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  1. Book: High content screening

    Johnston, Paul A. / Trask, Oscar J.

    a powerful approach to systems cell biology and phenotypic drug discovery

    (Methods in molecular biology ; 1683 ; Springer protocols ; Chemistry)

    2018  

    Author's details edited by Paul A. Johnston (Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA), Oscar J. Trask (Bahama Bio, LLC, Bahama, NC, USA; Perkin Elmer Inc., Waltham, MA, USA)
    Series title Methods in molecular biology ; 1683
    Springer protocols
    Chemistry
    Collection
    Keywords measure cells ; cell phenotypes ; HCS data ; data handling ; HCS/HCA/HCI
    Subject code 570
    Language English
    Size xiii, 397 Seiten, Illustrationen, 25.4 cm x 17.8 cm
    Edition Second edition
    Publisher Humana Press
    Publishing place New York, NY
    Publishing country United States
    Document type Book
    HBZ-ID HT019509018
    ISBN 978-1-4939-7355-2 ; 1-4939-7355-X ; 9781493973576 ; 1493973576
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: WITHDRAWN: Detection and impact of hypoxic regions in multicellular tumor spheroid cultures formed by head and neck squamous cell carcinoma cells lines.

    Close, David A / Johnston, Paul A

    SLAS discovery : advancing life sciences R & D

    2023  Volume 29, Issue 1F, Page(s) 130

    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Retraction of Publication
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1016/j.slasd.2023.12.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Detection and impact of hypoxic regions in multicellular tumor spheroid cultures formed by head and neck squamous cell carcinoma cells lines.

    Close, David A / Johnston, Paul A

    SLAS discovery : advancing life sciences R & D

    2021  Volume 27, Issue 1, Page(s) 39–54

    Abstract: In solid tumors like head and neck cancer (HNC), chronic and acute hypoxia have serious adverse clinical consequences including poorer overall patient prognosis, enhanced metastasis, increased genomic instability, and resistance to radiation-, chemo-, or ...

    Abstract In solid tumors like head and neck cancer (HNC), chronic and acute hypoxia have serious adverse clinical consequences including poorer overall patient prognosis, enhanced metastasis, increased genomic instability, and resistance to radiation-, chemo-, or immuno-therapies. However, cells in the two-dimensional monolayer cultures typically used for cancer drug discovery experience 20%-21% O
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/genetics ; Humans ; Hypoxia/drug therapy ; Spheroids, Cellular ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/genetics ; Tumor Microenvironment
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2021-10-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1016/j.slasd.2021.10.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: High-Content Imaging and Informatics: A Joint Special Issue with Society for Biomolecular Imaging and Informatics and SLAS.

    Fennell, Myles / Johnston, Paul A

    SLAS discovery : advancing life sciences R & D

    2020  Volume 25, Issue 7, Page(s) 668–671

    MeSH term(s) Computational Biology/trends ; Humans ; Informatics/trends ; Molecular Imaging/trends
    Keywords covid19
    Language English
    Publishing date 2020-07-13
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/2472555220937652
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Phenotypic characterization of the Hordeum bulbosum derived leaf rust resistance genes Rph22 and Rph26 in barley

    Yu, Xiaohui / Casonato, Seona / Jones, Eirian / Butler, Ruth C. / Johnston, Paul A. / Chng, Soonie

    Journal of applied microbiology. 2022 Sept., v. 133, no. 3

    2022  

    Abstract: AIMS: Two introgression lines (ILs), 182Q20 and 200A12, which had chromosomal segments introgressed from Hordeum bulbosum in H. vulgare backgrounds, were identified to show seedling resistance against Puccinia hordei, possibly attributed to two ... ...

