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  1. Article ; Online: Inhibition of IL-25/IL-17RA improves immune-related adverse events of checkpoint inhibitors and reveals antitumor activity.

    Hu, Xizi / Bukhari, Shoiab M / Tymm, Carly / Adam, Kieran / Lerrer, Shalom / Henick, Brian S / Winchester, Robert J / Mor, Adam

    Journal for immunotherapy of cancer

    2024  Volume 12, Issue 3

    Abstract: Background: Immune checkpoint inhibitors (ICIs) have improved outcomes and extended patient survival in several tumor types. However, ICIs often induce immune-related adverse events (irAEs) that warrant therapy cessation, thereby limiting the overall ... ...

    Abstract Background: Immune checkpoint inhibitors (ICIs) have improved outcomes and extended patient survival in several tumor types. However, ICIs often induce immune-related adverse events (irAEs) that warrant therapy cessation, thereby limiting the overall effectiveness of this class of therapeutic agents. Currently, available therapies used to treat irAEs might also blunt the antitumor activity of the ICI themselves. Therefore, there is an urgent need to identify treatments that have the potential to be administered alongside ICI to optimize their use.
    Methods: Using a translationally relevant murine model of anti-PD-1 and anti-CTLA-4 antibodies-induced irAEs, we compared the safety and efficacy of prednisolone, anti-IL-6, anti-TNFɑ, anti-IL-25 (IL-17E), and anti-IL-17RA (the receptor for IL-25) administration to prevent irAEs and to reduce tumor size.
    Results: While all interventions were adequate to inhibit the onset of irAEs pneumonitis and hepatitis, treatment with anti-IL-25 or anti-IL-17RA antibodies also exerted additional antitumor activity. Mechanistically, IL-25/IL-17RA blockade reduced the number of organ-infiltrating lymphocytes.
    Conclusion: These findings suggest that IL-25/IL-17RA may serve as an additional target when treating ICI-responsive tumors, allowing for better tumor control while suppressing immune-related toxicities.
    MeSH term(s) Humans ; Animals ; Mice ; Ipilimumab/therapeutic use ; Neoplasms ; Immunotherapy/adverse effects ; Tumor Necrosis Factor-alpha
    Chemical Substances Ipilimumab ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2024-03-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-008482
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Scalable COVID-19 Detection Enabled by Lab-on-Chip Biosensors.

    Tymm, Carly / Zhou, Junhu / Tadimety, Amogha / Burklund, Alison / Zhang, John X J

    Cellular and molecular bioengineering

    2020  Volume 13, Issue 4, Page(s) 313–329

    Abstract: Introduction: The emergence of a novel coronavirus, SARS-CoV-2, has highlighted the need for rapid, accurate, and point-of-care diagnostic testing. As of now, there is not enough testing capacity in the world to meet the stated testing targets, which ... ...

    Abstract Introduction: The emergence of a novel coronavirus, SARS-CoV-2, has highlighted the need for rapid, accurate, and point-of-care diagnostic testing. As of now, there is not enough testing capacity in the world to meet the stated testing targets, which are expected to skyrocket globally for broader testing during reopening.
    Aim: This review focuses on the development of lab-on-chip biosensing platforms for diagnosis of COVID-19 infection.
    Results: We discuss advantages of utilizing lab-on-chip technologies in response to the current global pandemic, including their potential for low-cost, rapid sample-to-answer processing times, and ease of integration into a range of healthcare settings. We then highlight the development of magnetic, colorimetric, plasmonic, electrical, and lateral flow-based lab-on-chip technologies for the detection of SARS-CoV-2, in addition to other viruses. We focus on rapid, point-of-care technologies that can be deployed at scale, as such devices could be promising alternatives to the current gold standard of reverse transcription-polymerase chain reaction (RT-PCR) diagnostic testing.
    Conclusion: This review is intended to provide an overview of the current state-of-the-field and serve as a resource for innovative development of new lab-on-chip assays for COVID-19 detection.
    Keywords covid19
    Language English
    Publishing date 2020-08-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2416037-4
    ISSN 1865-5033 ; 1865-5025
    ISSN (online) 1865-5033
    ISSN 1865-5025
    DOI 10.1007/s12195-020-00642-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Hippo Signaling Pathway Regulates Cancer Cell-Intrinsic MHC-II Expression.

    Zeng, Zexian / Gu, Shengqing Stan / Ouardaoui, Nofal / Tymm, Carly / Yang, Lin / Wong, Cheryl J / Li, Dian / Zhang, Wubing / Wang, Xiaoqing / Weirather, Jason L / Rodig, Scott J / Hodi, F Stephen / Brown, Myles / Liu, X Shirley

    Cancer immunology research

    2022  Volume 10, Issue 12, Page(s) 1559–1569

    Abstract: MHC-II is known to be mainly expressed on the surface of antigen-presenting cells. Evidence suggests MHC-II is also expressed by cancer cells and may be associated with better immunotherapy responses. However, the role and regulation of MHC-II in cancer ... ...

