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  1. AU="Jole Costanza"
  2. AU="Paula, Camila S Y"
  3. AU="Azevedo, Helena S"
  4. AU=Molyneaux Phillip L.
  5. AU=Shimizu Kazuki
  6. AU=Pell Robert AU=Pell Robert
  7. AU="Aguiar, Liza"
  8. AU="Bahls, Christine"
  9. AU="Dongho Lee"
  10. AU=Houser Steven R.
  11. AU="Morgom M.M."
  12. AU="Jordana-Comajuncosa, Rosa"
  13. AU="Kaushansky, Alexis"
  14. AU="Bhatjiwale, Mohinish"
  15. AU="Velu, Chinavenmeni S"
  16. AU=Trayanova Natalia A
  17. AU=Jimeno-Gonzlez Silvia
  18. AU=Bussolino F
  19. AU="Almulla, Hanan"
  20. AU="Chen, Wenmei"
  21. AU=Zeng Weiqing

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  1. Artikel ; Online: Molecular Insights into the Classification of Luminal Breast Cancers

    Gianluca Lopez / Jole Costanza / Matteo Colleoni / Laura Fontana / Stefano Ferrero / Monica Miozzo / Nicola Fusco

    International Journal of Molecular Sciences, Vol 20, Iss 3, p

    The Genomic Heterogeneity of Progesterone-Negative Tumors

    2019  Band 510

    Abstract: Estrogen receptor (ER)-positive progesterone receptor (PR)-negative breast cancers are infrequent but clinically challenging. Despite the volume of genomic data available on these tumors, their biology remains poorly understood. Here, we aimed to ... ...

    Abstract Estrogen receptor (ER)-positive progesterone receptor (PR)-negative breast cancers are infrequent but clinically challenging. Despite the volume of genomic data available on these tumors, their biology remains poorly understood. Here, we aimed to identify clinically relevant subclasses of ER+/PR− breast cancers based on their mutational landscape. The Cancer Genomics Data Server was interrogated for mutational and clinical data of all ER+ breast cancers with information on PR status from The Cancer Genome Atlas (TCGA), Memorial Sloan Kettering (MSK), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) projects. Clustering analysis was performed using gplots, ggplot2, and ComplexHeatmap packages. Comparisons between groups were performed using the Student’s t-test and the test of Equal or Given Proportions. Survival curves were built according to the Kaplan⁻Meier method; differences in survival were assessed with the log-rank test. A total of 3570 ER+ breast cancers (PR− n = 959, 27%; PR+ n = 2611, 73%) were analyzed. Mutations in well-known cancer genes such as TP53 , GATA3 , CDH1 , HER2 , CDH1 , and BRAF were private to or enriched for in PR− tumors. Mutual exclusivity analysis revealed the presence of four molecular clusters with significantly different prognosis on the basis of PIK3CA and TP53 status. ER+/PR− breast cancers are genetically heterogeneous and encompass a variety of distinct entities in terms of prognostic and predictive information.
    Schlagwörter breast cancer ; progesterone receptor negative ; mutational profiling ; PI3K pathway ; TP53 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2019-01-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Correction

    Ornella Rondinone / Alessio Murgia / Jole Costanza / Silvia Tabano / Margherita Camanni / Luigi Corsaro / Laura Fontana / Patrizia Colapietro / Luciano Calzari / Silvia Motta / Carlo Santaniello / Tatjana Radaelli / Enrico Ferrazzi / Silvano Bosari / Davide Gentilini / Silvia Maria Sirchia / Monica Miozzo

    International Journal of Molecular Sciences, Vol 23, Iss 5298, p

    Rondinone et al. Extensive Placental Methylation Profiling in Normal Pregnancies. Int. J. Mol. Sci. 2021, 22 , 2136

    2022  Band 5298

    Abstract: In the original publication [.] ...

    Abstract In the original publication [.]
    Schlagwörter n/a ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Sprache Englisch
    Erscheinungsdatum 2022-05-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Multi-Target Analysis and Design of Mitochondrial Metabolism.

    Claudio Angione / Jole Costanza / Giovanni Carapezza / Pietro Lió / Giuseppe Nicosia

    PLoS ONE, Vol 10, Iss 9, p e

    2015  Band 0133825

    Abstract: Analyzing and optimizing biological models is often identified as a research priority in biomedical engineering. An important feature of a model should be the ability to find the best condition in which an organism has to be grown in order to reach ... ...

    Abstract Analyzing and optimizing biological models is often identified as a research priority in biomedical engineering. An important feature of a model should be the ability to find the best condition in which an organism has to be grown in order to reach specific optimal output values chosen by the researcher. In this work, we take into account a mitochondrial model analyzed with flux-balance analysis. The optimal design and assessment of these models is achieved through single- and/or multi-objective optimization techniques driven by epsilon-dominance and identifiability analysis. Our optimization algorithm searches for the values of the flux rates that optimize multiple cellular functions simultaneously. The optimization of the fluxes of the metabolic network includes not only input fluxes, but also internal fluxes. A faster convergence process with robust candidate solutions is permitted by a relaxed Pareto dominance, regulating the granularity of the approximation of the desired Pareto front. We find that the maximum ATP production is linked to a total consumption of NADH, and reaching the maximum amount of NADH leads to an increasing request of NADH from the external environment. Furthermore, the identifiability analysis characterizes the type and the stage of three monogenic diseases. Finally, we propose a new methodology to extend any constraint-based model using protein abundances.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 670
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer

    Gianluca Lopez / Marianna Noale / Chiara Corti / Gabriella Gaudioso / Elham Sajjadi / Konstantinos Venetis / Donatella Gambini / Letterio Runza / Jole Costanza / Chiara Pesenti / Francesco Grossi / Stefania Maggi / Stefano Ferrero / Silvano Bosari / Nicola Fusco

    International Journal of Molecular Sciences, Vol 21, Iss 4, p

    2020  Band 1461

    Abstract: Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite ... ...

