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  1. Article ; Online: Antibiotic Treatment in an Animal Model of Inflammatory Lung Disease.

    Cait, Alissa / Messing, Melina / Cait, Jessica / Canals Hernaez, Diana / McNagny, Kelly M

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2223, Page(s) 281–293

    Abstract: Allergic disease is on the rise and yet the underlying cause and risk factors are not fully understood. While lifesaving in many circumstances, the use of antibiotics and the subsequent disruption of the microbiome are positively correlated with the ... ...

    Abstract Allergic disease is on the rise and yet the underlying cause and risk factors are not fully understood. While lifesaving in many circumstances, the use of antibiotics and the subsequent disruption of the microbiome are positively correlated with the development of allergies. Here, we describe the use of the antibiotic vancomycin in combination with the papain-induced mouse model of allergic disease that allows for the assessment of microbiome perturbations and the impact on allergy development.
    MeSH term(s) Animals ; Animals, Newborn ; Anti-Bacterial Agents/pharmacology ; Asthma/chemically induced ; Asthma/genetics ; Asthma/immunology ; Asthma/microbiology ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/immunology ; Bronchoalveolar Lavage Fluid/microbiology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Disease Models, Animal ; Eosine Yellowish-(YS)/chemistry ; Female ; Hematoxylin/chemistry ; Humans ; Immunoglobulin E/genetics ; Immunoglobulin E/immunology ; Interleukin-13/genetics ; Interleukin-13/immunology ; Interleukin-4/genetics ; Interleukin-4/immunology ; Interleukin-5/genetics ; Interleukin-5/immunology ; Lung/pathology ; Macrophages, Alveolar/drug effects ; Macrophages, Alveolar/immunology ; Macrophages, Alveolar/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota/drug effects ; Papain/administration & dosage ; Staining and Labeling/methods ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; Vancomycin/pharmacology
    Chemical Substances Anti-Bacterial Agents ; Il4 protein, mouse ; Interleukin-13 ; Interleukin-5 ; Interleukin-4 (207137-56-2) ; Immunoglobulin E (37341-29-0) ; Vancomycin (6Q205EH1VU) ; Papain (EC 3.4.22.2) ; Eosine Yellowish-(YS) (TDQ283MPCW) ; Hematoxylin (YKM8PY2Z55)
    Language English
    Publishing date 2020-11-23
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1001-5_19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A sticky wicket: Defining molecular functions for CD34 in hematopoietic cells.

    Hughes, Michael R / Canals Hernaez, Diana / Cait, Jessica / Refaeli, Ido / Lo, Bernard C / Roskelley, Calvin D / McNagny, Kelly M

    Experimental hematology

    2020  Volume 86, Page(s) 1–14

    Abstract: The CD34 cell surface antigen is widely expressed in tissues on cells with progenitor-like properties and on mature vascular endothelia. In adult human bone marrow, CD34 marks hematopoietic stem and progenitor cells (HSPCs) starting from the bulk of ... ...

    Abstract The CD34 cell surface antigen is widely expressed in tissues on cells with progenitor-like properties and on mature vascular endothelia. In adult human bone marrow, CD34 marks hematopoietic stem and progenitor cells (HSPCs) starting from the bulk of hematopoietic stem cells with long-term repopulating potential (LT-HSCs) throughout expansion and differentiation of oligopotent and unipotent progenitors. CD34 protein surface expression is typically lost as cells mature into terminal effectors. Because of this expression pattern of HSPCs, CD34 has had a central role in the evaluation or selection of donor graft tissue in HSC transplant (HSCT). Given its clinical importance, it is surprising that the biological functions of CD34 are still poorly understood. This enigma is due, in part, to CD34's context-specific role as both a pro-adhesive and anti-adhesive molecule and its potential functional redundancy with other sialomucins. Moreover, there are also critical differences in the regulation of CD34 expression on HSPCs in humans and experimental mice. In this review, we highlight some of the more well-defined functions of CD34 in HSPCs with a focus on proposed functions most relevant to HSCT biology.
    MeSH term(s) Animals ; Antigens, CD34/metabolism ; Bone Marrow/metabolism ; Cell Differentiation ; Gene Expression Regulation ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Humans ; Mice
    Chemical Substances Antigens, CD34
    Language English
    Publishing date 2020-05-16
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 185107-x
    ISSN 1873-2399 ; 0531-5573 ; 0301-472X
    ISSN (online) 1873-2399
    ISSN 0531-5573 ; 0301-472X
    DOI 10.1016/j.exphem.2020.05.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 922: 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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  3. Article: Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models.

