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  1. Article ; Online: Molecular techniques drive cutting edge advancements in management of cutaneous T cell lymphoma.

    Lefebvre, Mitchell N / Borcherding, Nicholas / Reis, Ryan J / Mou, Eric / Liu, Vincent / Jabbari, Ali

    Frontiers in immunology

    2023  Volume 14, Page(s) 1228563

    Abstract: Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective ... ...

    Abstract Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective and standardized diagnostic and prognostic clinical tools. Currently, diagnosis of CTCL practically relies on clinical presentation, histopathology, and immunohistochemistry. These methods are collectively fraught with limitations in sensitivity and specificity. Fortunately, recent advances in flow cytometry, polymerase chain reaction, high throughput sequencing, and other molecular techniques have shown promise in improving diagnosis and treatment of CTCL. Examples of these advances include T cell receptor clonotyping via sequencing to detect CTCL earlier in the disease course and single-cell RNA sequencing to identify gene expression patterns that commonly drive CTCL pathogenesis. Experience with these techniques has afforded novel insights which may translate into enhanced diagnostic and therapeutic approaches for CTCL.
    MeSH term(s) Humans ; Lymphoma, T-Cell, Cutaneous/diagnosis ; Lymphoma, T-Cell, Cutaneous/genetics ; Lymphoma, T-Cell, Cutaneous/therapy ; Skin ; Lymphoma, Non-Hodgkin ; Disease Progression ; Skin Neoplasms/diagnosis ; Skin Neoplasms/genetics ; Skin Neoplasms/therapy
    Language English
    Publishing date 2023-08-15
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1228563
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: New monoclonal antibodies that recognize an unglycosylated, conserved, extracellular region of CD44 in vitro and in vivo, and can block tumorigenesis.

    Lusche, Daniel F / Wessels, Deborah J / Reis, Ryan J / Forrest, Cristopher C / Thumann, Alexis R / Soll, David R

    PloS one

    2021  Volume 16, Issue 4, Page(s) e0250175

    Abstract: CD44 is a transmembrane glycoprotein that binds to hyaluronic acid, plays roles in a number of cellular processes and is expressed in a variety of cell types. It is up-regulated in stem cells and cancer. Anti-CD44 monoclonal antibodies affect cell ... ...

    Abstract CD44 is a transmembrane glycoprotein that binds to hyaluronic acid, plays roles in a number of cellular processes and is expressed in a variety of cell types. It is up-regulated in stem cells and cancer. Anti-CD44 monoclonal antibodies affect cell motility and aggregation, and repress tumorigenesis and metastasis. Here we describe four new anti-CD44 monoclonal antibodies originating from B cells of a mouse injected with a plasmid expressing CD44 isoform 12. The four monoclonal antibodies bind to the terminal, extracellular, conserved domain of CD44 isoforms. Based on differences in western blot patterns of cancer cell lysates, the four anti-CD44 mAbs separated into three distinct categories that include P4G9, P3D2, and P3A7, and P3G4. Spot assay analysis with peptides generated in Escherichia coli support the conclusion that the monoclonal antibodies recognize unglycosylated sequences in the N-terminal conserved region between amino acid 21-220, and analyses with a peptide generated in human embryonic kidney 293 cells, demonstrate that these monoclonal antibodies bind to these peptides only after deglycosylation. Western blots with lysates from three cancer cell lines demonstrate that several CD44 isoforms are unglycosylated in the anti-CD44 target regions. The potential utility of the monoclonal antibodies in blocking tumorigenesis was tested by co-injection of cells of the breast cancer-derived tumorigenic cell line MDA-MB-231 with the anti-CD44 monoclonal antibody P3D2 into the mammary fat pads of mice. All five control mice injected with MDA-MB-231 cells plus anti-IgG formed palpable tumors, while only one of the six test mice injected with MDA-MB-231 cells plus P3D2 formed a tiny tumor, while the remaining five were tumor-free, indicating that the four anti-CD44 mAbs may be useful therapeutically.
    MeSH term(s) Antibodies, Monoclonal ; Carcinogenesis/immunology ; HEK293 Cells ; Humans ; Hyaluronan Receptors/immunology ; MCF-7 Cells
    Chemical Substances Antibodies, Monoclonal ; Hyaluronan Receptors
    Language English
    Publishing date 2021-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0250175
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Integrin α-3 ß-1's central role in breast cancer, melanoma and glioblastoma cell aggregation revealed by antibodies with blocking activity.

    Lusche, Daniel F / Klemme, Michael R / Soll, Benjamin A / Reis, Ryan J / Forrest, Cristopher C / Nop, Tiffany S / Wessels, Deborah J / Berger, Brian / Glover, Rebecca / Soll, David R

    mAbs

    2019  Volume 11, Issue 4, Page(s) 691–708

    Abstract: Breast cancer, melanoma and glioblastoma cells undergo cell-mediated aggregation and aggregate coalescence in a transparent 3D Matrigel environment. Cells from normal tissue and non-tumorigenic cell lines do not exhibit these behaviors. Here, 266 ... ...

    Abstract Breast cancer, melanoma and glioblastoma cells undergo cell-mediated aggregation and aggregate coalescence in a transparent 3D Matrigel environment. Cells from normal tissue and non-tumorigenic cell lines do not exhibit these behaviors. Here, 266 monoclonal antibodies (mAbs) demonstrated to interact with a wide variety of membrane, secreted and matrix proteins, have been screened for their capacity to block these tumorigenic cell-specific behaviors in a 3D environment. Remarkably, only six of the 266 tested mAbs exhibited blocking activity, four targeting integrin ß-1, one targeting integrin α-3 and one targeting CD44. Colocalization of integrins ß-1 and α-3 in fixed cells and in live aggregates suggests that the integrin α-3 ß-1 dimer plays a central role in cancer cell aggregation in the 3D environment provided by Matrigel. Our results suggest that blocking by anti-integrin and anti-CD44 mAbs involves interference in cell-cell interactions.
    MeSH term(s) Antibodies, Blocking/metabolism ; Antibodies, Monoclonal/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Adhesion ; Cell Aggregation ; Cell Line, Tumor ; Cell Movement ; Collagen ; Drug Combinations ; Female ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Hyaluronan Receptors/immunology ; Hyaluronan Receptors/metabolism ; Integrin alpha3beta1/immunology ; Integrin alpha3beta1/metabolism ; Laminin ; Melanoma/metabolism ; Melanoma/pathology ; Proteoglycans
    Chemical Substances Antibodies, Blocking ; Antibodies, Monoclonal ; CD44 protein, human ; Drug Combinations ; Hyaluronan Receptors ; Integrin alpha3beta1 ; Laminin ; Proteoglycans ; matrigel (119978-18-6) ; Collagen (9007-34-5)
    Language English
    Publishing date 2019-04-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2537838-7
    ISSN 1942-0870 ; 1942-0862
    ISSN (online) 1942-0870
    ISSN 1942-0862
    DOI 10.1080/19420862.2019.1583987
    Database MEDical Literature Analysis and Retrieval System OnLINE

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