    Abstract AIMS: Two introgression lines (ILs), 182Q20 and 200A12, which had chromosomal segments introgressed from Hordeum bulbosum in H. vulgare backgrounds, were identified to show seedling resistance against Puccinia hordei, possibly attributed to two resistance genes, Rph22 and Rph26, respectively. This study characterized the phenotypic responses of the two genes against P. hordei over different plant development stages. METHODS AND RESULTS: Using visual and fungal biomass assessments, responses of ILs 182Q20, 200A12 and four other barley cultivars against P. hordei were determined at seedling, tillering, stem elongation and booting stages. Plants carrying either Rph22 or Rph26 were found to confer gradually increasing resistance over the course of different development stages, with partial resistant phenotypes (i.e. prolonged rust latency periods, reduced uredinia numbers but with susceptible infection types) observed at seedling stage and adult plant resistance (APR) at booting stage. A definitive switch between the two types of resistance occurred at tillering stage. CONCLUSIONS: Rph22 and Rph26 derived from H. bulbosum were well characterized and had typical APR phenotypes against P. hordei. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides important insights on the effectiveness and expression of Rph22 and Rph26 against P. hordei during plant development and underpins future barley breeding programmes using non‐host as a genetic resource for leaf rust management.
    Keywords Hordeum bulbosum ; Puccinia hordei ; barley ; cultivars ; fungal biomass ; introgression ; leaf rust ; mature plants ; microbiology ; phenotype ; seedlings ; stem elongation ; tillering
    Language English
    Dates of publication 2022-09
    Size p. 2083-2094.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 1358023-1
    ISSN 1365-2672 ; 1364-5072
    ISSN (online) 1365-2672
    ISSN 1364-5072
    DOI 10.1111/jam.15710
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Phenotypic characterization of the Hordeum bulbosum derived leaf rust resistance genes Rph22 and Rph26 in barley.

    Yu, Xiaohui / Casonato, Seona / Jones, Eirian / Butler, Ruth C / Johnston, Paul A / Chng, Soonie

    Journal of applied microbiology

    2022  Volume 133, Issue 3, Page(s) 2083–2094

    Abstract: Aims: Two introgression lines (ILs), 182Q20 and 200A12, which had chromosomal segments introgressed from Hordeum bulbosum in H. vulgare backgrounds, were identified to show seedling resistance against Puccinia hordei, possibly attributed to two ... ...

    Abstract Aims: Two introgression lines (ILs), 182Q20 and 200A12, which had chromosomal segments introgressed from Hordeum bulbosum in H. vulgare backgrounds, were identified to show seedling resistance against Puccinia hordei, possibly attributed to two resistance genes, Rph22 and Rph26, respectively. This study characterized the phenotypic responses of the two genes against P. hordei over different plant development stages.
    Methods and results: Using visual and fungal biomass assessments, responses of ILs 182Q20, 200A12 and four other barley cultivars against P. hordei were determined at seedling, tillering, stem elongation and booting stages. Plants carrying either Rph22 or Rph26 were found to confer gradually increasing resistance over the course of different development stages, with partial resistant phenotypes (i.e. prolonged rust latency periods, reduced uredinia numbers but with susceptible infection types) observed at seedling stage and adult plant resistance (APR) at booting stage. A definitive switch between the two types of resistance occurred at tillering stage.
    Conclusions: Rph22 and Rph26 derived from H. bulbosum were well characterized and had typical APR phenotypes against P. hordei.
    Significance and impact of the study: This study provides important insights on the effectiveness and expression of Rph22 and Rph26 against P. hordei during plant development and underpins future barley breeding programmes using non-host as a genetic resource for leaf rust management.
    MeSH term(s) Basidiomycota/genetics ; Chromosome Mapping ; Disease Resistance/genetics ; Hordeum/genetics ; Hordeum/microbiology ; Phenotype ; Plant Breeding ; Plant Diseases/genetics ; Plant Diseases/microbiology
    Language English
    Publishing date 2022-07-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 1358023-1
    ISSN 1365-2672 ; 1364-5072
    ISSN (online) 1365-2672
    ISSN 1364-5072
    DOI 10.1111/jam.15710
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The production of 3D tumor spheroids for cancer drug discovery.

    Sant, Shilpa / Johnston, Paul A

    Drug discovery today. Technologies

    2017  Volume 23, Page(s) 27–36

    Abstract: New cancer drug approval rates are ≤5% despite significant investments in cancer research, drug discovery and development. One strategy to improve the rate of success of new cancer drugs transitioning into the clinic would be to more closely align the ... ...