    Abstract Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors ( p < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2- tumors to 100% in HER2-amplified and ER-/HER2- cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers.
    Schlagwörter breast cancer ; mismatch repair ; pten ; immunohistochemistry ; biomarkers ; immunotherapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2020-02-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Extensive Placental Methylation Profiling in Normal Pregnancies

    Ornella Rondinone / Alessio Murgia / Jole Costanza / Silvia Tabano / Margherita Camanni / Luigi Corsaro / Laura Fontana / Patrizia Colapietro / Luciano Calzari / Silvia Motta / Carlo Santaniello / Tatjana Radaelli / Enrico Ferrazzi / Silvano Bosari / Davide Gentilini / Silvia Maria Sirchia / Monica Miozzo

    International Journal of Molecular Sciences, Vol 22, Iss 4, p

    2021  Band 2136

    Abstract: The placental methylation pattern is crucial for the regulation of genes involved in trophoblast invasion and placental development, both key events for fetal growth. We investigated LINE-1 methylation and methylome profiling using a methylation EPIC ... ...

    Abstract The placental methylation pattern is crucial for the regulation of genes involved in trophoblast invasion and placental development, both key events for fetal growth. We investigated LINE-1 methylation and methylome profiling using a methylation EPIC array and the targeted methylation sequencing of 154 normal, full-term pregnancies, stratified by birth weight percentiles. LINE-1 methylation showed evidence of a more pronounced hypomethylation in small neonates compared with normal and large for gestational age. Genome-wide methylation, performed in two subsets of pregnancies, showed very similar methylation profiles among cord blood samples while placentae from different pregnancies appeared very variable. A unique methylation profile emerged in each placenta, which could represent the sum of adjustments that the placenta made during the pregnancy to preserve the epigenetic homeostasis of the fetus. Investigations into the 1000 most variable sites between cord blood and the placenta showed that promoters and gene bodies that are hypermethylated in the placenta are associated with blood-specific functions, whereas those that are hypomethylated belong mainly to pathways involved in cancer. These features support the functional analogies between a placenta and cancer. Our results, which provide a comprehensive analysis of DNA methylation profiling in the human placenta, suggest that its peculiar dynamicity can be relevant for understanding placental plasticity in response to the environment.
    Schlagwörter placenta ; methylome ; LINE-1 ; birth weight ; normal pregnancies ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 570 ; 610
    Sprache Englisch
    Erscheinungsdatum 2021-02-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: The Genetic Landscape of Human Glioblastoma and Matched Primary Cancer Stem Cells Reveals Intratumour Similarity and Intertumour Heterogeneity

    Chiara Pesenti / Stefania Elena Navone / Laura Guarnaccia / Andrea Terrasi / Jole Costanza / Rosamaria Silipigni / Silvana Guarneri / Nicola Fusco / Laura Fontana / Marco Locatelli / Paolo Rampini / Rolando Campanella / Silvia Tabano / Monica Miozzo / Giovanni Marfia

    Stem Cells International, Vol

    2019  Band 2019

    Abstract: Glioblastoma (GBM) is the most malignant human brain tumour, characterized by rapid progression, invasion, intense angiogenesis, high genomic instability, and resistance to therapies. Despite countless experimental researches for new therapeutic ... ...

    Abstract Glioblastoma (GBM) is the most malignant human brain tumour, characterized by rapid progression, invasion, intense angiogenesis, high genomic instability, and resistance to therapies. Despite countless experimental researches for new therapeutic strategies and promising clinical trials, the prognosis remains extremely poor, with a mean survival of less than 14 months. GBM aggressive behaviour is due to a subpopulation of tumourigenic stem-like cells, GBM stem cells (GSCs), which hierarchically drive onset, proliferation, and tumour recurrence. The morbidity and mortality of this disease strongly encourage exploring genetic characteristics of GSCs. Here, using array-CGH platform, we investigated genetic and genomic aberration profiles of GBM parent tumour (n=10) and their primarily derived GSCs. Statistical analysis was performed by using R software and complex heatmap and corrplot packages. Pearson correlation and K-means algorithm were exploited to compare genetic alterations and to group similar genetic profiles in matched pairs of GBM and derived GSCs. We identified, in both GBM and matched GSCs, recurrent copy number alterations, as chromosome 7 polysomy, chromosome 10 monosomy, and chromosome 9p21deletions, which are typical features of primary GBM, essential for gliomagenesis. These observations suggest a condition of strong genomic instability both in GBM as GSCs. Our findings showed the robust similarity between GBM mass and GSCs (Pearson corr.≥0.65) but also highlighted a marked variability among different patients. Indeed, the heatmap reporting Gain/Loss State for 21022 coding/noncoding genes demonstrated high interpatient divergence. Furthermore, K-means algorithm identified an impairment of pathways related to the development and progression of cancer, such as angiogenesis, as well as pathways related to the immune system regulation, such as T cell activation. Our data confirmed the preservation of the genomic landscape from tumour tissue to GSCs, supporting the relevance of this cellular model to test in vitro new target therapies for GBM.
    Schlagwörter Internal medicine ; RC31-1245
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2019-01-01T00:00:00Z
    Verlag Hindawi Limited
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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