    Canals Hernaez, Diana / Hughes, Michael R / Li, Yicong / Mainero Rocca, Ilaria / Dean, Pamela / Brassard, Julyanne / Bell, Erin M / Samudio, Ismael / Mes-Masson, Anne-Marie / Narimatsu, Yoshiki / Clausen, Henrik / Blixt, Ola / Roskelley, Calvin D / McNagny, Kelly M

    Frontiers in oncology

    2022  Volume 12, Page(s) 856424

    Abstract: Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. Importantly, it is also frequently upregulated on a wide ... ...

    Abstract Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. Importantly, it is also frequently upregulated on a wide array of human tumors and its expression often correlates with poor prognosis. We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive. Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines
    Language English
    Publishing date 2022-05-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.856424
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: PODO447: a novel antibody to a tumor-restricted epitope on the cancer antigen podocalyxin.

    Canals Hernaez, Diana / Hughes, Michael R / Dean, Pamela / Bergqvist, Peter / Samudio, Ismael / Blixt, Ola / Wiedemeyer, Katharina / Li, Yicong / Bond, Chris / Cruz, Eric / Köbel, Martin / Gilks, Blake / Roskelley, Calvin D / McNagny, Kelly M

    Journal for immunotherapy of cancer

    2020  Volume 8, Issue 2

    Abstract: Background: The success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus ... ...

    Abstract Background: The success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus emerging as an important prognostic and theragnostic marker in several human cancers. Moreover, in human tumor xenograft models, Podxl expression promotes tumor growth and metastasis. Although a promising target for immunotherapy, the expression of Podxl on normal vascular endothelia and kidney podocytes could hamper efforts to therapeutically target this molecule. Since pathways regulating post-translational modifications are frequently perturbed in cancer cells, we sought to produce novel anti-Podxl antibodies (Abs) that selectively recognize tumor-restricted glycoepitopes on the extracellular mucin domain of Podxl.
    Methods: Splenic B cells were isolated from rabbits immunized with a Podxl-expressing human tumor cell line. Abs from these B cells were screened for potent reactivity to Podxl
    Results: One mAb (PODO447) showed strong reactivity with a variety of Podxl+ tumor cell lines but not with normal primary human tissue including Podxl+ kidney podocytes and most vascular endothelia. Screening of an ovarian carcinoma TMA (219 cases) revealed PODO447 reactivity with the majority of tumors, including 65% of the high-grade serous histotype. Subsequent biochemical analyses determined that PODO447 reacts with a highly unusual terminal N-acetylgalactosamine beta-1 (GalNAcβ1) motif predominantly found on the Podxl protein core. Finally, Ab-drug conjugates showed specific efficacy in killing tumor cells
    Conclusions: We have generated a novel and exquisitely tumor-restricted mAb, PODO447, that recognizes a glycoepitope on Podxl expressed at high levels by a variety of tumors including the majority of life-threatening high-grade serous ovarian tumors. Thus, tumor-restricted PODO447 exhibits the appropriate specificity for further development as a targeted immunotherapy.
    MeSH term(s) Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Biomarkers, Tumor/immunology ; CHO Cells ; Cell Line, Tumor ; Cricetulus ; Epitopes/immunology ; Female ; HEK293 Cells ; Humans ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/therapy ; Rabbits ; Sialoglycoproteins/immunology
    Chemical Substances Antibodies, Monoclonal ; Biomarkers, Tumor ; Epitopes ; Sialoglycoproteins ; podocalyxin
    Language English
    Publishing date 2020-11-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2020-001128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Transcription Factor RORα Preserves ILC3 Lineage Identity and Function during Chronic Intestinal Infection.

    Lo, Bernard C / Canals Hernaez, Diana / Scott, R Wilder / Hughes, Michael R / Shin, Samuel B / Underhill, T Michael / Takei, Fumio / McNagny, Kelly M

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Volume 203, Issue 12, Page(s) 3209–3215

    Abstract: Innate lymphoid cells (ILCs) are critical for host defense and tissue repair but can also contribute to chronic inflammatory diseases. The transcription factor RORα is required for ILC2 development but is also highly expressed by other ILC subsets where ... ...

