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Traditionally, the monolayer (two-dimensional) cell cultures are used for initial evaluation of the effectiveness of anticancer drugs. In particular, these experiments provide the IC 50 curves that determine drug concentration that can inhibit growth of a tumor colony by half when compared to the cells grown with no exposure to the drug. Low IC 50 value means that the drug is effective at low concentrations, and thus will show lower systemic toxicity when administered to the patient. However, in these experiments cells are grown in a monolayer, all well exposed to the drug, while in vivo tumors expand as three-dimensional multicellular masses, where inner cells have a limited access to the drug. Therefore, we performed computational studies to compare the IC 50 curves for cells grown as a two-dimensional monolayer and a cross section through a three-dimensional spheroid. Our results identified conditions (drug diffusivity, drug action mechanisms and cell proliferation capabilities) under which these IC 50 curves differ significantly. This will help experimentalists to better determine drug dosage for future in vivo experiments and clinical trials. [ABSTRACT FROM AUTHOR]

Vector-borne disease transmission is a common dissemination mode used by many pathogens to spread in a host population. Similar to directly transmitted diseases, the within-host interaction of a vector-borne pathogen and a host's immune system influences the pathogen's transmission potential between hosts via vectors. Yet there are few theoretical studies on virulence-transmission trade-offs and evolution in vector-borne pathogen-host systems. Here, we consider an immuno-epidemiological model that links the within-host dynamics to between-host circulation of a vector-borne disease. On the immunological scale, the model mimics antibody-pathogen dynamics for arbovirus diseases, such as Rift Valley fever and West Nile virus. The within-host dynamics govern transmission and host mortality and recovery in an age-since-infection structured host-vector-borne pathogen epidemic model. By considering multiple pathogen strains and multiple competing host populations differing in their within-host replication rate and immune response parameters, respectively, we derive evolutionary optimization principles for both pathogen and host. Invasion analysis shows that the $${\mathcal {R}}_0$$ maximization principle holds for the vector-borne pathogen. For the host, we prove that evolution favors minimizing case fatality ratio (CFR). These results are utilized to compute host and pathogen evolutionary trajectories and to determine how model parameters affect evolution outcomes. We find that increasing the vector inoculum size increases the pathogen $${\mathcal {R}}_0$$ , but can either increase or decrease the pathogen virulence (the host CFR), suggesting that vector inoculum size can contribute to virulence of vector-borne diseases in distinct ways. [ABSTRACT FROM AUTHOR]