A mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering system
Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, pre...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1797073654899539968 |
|---|---|
| author | Martin, N Gaffney, E Gatenby, R Gillies, R Robey, I Maini, P |
| author_facet | Martin, N Gaffney, E Gatenby, R Gillies, R Robey, I Maini, P |
| author_sort | Martin, N |
| collection | OXFORD |
| description | Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the HCO3-/CO2 buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe. © 2010 Elsevier Inc. |
| first_indexed | 2024-03-06T23:25:10Z |
| format | Journal article |
| id | oxford-uuid:6a1de8f2-73bb-4371-a918-1f642c8f4ee6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:25:10Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:6a1de8f2-73bb-4371-a918-1f642c8f4ee62022-03-26T18:55:21ZA mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering systemJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6a1de8f2-73bb-4371-a918-1f642c8f4ee6EnglishSymplectic Elements at Oxford2011Martin, NGaffney, EGatenby, RGillies, RRobey, IMaini, PMalignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the HCO3-/CO2 buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe. © 2010 Elsevier Inc. |
| spellingShingle | Martin, N Gaffney, E Gatenby, R Gillies, R Robey, I Maini, P A mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering system |
| title | A mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering system |
| title_full | A mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering system |
| title_fullStr | A mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering system |
| title_full_unstemmed | A mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering system |
| title_short | A mathematical model of tumour and blood pHe regulation: The HCO 3 -/CO 2 buffering system |
| title_sort | mathematical model of tumour and blood phe regulation the hco 3 co 2 buffering system |
| work_keys_str_mv | AT martinn amathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT gaffneye amathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT gatenbyr amathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT gilliesr amathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT robeyi amathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT mainip amathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT martinn mathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT gaffneye mathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT gatenbyr mathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT gilliesr mathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT robeyi mathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem AT mainip mathematicalmodeloftumourandbloodpheregulationthehco3co2bufferingsystem |