Hu2019 - Pancreatic cancer dynamics

  public model
Short description
The paper describes a model on the size of pancreatic tumour. 
Created by COPASI 4.25 (Build 207) 

This model is described in the article: 
Modeling Pancreatic Cancer Dynamics with Immunotherapy 
Xiaochuan Hu, Guoyi Ke and Sophia R.-J. Jang 
Bulletin of Mathematical Biology (2019) 81:1885–1915 

Abstract: 
We develop a mathematical model of pancreatic cancer that includes pancreatic cancer cells, pancreatic stellate cells, effector cells and tumor-promoting and tumor- suppressing cytokines to investigate the effects of immunotherapies on patient survival. The model is first validated using the survival data of two clinical trials. Local sen- sitivity analysis of the parameters indicates there exists a critical activation rate of pro-tumor cytokines beyond which the cancer can be eradicated if four adoptive trans- fers of immune cells are applied. Optimal control theory is explored as a potential tool for searching the best adoptive cellular immunotherapies. Combined immunother- apies between adoptive ex vivo expanded immune cells and TGF-β inhibition by siRNA treatments are investigated. This study concludes that mono-immunotherapy is unlikely to control the pancreatic cancer and combined immunotherapies between anti-TGF-β and adoptive transfers of immune cells can prolong patient survival. We show through numerical explorations that how these two types of immunotherapies are scheduled is important to survival. Applying TGF-β inhibition first followed by adoptive immune cell transfers can yield better survival outcomes. 

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Format
SBML (L3V1)
Related Publication
  • Modeling Pancreatic Cancer Dynamics with Immunotherapy
  • Xiaochuan Hu, Guoyi Ke, Sophia R.-J. Jang
  • Bulletin of Mathematical Biology , 3/ 2019 , Volume 81 , pages: 1885-1915
  • Correspondence: Sophia R.-J. Jang E-mail address: sophia.jang@ttu.edu Department of Mathematics and Statistics, Texas Tech University, Lubbock, TX 79409-1042, USA
  • We develop a mathematical model of pancreatic cancer that includes pancreatic cancer cells, pancreatic stellate cells, effector cells and tumor-promoting and tumor- suppressing cytokines to investigate the effects of immunotherapies on patient survival. The model is first validated using the survival data of two clinical trials. Local sen- sitivity analysis of the parameters indicates there exists a critical activation rate of pro-tumor cytokines beyond which the cancer can be eradicated if four adoptive trans- fers of immune cells are applied. Optimal control theory is explored as a potential tool for searching the best adoptive cellular immunotherapies. Combined immunother- apies between adoptive ex vivo expanded immune cells and TGF-β inhibition by siRNA treatments are investigated. This study concludes that mono-immunotherapy is unlikely to control the pancreatic cancer and combined immunotherapies between anti-TGF-β and adoptive transfers of immune cells can prolong patient survival. We show through numerical explorations that how these two types of immunotherapies are scheduled is important to survival. Applying TGF-β inhibition first followed by adoptive immune cell transfers can yield better survival outcomes.
Contributors
Jinghao Men

Metadata information

hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
0002618
isDescribedBy
occursIn
Brenda Tissue Ontology pancreas

Curation status
Curated


Tags
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Model files

Hu2019.xml SBML L2V4 representation of tumour size model 104.83 KB Preview | Download

Additional files

Hu2019.sedml auto-generated SEDML file 1.11 KB Preview | Download
Hu2019.cps CPS file of the model in COPASI 108.88 KB Preview | Download

  • Model originally submitted by : Jinghao Men
  • Submitted: 10-Jul-2019 11:51:49
  • Last Modified: 10-Jul-2019 11:51:49
Revisions
  • Version: 7 public model Download this version
    • Submitted on: 10-Jul-2019 11:51:49
    • Submitted by: Jinghao Men
    • With comment: Automatically added model identifier BIOMD0000000744
Curator's comment:
(added: 09 Jul 2019, 09:32:05, updated: 09 Jul 2019, 09:32:05)
Publication figure 2 tumour cell count reproduced as per literature. Other figures need further parameters of treatment. Figure data is generated using COPASI 4.25 (build 197).