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  1. AU="Mads Daugaard"
  2. AU=McKinney Marcus M
  3. AU="Rodríguez-Cobos, J"
  4. AU="Graham, S. Elizabeth"
  5. AU="Piñero, Fernando L"
  6. AU="LUBAN-PLOZZA, B"
  7. AU="Dewitte, Olivier"
  8. AU="Low, Zhen Luan"
  9. AU="Song, Jin-Ju"
  10. AU="Liu-Xia Zhang"
  11. AU="Ahmed, Abdallah M Said"
  12. AU=Hover Alexander R
  13. AU="Zaniar Ghazizadeh"
  14. AU="Rathod, Aniruddha"
  15. AU=Ong Edison
  16. AU="Hoffmann, Daniela"
  17. AU="Mallett, Garry"
  18. AU=Lemos Pedro A
  19. AU="Bakris, George L."
  20. AU="Tun-Linn Thein"
  21. AU="Michelle Schinkel"
  22. AU="Scolieri, G"

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  1. Artikel ; Online: A genome-wide CRISPR screen maps endogenous regulators of PPARG gene expression in bladder cancer

    Davide Tortora / Morgan E. Roberts / Gunjan Kumar / Sudha S. Kotapalli / Elie Ritch / Joshua M. Scurll / Brian McConeghy / Sunita Sinha / Alexander W. Wyatt / Peter C. Black / Mads Daugaard

    iScience, Vol 26, Iss 5, Pp 106525- (2023)

    2023  

    Abstract: Summary: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor central in the regulation of key cellular processes including cell metabolism, tissue differentiation, and regulation of the immune system. PPARγ is required for ... ...

    Abstract Summary: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor central in the regulation of key cellular processes including cell metabolism, tissue differentiation, and regulation of the immune system. PPARγ is required for normal differentiation of the urothelium and is thought to be an essential driver of the luminal subtype of bladder cancer. However, the molecular components that regulate PPARG gene expression in bladder cancer remain unclear. Here, we developed an endogenous PPARG reporter system in luminal bladder cancer cells and performed genome-wide CRISPR knockout screening to identify bona fide regulators of PPARG gene expression. Functional validation of the dataset confirmed GATA3, SPT6, and the cohesin complex components SMC1A, and RAD21, as permissive upstream positive regulators of PPARG gene expression in luminal bladder cancer. In summary, this work provides a resource and biological insights to aid our understanding of PPARG regulation in bladder cancer.
    Schlagwörter Biological sciences ; Molecular biology ; Molecular mechanism of gene regulation ; Cancer ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2023-05-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: A Potential Role for HUWE1 in Modulating Cisplatin Sensitivity

    Stijn Wenmaekers / Bastiaan J. Viergever / Gunjan Kumar / Onno Kranenburg / Peter C. Black / Mads Daugaard / Richard P. Meijer

    Cells, Vol 10, Iss 1262, p

    2021  Band 1262

    Abstract: Cisplatin is a widely used antineoplastic agent, whose efficacy is limited by primary and acquired therapeutic resistance. Recently, a bladder cancer genome-wide CRISPR/Cas9 knock-out screen correlated cisplatin sensitivity to multiple genetic biomarkers. ...

    Abstract Cisplatin is a widely used antineoplastic agent, whose efficacy is limited by primary and acquired therapeutic resistance. Recently, a bladder cancer genome-wide CRISPR/Cas9 knock-out screen correlated cisplatin sensitivity to multiple genetic biomarkers. Among the screen’s top hits was the HECT domain-containing ubiquitin E3 ligase (HUWE1). In this review, HUWE1 is postulated as a therapeutic response modulator, affecting the collision between platinum-DNA adducts and the replication fork, the primary cytotoxic action of platins. HUWE1 can alter the cytotoxic response to platins by targeting essential components of the DNA damage response including BRCA1, p53, and Mcl-1. Deficiency of HUWE1 could lead to enhanced DNA damage repair and a dysfunctional apoptotic apparatus, thereby inducing resistance to platins. Future research on the relationship between HUWE1 and platins could generate new mechanistic insights into therapy resistance. Ultimately, HUWE1 might serve as a clinical biomarker to tailor cancer treatment strategies, thereby improving cancer care and patient outcomes.
    Schlagwörter chemotherapy ; resistance ; biomarkers ; translational medicine research ; ubiquitination ; DNA damage response ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-05-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Oncofetal Chondroitin Sulfate

