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  1. Article ; Online: Effects of anticoagulants and Ficoll on human serum antibody reactivities and functions against Mycobacterium tuberculosis.

    Gadsden, Nicholas J / Liu, Yanyan / Gati, Stephanie / Chen, Tingting / Jenny-Avital, Elizabeth R / Achkar, Jacqueline M

    Tuberculosis (Edinburgh, Scotland)

    2020  Volume 120, Page(s) 101901

    Abstract: The ability to utilize leftover samples containing anticoagulants or Ficoll would provide substantial opportunities for future antibody and biomarker studies. Some anticoagulants might influence antibody reactivity against pathogens, but comprehensive ... ...

    Abstract The ability to utilize leftover samples containing anticoagulants or Ficoll would provide substantial opportunities for future antibody and biomarker studies. Some anticoagulants might influence antibody reactivity against pathogens, but comprehensive studies investigating effects in the context of TB are lacking. We enrolled 24 individuals with and without history of M. tuberculosis and/or HIV-infection and investigated TB antibody reactivities, function, and other host protein biomarkers in simultaneously obtained serum and plasma from serum separation, EDTA, heparin, acid citrate dextrose (ACD), or mononuclear cell preparation (CPT™) tubes which contain heparin and Ficoll. Antibody isotype reactivities to two mycobacterial antigens, as well as phagocytosis of M. tuberculosis, correlated strongly and significantly between serum and plasma, irrespective of type of anticoagulant or Ficoll present (r ≥ 0.85, p < 0.0001). However, the presence of ACD resulted in slightly lower values than those obtained with serum in both indirect (antibody reactivities to mycobacterial antigens) and Sandwich ELISAs (soluble CD14 measurements). Our data demonstrate that leftover plasma, regardless of containing anticoagulants or Ficoll, can be used in TB antibody or other host protein biomarker studies but suggest the value of a correction factor when using ACD plasma interchangeably with serum in antibody binding studies.
    MeSH term(s) Adult ; Aged ; Antibodies, Bacterial/blood ; Antibodies, Bacterial/drug effects ; Antibody Specificity/drug effects ; Anticoagulants/pharmacology ; Antigens, Bacterial/immunology ; Binding Sites, Antibody ; Blood Specimen Collection ; Citric Acid/pharmacology ; Coinfection ; Edetic Acid/pharmacology ; Female ; Ficoll/pharmacology ; Glucose/analogs & derivatives ; Glucose/pharmacology ; HIV Infections/blood ; HIV Infections/immunology ; HIV Infections/virology ; Heparin/pharmacology ; Humans ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/microbiology ; Male ; Middle Aged ; Mycobacterium tuberculosis/immunology ; Phagocytosis/drug effects ; THP-1 Cells ; Tuberculosis/blood ; Tuberculosis/immunology ; Tuberculosis/microbiology
    Chemical Substances Antibodies, Bacterial ; Anticoagulants ; Antigens, Bacterial ; acid citrate dextrose (13838-07-8) ; Ficoll (25702-74-3) ; Citric Acid (2968PHW8QP) ; Heparin (9005-49-6) ; Edetic Acid (9G34HU7RV0) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2020-01-10
    Publishing country Scotland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2046804-0
    ISSN 1873-281X ; 1472-9792
    ISSN (online) 1873-281X
    ISSN 1472-9792
    DOI 10.1016/j.tube.2020.101901
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Palbociclib Renders Human Papilloma Virus-Negative Head and Neck Squamous Cell Carcinoma Vulnerable to the Senolytic Agent Navitoclax.

    Gadsden, Nicholas J / Fulcher, Cory D / Li, Daniel / Shrivastava, Nitisha / Thomas, Carlos / Segall, Jeffrey E / Prystowsky, Michael B / Schlecht, Nicolas F / Gavathiotis, Evripidis / Ow, Thomas J

    Molecular cancer research : MCR

    2021  Volume 19, Issue 5, Page(s) 862–873

    Abstract: We demonstrate that inhibition of cyclin-dependent kinases 4/6 (CDK4/6) leads to senescence in human papillomavirus (HPV)-negative (-) head and neck squamous cell carcinoma (HNSCC), but not in HPV-positive (+) HNSCC. The BCL-2 family inhibitor, ... ...