    Abstract Innate lymphoid cells (ILCs) are critical for host defense and tissue repair but can also contribute to chronic inflammatory diseases. The transcription factor RORα is required for ILC2 development but is also highly expressed by other ILC subsets where its function remains poorly defined. We previously reported that
    MeSH term(s) Animals ; Biomarkers ; Chronic Disease ; Disease Models, Animal ; Enteritis/etiology ; Enteritis/metabolism ; Enteritis/pathology ; Fibrosis ; Immunity, Innate ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Lymphoid Tissue/immunology ; Lymphoid Tissue/metabolism ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism
    Chemical Substances Biomarkers ; Nuclear Receptor Subfamily 1, Group F, Member 1 ; Rora protein, mouse
    Language English
    Publishing date 2019-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1900781
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.37: 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)
    Zs.MG 28: Show issues

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  6. Article ; Online: IL-22 Preserves Gut Epithelial Integrity and Promotes Disease Remission during Chronic

    Lo, Bernard C / Shin, Samuel B / Canals Hernaez, Diana / Refaeli, Ido / Yu, Hong B / Goebeler, Verena / Cait, Alissa / Mohn, William W / Vallance, Bruce A / McNagny, Kelly M

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Volume 202, Issue 3, Page(s) 956–965

    Abstract: The cytokine IL-22 is rapidly induced at barrier surfaces where it regulates host-protective antimicrobial immunity and tissue repair but can also enhance disease severity in some chronic inflammatory settings. Using the ... ...

    Abstract The cytokine IL-22 is rapidly induced at barrier surfaces where it regulates host-protective antimicrobial immunity and tissue repair but can also enhance disease severity in some chronic inflammatory settings. Using the chronic
    MeSH term(s) Animals ; Antibodies, Bacterial/immunology ; Antibodies, Neutralizing/immunology ; Bacteroides ; Cecum/immunology ; Cecum/pathology ; Crohn Disease/immunology ; Crohn Disease/pathology ; Cytokines/immunology ; Gastroenteritis/immunology ; Gastroenteritis/microbiology ; Gastrointestinal Microbiome ; Inflammation ; Interleukins/antagonists & inhibitors ; Interleukins/immunology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/pathology ; Mice ; Mice, Inbred C57BL ; Remission Induction ; Salmonella Infections, Animal/immunology ; Salmonella Infections, Animal/therapy ; Salmonella typhimurium ; Interleukin-22
    Chemical Substances Antibodies, Bacterial ; Antibodies, Neutralizing ; Cytokines ; Interleukins
    Language English
    Publishing date 2019-01-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1801308
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.37: 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)
    Zs.MG 28: Show issues

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  7. Article ; Online: Podocalyxin is required for maintaining blood-brain barrier function during acute inflammation.

    Cait, Jessica / Hughes, Michael R / Zeglinski, Matthew R / Chan, Allen W / Osterhof, Sabrina / Scott, R Wilder / Canals Hernaez, Diana / Cait, Alissa / Vogl, A Wayne / Bernatchez, Pascal / Underhill, T Michael / Granville, David J / Murphy, Timothy H / Roskelley, Calvin D / McNagny, Kelly M

    Proceedings of the National Academy of Sciences of the United States of America

    2019  Volume 116, Issue 10, Page(s) 4518–4527

    Abstract: Podocalyxin (Podxl) is broadly expressed on the luminal face of most blood vessels in adult vertebrates, yet its function on these cells is poorly defined. In the present study, we identified specific functions for Podxl in maintaining endothelial ... ...

    Abstract Podocalyxin (Podxl) is broadly expressed on the luminal face of most blood vessels in adult vertebrates, yet its function on these cells is poorly defined. In the present study, we identified specific functions for Podxl in maintaining endothelial barrier function. Using electrical cell substrate impedance sensing and live imaging, we found that, in the absence of Podxl, human umbilical vein endothelial cells fail to form an efficient barrier when plated on several extracellular matrix substrates. In addition, these monolayers lack adherens junctions and focal adhesions and display a disorganized cortical actin cytoskeleton. Thus, Podxl has a key role in promoting the appropriate endothelial morphogenesis required to form functional barriers. This conclusion is further supported by analyses of mutant mice in which we conditionally deleted a floxed allele of
    MeSH term(s) Blood-Brain Barrier ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Inflammation/metabolism ; Morphogenesis ; Sialoglycoproteins/metabolism
    Chemical Substances Sialoglycoproteins ; podocalyxin
    Language English
    Publishing date 2019-02-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1814766116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: 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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