    Nastaran Khazamipour / Nader Al-Nakouzi / Htoo Zarni Oo / Maj Ørum-Madsen / Anne Steino / Poul H Sorensen / Mads Daugaard

    Cells, Vol 9, Iss 818, p

    A Putative Therapeutic Target in Adult and Pediatric Solid Tumors

    2020  Band 818

    Abstract: Solid tumors remain a major challenge for targeted therapeutic intervention strategies such as antibody-drug conjugates and immunotherapy. At a minimum, clear and actionable solid tumor targets have to comply with the key biological requirement of being ... ...

    Abstract Solid tumors remain a major challenge for targeted therapeutic intervention strategies such as antibody-drug conjugates and immunotherapy. At a minimum, clear and actionable solid tumor targets have to comply with the key biological requirement of being differentially over-expressed in solid tumors and metastasis, in contrast to healthy organs. Oncofetal chondroitin sulfate is a cancer-specific secondary glycosaminoglycan modification to proteoglycans expressed in a variety of solid tumors and metastasis. Normally, this modification is found to be exclusively expressed in the placenta, where it is thought to facilitate normal placental implantation during pregnancy. Informed by this biology, oncofetal chondroitin sulfate is currently under investigation as a broad and specific target in solid tumors. Here, we discuss oncofetal chondroitin sulfate as a potential therapeutic target in childhood solid tumors in the context of current knowhow obtained over the past five years in adult cancers.
    Schlagwörter oncofetal chondroitin sulfate ; chondroitin sulfate ; cancer ; solid tumors ; target ; pediatric cancer ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2020-03-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Internalization and trafficking of CSPG-bound recombinant VAR2CSA lectins in cancer cells

    Chris Kedong Wang / Irina Nelepcu / Desmond Hui / Htoo Zarni Oo / Sarah Truong / Sarah Zhao / Zakir Tahiry / Shaghayegh Esfandnia / Fariba Ghaidi / Hans Adomat / Robert Dagil / Tobias Gustavsson / Swati Choudhary / Ali Salanti / Poul H. Sorensen / Nader Al Nakouzi / Mads Daugaard

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Band 13

    Abstract: Abstract Proteoglycans are proteins that are modified with glycosaminoglycan chains. Chondroitin sulfate proteoglycans (CSPGs) are currently being exploited as targets for drug-delivery in various cancer indications, however basic knowledge on how CSPGs ... ...

    Abstract Abstract Proteoglycans are proteins that are modified with glycosaminoglycan chains. Chondroitin sulfate proteoglycans (CSPGs) are currently being exploited as targets for drug-delivery in various cancer indications, however basic knowledge on how CSPGs are internalized in tumor cells is lacking. In this study we took advantage of a recombinant CSPG-binding lectin VAR2CSA (rVAR2) to track internalization and cell fate of CSPGs in tumor cells. We found that rVAR2 is internalized into cancer cells via multiple internalization mechanisms after initial docking on cell surface CSPGs. Regardless of the internalization pathway used, CSPG-bound rVAR2 was trafficked to the early endosomes in an energy-dependent manner but not further transported to the lysosomal compartment. Instead, internalized CSPG-bound rVAR2 proteins were secreted with exosomes to the extracellular environment in a strictly chondroitin sulfate-dependent manner. In summary, our work describes the cell fate of rVAR2 proteins in tumor cells after initial binding to CSPGs, which can be further used to inform development of rVAR2-drug conjugates and other therapeutics targeting CSPGs.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2022-02-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Author Correction

    Mette Ø. Agerbæk / Sara R. Bang-Christensen / Ming-Hsin Yang / Thomas M. Clausen / Marina A. Pereira / Shreya Sharma / Sisse B. Ditlev / Morten A. Nielsen / Swati Choudhary / Tobias Gustavsson / Poul H. Sorensen / Tim Meyer / David Propper / Jonathan Shamash / Thor G. Theander / Alexandra Aicher / Mads Daugaard / Christopher Heeschen / Ali Salanti

