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Search Results: 1 - 10 of 4680 matches for " Cecilia Hegardt "
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Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns
Karolina Holm, Cecilia Hegardt, Johan Staaf, Johan Vallon-Christersson, G?ran J?nsson, H?kan Olsson, ?ke Borg, Markus Ringnér
Breast Cancer Research , 2010, DOI: 10.1186/bcr2590
Abstract: We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay.Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation.We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers.Breast cancer is a complex and heterogeneous disease and one of the leading causes of death among women. Tumourigenesis is a multistep process resulting from the accumulation of genetic alterations such as mutations, rearrangements and copy number variations, but also epigenetic alterations such as promoter methylation and histone modification [1,2]. DNA methylation plays an essential role in development, chromosomal stability, and for maintaining gene expression states [1]. DNA methylation occurs when methyl groups are added to cytosines in CpG dinucleotides, leading to a closed chromatin conformation and gene silencing. CpGs are often found at increased frequ
The CD44+/CD24- phenotype is enriched in basal-like breast tumors
Gabriella Honeth, P?r-Ola Bendahl, Markus Ringnér, Lao H Saal, Sofia K Gruvberger-Saal, Kristina L?vgren, Dorthe Grabau, M?rten Fern?, ?ke Borg, Cecilia Hegardt
Breast Cancer Research , 2008, DOI: 10.1186/bcr2108
Abstract: Double-staining immunohistochemistry was used to quantify CD44 and CD24 expression in 240 human breast tumors for which information on other tumor markers and clinical characteristics was available. Gene expression data were also accessible for a cohort of the material.A considerable heterogeneity in CD44 and CD24 expression was seen both between and within tumors. A complete lack of both proteins was evident in 35% of the tumors, while 13% contained cells of more than one of the CD44+/CD24-, CD44-/CD24+ and CD44+/CD24+ phenotypes. CD44+/CD24- cells were detected in 31% of the tumors, ranging in proportion from only a few to close to 100% of tumor cells. The CD44+/CD24- phenotype was most common in the basal-like subgroup – characterized as negative for the estrogen and progesterone receptors as well as for HER2, and as positive for cytokeratin 5/14 and/or epidermal growth factor receptor, and particularly common in BRCA1 hereditary tumors, of which 94% contained CD44+/CD24- cells. The CD44+/CD24- phenotype was surprisingly scarce in HER2+ tumors, which had a predominantly CD24+ status. A CD44+/CD24- gene expression signature was generated, which included CD44 and α6-integrin (CD49f) among the top-ranked overexpressed genes.We demonstrate an association between basal-like and particularly BRCA1 hereditary breast cancer and the presence of CD44+/CD24- cells. Not all basal-like tumors and very few HER2+ tumors, however, contain CD44+/CD24- cells, emphasizing that a putative tumorigenic ability may not be confined to cells of this phenotype and that other breast cancer stem cell markers remain to be identified.Human breast cancer is a truly complex disease with a large inter-tumoral and intra-tumoral heterogeneity resulting in highly variable clinical behavior and response to therapy. The maintenance of the heterogeneity of cells within a tumor is not fully understood. Possibly, every cell within a tumor may have a capacity to proliferate and form new tumors, although
CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers
Eleonor Olsson, Gabriella Honeth, P?r-Ola Bendahl, Lao H Saal, Sofia Gruvberger-Saal, Markus Ringnér, Johan Vallon-Christersson, G?ran J?nsson, Karolina Holm, Kristina L?vgren, M?rten Fern?, Dorthe Grabau, ?ke Borg, Cecilia Hegardt
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-418
Abstract: We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA.Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival.We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to CSCs and tumor progression should consider the expression of various CD44 isoforms.Breast cancer is characterized by a remarkable biological heterogeneity both between and within tumors. Breast tumors can be stratified into molecular subtypes using gene expression profiling [1-3] and within a tumor, a variety of cell populations with different phenotypes can be found. E
Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics
G?ran J?nsson, Johan Staaf, Johan Vallon-Christersson, Markus Ringnér, Karolina Holm, Cecilia Hegardt, Haukur Gunnarsson, Rainer Fagerholm, Carina Strand, Bjarni A Agnarsson, Outi Kilpivaara, Lena Luts, P?ivi Heikkil?, Kristiina Aittom?ki, Carl Blomqvist, Niklas Loman, Per Malmstr?m, H?kan Olsson, Oskar Th Johannsson, Adalgeir Arason, Heli Nevanlinna, Rosa B Barkardottir, ?ke Borg
Breast Cancer Research , 2010, DOI: 10.1186/bcr2596