    Abstract MHC-II is known to be mainly expressed on the surface of antigen-presenting cells. Evidence suggests MHC-II is also expressed by cancer cells and may be associated with better immunotherapy responses. However, the role and regulation of MHC-II in cancer cells remain unclear. In this study, we leveraged data mining and experimental validation to elucidate the regulation of MHC-II in cancer cells and its role in modulating the response to immunotherapy. We collated an extensive collection of omics data to examine cancer cell-intrinsic MHC-II expression and its association with immunotherapy outcomes. We then tested the functional relevance of cancer cell-intrinsic MHC-II expression using a syngeneic transplantation model. Finally, we performed data mining to identify pathways potentially involved in the regulation of MHC-II expression, and experimentally validated candidate regulators. Analyses of preimmunotherapy clinical samples in the CheckMate 064 trial revealed that cancer cell-intrinsic MHC-II protein was positively correlated with more favorable immunotherapy outcomes. Comprehensive meta-analyses of multiomics data from an exhaustive collection of data revealed that MHC-II is heterogeneously expressed in various solid tumors, and its expression is particularly high in melanoma. Using a syngeneic transplantation model, we further established that melanoma cells with high MHC-II responded better to anti-PD-1 treatment. Data mining followed by experimental validation revealed the Hippo signaling pathway as a potential regulator of melanoma MHC-II expression. In summary, we identified the Hippo signaling pathway as a novel regulator of cancer cell-intrinsic MHC-II expression. These findings suggest modulation of MHC-II in melanoma could potentially improve immunotherapy response.
    MeSH term(s) Humans ; Hippo Signaling Pathway ; Melanoma/drug therapy ; Immunotherapy ; Antigen-Presenting Cells/metabolism
    Language English
    Publishing date 2022-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-22-0227
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Scalable COVID-19 Detection Enabled by Lab-on-Chip Biosensors

    Tymm, Carly / Zhou, Junhu / Tadimety, Amogha / Burklund, Alison / Zhang, John X. J.

    Cellular and Molecular Bioengineering

    2020  Volume 13, Issue 4, Page(s) 313–329

    Keywords General Biochemistry, Genetics and Molecular Biology ; Modelling and Simulation ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2416037-4
    ISSN 1865-5033 ; 1865-5025
    ISSN (online) 1865-5033
    ISSN 1865-5025
    DOI 10.1007/s12195-020-00642-z
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.

    Werlang, Caroline A / Chen, Wesley G / Aoki, Kazuhiro / Wheeler, Kelsey M / Tymm, Carly / Mileti, Cassidy J / Burgos, Ana C / Kim, Kris / Tiemeyer, Michael / Ribbeck, Katharina

    Nature microbiology

    2021  Volume 6, Issue 5, Page(s) 574–583

    Abstract: Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic ... ...

    Abstract Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic colonization
    MeSH term(s) Dental Caries/genetics ; Dental Caries/metabolism ; Dental Caries/microbiology ; Host-Pathogen Interactions ; Humans ; Mucin-5B/chemistry ; Mucin-5B/genetics ; Mucin-5B/metabolism ; Polysaccharides/chemistry ; Polysaccharides/metabolism ; Quorum Sensing ; Saliva/metabolism ; Saliva/microbiology ; Streptococcus mutans/genetics ; Streptococcus mutans/pathogenicity ; Streptococcus mutans/physiology ; Transformation, Bacterial ; Virulence
    Chemical Substances MUC5B protein, human ; Mucin-5B ; Polysaccharides
    Language English
    Publishing date 2021-03-18
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-021-00876-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Scalable COVID-19 Detection Enabled by Lab-on-Chip Biosensors

    Tymm, Carly / Zhou, Junhu / Tadimety, Amogha / Burklund, Alison / Zhang, John X J

    Cell Mol Bioeng

    Abstract: Introduction: The emergence of a novel coronavirus, SARS-CoV-2, has highlighted the need for rapid, accurate, and point-of-care diagnostic testing. As of now, there is not enough testing capacity in the world to meet the stated testing targets, which are ...

    Abstract Introduction: The emergence of a novel coronavirus, SARS-CoV-2, has highlighted the need for rapid, accurate, and point-of-care diagnostic testing. As of now, there is not enough testing capacity in the world to meet the stated testing targets, which are expected to skyrocket globally for broader testing during reopening. Aim: This review focuses on the development of lab-on-chip biosensing platforms for diagnosis of COVID-19 infection. Results: We discuss advantages of utilizing lab-on-chip technologies in response to the current global pandemic, including their potential for low-cost, rapid sample-to-answer processing times, and ease of integration into a range of healthcare settings. We then highlight the development of magnetic, colorimetric, plasmonic, electrical, and lateral flow-based lab-on-chip technologies for the detection of SARS-CoV-2, in addition to other viruses. We focus on rapid, point-of-care technologies that can be deployed at scale, as such devices could be promising alternatives to the current gold standard of reverse transcription-polymerase chain reaction (RT-PCR) diagnostic testing. Conclusion: This review is intended to provide an overview of the current state-of-the-field and serve as a resource for innovative development of new lab-on-chip assays for COVID-19 detection.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #714370
    Database COVID19

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