Ovarian Tumor Simulation

1. Ovarian Tumor Simulation By Arthur Renkwitz and Douglas Becker

2. With the completion of Evolution and Ovarian Cancer you have gained the knowledge of the evolutionary etiology of ovarian cancer and the theory behind the chemotherapy modality. Now it's time to apply this knowledge in a Ovarian Cancer Simulator. Continue your Evolutionary Cancer Quest by attempting to affect a cure or remission of a ovarian tumor. Begin the process by Downloading and installing the application NetLogo.

3. This model illustrates the growth of a tumor and how it reacts to chemical treatment. This tumor model starts with two kinds of cells: parent cells (blue turtles) and transitory cells (all other turtles). This green square, which is generated at the setup of the simulation, represents two parent cells and one transitory cell stacked on top of each other.

4. During mitosis, a parent cell can divide either asymmetrically or symmetrically. In asymmetric mitosis, one of the two daughter cells remains a parent cell, replacing its progenitor. So a parent cell effectively never dies - it is quasi reincarnated after each division. The other daughter cell turns into a transitory cell that moves outward. Young transitory cells may divide, breeding other transitory cells. Parent Cell Telophase Transitory Cell Metaphase

5. A progenitor cell may also divide symmetrically into two parent cells (blue turtles). In this example the original progenitor cell divides symmetrically only once. The first parent cell remains static, but the second stem cell moves to the right. This activity, in which the cell advances into distant sites and creates another tumor colony, is called metastasis. Notice that the metastasis is made of cells that die young. Click on picture above for a more complete description of metastasis.

6. Table of Contents • How to Use the Model • Untreated Tumor Growth • Treatment Modalities • Experiments

7. How to Use the Model Click on each of the hot buttons on the picture to see its function Click the button at bottom of that page to return here Table of Contents | Next

8. Untreated Tumor Growth First, notice the blue dot which begins underneath the green mutant cell. It represents a normal parent cell that has been transformed into a tumor stem cell. Set the "leave-trail" switch to On, and click 'go'. A tumor is formed as the stem cell creates transitory cells, which reproduce themselves.

9. It grows to a certain size. As it grows, a bulge appears on the right side. This is a tumor outgrowth, caused by symmetric mitosis of the parent cell. The outgrowth will turn into a metastasis and grow into remote regions. After a while the tumor and metastasis appear to reach their ultimate size and nothing interesting seems to be happening. This illustrates how the tumor presents itself to the physician - as a solid cell mass.

10. In reality, this seemingly solid mass conceals active cell turnover.

11. It is now time for you to start using the Tumor Simulation. Read the following instructions to reproduce what you have just seen. Slow down the model so you can follow individual steps. Set the SLOWDOWN slider to 10, click on SETUP and GO, and observe the blue stem cell. It divides into two blue stem cells. One remains static, and the other moves to the right. Look at the static stem cell (blue). It breeds red cells which move outward and change their color as they age. They are red and create more transitory cells. Tumor Simulation Return to presentation by exiting netlogo Table of Contents | Next

12. Treatment Modalities Try a simulated treatment: click on the 'Taxol' button while the model is running. The agent eliminates young (red) cells that divide, and it spares older cells. Note that the tumor shrinks and grows again. Continue with this "chemotherapy" by clicking on the button again and watch the plot. Repeat the treatment several times until you have an hypothesis as to why it fails. Tumor Simulation Return to presentation by exiting netlogo Table of Contents | Next

13. Experiments You have just completed a chemotherapeutic treatment using the “Taxol” button in the tumor simulation program, now link to the Ovarian Tumor Simulation Worksheet to run and explain other experimental chemotherapeutic modalities. Table of Contents | Next

14. SETUP: Clears the display window and creates two blue neoplastic (cancerous) stem cells. One cell stays put and the other moves to the right.

15. GO: Runs the simulation.

16. TAXOL: This button introduces taxol to the tumor killing young transitory cells. CARBOPLATIN: This button introduces carboplatin to the tumor killing young transitory cells. COMBINATION: This button introduces a combination of taxol and carboplatin to the tumor killing young transitory cells.

17. KILL ORIGINAL PARENT CELL: Kills the stationary parent cell. KILL MOVING PARENT CELL: Kills the metatatic parent cell.

18. TIME: Displays how many times the “go” procedure has been run CELL-COUNT: Displays the total number of living cells.

19. LIVING CELLS PLOT: plots the number of living cells.

20. SLOWDOWN: A high value slows down the process. LEAVE-TRAIL: If it's ON, the cells trace their paths; if it's OFF, they do not.

21. HALT: Stops the model at any given point. Model can be restarted by pressing “Go”.