Abstract: We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer.We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis.Global DNA copy-number analysis integrated with gene-expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may pro
On the Detection of Visual Features from Digital Curves Using a Metaheuristic Approach  [PDF]
Cecilia Di Ruberto
Applied Mathematics (AM) , 2012, DOI: 10.4236/am.2012.331241
Abstract: In computational shape analysis a crucial step consists in extracting meaningful features from digital curves. Dominant points are those points with curvature extreme on the curve that can suitably describe the curve both for visual perception and for recognition. Many approaches have been developed for detecting dominant points. In this paper we present a novel method that combines the dominant point detection and the ant colony optimization search. The method is inspired by the ant colony search (ACS) suggested by Yin in [1] but it results in a much more efficient and effective approximation algorithm. The excellent results have been compared both to works using an optimal search approach and to works based on exact approximation strategy.
Urban Simulation Models: Contributions as Analysis-Methodology in a Project of Urban Renewal*  [PDF]
María Cecilia Marengo
Current Urban Studies (CUS) , 2014, DOI: 10.4236/cus.2014.23028
Abstract: The recent urban transformations produced in cities indicate the need to propose new theoretical and methodological approaches in physical planning. Based on the idea of complexity, it is required to integrate, in the analysis, multiplicity of interrelated factors involved in urban development, moreover, to develop planning tools that can incorporate variables not initially considered (for example when the norms were sanctioned) and instruments that would provide assessment alternatives to planning decisions in real time. The simulation models are suggested as tools to detect the elements, relationships and the dynamics in a simplified form that allow experiencing on the results. That is to say, a theoretical position on to a computer model is translated to investigate (in an experimental way) possible solutions derived from manipulating the variables, before the phenomenon is materialized. In the case of urban planning, this condition is of particular relevance, given the importance to anticipate unwanted effects in the intervention context that may arise when urban projects are built. The paper evaluates the application of a simulation methodology, based on the dynamics of systems and the application of software that can anticipate the effects of certain decisions in an urban renewal project in the city of Córdoba, Argentina. It applies the General Systems Theory that is a contribution to the notion of complex thought and is trans-disciplinary. Based on the idea of complex and multidimensional city, the effects of a real estate development are analyzed and conclusions on the limits and possibilities of using this tool during the processes of urban management are provided.
Density and Housing: Comparative Evaluation towards a Residential Quality Index. The Case of Collective Dwellings in Córdoba—Argentina  [PDF]
María Cecilia Marengo
Current Urban Studies (CUS) , 2017, DOI: 10.4236/cus.2017.51003
Abstract: The crisis on infrastructure systems, mobility and the demands of service provision in increasingly remote areas with less values of urbanity that result from the dispersed city model, leads to reexamining the consolidated and dense tissues. While presenting a more compact land-use, there should be conditions of urban habitability of higher quality than those in the new undifferentiated and diffuse peripheries. In this context, the research analyzes comparatively different residential proposals of collective dwellings as a function of density. The objective of the work is to evaluate, from an architectural design dimension, significant cases of collective housing built in Córdoba city that offer higher levels of densification in relation to the building environment where they are located. It seeks to identify the advantages in terms of residential quality in the different housing proposals that integrate the cases of study and link it with the density adopted in its design. The methodological approach integrates an evaluation matrix that compares housing complexes with different density values. Analytical dimensions related to urban indicators are selected and others with indicators relating to the design of collective housing. Weighting criteria are used to construct a residential quality index (RQI), and to integrate in a simulation model of the concepts: Density and Residential quality. Finally, the results obtained in this first analytical approach of the problem of study are evaluated new interrogations proposed to advance in the analysis of the different levels of densification that are presented in the proposals and their adequacy.
