This page includes Agent-based three-dimensional cancer-tumour-microenvironment (TME) models developed within the scope of the TÜBİTAK 1001 Project with the number 120S987.
The models were developed by using scRNA data from healthy brain tissue and glioblastoma, cell type specific metabolic models and mechanistic information on cell-cell interactions from literature, see the HIBIT24 poster on overview of the project.
The models had few tumour cells at the initial time, the tumour growth and treatment under given conditions were simulated for about 45 days. Videos of the simulations are given below:
Oxygen availability (low, medium, high)
Below videos show the effect of oxygen levels on the tissue, oxygen both effects the metabolism and also signalling between the cells (HIF is released under hypoxia). Higher oxygen levels lead to faster growth.
Oxygen Level – Low
Oxygen Level – Mid
Oxygen Level- High
Glucose availability (low, medium, high)
Glucose availability effects the biomass production rate, cell divide when they are able to accumulate enough biomass. Also lactate is produced by cell types that are capable of producing lactate, which is turn used by cell types which can metabololise lactate. Metabolic behaviour of the cell is calculated via FBA based on their metabolic models.
Glucose Level – Low
Glucose Level – Mid
Glucose Level – High
Cell division rate (low, mediım high as a proxy of effects of mutations on regulation of cell division)
Cell division takes place when accumulated biomass passes a threshold, this threshold is used as a proxy for deregulation of cell division by mutated cell cycle check inhibitors. Cells divide faster if they are mutated.
Brain – Max Biomass 3e-4
Brain – Max Biomass 6e-4
Brain – Max Biomass 15e-4
Cell mobility
Migration Speed – 2.5
Migration Speed – 5
Migration Speed – 10
CAR-T therapy (small, medium, large number of CAR-T cell administration)
Cart Dose cn – 375
Cart Dose cn -750
Cart Dose cn – 1500
CAR-T therapy (under low-medium-high glucose conditions)
Brain – cart_optxglucose Low
Brain – cart_optxglucose Mid
Brain – cart_optxglucose High
ICI therapy (administration of ICI agent at early- advanced-very late stages of tumor progression)
Ici Initial Time – 7
Ici Initial Time – 15
Ici Initial Time – 30
ICI therapy (weekly, bi-weekly, monthly administration of ICI agent)
Ici Period – 7
Ici Period – 14
Ici Period – 28
Initial number of CAR-T cells (dose effect)
Brain – crat_init_thres 250
Brain – crat_init_thres 500
Brain – crat_init_thres 750
ICI therapy (under low-medium-high glucose conditions)
Brain – cartopxglucose_var High
Brain – cartopxglucose_var Mid
Brain – cartopxglucose_var Low
Brain – No Cancer
Brain – ici_optxglucose_var – High
Brain – ici_optxglucose_var – Mid
Brain – ici_optxglucose_var – Low
Brain – cart_optxglucose_var – High
Brain – cart_optxglucose_var – Mid
Brain – cart_optxglucose_var – Low