Figure 1

Schematic representation of the known molecular pathways and biochemical events induced by PDT. A schematic representation of the known molecular pathways and biochemical events induced by PDT treatment leading to cell death. A molecular interaction graph with information about the potential dynamic behavior of a cellular system that can be translated into mathematical terms that are suitable for computer simulation. Blue color: Reactions that lead to the activation of the photosensitizer(Photofrin in our case) and the generation of reactive oxygen species (ROS). The kinetic mathematical model of [5] is used to describe the molecular pathways. Red color: Exposition to tumour necrosis factor (TNF) or TNF-related apoptosis-inducing ligand (TRAIL) as a result PDT treatment activate effector caspases that dismantle the cell. The kinetic mathematical model of [3] is used to describe the molecular dynamics. Light blue (aqua): The interplay between autophagy and apoptosis in response to oxidative stress. A signaling mathematical model introduced in [4] is used to describe the dynamics. Yellow color: Components and interactions that have either been observed or conjectured in the literature but no equation has been identified (thin lines) or they have been observed and we have a mathematical equation to describe them (thick lines). An arrow signifies the up regulation process of a cellular molecular component as a signalling response to another molecular component, and a line with a vertical line segment signifies the down regulation process of a cellular molecular component as a signalling response to another molecular component. A coherent PDT mathematical model has been synthesized from the three kinetic models, with the necessary modifications to account for biochemical events, such as the initiation of the degradation process of Bcl-2 by ROS that could bind to Bax to prevent its activation. All rate equations, initial molecular concentrations, coefficients and constants can be found in the supplementary information tables in the author's dissertation ("Mathematical Modelling of Oxygen Transport, Cell Killing and Cell Decision Making in Photodynamic Therapy of Cancer Gkigkitzis, Ioannis ECU, 2012) as well as the above mentioned references.