Jung2019 - Regulating glioblastoma signaling pathways and anti-invasion therapy - core control model

  public model
Model Identifier
BIOMD0000000828
Short description
This model is based on paper: Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy Abstract: Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451–AMPK–mTOR–cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.
Format
SBML (L3V1)
Related Publication
  • Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy.
  • Jung E, de Los Reyes V AA, Pumares KJA, Kim Y
  • PloS one , 1/ 2019 , Volume 14 , Issue 4 , pages: e0215547 , PubMed ID: 31009513
  • Department of Mathematics, Konkuk University, Seoul, Republic of Korea.
  • Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451-AMPK-mTOR-cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.
Contributors
Submitter of the first revision: Szeyi Ng
Submitter of this revision: Rahuman Sheriff
Modellers: Rahuman Sheriff, Szeyi Ng

Metadata information

is (2 statements)
BioModels Database MODEL1909300005
BioModels Database BIOMD0000000828

isDescribedBy (1 statement)
PubMed 31009513

hasProperty (5 statements)
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Glioblastoma
NCIt Signaling Pathway
Gene Ontology signaling
Experimental Factor Ontology cancer

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

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files
Jung2019 model.xml SBML L3V1 model file 75.92 KB Preview | Download

Additional files
Fig 8.png PNG plot of the model simulation Fig 8 37.44 KB Preview | Download
Jung2019 simulation.sedml SED-ML L2V1 for model simulation experiment description 6.45 KB Preview | Download
Jung2019.cps Copasi file for model simulation 98.46 KB Preview | Download

  • Model originally submitted by : Szeyi Ng
  • Submitted: Sep 30, 2019 4:10:13 PM
  • Last Modified: Mar 3, 2020 12:51:25 PM
Revisions
  • Version: 10 public model Download this version
    • Submitted on: Mar 3, 2020 12:51:25 PM
    • Submitted by: Rahuman Sheriff
    • With comment: Automatically added model identifier BIOMD0000000828
  • Version: 5 public model Download this version
    • Submitted on: Oct 2, 2019 12:01:24 PM
    • Submitted by: Szeyi Ng
    • With comment: Edited model metadata online.
  • Version: 3 public model Download this version
    • Submitted on: Sep 30, 2019 4:10:13 PM
    • Submitted by: Szeyi Ng
    • With comment: Automatically added model identifier BIOMD0000000828

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Glucose G

glucose 		6.64215616170866E-22 mmol
mTOR R

CCO:2475 ; MTOR Gene ; Serine/threonine-protein kinase mTOR 		4.58308775157897E-21 mmol
Drug D

drug 		0.0 mmol
AMPK A

5'-AMP-activated protein kinase catalytic subunit alpha-2 ; 5'-AMP-Activated Protein Kinase 		2.07567380053396E-21 mmol
miR 451 M

MIR451A Pre-miRNA ; cAMP-regulated phosphoprotein 19 		3.05539183438598E-21 mmol
Reactions
Reactions Rate Parameters
=> Glucose_G compartment*u_1 u_1 = 0.0
mTOR_R => ; mTOR_R compartment*mTOR_R/epsilon_2 epsilon_2 = 0.02
=> Drug_D compartment*u_2 u_2 = 0.0
Glucose_G => compartment*myu_G*Glucose_G myu_G = 0.5
Drug_D => compartment*myu_D*Drug_D myu_D = 1.316
=> mTOR_R; deltaD, AMPK_A compartment*l_5*l_6^2/(epsilon_2*(l_6^2+deltaD*gamma*AMPK_A^2)) l_6 = 1.0; epsilon_2 = 0.02; gamma = 1.0; l_5 = 4.0
AMPK_A => compartment*AMPK_A/epsilon_1 epsilon_1 = 0.02
miR_451_M => compartment*miR_451_M []
=> mTOR_R compartment*S_2/epsilon_2 S_2 = 1.2; epsilon_2 = 0.02
=> AMPK_A compartment*S_1/epsilon_1 S_1 = 0.2; epsilon_1 = 0.02
Curator's comment:
(added: 30 Sep 2019, 16:09:04, updated: 30 Sep 2019, 16:09:04)
I reproduced this figure by using COPASI 4.24(Build 197), while G=0.04, using the uploaded COPASI file. The reproduced figure is very similar to the original figure, the differences are the threshold values and the initial values. i couldn't find the initial values of G, M, R in the publication. So that might be the reason.