366 research outputs found
Aberrant expression of genes associated with stemness and cancer in endometria and endometrioma in a subset of women with endometriosis
STUDY QUESTION
Is there molecular evidence for a link between endometriosis and endometriosis-associated ovarian cancers (EAOC)?
STUDY ANSWER
We identified aberrant gene expression signatures associated with malignant transformation in a small subgroup of women with ovarian endometriosis.
WHAT IS KNOWN ALREADY
Epidemiological studies have shown an increased risk of EAOC in women with ovarian endometriosis. However, the cellular and molecular changes leading to EAOC are largely unexplored.
STUDY DESIGN, SIZE, DURATION
CD73+CD90+CD105+ multipotent stem cells/progenitors (SC cohort) were isolated from endometrium (n = 18) and endometrioma (n = 11) of endometriosis patients as well as from the endometrium of healthy women (n = 14). Extensive phenotypic and functional analyses were performed in vitro on expanded multipotent stem cells/progenitors to confirm their altered characteristics. Aberrant gene signatures were also validated in paired-endometrium and -endometrioma tissue samples from another cohort (Tissue cohort, n = 19) of endometriosis patients.
PARTICIPANTS/MATERIALS, SETTINGS, METHODS
Paired-endometrial and -endometriotic biopsies were obtained from women with endometriosis (ASRM stage III–IV) undergoing laparoscopic surgery. Control endometria were obtained from healthy volunteers. Isolated CD73+CD90+CD105+ SC were evaluated for the presence of known endometrial surface markers, colony forming efficiency, multi-lineage differentiation, cell cycle distribution and 3D-spheroid formation capacity. Targeted RT-PCR arrays, along with hierarchical and multivariate clustering tools, were used to determine both intergroup and intragroup gene expression variability for stem cell and cancer-associated markers, in both SC+ and tissue cohorts.
MAIN RESULTS AND THE ROLE OF CHANCE
Isolated and expanded SC+ from both control and patient groups showed significantly higher surface expression of W5C5+, clonal expansion and 3D-spheroid formation capacity (P < 0.05) compared with SC−. The SC+ cells also undergo mesenchymal lineage differentiation, unlike SC−. Gene expression from paired-endometriosis samples showed significant downregulation of PTEN, ARID1A and TNFα (P < 0.05) in endometrioma compared with paired-endometrium SC+ samples. Hierarchical and multivariate clustering from both SC+ and tissue cohorts together identified 4 out of 30 endometrioma samples with aberrant expression of stem cell and cancer-associated genes, such as KIT, HIF2α and E-cadherin, altered expression ratio of ER-β/ER-α and downregulation of tumour suppressor genes (PTEN and ARID1A). Thus, we speculate that above changes may be potentially relevant to the development of EAOC.
LARGE-SCALE DATA
N/A.
LIMITATIONS, REASON FOR CAUTION
As the reported frequency of EAOC is very low, we did not have access to those samples in our study. Moreover, by adopting a targeted gene array approach, we might have missed several other potentially-relevant genes associated with EAOC pathogenesis. The above panel of markers should be further validated in archived tissue samples from women with endometriosis who later in life developed EAOC.
WIDER IMPLICATIONS OF THE FINDINGS
Knowledge gained from this study, with further confirmation on EAOC cases, may help in developing screening methods to identify women with increased risk of EAOC.
STUDY FUNDING/COMPETING INTEREST(S)
The study is funded by the Swedish Research Council (2012-2844), a joint grant from Stockholm County and Karolinska Institutet (ALF), RGD network at Karolinska Institutet, Karolinska Institutet for doctoral education (KID), Estonian Ministry of Education and Research (IUT34-16), Enterprise Estonia (EU48695), Horizon 2020 innovation program (WIDENLIFE, 692065), European Union’s FP7 Marie Curie Industry-Academia Partnerships and Pathways funding (IAPP, SARM, EU324509) and MSCA-RISE-2015 project MOMENDO (691058). All authors have no competing interest
Применение тригенерационной биогазовой установки, работающей на отходах мясопереработки (на примере ОАО «Калинковичский мясокомбинат»)
Материалы XIV Междунар. науч.-техн. конф. студентов, аспирантов и молодых ученых, Гомель, 24–25 апр. 2014 г
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Solving geoinformatics parametric polynomial systems using the improved Dixon resultant
Improvements in computational and observational technologies in geoinformatics, e.g., the use of laser scanners that produce huge point cloud data sets, or the proliferation of global navigation satellite systems (GNSS) and unmanned aircraft vehicles (UAVs), have brought with them the challenges of handling and processing this “big data”. These call for improvement or development of better processing algorithms. One way to do that is integration of symbolically presolved sub-algorithms to speed up computations. Using examples of interest from real geoinformatic problems, we will discuss the Dixon-EDF resultant as an improved resultant method for the symbolic solution of parametric polynomial systems. We will briefly describe the method itself, then discuss geoinformatics problems arising in minimum distance mapping (MDM), parameter transformations, and pose estimation essential for resection. Dixon-EDF is then compared to older notions of “Dixon resultant”, and to several respected implementations of Gröbner bases algorithms on several systems. The improved algorithm, Dixon-EDF, is found to be greatly superior, usually by orders of magnitude, in both CPU usage and RAM usage. It can solve geoinformatics problems on which the other methods fail, making symbolic solution of parametric systems feasible for many problems
PDGF-B-driven gliomagenesis can occur in the absence of the proteoglycan NG2
<p>Abstract</p> <p>Background</p> <p>In the last years, the transmembrane proteoglycan NG2 has gained interest as a therapeutic target for the treatment of diverse tumor types, including gliomas, because increases of its expression correlate with dismal prognosis. NG2 has been shown to function as a co-receptor for PDGF ligands whose aberrant expression is common in gliomas. We have recently generated a glioma model based on the overexpression of PDGF-B in neural progenitors and here we investigated the possible relevance of NG2 during PDGF-driven gliomagenesis.</p> <p>Methods</p> <p>The survival curves of NG2-KO mice overexpressing PDGF-B were compared to controls by using a Log-rank test. The characteristics of tumors induced in NG2-KO were compared to those of tumors induced in wild type mice by immunostaining for different cell lineage markers and by transplantation assays in adult mice.</p> <p>Results</p> <p>We showed that the lack of NG2 does not appreciably affect any of the characterized steps of PDGF-driven brain tumorigenesis, such as oligodendrocyte progenitor cells (OPC) induction, the recruitment of bystander OPCs and the progression to full malignancy, which take place as in wild type animals.</p> <p>Conclusions</p> <p>Our analysis, using both NG2-KO mice and a miRNA based silencing approach, clearly demonstrates that NG2 is not required for PDGF-B to efficiently induce and maintain gliomas from neural progenitors. On the basis of the data obtained, we therefore suggest that the role of NG2 as a target molecule for glioma treatment should be carefully reconsidered.</p
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