Objectives: Infliximab (IFX), ipilimumab (IPI), and nivolumab (NIVO) have been associated with hepatotoxicity. BIOLOGXsym™, a quantitative systems toxicology model, integrates hepatic interstitial concentrations in vitro mechanistic toxicity data to predict extent of liver toxicity. Physiologically based pharmacokinetic (PBPK) models can be used make these exposure predictions. The objective this work was use modeling simulation estimate after administration the three large...

Background/Objectives: Infliximab, ipilimumab, and nivolumab are three monoclonal antibodies that have been associated with hepatotoxicity. Three separate physiologically based pharmacokinetic (PBPK) models were developed in GastroPlus® to simulate plasma liver concentrations patient populations after administration of either infliximab, or nivolumab. Methods: The include distribution clearance mechanisms specific large molecules, FcRn binding dynamics, target-mediated drug disposition...

Tumour hypoxia is a well-studied phenomenon with implications in cancer progression, treatment resistance, and patient survival. While clear adverse prognosticator, also theoretically ideal target for guided drug delivery. This idea has lead to the development of hypoxia-activated prodrugs (HAPs): class chemotherapeutics which remain inactive body until metabolized within hypoxic regions. In theory, these drugs have potential increased tumour selectivity therefore been focus numerous...

Tumour hypoxia has been associated with increased resistance to various cancer treatments, particularly radiation therapy. Conversely, tumour is a validated and ideal target for guided drug delivery. For this reason, hypoxia-activated prodrugs (HAPs) have developed, which remain inactive in the body until presence of tissue hypoxia, allowing an activation tendency hypoxic regions. We present here experimentally motivated mathematical model predicting effectiveness HAPs variety clinical...

Abstract Liposome-based anticancer agents take advantage of the increased vascular permeability and transvascular pressure gradients for selective accumulation in tumors, a phenomenon known as enhanced retention(EPR) effect. The EPR effect has motivated clinical use nano-therapeutics, with mixed results on treatment outcome. High interstitial fluid (IFP) been shown to limit liposome drug delivery central tumour regions. Furthermore, high IFP is an independent prognostic biomarker efficacy...

Glioblastomas are the most common primary brain tumours. They known for their highly aggressive growth and invasion, leading to short survival times. Treatments glioblastomas commonly involve a combination of surgical intervention, chemotherapy, external beam radiation therapy (XRT). Previous works have not only successfully modelled natural in vivo, but also show potential prediction response prior treatment. This suggests that efficacy XRT can be optimized before treatment order yield...

Angiogenesis is an important process in the formation and maintenance of tissues which driven by a complex system intracellular intercellular signaling mechanisms. Endothelial cells taking part early angiogenesis must select their phenotype as either tip (leading, migratory) or stalk (following). Recent experiments have demonstrated that rapid calcium oscillations within active characterize this selection these play necessary role governing eventual vessel architecture. In work, we develop...

Abstract The outbreak of SARS-CoV-2 in China has spread around the world, infecting millions and causing governments to implement strict policies counteract disease. One most effective strategies reducing severity pandemic is social distancing, where members population systematically reduce their interactions with others limit transmission rate virus. However, implementation distancing can be difficult costly, making it imperative that both policy makers citizenry understand potential...

The outbreak of SARS-CoV-2 is thought to have originated in Wuhan, China late 2019 and has since spread quickly around the world. To date, virus infected tens millions people worldwide, compelling governments implement strict policies counteract community spread. Federal, provincial, municipal employed various public health policies, including social distancing, mandatory mask wearing, closure schools businesses. However, implementation these can be difficult costly, making it imperative...

Abstract Glioblastoma multiforme (GBM) is one of the most deadly forms cancer. Methods characterizing these tumours are valuable for improving predictions their progression and response to treatment. A mathematical model called proliferation-invasion (PI) has been used extensively in literature tumours, though it relies on known values two key parameters: tumour cell diffusivity proliferation rate. Unfortunately, parameters difficult estimate a patient-specific manner, making personalized...

Abstract External beam radiation therapy is a key part of modern cancer treatments which uses high doses to destroy tumour cells. Despite its widespread usage and extensive study in theoretical, experimental, clinical works, many questions still remain about how best administer it. Many mathematical studies have examined optimal scheduling radiotherapy, most come similar conclusions. Importantly though, these generally assume intratumoral homogeneity. But recent years, it has become clear...