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  1. Article ; Online: Characterization of Plasmacytoid Dendritic Cells, Microbial Sequences, and Identification of a Candidate Public T-Cell Clone in Kikuchi-Fujimoto Disease.

    Nelson, Nya D / Meng, Wenzhao / Rosenfeld, Aaron M / Bullman, Susan / Sekhar Pedamallu, Chandra / Nomburg, Jason L / Wertheim, Gerald B / Paessler, Michele E / Pinkus, Geraldine / Hornick, Jason L / Meyerson, Matthew / Luning Prak, Eline T / Pillai, Vinodh

    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society

    2021  Volume 24, Issue 3, Page(s) 193–205

    Abstract: Objectives: Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenitis of unclear etiology. We aimed to further characterize this disease in pediatric patients, including evaluation of the CD123 immunohistochemical (IHC) staining and investigation ... ...

    Abstract Objectives: Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenitis of unclear etiology. We aimed to further characterize this disease in pediatric patients, including evaluation of the CD123 immunohistochemical (IHC) staining and investigation of potential immunologic and infectious causes.
    Methods: Seventeen KFD cases and 12 controls were retrospectively identified, and the histologic and clinical features were evaluated. CD123 IHC staining was quantified by digital image analysis. Next generation sequencing was employed for comparative microbial analysis via RNAseq (5 KFD cases) and to evaluate the immune repertoire (9 KFD cases).
    Results: In cases of lymphadenitis with necrosis, >0.85% CD123+ cells by IHC was found to be six times more likely in cases with a final diagnosis of KFD (sensitivity 75%, specificity 87.5%). RNAseq based comparative microbial analysis did not detect novel or known pathogen sequences in KFD. A shared complementarity determining region 3 (CDR3) sequence and use of the same T-cell receptor beta variable region family was identified in KFD LNs but not controls, and was not identified in available databases.
    Conclusions: Digital quantification of CD123 IHC can distinguish KFD from other necrotizing lymphadenitides. The presence of a unique shared CDR3 sequence suggests that a shared antigen underlies KFD pathogenesis.
    MeSH term(s) Adolescent ; Biomarkers/analysis ; Child ; Child, Preschool ; Clone Cells ; Complementarity Determining Regions/immunology ; Dendritic Cells/immunology ; Diagnosis, Differential ; Female ; Histiocytic Necrotizing Lymphadenitis/diagnosis ; Histiocytic Necrotizing Lymphadenitis/immunology ; Humans ; Interleukin-3 Receptor alpha Subunit/analysis ; Interleukin-3 Receptor alpha Subunit/immunology ; Male ; T-Lymphocytes/immunology
    Chemical Substances Biomarkers ; Complementarity Determining Regions ; IL3RA protein, human ; Interleukin-3 Receptor alpha Subunit
    Language English
    Publishing date 2021-02-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1463498-3
    ISSN 1615-5742 ; 1093-5266
    ISSN (online) 1615-5742
    ISSN 1093-5266
    DOI 10.1177/1093526620987961
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Rapid Intraoperative Molecular Characterization of Glioma.

    Shankar, Ganesh M / Francis, Joshua M / Rinne, Mikael L / Ramkissoon, Shakti H / Huang, Franklin W / Venteicher, Andrew S / Akama-Garren, Elliot H / Kang, Yun Jee / Lelic, Nina / Kim, James C / Brown, Loreal E / Charbonneau, Sarah K / Golby, Alexandra J / Sekhar Pedamallu, Chandra / Hoang, Mai P / Sullivan, Ryan J / Cherniack, Andrew D / Garraway, Levi A / Stemmer-Rachamimov, Anat /
    Reardon, David A / Wen, Patrick Y / Brastianos, Priscilla K / Curry, William T / Barker, Fred G / Hahn, William C / Nahed, Brian V / Ligon, Keith L / Louis, David N / Cahill, Daniel P / Meyerson, Matthew

    JAMA oncology

    2015  Volume 1, Issue 5, Page(s) 662–667

    Abstract: Importance: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low- ... ...

