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Mechanistic Model of Tumor Response to Immunotherapy
Published in Vittorio Cristini, Eugene J. Koay, Zhihui Wang, An Introduction to Physical Oncology, 2017
Geoffrey V. Martin, Eman Simbawa
Similar to modeling vaccine strategies, systems of ODEs can be used to model systemic immune activating agents. One example of this strategy was an investigation by de Pillis et al. that studied the role of interleukin-21 (IL-21) as an immune stimulating agent for anticancer therapy [340]. IL-21 has been found to exhibit antitumor effects by increasing immune cell–mediated killing of tumor cells, inducing lasting antitumor immune cell memory, and reducing angiogenic and metastases in various tumors [341,342]. One important proposed mechanism for IL-21 efficacy is the transition from an innate natural killer (NK) cell response to a more effective and specific cytotoxic T-cell (CD8+) antitumor response. To model these interactions, de Pillis et al. used six ODEs representing the IL-21 concentration in blood, population dynamics of NK cells in the spleen, population dynamics of specific antitumor CD8+ T cells in the lymph nodes, an element facilitating CD8+ T-cell memory, a cytotoxic protein affecting tumor lysis, and tumor mass. Their model consisted of 21 parameters that were estimated by fitting to experimental murine data or obtaining biologically relevant estimates from the literature. The model was able to predict the growth patterns of multiple types of tumors after receiving a variety of IL-21 dosing schedules, and predicts that different amounts of IL-21 lead to tumor eradication based on tumor mass and tumor antigenic properties. These examples of immunotherapy in cancer show that simple systems of ODEs are able to predict experimental or clinical results, but their full utility in tailoring treatment to individual patients remains a task for future validation.
Dietary ingestion of 2-aminoanthracene (2AA) and the risk for type-1 diabetes (T1D)
Published in Journal of Environmental Science and Health, Part A, 2020
Isaiah Seise, Zachary A. Pilz, Moses Yeboah Kusi, Bethany Bogan, Brittany Jean McHale, Worlanyo E. Gato
Gene transcripts that play a role in inflammatory and diabetic processes were quantified via quantitative RT-PCR. The pro-inflammatory cytokines that were examined included; tumor necrosis alpha (TNF-α), interleukin-1β (IL-1β), interleukin-21 (IL-21), interleukin-7 (IL-7), CD68, interleukin-6 (IL-6), and insulin 1 gene (INS1). Further, apoptotic related genes were also quantified. Primer sequences are listed in Table 1.