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  1. Article: Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells.

    Gruijs, Mandy / Braster, Rens / Overdijk, Marije B / Hellingman, Tessa / Verploegen, Sandra / Korthouwer, Rianne / van der Wilk, Berend J / Parren, Paul W H I / van der Vliet, Hans J / Bögels, Marijn / van Egmond, Marjolein

    Journal of oncology

    2022  Volume 2022, Page(s) 3577928

    Abstract: Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis ... ...

    Abstract Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment with specific tumor-targeting monoclonal antibodies (mAb) prevented surgery-induced liver metastasis development in rats. This study investigated whether the epidermal growth factor receptor (EGFR) represents a suitable target for preoperative antibody treatment of colorectal cancer patients undergoing surgery. The majority of patients with resectable colorectal liver metastases were shown to have EGFR + CTCs. Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. Additionally, all three mAbs induced antibody-dependent cellular phagocytosis (ADCP) of tumor cells by macrophages at low antibody concentrations
    Language English
    Publishing date 2022-01-07
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2461349-6
    ISSN 1687-8469 ; 1687-8450
    ISSN (online) 1687-8469
    ISSN 1687-8450
    DOI 10.1155/2022/3577928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Afucosylated IgG Targets FcγRIV for Enhanced Tumor Therapy in Mice.

    Braster, Rens / Bögels, Marijn / Benonisson, Hreinn / Wuhrer, Manfred / Plomp, Rosina / Bentlage, Arthur E H / Korthouwer, Rianne / Visser, Remco / Verbeek, J Sjef / van Egmond, Marjolein / Vidarsson, Gestur

    Cancers

    2021  Volume 13, Issue 10

    Abstract: Promising strategies for maximizing IgG effector functions rely on the introduction of natural and non-immunogenic modifications. The Fc domain of IgG antibodies contains an N-linked oligosaccharide at position 297. Human IgG antibodies lacking the core ... ...

    Abstract Promising strategies for maximizing IgG effector functions rely on the introduction of natural and non-immunogenic modifications. The Fc domain of IgG antibodies contains an N-linked oligosaccharide at position 297. Human IgG antibodies lacking the core fucose in this glycan have enhanced binding to human (FcγR) IIIa/b, resulting in enhanced antibody dependent cell cytotoxicity and phagocytosis through these receptors. However, it is not yet clear if glycan-enhancing modifications of human IgG translate into more effective treatment in mouse models. We generated humanized hIgG1-TA99 antibodies with and without core-fucose. C57Bl/6 mice that were injected intraperitoneally with B16F10-gp75 mouse melanoma developed significantly less metastasis outgrowth after treatment with afucosylated hIgG1-TA99 compared to mice treated with wildtype hhIgG1-TA99. Afucosylated human IgG1 showed stronger interaction with the murine FcγRIV, the mouse orthologue of human FcγRIIIa, indicating that this glycan change is functionally conserved between the species. In agreement with this, no significant differences were observed in tumor outgrowth in FcγRIV
    Language English
    Publishing date 2021-05-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13102372
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration.

    Heineke, Marieke H / van der Steen, Lydia P E / Korthouwer, Rianne M / Hage, J Joris / Langedijk, Johannes P M / Benschop, Joris J / Bakema, Jantine E / Slootstra, Jerry W / van Egmond, Marjolein

    European journal of immunology

    2017  Volume 47, Issue 10, Page(s) 1835–1845

    Abstract: The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce ... ...

    Abstract The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life. IgA and FcαRI peptides reduced phagocytosis of IgA-coated beads, as well as IgA-induced ROS production and neutrophil migration in in vitro and ex vivo (human skin) experiments. Since topical application would be the preferential route of administration, Cetomacrogol cream containing an IgA CLIPS peptide was developed. In the presence of a skin permeation enhancer, peptides in this cream were shown to penetrate the skin, while not diffusing systemically. Finally, epitope mapping was used to discover sequences important for binding between IgA and FcαRI. In conclusion, a cream containing IgA or FcαRI peptide mimetics, which block IgA-induced neutrophil activation and migration in the skin may have therapeutic potential for patients with IgA-mediated blistering skin diseases.
    MeSH term(s) Administration, Topical ; Antigens, CD/chemistry ; Antigens, CD/immunology ; Antigens, CD/metabolism ; Autoantibodies/chemistry ; Autoantibodies/immunology ; Autoantibodies/metabolism ; Autoimmune Diseases/therapy ; Cetomacrogol/administration & dosage ; Cetomacrogol/chemistry ; Epitope Mapping ; Half-Life ; Humans ; Immune System Diseases/immunology ; Immunoglobulin A/chemistry ; Immunoglobulin A/immunology ; Immunoglobulin A/metabolism ; Leukocyte Disorders/immunology ; Leukotriene B4/metabolism ; Neutrophil Activation/drug effects ; Neutrophil Infiltration/drug effects ; Neutrophils/drug effects ; Neutrophils/immunology ; Peptide Library ; Peptidomimetics/chemistry ; Peptidomimetics/immunology ; Peptidomimetics/metabolism ; Phagocytosis ; Protein Binding ; Reactive Oxygen Species/metabolism ; Receptors, Fc/chemistry ; Receptors, Fc/immunology ; Receptors, Fc/metabolism ; Skin/drug effects ; Skin/immunology ; Skin/pathology ; Skin Absorption ; Skin Diseases/immunology ; Skin Diseases/therapy
    Chemical Substances Antigens, CD ; Autoantibodies ; Fc(alpha) receptor ; Immunoglobulin A ; Peptide Library ; Peptidomimetics ; Reactive Oxygen Species ; Receptors, Fc ; Leukotriene B4 (1HGW4DR56D) ; Cetomacrogol (9004-95-9)
    Language English
    Publishing date 2017-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201646782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 489: 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)
    Zs.MG 85: Show issues

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  4. Article: Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model.

