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  1. Article ; Online: Correction to: Peroxidasin Enhances Basal Phenotype and Inhibits Branching Morphogenesis in Breast Epithelial Progenitor Cell Line D492.

    Sigurdardottir, Anna Karen / Jonasdottir, Arna Steinunn / Asbjarnarson, Arni / Helgudottir, Hildur Run / Gudjonsson, Thorarinn / Traustadottir, Gunnhildur Asta

    Journal of mammary gland biology and neoplasia

    2022  Volume 26, Issue 4, Page(s) 339

    Language English
    Publishing date 2022-02-12
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1327345-0
    ISSN 1573-7039 ; 1083-3021
    ISSN (online) 1573-7039
    ISSN 1083-3021
    DOI 10.1007/s10911-022-09513-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4478: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  2. Article ; Online: Peroxidasin Enhances Basal Phenotype and Inhibits Branching Morphogenesis in Breast Epithelial Progenitor Cell Line D492.

    Sigurdardottir, Anna Karen / Jonasdottir, Arna Steinunn / Asbjarnarson, Arni / Helgudottir, Hildur Run / Gudjonsson, Thorarinn / Traustadottir, Gunnhildur Asta

    Journal of mammary gland biology and neoplasia

    2021  Volume 26, Issue 4, Page(s) 321–338

    Abstract: The human breast is composed of terminal duct lobular units (TDLUs) that are surrounded by stroma. In the TDLUs, basement membrane separates the stroma from the epithelial compartment, which is divided into an inner layer of luminal epithelial cells and ... ...

    Abstract The human breast is composed of terminal duct lobular units (TDLUs) that are surrounded by stroma. In the TDLUs, basement membrane separates the stroma from the epithelial compartment, which is divided into an inner layer of luminal epithelial cells and an outer layer of myoepithelial cells. Stem cells and progenitor cells also reside within the epithelium and drive a continuous cycle of gland remodelling that occurs throughout the reproductive period. D492 is an epithelial cell line originally isolated from the stem cell population of the breast and generates both luminal and myoepithelial cells in culture. When D492 cells are embedded into 3D reconstituted basement membrane matrix (3D-rBM) they form branching colonies mimicking the TDLUs of the breast, thereby providing a well-suited in vitro model for studies on branching morphogenesis and breast development. Peroxidasin (PXDN) is a heme-containing peroxidase that crosslinks collagen IV with the formation of sulfilimine bonds. Previous studies indicate that PXDN plays an integral role in basement membrane stabilisation by crosslinking collagen IV and as such contributes to epithelial integrity. Although PXDN has been linked to fibrosis and cancer in some organs there is limited information on its role in development, including in the breast. In this study, we demonstrate expression of PXDN in breast epithelium and stroma and apply the D492 cell line to investigate the role of PXDN in cell differentiation and branching morphogenesis in the human breast. Overexpression of PXDN induced basal phenotype in D492 cells, loss of plasticity and inhibition of epithelial-to-mesenchymal transition as is displayed by complete inhibition of branching morphogenesis in 3D culture. This is supported by results from RNA-sequencing which show significant enrichment in genes involved in epithelial differentiation along with significant negative enrichment of EMT factors. Taken together, we provide evidence for a novel role of PXDN in breast epithelial differentiation and mammary gland development.
    MeSH term(s) Collagen/metabolism ; Epithelial Cells/metabolism ; Extracellular Matrix Proteins ; Humans ; Morphogenesis/physiology ; Peroxidase ; Phenotype ; Stem Cells ; Peroxidasin
    Chemical Substances Extracellular Matrix Proteins ; Collagen (9007-34-5) ; Peroxidase (EC 1.11.1.7)
    Language English
    Publishing date 2021-12-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1327345-0
    ISSN 1573-7039 ; 1083-3021
    ISSN (online) 1573-7039
    ISSN 1083-3021
    DOI 10.1007/s10911-021-09507-1
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4478: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Ventilator-induced lung injury results in oxidative stress response and mitochondrial swelling in a mouse model.

    Joelsson, Jon Petur / Asbjarnarson, Arni / Sigurdsson, Snaevar / Kricker, Jennifer / Valdimarsdottir, Bryndis / Thorarinsdottir, Holmfridur / Starradottir, Eir / Gudjonsson, Thorarinn / Ingthorsson, Saevar / Karason, Sigurbergur

    Laboratory animal research

    2022  Volume 38, Issue 1, Page(s) 23

    Abstract: Background: Mechanical ventilation is a life-saving therapy for critically ill patients, providing rest to the respiratory muscles and facilitating gas exchange in the lungs. Ventilator-induced lung injury (VILI) is an unfortunate side effect of ... ...

