Hu2019 - Pancreatic cancer dynamics

  public model
Model Identifier
BIOMD0000000744
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 , DOI: 10.1007/s11538-019-00591-3
  • 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
Submitter of the first revision: Jinghao Men
Submitter of this revision: Jinghao Men
Modellers: Jinghao Men

Metadata information

is (2 statements)
BioModels Database MODEL1907050003
BioModels Database BIOMD0000000744

isDescribedBy (1 statement)
PubMed 30843136

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (1 statement)
hasProperty (2 statements)
Mathematical Modelling Ontology Ordinary differential equation model
Experimental Factor Ontology pancreatic carcinoma

occursIn (1 statement)
Brenda Tissue Ontology pancreas

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags
Immuno-oncology

Connected external resources

Name Description Size Actions

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

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

  • Model originally submitted by : Jinghao Men
  • Submitted: Jul 10, 2019 11:51:49 AM
  • Last Modified: Jul 10, 2019 11:51:49 AM
Revisions
  • Version: 7 public model Download this version
    • Submitted on: Jul 10, 2019 11:51:49 AM
    • Submitted by: Jinghao Men
    • With comment: Automatically added model identifier BIOMD0000000744
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
x

Malignant Cell ; malignant cell 		1.0E9 mmol
y

Pancreatic Stellate Cell ; pancreatic stellate cell 		5600000.0 mmol
w

Cytokine 		50000.0 mmol
z

Natural Killer Cell ; CD8-Positive T-Lymphocyte 		1.9E8 mmol
v

Cytokine 		9.4 mmol
Reactions
Reactions Rate Parameters
=> x Pancreatic_tumor*r1*x*(1-x*b1) r1 = 0.0195 1/d; b1 = 1.02E-11 1
x => ; z, w Pancreatic_tumor*delta1*x*z/(m1+w) m1 = 1.0E8 1; delta1 = 0.96 1/d
=> y Pancreatic_tumor*r2*y*(1-b2*y) b2 = 1.7857E-9 1; r2 = 0.00195 1/d
=> w; x, y, v Pancreatic_tumor*r4*x*y/(m4+v) m4 = 8.9E10 1; r4 = 12500.0 1/d
=> w; x, z Pancreatic_tumor*beta4*x*z/(k4+x) beta4 = 5.85 1/d; k4 = 1000000.0 1
=> z; v, w Pancreatic_tumor*beta3*z*v/((k3+v)*(m3+w)) beta3 = 124.5 1/d; m3 = 1000000.0 1; k3 = 2.0E10 1
=> v; x, z Pancreatic_tumor*beta5*x*z/(k5+x) beta5 = 7.3 1/d; k5 = 1000000.0 1
=> x; y Pancreatic_tumor*beta1*y*x*(1-x*b1) beta1 = 3.482115E-12 1/d; b1 = 1.02E-11 1
v => Pancreatic_tumor*u5*v u5 = 0.034 1/d
=> z Pancreatic_tumor*r3 r3 = 3500.0 1/d
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).