    Grewal, Simran / Korthouwer, Rianne / Bögels, Marijn / Braster, Rens / Heemskerk, Niels / Budding, Andries E / Pouw, Stephan M / van Horssen, Jack / Ankersmit, Marjolein / Meijerink, Jeroen / van den Tol, Petrousjka / Oosterling, Steven / Bonjer, Jaap / Gül, Nuray / van Egmond, Marjolein

    Oncoimmunology

    2018  Volume 7, Issue 9, Page(s) e1461302

    Abstract: Surgical resection of the primary tumor provides the best chance of cure for patients with colorectal carcinoma (CRC). However, bacterial translocation during intestinal surgery has been correlated with poor long-term oncological outcome. Therefore, we ... ...

    Abstract Surgical resection of the primary tumor provides the best chance of cure for patients with colorectal carcinoma (CRC). However, bacterial translocation during intestinal surgery has been correlated with poor long-term oncological outcome. Therefore, we investigated the influence of bacterial contamination during colon surgery on CRC liver metastases development. Blood and liver samples of patients undergoing resection of primary CRC or liver metastases were collected. Cell numbers, activation markers and inflammatory mediators were determined. Tumor cell adhesion and outgrowth after sham- or colectomy operations were determined in a rat model, in which tumor cells had been injected into the portal vein. White blood cells and granulocytes were increased in per- and post-operative patient blood samples. IL-6 was also increased post-operatively compared to the preoperative level. Expression of NOX-2, NOX-4 and polymorphonuclear cells (PMNs) numbers were elevated in post-operative human liver samples.
    Language English
    Publishing date 2018-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-4011
    ISSN (online) 2162-402X
    ISSN 2162-4011
    DOI 10.1080/2162402X.2018.1461302
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Macrophages eliminate circulating tumor cells after monoclonal antibody therapy.

    Gül, Nuray / Babes, Liane / Siegmund, Kerstin / Korthouwer, Rianne / Bögels, Marijn / Braster, Rens / Vidarsson, Gestur / ten Hagen, Timo L M / Kubes, Paul / van Egmond, Marjolein

    The Journal of clinical investigation

    2014  Volume 124, Issue 2, Page(s) 812–823

    Abstract: The use of monoclonal antibodies (mAbs) as therapeutic tools has increased dramatically in the last decade and is now one of the mainstream strategies to treat cancer. Nonetheless, it is still not completely understood how mAbs mediate tumor cell ... ...

    Abstract The use of monoclonal antibodies (mAbs) as therapeutic tools has increased dramatically in the last decade and is now one of the mainstream strategies to treat cancer. Nonetheless, it is still not completely understood how mAbs mediate tumor cell elimination or the effector cells that are involved. Using intravital microscopy, we found that antibody-dependent phagocytosis (ADPh) by macrophages is a prominent mechanism for removal of tumor cells from the circulation in a murine tumor cell opsonization model. Tumor cells were rapidly recognized and arrested by liver macrophages (Kupffer cells). In the absence of mAbs, Kupffer cells sampled tumor cells; however, this sampling was not sufficient for elimination. By contrast, antitumor mAb treatment resulted in rapid phagocytosis of tumor cells by Kupffer cells that was dependent on the high-affinity IgG-binding Fc receptor (FcγRI) and the low-affinity IgG-binding Fc receptor (FcγRIV). Uptake and intracellular degradation were independent of reactive oxygen or nitrogen species production. Importantly, ADPh prevented the development of liver metastases. Tumor cell capture and therapeutic efficacy were lost after Kupffer cell depletion. Our data indicate that macrophages play a prominent role in mAb-mediated eradication of tumor cells. These findings may help to optimize mAb therapeutic strategies for patients with cancer by helping us to aim to enhance macrophage recruitment and activity.
    MeSH term(s) Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/therapeutic use ; Bone Marrow Cells/cytology ; Cell Line, Tumor ; Humans ; Immunoglobulin G/chemistry ; Kupffer Cells/cytology ; Liver/metabolism ; Liver/pathology ; Macrophages/metabolism ; Melanoma, Experimental ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Neoplasm Metastasis ; Neoplasm Transplantation ; Neoplasms/immunology ; Neoplastic Cells, Circulating/metabolism ; Phagocytosis ; Reactive Nitrogen Species ; Reactive Oxygen Species
    Chemical Substances Antibodies, Monoclonal ; Immunoglobulin G ; Reactive Nitrogen Species ; Reactive Oxygen Species
    Language English
    Publishing date 2014-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI66776
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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