption in Soay sheep

Spectroscopic study performed on films of (3-trimethoxysilylpropyl)ethylenediamine and a dental material (acrylic resin) doped with the luminescent complexes Eu(fod)(3)center dot 2H(2)O and Eu(fod)(3)center dot terpy

By using (3-trimethoxysilylpropyl) ethylenediamine (TSPED) and a dental material (acrylic resin) as precursors, self-standing films doped with the luminescent complexes Eu(fod)(3).2H(2)O and Eu(fod)(3).terpy were prepared. The doped films were so studied from a spectroscopic point of view. Is verified that the film composition exerts remarkable effects on both, the intensity and lifetime of the emission process. Acrylic resin films reduces the intensity of the emission process, but increases the lifetime,of a such process, in comparison with TSPED films, for which an opposite behavior is observed. The measured lifetimes for the emission process for the compounds Eu(fod)(3).2H(2)O in TSPED and acrylic resin films are 306 and 369 mus, respectively. For the same film matrices, the measured lifetimes for the complex Eu(fod)(3).terpy gave the values 347 and 880 mus, respectively. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.4101343134