- Author:
- Ethan Choi <mcho099@aucklanduni.ac.nz>
- Date:
- 2010-02-19 15:13:59+13:00
- Desc:
- added model status and tidied code and rdf. shape of figures produced seems correct but scales are off
- Permanent Source URI:
- http://models.cellml.org/workspace/swanson_true_lin_buhler_vessella_murray_2001/rawfile/a20c6cc62612f42db69dfdabb22215b591b492c4/swanson_true_lin_buhler_vessella_murray_2001.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : swanson_model_2001.xml
CREATED : 6th December 2002
LAST MODIFIED : 9th April 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Swanson et al's 2001 mathematical model for the dynamics of serum prostate-specific antigen as a marker for cancerous growth.
-->
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<article>
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<title>A Model for the Dynamics of Serum Prostate-Specific Antigen as a Marker for Cancerous Growth</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
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<shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>This model has been built with the differential expressions in Swanson's 2001 paper. This file is known to run in PCEnv and COR, and parameters for constants have been set to LuCaP23.1. The general shape of the figure produced seems correct (figure 1), however the scale is not the same as the figures in the picture.</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>Prostate-specific antigen (PSA) is an enzyme that is produced by both healthy and cancerous prostate epithelial cells. PSA is widely used as a tumour marker for the diagnosis of prostate cancer and for monitoring patients with prostatic adenocarcinoma. The blood serum concentration of PSA correlates with the age of the patient, the size of the prostate in men without prostate carcinoma, the volume of the tumour in men with carcinoma, and the developmental stage of the carcinoma. On average, serum levels of PSA in men with carcinoma are significantly higher than PSA levels in men without carcinoma. However, the correlation between serum PSA and the volume of the cancerous tumour is less clear, and the variance is high between patients with prostate carcinoma. </para>
<para>In 2001, Swanson <emphasis>et al.</emphasis> published a mathematical model which described the dynamics of serum PSA as a marker for cancerous growth (see the figure below). They hypothesised that the differences in growth rates of prostate cancers could help to explain the variance in correlations of serum PSA concentrations with tumour size. Because the volume of human prostate cancer tumours cannot be determined in patients with any accuracy, they chose to work with xenografts of human prostate cancers in immunocompromised mice. They then developed a quantitative mathematical model that accounted for the contribution of independent variables to the size of the xenograft and the serum level of PSA.</para>
<para>Model simulations were supported by experimental observations, and they provided an explanation for the existence of significant prostatic tumour mass despite a low serum PSA. The model suggests that there could be a delay between tumour growth and PSA production. This delay is dependent on the parameter mu, defined as the ratio of PSA decay rate to the tumour growth rate. If mu is large, the serum PSA level increases with tumour volume, otherwise there is a delay between tumour growth and elevated serum PSA levels. All this suggests that serum PSA concentrations are not a reliable indicator of tumour size, and that in the future, mathematical modelling may help to determine a more accurate measurement of PSA to be used to indicate tumour growth. </para>
<para>The complete original paper reference is cited below:</para>
<para>A Quantitative Model for the Dynamics of Serum Prostate-Specific Antigen as a Marker for Cancerous Growth, Kristin R. Swanson, Lawrence D. True, Daniel W. Lin, Kent R. Buhler, Robert Vessella, and James D. Murray, 2001, <emphasis>American Journal of Pathology</emphasis>, 158, 2195-2199. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/11395397">PubMed ID: 11395397</ulink></para>
<informalfigure float="0" id="fig_cell_diagram">
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<title>reaction schematic for the model</title>
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<caption>The mathematical model shown visually in the above diagram can be written in words as: the rate of change of PSA equals the secretion of PSA from benign cells plus the secretion of PSA from cancerous cells minus the loss of PSA from the blood due to its metabolism and clearance. Cancer cells secrete more PSA than do benign cells. The volume of benign cells is assumed to remain constant, and the volume of cancerous cells is dependent on the size of the initial implanted tumour and the rate of tumour growth.</caption>
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<!-- units -->
<units name="day">
<unit units="second" multiplier="86400"/>
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<units name="per_day">
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<units name="mm3">
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