    Abstract Importance: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1).
    Observations: This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%-99%) and 100% specificity (95% CI, 95%-100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe.
    Conclusions and relevance: The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations.
    MeSH term(s) Biomarkers, Tumor/genetics ; Brain Neoplasms/enzymology ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Brain Neoplasms/surgery ; Female ; Frozen Sections ; Glioma/enzymology ; Glioma/genetics ; Glioma/pathology ; Glioma/surgery ; Humans ; Immunohistochemistry ; Intraoperative Period ; Isocitrate Dehydrogenase/genetics ; Magnetic Resonance Imaging ; Male ; Molecular Diagnostic Techniques ; Neoplasm Grading ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; Promoter Regions, Genetic ; Telomerase/genetics ; Time Factors ; Tissue Fixation
    Chemical Substances Biomarkers, Tumor ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.) ; TERT protein, human (EC 2.7.7.49) ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2015-07-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2015.0917
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients

    van de Wetering, Marc / Francies, Hayley E / Francis, Joshua M / Bounova, Gergana / Iorio, Francesco / Pronk, Apollo / van Houdt, Winan / van Gorp, Joost / Taylor-Weiner, Amaro / Kester, Lennart / McLaren-Douglas, Anne / Blokker, Joyce / Jaksani, Sridevi / Bartfeld, Sina / Volckman, Richard / van Sluis, Peter / Li, Vivian S.W / Seepo, Sara / Sekhar Pedamallu, Chandra /
    Cibulskis, Kristian / Carter, Scott L / McKenna, Aaron / Lawrence, Michael S / Lichtenstein, Lee / Stewart, Chip / Koster, Jan / Versteeg, Rogier / van Oudenaarden, Alexander / Saez-Rodriguez, Julio / Vries, Robert G.J / Getz, Gad / Wessels, Lodewyk / Stratton, Michael R / McDermott, Ultan / Meyerson, Matthew / Garnett, Mathew J / Clevers, Hans

    Cell. 2015 May 07, v. 161

    2015  

    Abstract: In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. ...

    Abstract In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the “living biobank” agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design.[Display omitted]
    Keywords colorectal neoplasms ; complement ; drugs ; epithelium ; gene expression ; mutation ; patients ; secretion ; stem cells ; therapeutics
    Language English
    Dates of publication 2015-0507
    Size p. 933-945.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2015.03.053
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Prospective derivation of a living organoid biobank of colorectal cancer patients.

    van de Wetering, Marc / Francies, Hayley E / Francis, Joshua M / Bounova, Gergana / Iorio, Francesco / Pronk, Apollo / van Houdt, Winan / van Gorp, Joost / Taylor-Weiner, Amaro / Kester, Lennart / McLaren-Douglas, Anne / Blokker, Joyce / Jaksani, Sridevi / Bartfeld, Sina / Volckman, Richard / van Sluis, Peter / Li, Vivian S W / Seepo, Sara / Sekhar Pedamallu, Chandra /
    Cibulskis, Kristian / Carter, Scott L / McKenna, Aaron / Lawrence, Michael S / Lichtenstein, Lee / Stewart, Chip / Koster, Jan / Versteeg, Rogier / van Oudenaarden, Alexander / Saez-Rodriguez, Julio / Vries, Robert G J / Getz, Gad / Wessels, Lodewyk / Stratton, Michael R / McDermott, Ultan / Meyerson, Matthew / Garnett, Mathew J / Clevers, Hans

    Cell

    2015  Volume 161, Issue 4, Page(s) 933–945

    Abstract: In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. ...

    Abstract In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the "living biobank" agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design. PAPERCLIP.
    MeSH term(s) Biological Specimen Banks ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; DNA-Binding Proteins/metabolism ; Drug Screening Assays, Antitumor/methods ; Humans ; Oncogene Proteins/metabolism ; Organ Culture Techniques ; Organoids/drug effects ; Precision Medicine
    Chemical Substances DNA-Binding Proteins ; Oncogene Proteins ; RNF43 protein, human (EC 2.3.2.27)
    Language English
    Publishing date 2015-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2015.03.053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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