    Abstract We demonstrate that inhibition of cyclin-dependent kinases 4/6 (CDK4/6) leads to senescence in human papillomavirus (HPV)-negative (-) head and neck squamous cell carcinoma (HNSCC), but not in HPV-positive (+) HNSCC. The BCL-2 family inhibitor, navitoclax, has been shown to eliminate senescent cells effectively. We evaluated the efficacy of combining palbociclib and navitoclax in HPV
    MeSH term(s) Aniline Compounds/administration & dosage ; Aniline Compounds/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Cell Line, Tumor ; Drug Synergism ; Head and Neck Neoplasms/drug therapy ; Humans ; Piperazines/administration & dosage ; Piperazines/pharmacology ; Pyridines/administration & dosage ; Pyridines/pharmacology ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Sulfonamides/administration & dosage ; Sulfonamides/pharmacology
    Chemical Substances Aniline Compounds ; Piperazines ; Pyridines ; Sulfonamides ; palbociclib (G9ZF61LE7G) ; navitoclax (XKJ5VVK2WD)
    Language English
    Publishing date 2021-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-20-0915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Establishment of a diverse head and neck squamous cancer cell bank using conditional reprogramming culture methods.

    Li, Daniel / Thomas, Carlos / Shrivastava, Nitisha / Gersten, Adam / Gadsden, Nicholas / Schlecht, Nicolas / Kawachi, Nicole / Schiff, Bradley A / Smith, Richard V / Rosenblatt, Gregory / Augustine, Stelby / Gavathiotis, Evripidis / Burk, Robert / Prystowsky, Michael B / Guha, Chandan / Mehta, Vikas / Ow, Thomas J

    Journal of medical virology

    2022  Volume 95, Issue 2, Page(s) e28388

    Abstract: Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional ... ...

    Abstract Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional reprogramming" (CR) method, which utilizes a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Sixteen CR cultures were successfully generated from 19 consecutively enrolled ethnically and racially diverse patients with HNSCC at a tertiary care center in the Bronx, NY. Of the 16 CR cultures, 9/16 were derived from the oral cavity, 4/16 were derived from the oropharynx, and 3/16 were from laryngeal carcinomas. Short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue DNA. All CR cultures expressed ΔNp63 and cytokeratin 5/6, which are markers of squamous identity. Human papillomavirus (HPV) testing was assessed utilizing clinical p16 staining on primary tumors, reverse transcription polymerase chain reaction (RT-PCR) of HPV16/18-specific viral oncogenes E6 and E7 in RNA extracted from tumor samples, and HPV DNA sequencing. Three of four oropharyngeal tumors were p16 and HPV-positive and maintained HPV in culture. CR cultures were able to establish three-dimensional spheroid and murine flank and orthotopic tongue models. CR methods can be readily applied to all HNSCC tumors regardless of patient characteristics, disease site, and molecular background, providing a translational research model that properly includes patient and tumor diversity.
    MeSH term(s) Animals ; Humans ; Mice ; Carcinoma, Squamous Cell/pathology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; DNA, Viral/genetics ; Head and Neck Neoplasms ; Human papillomavirus 16/genetics ; Human papillomavirus 18/genetics ; Papillomavirus Infections ; Squamous Cell Carcinoma of Head and Neck ; Biological Specimen Banks
    Chemical Substances Cyclin-Dependent Kinase Inhibitor p16 ; DNA, Viral
    Language English
    Publishing date 2022-12-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 752392-0
    ISSN 1096-9071 ; 0146-6615
    ISSN (online) 1096-9071
    ISSN 0146-6615
    DOI 10.1002/jmv.28388
    Database MEDical Literature Analysis and Retrieval System OnLINE

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