Diagram of global processes and signalling pathways modelled in CYCLOPS.

<p><b>(a)</b> Cell cycle partition, checkpoint and apoptosis process. <b>(b)</b> Signalling processes modelled in the G1-S and <b>(c)</b> spindle assembly checkpoints. <b>(d)</b> Signalling modelled in the MAP kinase and <b>(e)</b> apoptosis pathways.</p

Simulations of palbociclib and gemcitabine effects.

<p><b>(a)</b> palbociclib effects on malignant (left) and normal (right) at several concentrations (“proportion cells” correspond to the increase in number of cells i.e. 10 = 10 times more cells). <b>(b)</b> Modulation of the cell cycle distribution (left malignant, right normal, arrows indicate changes with increasing concentrations). <b>(c)</b> gemcitabine effects on malignant (left) and normal (right) at several concentrations. <b>(d)</b> Simulated dose-response surface for the palbociclib+gemcitabine combination. The arrow shows the rise of antagonistic effect with normal cells when increasing palbociclib concentration. <b>(e)</b> gemcitabine delayed administration protocol. (f) Effects of varying the time delay on normal (blue line, shown as % control) and malignant cells (red line). The ratio of normal to malignant is shown in green.</p

Simulation in CYCLOPS of cell cycle and ligand modulation.

<p>EGF stimulation of malignant <b>(a)</b> and normal cells <b>(b)</b>. “Proportion cells” correspond to the increase in number of cells i.e. 10 = 10 times more cells.</p

Properties of the cell lines modelled.

<p>Most values were from the ATCC website.[<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005529#pcbi.1005529.ref055" target="_blank">55</a>] It should be noted that the cytokinetic properties of cell lines vary substantially according to culture medium, concentration of serum and growth factors, inoculum density and oxygen and CO₂ concentration. The values shown are the ones used in CYCLOPS and may be regarded as typical values for early-stage cultures at low cell density under standard levels of O2 and CO₂.</p

CYCLOPS simulations of actinomycin D and paclitaxel combinations.

<p><b>(a)</b> Actinomycin D dose-response are shown for malignant (left) and normal (right) cells. <b>(b)</b> Combination dose-response for actinomycin D+paclitaxel for simultaneous administration (24 hours) and <b>(c)</b> when delaying actinomycin D by 12 hours (malignant left, normal right). Arrows highlight magnitude of antagonistic effect when adding paclitaxel to 30nM actinomycin D.</p

Paclitaxel modulation of the cell cycle distribution.

<p>24hours paclitaxel treatment was simulated and the resulting cell cycle distribution is shown at 12, 24 and 27 hours (3 hours after wash-out) for <b>(a)</b> normal and <b>(b)</b> malignant cells. Plain bars show the reference cell cycle distribution prior to treatment while broken-line bars show the distribution evolution over time.</p