Abstract
Bioreductive drugs are in clinical practice to exploit the resistance from tumour microenvironments especially in the hypoxic region of tumour. We presented a tumour treatment model to capture the pharmacology of one of the most prominent bioreductive drugs, Tirapazamine (TPZ) which is in clinical trials I and II. We calculated solid tumour mass in our previous work and then integrated that model with TPZ infusion. We calculated TPZ cytotoxicity, concentration, penetration with increasing distance from blood vessel and offered resistance from microenvironments for drug penetration inside the tumour while considering each cell as an individual entity. The impact of these factors on tumour morphology is also showed to see the drug behaviour inside animals/humans tumours. We maintained the heterogeneity factors in presented model as observed in real tumour mass especially in terms of cells proliferation, cell movement, extracellular matrix (ECM) interaction, and the gradients of partial oxygen pressure (pO2) inside tumour cells during the whole growth and treatment activity. The results suggest that TPZ high concentration in combination with chemotherapy should be given to get maximum abnormal cell killing. This model can be a good choice for oncologists and researchers to explore more about TPZ action inside solid tumour.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Perumpanani, A.J., Byrne, H.M.: Extracellular matrix concentration exerts selection pressure on invasive cells. Journal of Cancer 35, 1274–1280 (1999)
Minchinton, A.I., Tannock, I.F.: Drug penetration in solid tumours. Nature Reviews Cancer 6, 583–592 (2006)
Anderson, A.R.A., Weaver, A.M., Cummings, P.T., Quaranta, V.: Tumor morphology and phenotypic evolution by selective pressure from the microenvironment. Cell 127 (2006)
Anderson, A.R.A., Chaplain, M.A.J., Newman, E.L., Steele, R.J.C.: Mathematical modelling of tumour invasion and metastasis. Journal of Theoretical Medicine, 129–154 (1999)
Shannon, A.M., Bouchier-Hayes, D.J., Condron, C.M., Toomey, D.: Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treatment Reviews 29, 297–307 (2003)
Siim, B.G., Menke, D.R., Dorie, M.J., Brown, J.M.: Tirapazamine-induced cytotoxicity and DNA damage in transplanted tumors: relationship to tumor hypoxia. Cancer Research 57, 2922–2928 (1997)
Hanahan, D., Weinberg, R.A.: The hallmarks of cancer, Department of Biochemistry and Biophysics. Cell, 57–70 (2000)
Lartigau, E., Guichard, M.: Does tirapazamine (SR-4233) have any cytotoxic or sensitizing effect on three human tumour cell lines at clinically relevant partial oxygen pressure? International Journal of Radiation Biology 67, 211–216 (1995)
Kozusko, F., Bajzer, Z.: Combining Gompertzian Growth and Cell Population Dynamics. Mathematical Biosciences 185, 153–167 (2003)
Enderling, H., Chaplain, M.A.J., Anderson, A.R.A., Vaidya, J.S.: A mathematical model of breast cancer development, local treatment and recurrence. Journal of Theoretical Biology 246, 245–259 (2007)
Byrne, H.M.: Using mathematics to study solid tumour growth. In: The Proceedings of the 9th General Meetings of Euorpean Women in Mathematics, pp. 81–107 (1999)
Byrne, H.M., Chaplain, M.A.J.: Growth of nonnecrotic tumours in the presence and absence of inhibitors. Journal of Mathematical Biosciences 130, 151–181 (1995)
Conde, I.R., Chaplain, M.A.J., Anderson, A.R.A.: Mathematical modeling of cancer cell invasion of tissue. Mathematical and Computer Modelling (2007)
Kim, J.J., Tannock, L.F.: Repopulation of Cancer Cells during Therapy: an Important Cause of Treatment Failure. Nature Cancer Review 5, 516 (2005)
Brown, J.M.: Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Molecular Medicine Today 6, 157–162 (2000)
Brown, J.M.: SR 4233 (Tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours. British Journal of Cancer 67, 1163–1170 (1993)
Folkman, J.: Tumor angiogenesis. Advance Cancer Research 19, 331–358 (1974)
Vohardsky, J.: Neural model of the Genetic Network. Journal of Biological Chemistry 276, 36168–36173 (2001)
Patterson, L.H., Mckeown, S.R.: AQ4N: a new approach to hypoxia-activated cancer chemotherapy. British Journal of Cancer 83, 1589–1593 (2000)
Marcu, L., Olver, I.: Tirapazamine: From Bench to Clinical Trials. Current Clinical Pharmacology 1, 71–79 (2006)
Preziosi, L., Farina, A.: On decay‘s law for growing porous media. Journal of Non-Linear Mathematic 37, 485–491 (2002)
Ferrara, N., Kerbel, R.S.: Angiogenesis as a Therapeutic Target. Nature 438, 967–974 (2005)
Kazmi, N., Hossain, M.A., Phillips, R.M.: Intelligent modeling of benign tumour growth with cell-cell and cell-matrix adhesion. In: 10th IEEE International Conference on Computer and Information Technology (2010)
Gerlee, P., Anderson, A.R.A.: A hybrid cellular automaton model of clonal evolution in cancer: the emergence of the glycolytic phenotype. Journal of Theoretical Biology, 705–722 (2007)
Gerlee, P., Anderson, A.R.A.: An evolutionary hybrid cellular automaton model of solid tumour growth. Journal of Theoretical Biology (2007)
Durand, R.E., Olive, P.L.: Physiologic and cytotoxic effects of tirapazamine in tumor-bearing mice. Radiation Oncology Investigations 5, 213–219 (1997)
Tse, S.M., Liang, Y., Leung, K.S., Lee, K.H., Mok, T.S.: A mimetic algorithm for multiple-drug cancer chemotherapy schedule optimization. IEEE transaction on systems man, cybernatics 37, 84–91 (2007)
Algoul, S., Hossain, M.A., Majumderand, M.A.A., Alam, M.S.: Multi-objective optimal chemotherapy model for cancer treatment. Medical Biology Engineering and Computing (2010)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Kazmi, N., Hossain, M.A., Phillips, R.M. (2011). Modelling of Tirapazamine Effects on Solid Tumour Morphology. In: Rocha, M.P., RodrÃguez, J.M.C., Fdez-Riverola, F., Valencia, A. (eds) 5th International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB 2011). Advances in Intelligent and Soft Computing, vol 93. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-19914-1_18
Download citation
DOI: https://doi.org/10.1007/978-3-642-19914-1_18
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-19913-4
Online ISBN: 978-3-642-19914-1
eBook Packages: EngineeringEngineering (R0)