    Abstract Background: Mechanical ventilation is a life-saving therapy for critically ill patients, providing rest to the respiratory muscles and facilitating gas exchange in the lungs. Ventilator-induced lung injury (VILI) is an unfortunate side effect of mechanical ventilation that may lead to serious consequences for the patient and increase mortality. The four main injury mechanisms associated with VILI are: baro/volutrauma caused by overstretching the lung tissues; atelectrauma, caused by repeated opening and closing of the alveoli resulting in shear stress; oxygen toxicity due to use of high ratio of oxygen in inspired air, causing formation of free radicals; and biotrauma, the resulting biological response to tissue injury, that leads to a cascade of events due to excessive inflammatory reactions and may cause multi-organ failure. An often-overlooked part of the inflammatory reaction is oxidative stress. In this research, a mouse model of VILI was set up with three tidal volume settings (10, 20 and 30 mL/kg) at atmospheric oxygen level. Airway pressures and heart rate were monitored and bronchoalveolar lavage fluid (BALF) and lung tissue samples were taken.
    Results: We show a correlation between increased inflammation and barrier failure, and higher tidal volumes, evidenced by increased IL-6 expression, high concentration of proteins in BALF along with changes in expression of adhesion molecules. Furthermore, swelling of mitochondria in alveolar type II cells was seen indicating their dysfunction and senescence-like state. RNA sequencing data present clear increases in inflammation, mitochondrial biogenesis and oxidative stress as tidal volume is increased, supported by degradation of Keap1, a redox-regulated substrate adaptor protein.
    Conclusions: Oxidative stress seems to be a more prominent mechanism of VILI than previously considered, indicating that possible treatment methods against VILI might be identified by impeding oxidative pathways.
    Language English
    Publishing date 2022-07-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2623220-0
    ISSN 2233-7660 ; 1738-6055
    ISSN (online) 2233-7660
    ISSN 1738-6055
    DOI 10.1186/s42826-022-00133-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Wittig bioconjugation of maleimide derived, water soluble phosphonium ylides to aldehyde-tagged proteins.

    Hartmann, Rafael W / Pijnappel, Matthijs / Nilvebrant, Johan / Helgudottir, Hildur Run / Asbjarnarson, Arni / Traustadottir, Gunnhildur Asta / Gudjonsson, Thorarinn / Nygren, Per-Åke / Lehmann, Fredrik / Odell, Luke R

    Organic & biomolecular chemistry

    2021  Volume 19, Issue 47, Page(s) 10417–10423

    Abstract: Herein we disclose the transformation of maleimides into water-soluble tris(2-carboxyethyl)phosphonium ylides and their subsequent application in the bioconjugation of protein- and peptide-linked aldehydes. The new entry into Wittig bioconjugate ... ...

    Abstract Herein we disclose the transformation of maleimides into water-soluble tris(2-carboxyethyl)phosphonium ylides and their subsequent application in the bioconjugation of protein- and peptide-linked aldehydes. The new entry into Wittig bioconjugate chemistry proceeds under mild conditions and relies on highly water soluble reagents, which are likely already part of most biochemists' inventory.
    MeSH term(s) Maleimides
    Chemical Substances Maleimides ; maleimide (2519R1UGP8)
    Language English
    Publishing date 2021-12-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2097583-1
    ISSN 1477-0539 ; 1477-0520
    ISSN (online) 1477-0539
    ISSN 1477-0520
    DOI 10.1039/d1ob01155c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers.

    Hasan, Shakir / Kulkarni, Nikhil Nitin / Asbjarnarson, Arni / Linhartova, Irena / Osicka, Radim / Sebo, Peter / Gudmundsson, Gudmundur H

    Infection and immunity

    2018  Volume 86, Issue 3

    Abstract: The airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent, ...