    Nature Communications, Vol 13, Iss 1, Pp 1-

    The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

    2022  Band 4

    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-06-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer

    Nader Al-Nakouzi / Chris Kedong Wang / Htoo Zarni Oo / Irina Nelepcu / Nada Lallous / Charlotte B. Spliid / Nastaran Khazamipour / Joey Lo / Sarah Truong / Colin Collins / Desmond Hui / Shaghayegh Esfandnia / Hans Adomat / Thomas Mandel Clausen / Tobias Gustavsson / Swati Choudhary / Robert Dagil / Eva Corey / Yuzhuo Wang /
    Anne Chauchereau / Ladan Fazli / Jeffrey D. Esko / Ali Salanti / Peter S. Nelson / Martin E. Gleave / Mads Daugaard

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Band 14

    Abstract: Chondroitin sulfate (CS) is one of the most abundant glycosaminoglycans in prostate cancers. Here the authors show that inhibition of the androgen receptor pathway leads to the upregulation of CS, which promotes prostate cancer growth and metastasis. ...

    Abstract Chondroitin sulfate (CS) is one of the most abundant glycosaminoglycans in prostate cancers. Here the authors show that inhibition of the androgen receptor pathway leads to the upregulation of CS, which promotes prostate cancer growth and metastasis.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-08-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

    Mette Ø. Agerbæk / Sara R. Bang-Christensen / Ming-Hsin Yang / Thomas M. Clausen / Marina A. Pereira / Shreya Sharma / Sisse B. Ditlev / Morten A. Nielsen / Swati Choudhary / Tobias Gustavsson / Poul H. Sorensen / Tim Meyer / David Propper / Jonathan Shamash / Thor G. Theander / Alexandra Aicher / Mads Daugaard / Christopher Heeschen / Ali Salanti

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Band 13

    Abstract: Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal ... ...

    Abstract Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal chondroitin sulfate, which is expressed by all cancer cells
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2018-08-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

    Mette Ø. Agerbæk / Sara R. Bang-Christensen / Ming-Hsin Yang / Thomas M. Clausen / Marina A. Pereira / Shreya Sharma / Sisse B. Ditlev / Morten A. Nielsen / Swati Choudhary / Tobias Gustavsson / Poul H. Sorensen / Tim Meyer / David Propper / Jonathan Shamash / Thor G. Theander / Alexandra Aicher / Mads Daugaard / Christopher Heeschen / Ali Salanti

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Band 13

    Abstract: Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal ... ...

    Abstract Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal chondroitin sulfate, which is expressed by all cancer cells
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2018-08-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1.

    Marina Ayres Pereira / Thomas Mandel Clausen / Caroline Pehrson / Yang Mao / Mafalda Resende / Mads Daugaard / Anders Riis Kristensen / Charlotte Spliid / Line Mathiesen / Lisbeth E Knudsen / Peter Damm / Thor G Theander / Stefan R Hansson / Morten A Nielsen / Ali Salanti

    PLoS Pathogens, Vol 12, Iss 8, p e

    2016  Band 1005831

    Abstract: During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin ... ...

    Abstract During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2016-08-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer

    Jennifer Munkley / Ling Li / S R Gokul Krishnan / Gerald Hysenaj / Emma Scott / Caroline Dalgliesh / Htoo Zarni Oo / Teresa Mendes Maia / Kathleen Cheung / Ingrid Ehrmann / Karen E Livermore / Hanna Zielinska / Oliver Thompson / Bridget Knight / Paul McCullagh / John McGrath / Malcolm Crundwell / Lorna W Harries / Mads Daugaard /
    Simon Cockell / Nuno L Barbosa-Morais / Sebastian Oltean / David J Elliott

    eLife, Vol

    2019  Band 8

    Abstract: Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also ... ...

    Abstract Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression.
    Schlagwörter RNA ; splicing ; gene expression ; cancer ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2019-09-01T00:00:00Z
    Verlag eLife Sciences Publications Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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