    Abstract New cancer drug approval rates are ≤5% despite significant investments in cancer research, drug discovery and development. One strategy to improve the rate of success of new cancer drugs transitioning into the clinic would be to more closely align the cellular models used in the early lead discovery with pre-clinical animal models and patient tumors. For solid tumors, this would mandate the development and implementation of three dimensional (3D) in vitro tumor models that more accurately recapitulate human solid tumor architecture and biology. Recent advances in tissue engineering and regenerative medicine have provided new techniques for 3D spheroid generation and a variety of in vitro 3D cancer models are being explored for cancer drug discovery. Although homogeneous assay methods and high content imaging approaches to assess tumor spheroid morphology, growth and viability have been developed, the implementation of 3D models in HTS remains challenging due to reasons that we discuss in this review. Perhaps the biggest obstacle to achieve acceptable HTS assay performance metrics occurs in 3D tumor models that produce spheroids with highly variable morphologies and/or sizes. We highlight two methods that produce uniform size-controlled 3D multicellular tumor spheroids that are compatible with cancer drug research and HTS; tumor spheroids formed in ultra-low attachment microplates, or in polyethylene glycol dimethacrylate hydrogel microwell arrays.
    Language English
    Publishing date 2017-03
    Publishing country England
    Document type Journal Article ; Review
    ISSN 1740-6749
    ISSN (online) 1740-6749
    DOI 10.1016/j.ddtec.2017.03.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Erratum to: High Content Screening.

    Johnston, Paul A / Trask, Oscar J

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

    2017  Volume 1683, Page(s) E1

    Language English
    Publishing date 2017-12-18
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7357-6_23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Maximizing the Value of Cancer Drug Screening in Multicellular Tumor Spheroid Cultures: A Case Study in Five Head and Neck Squamous Cell Carcinoma Cell Lines.

    Kochanek, Stanton J / Close, David A / Camarco, Daniel P / Johnston, Paul A

    SLAS discovery : advancing life sciences R & D

    2020  Volume 25, Issue 4, Page(s) 329–349

    Abstract: With approval rates <5% and the probability of success in oncology clinical trials of 3.4%, more physiologically relevant in vitro three-dimensional models are being deployed during lead generation to select better drug candidates for solid tumors. ... ...

    Abstract With approval rates <5% and the probability of success in oncology clinical trials of 3.4%, more physiologically relevant in vitro three-dimensional models are being deployed during lead generation to select better drug candidates for solid tumors. Multicellular tumor spheroids (MCTSs) resemble avascular tumor nodules, micrometastases, or the intervascular regions of large solid tumors with respect to morphology, cell-cell and cell-extracellular matrix contacts, and volume growth kinetics. MCTSs develop gradients of nutrient and oxygen concentration resulting in diverse microenvironments with differential proliferation and drug distribution zones. We produced head and neck squamous cell carcinoma (HNSCC) MCTSs in 384-well U-bottom ultra-low-attachment microtiter plates and used metabolic viability and imaging methods to measure morphologies, growth phenotypes and the effects of 19 anticancer drugs. We showed that cell viability measurements underestimated the impact of drug exposure in HNSCC MCTS cultures, but that incorporating morphology and dead-cell staining analyses increased the number of drugs judged to have substantially impacted MCTS cultures. A cumulative multiparameter drug impact score enabled us to stratify MCTS drug responses into high-, intermediate-, and low-impact tiers, and maximized the value of these more physiologically relevant tumor cultures. It is conceivable that the viable cells present in MCTS cultures after drug exposure arise from drug-resistant populations that could represent a source of drug failure and recurrence. Long-term monitoring of treated MCTS cultures could provide a strategy to determine whether these drug-resistant populations represent circumstances where tumor growth is delayed and may ultimately give rise to regrowth.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Screening Assays, Antitumor ; Early Detection of Cancer ; Humans ; Spheroids, Cellular/drug effects ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/pathology ; Tumor Microenvironment/drug effects
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2020-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/2472555219896999
    Database MEDical Literature Analysis and Retrieval System OnLINE

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