Human Friendly Interface Design for Virtual Fitting Room Applications on Android Based Mobile Devices  [PDF]
Cecilia Garcia Martin, Erdal Oruklu
Journal of Signal and Information Processing (JSIP) , 2012, DOI: 10.4236/jsip.2012.34061
Abstract: This paper presents an image processing design flow for virtual fitting room (VFR) applications, targeting both personal computers and mobile devices. The proposed human friendly interface is implemented by a three-stage algorithm: Detection and sizing of the user's body, detection of reference points based on face detection and augmented reality markers, and superimposition of the clothing over the user's image. Compared to other existing VFR systems, key difference is the lack of any proprietary hardware components or peripherals. Proposed VFR is software based and designed to be universally compatible as long as the device has a camera. Furthermore, JAVA implementation on Android based mobile systems is computationally efficient and it can run in real-time on existing mobile devices.
Dentoalveolar Segmental Osteotomy Combined with Orthodontic Treatment for an Impacted and Ankylosed Upper Canine: A Case Report  [PDF]
Hanna Cecilia Aludden, Thomas Jensen
Open Journal of Stomatology (OJST) , 2016, DOI: 10.4236/ojst.2016.64012
Abstract: Ankylosis is the abnormal adhesion of alveolar bone to dentin or cementum and commonly seen after traumatic dental injuries. Treatment of impacted and ankylosed teeth solely by orthodontics alignment may be challenging. Consequently, several treatment alternatives have been proposed for the management of ankylosed teeth involving extraction, surgical luxation, and osteotomy followed by dentoalveolar distraction or conventional orthodontic treatment. This case report describes a 55-year-old female who was referred by her orthodontist due to an impacted and ankylosed maxillary upper left canine. A dentoalveolar segmental osteotomy with immediate repositioning of an upper canine was performed. One year after final orthodontic treatment a satisfying occlusal and esthetic treatment outcome was obtained.
Time for physicians to be aware of molecular genetic testing. Report from the 3rd Viareggio Health Festival
Cecilia Nardini
Multidisciplinary Respiratory Medicine , 2011, DOI: 10.1186/2049-6958-6-1-47
Abstract: However, so far, genetic knowledge has affected only marginally the everyday practice of medical professionals, who therefore run the risk of being "overcome" by their sudden impact in the near future. An opportunity to reflect upon genetic technologies and their impact on the medical profession was provided by the International Workshop held on September 22nd at the Ospedale della Versilia, within the 3rd edition of the Viareggio Health Festival. This year's Festival had the title "Genetic Testing and Hereditary Diseases: Between the Right not to Know and the Duty to Inform", and was aimed to investigate the ethical and legal aspects of medical genetic information, and the establishment of proper ways of handling it within the patient-clinician relationship.The first form of genetic knowledge is the deterministic one that exists in the case of Mendelian diseases like cystic fibrosis or chromosomal abnormalities such as the Down syndrome. These diseases cannot be cured, but the presence of the chromosomal or genetic abnormality can be established before birth by performing a test on the pregnant woman. In Italy, the law (DM 10/10/98, D. lgs. 22910/06/1999, "Decreto Bindi") has established that all pregnant women considered to be in a risk category - familial or age-related - have the right to free access to the test, leaving it to each region to set up specific screening programs. The tests in question are invasive and represent a risk for the pregnancy; therefore they are not suited for population-wide screening programs. In recent years, however, technical advances have made a non-invasive test possible, at least for the Down syndrome, by examining fetal proteins in maternal serum [1]. At present, non-invasive tests are not reliable on their own but they could be effective as a screening method (first step) for the pre-selection of candidates for the invasive tests, and for this reason they could be offered on a routine basis, as is already happening in some count
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