    Abstract The airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent,
    MeSH term(s) Adenylate Cyclase Toxin/genetics ; Adenylate Cyclase Toxin/metabolism ; Adenylate Cyclase Toxin/toxicity ; Bordetella pertussis/genetics ; Bordetella pertussis/metabolism ; Bronchi/cytology ; Bronchi/metabolism ; Bronchi/microbiology ; Cyclic AMP/metabolism ; Cytoskeleton/metabolism ; Epithelial Cells/metabolism ; Epithelial Cells/microbiology ; Humans ; Interleukin-6/metabolism ; Mucin 5AC/metabolism ; Signal Transduction/drug effects ; Whooping Cough/genetics ; Whooping Cough/metabolism ; Whooping Cough/microbiology
    Chemical Substances Adenylate Cyclase Toxin ; Interleukin-6 ; Mucin 5AC ; Cyclic AMP (E0399OZS9N)
    Language English
    Publishing date 2018-02-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00445-17
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 684: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Melflufen, a peptide-conjugated alkylator, is an efficient anti-neo-plastic drug in breast cancer cell lines.

    Schepsky, Alexander / Traustadottir, Gunnhildur Asta / Joelsson, Jon Petur / Ingthorsson, Saevar / Kricker, Jennifer / Bergthorsson, Jon Thor / Asbjarnarson, Arni / Gudjonsson, Thorkell / Nupponen, Nina / Slipicevic, Ana / Lehmann, Fredrik / Gudjonsson, Thorarinn

    Cancer medicine

    2020  Volume 9, Issue 18, Page(s) 6726–6738

    Abstract: Melphalan flufenamide (hereinafter referred to as "melflufen") is a peptide-conjugated drug currently in phase 3 trials for the treatment of relapsed or refractory multiple myeloma. Due to its lipophilic nature, it readily enters cells, where it is ... ...

    Abstract Melphalan flufenamide (hereinafter referred to as "melflufen") is a peptide-conjugated drug currently in phase 3 trials for the treatment of relapsed or refractory multiple myeloma. Due to its lipophilic nature, it readily enters cells, where it is converted to the known alkylator melphalan leading to enrichment of hydrophilic alkylator payloads. Here, we have analysed in vitro and in vivo the efficacy of melflufen on normal and cancerous breast epithelial lines. D492 is a normal-derived nontumorigenic epithelial progenitor cell line whereas D492HER2 is a tumorigenic version of D492, overexpressing the HER2 oncogene. In addition we used triple negative breast cancer cell line MDA-MB231. The tumorigenic D492HER2 and MDA-MB231 cells were more sensitive than normal-derived D492 cells when treated with melflufen. Compared to the commonly used anti-cancer drug doxorubicin, melflufen was significantly more effective in reducing cell viability in vitro while it showed comparable effects in vivo. However, melflufen was more efficient in inhibiting metastasis of MDA-MB231 cells. Melflufen induced DNA damage was confirmed by the expression of the DNA damage proteins ƴH2Ax and 53BP1. The effect of melflufen on D492HER2 was attenuated if cells were pretreated with the aminopeptidase inhibitor bestatin, which is consistent with previous reports demonstrating the importance of aminopeptidase CD13 in facilitating melflufen cleavage. Moreover, analysis of CD13
    MeSH term(s) Animals ; Antineoplastic Agents, Alkylating/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; CD13 Antigens/genetics ; CD13 Antigens/metabolism ; Cell Line, Tumor ; Chick Embryo ; DNA Damage ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Histones/metabolism ; Humans ; Leucyl Aminopeptidase/genetics ; Leucyl Aminopeptidase/metabolism ; Melphalan/analogs & derivatives ; Melphalan/pharmacology ; Phenylalanine/analogs & derivatives ; Phenylalanine/pharmacology ; Signal Transduction ; Tumor Suppressor p53-Binding Protein 1/genetics ; Tumor Suppressor p53-Binding Protein 1/metabolism
    Chemical Substances Antineoplastic Agents, Alkylating ; H2AX protein, human ; Histones ; TP53BP1 protein, human ; Tumor Suppressor p53-Binding Protein 1 ; melflufen (3412470A0V) ; Phenylalanine (47E5O17Y3R) ; LAP3 protein, human (EC 3.4.11.1) ; Leucyl Aminopeptidase (EC 3.4.11.1) ; CD13 Antigens (EC 3.4.11.2) ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; dipeptidyl peptidase II (EC 3.4.14.2) ; Melphalan (Q41OR9510P)
    Language English
    Publishing date 2020-07-27
    Publishing country United States
    Document type Journal Article
    ISSN 2045-7634
    ISSN (online) 2045-7634
    DOI 10.1002/cam4.3300
    Database MEDical Literature Analysis and Retrieval System OnLINE

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