Abstract
Bioreductive drugs are a class of hypoxia selective drugs that are designed to eradicate the hypoxic fraction of solid tumors. Their activity depends upon a number of biological and pharmacological factors and we used a mathematical modeling approach to explore the dynamics of tumor growth, infusion, and penetration of the bioreductive drug Tirapazamine (TPZ). An in-silico model is implemented to calculate the tumor mass considering oxygen and glucose as key microenvironmental parameters. The next stage of the model integrated extra cellular matrix (ECM), cell-cell adhesion, and cell movement parameters as growth constraints. The tumor microenvironments strongly influenced tumor morphology and growth rates. Once the growth model was established, a hybrid model was developed to study drug dynamics inside the hypoxic regions of tumors. The model used 10, 50 and 100 M as TPZ initial concentrations and determined TPZ pharmacokinetic (PK) (transport) and pharmacodynamics (cytotoxicity) properties inside hypoxic regions of solid tumor. The model results showed that diminished drug transport is a reason for TPZ failure and recommend the optimization of the drug transport properties in the emerging TPZ generations. The modeling approach used in this study is novel and can be a step to explore the behavioral dynamics of TPZ.
| Original language | English |
|---|---|
| Pages (from-to) | 1595-1606 |
| Number of pages | 12 |
| Journal | IEEE/ACM Transactions on Computational Biology and Bioinformatics |
| Volume | 9 |
| Issue number | 6 |
| Early online date | 4 Sep 2012 |
| DOIs | |
| Publication status | Published - Nov 2012 |
| Externally published | Yes |
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A Hybrid Cellular Automaton Model of Solid Tumor Growth and Bioreductive Drug Transport. / Kazmi, Nabila; Hossain, M. A.; Phillips, Roger M.
In: IEEE/ACM Transactions on Computational Biology and Bioinformatics, Vol. 9, No. 6, 11.2012, p. 1595-1606.Research output: Contribution to journal › Article
TY - JOUR
T1 - A Hybrid Cellular Automaton Model of Solid Tumor Growth and Bioreductive Drug Transport
AU - Kazmi, Nabila
AU - Hossain, M. A.
AU - Phillips, Roger M.
PY - 2012/11
Y1 - 2012/11
N2 - Bioreductive drugs are a class of hypoxia selective drugs that are designed to eradicate the hypoxic fraction of solid tumors. Their activity depends upon a number of biological and pharmacological factors and we used a mathematical modeling approach to explore the dynamics of tumor growth, infusion, and penetration of the bioreductive drug Tirapazamine (TPZ). An in-silico model is implemented to calculate the tumor mass considering oxygen and glucose as key microenvironmental parameters. The next stage of the model integrated extra cellular matrix (ECM), cell-cell adhesion, and cell movement parameters as growth constraints. The tumor microenvironments strongly influenced tumor morphology and growth rates. Once the growth model was established, a hybrid model was developed to study drug dynamics inside the hypoxic regions of tumors. The model used 10, 50 and 100 M as TPZ initial concentrations and determined TPZ pharmacokinetic (PK) (transport) and pharmacodynamics (cytotoxicity) properties inside hypoxic regions of solid tumor. The model results showed that diminished drug transport is a reason for TPZ failure and recommend the optimization of the drug transport properties in the emerging TPZ generations. The modeling approach used in this study is novel and can be a step to explore the behavioral dynamics of TPZ.
AB - Bioreductive drugs are a class of hypoxia selective drugs that are designed to eradicate the hypoxic fraction of solid tumors. Their activity depends upon a number of biological and pharmacological factors and we used a mathematical modeling approach to explore the dynamics of tumor growth, infusion, and penetration of the bioreductive drug Tirapazamine (TPZ). An in-silico model is implemented to calculate the tumor mass considering oxygen and glucose as key microenvironmental parameters. The next stage of the model integrated extra cellular matrix (ECM), cell-cell adhesion, and cell movement parameters as growth constraints. The tumor microenvironments strongly influenced tumor morphology and growth rates. Once the growth model was established, a hybrid model was developed to study drug dynamics inside the hypoxic regions of tumors. The model used 10, 50 and 100 M as TPZ initial concentrations and determined TPZ pharmacokinetic (PK) (transport) and pharmacodynamics (cytotoxicity) properties inside hypoxic regions of solid tumor. The model results showed that diminished drug transport is a reason for TPZ failure and recommend the optimization of the drug transport properties in the emerging TPZ generations. The modeling approach used in this study is novel and can be a step to explore the behavioral dynamics of TPZ.
KW - Extra cellular matrix
KW - Hypoxia
KW - Mathematical modeling
KW - Microenvironment and Tirapazamine
UR - http://www.scopus.com/inward/record.url?scp=84880385696&partnerID=8YFLogxK
UR - http://ieeexplore.ieee.org/xpl/RecentIssue.jsp?punumber=8857
U2 - 10.1109/TCBB.2012.118
DO - 10.1109/TCBB.2012.118
M3 - Article
VL - 9
SP - 1595
EP - 1606
JO - IEEE/ACM Transactions on Computational Biology and Bioinformatics
JF - IEEE/ACM Transactions on Computational Biology and Bioinformatics
SN - 1545-5963
IS - 6
ER -