Jung2019 - egulating glioblastoma signaling pathways and anti-invasion therapy cell cycle dynamics model

Model Identifier
BIOMD0000000829
Short description
This model is based on paper, based on its cell cycle dynamics model:
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
(L2V4)
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: Szeyi Ng
Modellers: Szeyi Ng
Submitter of this revision: Szeyi Ng
Modellers: Szeyi Ng
Metadata information
is (2 statements)
isDescribedBy (1 statement)
hasProperty (5 statements)
isDescribedBy (1 statement)
hasProperty (5 statements)
Experimental Factor Ontology
cancer
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Glioblastoma
NCIt Signaling Pathway
Gene Ontology signaling
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Glioblastoma
NCIt Signaling Pathway
Gene Ontology signaling
Curation status
Curated
Modelling approach(es)
Tags
Connected external resources
Name | Description | Size | Actions |
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Model files |
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Jung2019 - egulating glioblastoma signaling pathways and anti-invasion therapy cell cycle dynamics model.xml | SBML L2V4 file for the model | 134.59 KB | Preview | Download |
Additional files |
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Fig 7 without mass.png | PNG plot of the model simulation for Fig 7 | 51.54 KB | Preview | Download |
Jung2019 - egulating glioblastoma signaling pathways and anti-invasion therapy cell cycle dynamics model.cps | COPASI 4.24 (Build 197) file for the model | 171.91 KB | Preview | Download |
mass.png | PNG plot of the model simulation for Fig 7 (mass) | 34.92 KB | Preview | Download |
- Model originally submitted by : Szeyi Ng
- Submitted: Oct 2, 2019 11:46:54 AM
- Last Modified: Oct 2, 2019 11:46:54 AM
Revisions
Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
Species | Initial Concentration/Amount |
---|---|
AMPK A 5'-AMP-activated protein kinase catalytic subunit alpha-2 ; 5'-AMP-Activated Protein Kinase |
2.07567380053396E-21 mmol |
Cdh1 Fizzy-related protein homolog |
1.0 mmol |
CycB G2/mitotic-specific cyclin-B3 |
0.1 mmol |
mass Mass |
0.45 mmol |
p55cdc T Cell division cycle protein 20 homolog |
1.0 mmol |
miR 451 M cAMP-regulated phosphoprotein 19 ; MIR451A Pre-miRNA |
3.05539183438598E-21 mmol |
deltaD | 1.0 mmol |
p55cdc A Cell division cycle protein 20 homolog |
0.85 mmol |
Glucose G glucose |
6.64215616170866E-22 mmol |
Reactions
Reactions | Rate | Parameters |
---|---|---|
=> AMPK_A; miR_451_M | compartment*l_3*l_4^2/(epsilon_1*(l_4^2+beta*miR_451_M^2)) | l_3 = 4.0; beta = 1.0; l_4 = 1.0; epsilon_1 = 0.02 |
=> Cdh1 | compartment*k_3*(1-Cdh1)/((J_3+1)-Cdh1) | J_3 = 0.04; k_3 = 3.0 |
=> CycB | compartment*k_1 | k_1 = 0.12 |
=> mass | compartment*myu_0*mass*(1-mass/m) | myu_0 = 0.033; m = 10.0 |
=> p55cdc_T | compartment*k_5 | k_5 = 0.015 |
=> miR_451_M; Glucose_G, AMPK_A | compartment*(Glucose_G+l_1*l_2^2/(l_2^2+alpha*AMPK_A^2)) | l_2 = 1.0; l_1 = 4.0; alpha = 1.6 |
deltaD = exp(-Drug_D) | [] | [] |
CycB => | compartment*k_2*CycB | k_2 = 0.12 |
p55cdc_A => | compartment*k_8*Mad*p55cdc_A/(J_8+p55cdc_A) | k_8 = 1.5; J_8 = 0.001; Mad = 1.0 |
=> Glucose_G | compartment*u_1 | u_1 = 0.0 |
Curator's comment:
(added: 02 Oct 2019, 11:46:11, updated: 02 Oct 2019, 11:46:11)
(added: 02 Oct 2019, 11:46:11, updated: 02 Oct 2019, 11:46:11)
I generated the figure using COPASI 4.24(Build 197) and the attached file.
The model was in a chaotic status before 70, but matches with the publication after 70h. Possible reasons might be lack on initial condition and the value of mass and mass_s are not based on the paper.