Publications by authors named "Jason E Ekert"

Article Synopsis
  • Tumors that do not respond to immunotherapy create barriers that hinder T-cell effectiveness, so improving T-cell movement into these tumors could enhance treatment success.
  • Advanced in-vitro models can mimic the complex conditions of tumors, making research findings more applicable to real patient scenarios.
  • The study introduced a new scalable microfluidic assay that allows researchers to examine T-cell movement and function in 3D tumor environments, providing insights crucial for developing better cancer immunotherapy strategies.
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The DNA damage response (DDR) is a fundamental readout for evaluating efficacy of cancer therapeutics, many of which target DNA associated processes. Current techniques to evaluate DDR rely on immunostaining for phosphorylated histone H2AX (γH2AX), which is an indicator of DNA double-strand breaks. While γH2AX immunostaining can provide a snapshot of DDR in fixed cell and tissue samples, this method is technically cumbersome due to temporal monitoring of DDR requiring timepoint replicates, extensive assay development efforts for 3D cell culture samples such as organoids, and time-consuming protocols for γH2AX immunostaining and its evaluation.

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Article Synopsis
  • * The workshop aimed to identify opportunities for standardizing MPS and finding pathways for their use in regulatory decision-making, involving representatives from the FDA and 26 global regulatory organizations.
  • * Participants agreed that while developing specific standards for every context may be challenging, creating broadly applicable standards could be a more feasible approach to enhance the acceptance of CIVM/MPS in regulatory frameworks.
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Complex in vitro models (CIVM) offer the potential to improve pharmaceutical clinical drug attrition due to safety and/ or efficacy concerns. For this technology to have an impact, the establishment of robust characterization and qualifi­cation plans constructed around specific contexts of use (COU) is required. This article covers the output from a workshop between the Food and Drug Administration (FDA) and Innovation and Quality Microphysiological Systems (IQ MPS) Affiliate.

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The pharmaceutical industry is continuing to face high research and development (R&D) costs and low overall success rates of clinical compounds during drug development. There is an increasing demand for development and validation of healthy or disease-relevant and physiological human cellular models that can be implemented in early-stage discovery, thereby shifting attrition of future therapeutics to a point in discovery at which the costs are significantly lower. There needs to be a paradigm shift in the early drug discovery phase (which is lengthy and costly), away from simplistic cellular models that show an inability to effectively and efficiently reproduce healthy or human disease-relevant states to steer target and compound selection for safety, pharmacology, and efficacy questions.

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Three-dimensional (3D) cell culture is gaining acceptance in response to the need for cellular models that better mimic physiologic tissues. Spheroids are one such 3D model where clusters of cells will undergo self-assembly to form viable, 3D tumor-like structures. However, to date little is known about how spheroid biology compares to that of the more traditional and widely utilized 2D monolayer cultures.

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Tumor-associated macrophages (TAMs) have been shown to promote tumor progression, and increased TAM infiltration often correlates with poor prognosis. However, questions remain regarding the phenotype of macrophages within the tumor and their role in mAb-dependent cytotoxicity. This study demonstrates that whereas TAMs have protumor properties, they maintain Fc-dependent anti-tumor function.

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Background: Fibrocytes are a population of circulating bone-marrow-derived cells that express surface markers for leukocytes and mesenchymal cells, and are capable of differentiating into myofibroblasts. They have been observed at sites of active fibrosis and increased circulating numbers correlate with mortality in idiopathic pulmonary fibrosis (IPF). Inhibition of chemokine (C-C motif) receptor 2 (CCR2) during experimental models of lung fibrosis reduces lung collagen deposition, as well as reducing lung fibrocyte accumulation.

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We explored the transduction kinetics of HIV-1-derived lentiviral vectors containing the CMV, EF1alpha, or PGK promoter expressing EGFP in fetal rhesus monkey bone marrow-derived mesenchymal stem cells (rhMSC). Studies included the effects of transduction (MOI 0-100) on growth, cell cycle, and differentiation toward an osteogenic lineage. Flow cytometric analysis indicated an approximate 8- to 10-fold greater quantity of EGFP-expressing rhMSC when cells were transduced with the CMV or EF1alpha promoter compared to PGK, although quantitative PCR revealed no differences at the DNA level.

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Maternal nutrition and growth hormone (GH) treatment during early- to mid-pregnancy can each alter the subsequent growth and differentiation of muscle in progeny. We have investigated the effects of varying maternal nutrition and maternal treatment with porcine (p) GH during the second quarter of pregnancy in gilts on semitendinosus muscle cross-sectional area and fibre composition of progeny, and relationships between maternal and progeny measures and progeny muscularity. Fifty-three Large White x Landrace gilts, pregnant to Large White x Duroc boars, were fed either 2.

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Tenofovir has been shown to cross the placenta in quantities sufficient to sustain reductions in viral load in simian immunodeficiency virus (SIV)-infected fetal monkeys. With chronic exposure (30 mg/kg), however, significant bone-related toxicity has been shown in approximately 25% of infants studied. Further investigations were conducted to determine whether the bone-related toxicity observed was initiated during fetal life.

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