Before starting the following experiments be sure that the Tumor 2 Simulation is open.  You will then be able to toggle back and forth between this worksheet and the simulation as needed by selecting either Internet Explorer or Netlogo on the taskbar (PC)at the bottom of the screen, or use the FINDER to toggle (MAC).

Use the Speed Slider to slow down the model so you can follow individual steps. Set the SLOWDOWN slider to 10, click on SETUP and notice the green mutant cell. Underneath the green mutant cell there is a blue cell that represents a normal parent cell that has been "transformed" into a tumor stem cell.

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.

DaughterParent

The other daughter cell turns into a transitory cell that moves outward. Young transitory cells may divide, breeding other transitory cells.

Transitory Cell Division

Set the "leave-trail" switch to ON, and click GO. Stop the cell growth quickly by clicking the GO button again. Now you can see the blue "transformed" tumor stem cell. Notice that the blue transformed tumor stem cell divides into two blue stem cells. One remains static, and the other moves to the right. A tumor is formed as the stem cell creates red transitory cells, which reproduce themselves and move outward.

The cell mass grows to a certain size. As it grows, a bulge appears on the right side (see below). 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.

In reality, this seemingly solid mass conceals active cell turnover. You've just seen the simulated uncontrolled growth of an ovarian tumor.

Ovarian Cancer Tumor Simulation

 Treatment Modality Experiments

Now, try a simulated treatment: click SETUP and then GO. 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.

Return to this worksheet when you are staisfied that you uderstand the effect of Taxol. Begin working and answering the problems described below.

 1.Try another simulated treatment: click on the 'Carboplatin' button while the model is running.  The agent eliminates young (red) cells that divide, and it spares older cells.  Note that the tumor shrinks again and grows again.  Continue with this "chemotherapy" by clicking on the button again and watch the plot.  Repeat the treatment several times and in the textbox below, describe any differences you see between Taxol's effects and those of Carboplatin.

2.The tumor shrank but grew again after the carboplatin treatment.  Offer a hypothesis to explain this regrowth of the ovarian tumor in the textbox below.

3.We have just simulated the effects of two individual chemotherapeutic agents.  Now, while the model is running, press the Combination button to administer a combined treatment using both Taxol and Carboplatin at the same time.  Describe the response of the cells to this new treatment modality in the textbox.

4.  In your opinion, why do you suppose this combination treatment is more effective than the either of the individual treatments? Recall from the Evolution and Ovarian Cancer WebQuest what happens to tumors as the continue to grow under the influence of chemotherapeutic agents. 

5.Let the tumor grow again. Click on 'kill moving parent cell' and continue running the model.  Now click on 'kill original parent cell' and note what happens.  Describe the response of the tumor to the death of the parent cells?

6.The simulator does not differentiate between when the chemotherapeutic agents are applied and their effect. In a real tumor the sooner the treatment occurs after the onset of the cancer, the higher the probability that  the parent cell could be affected by the Taxol and Carboplatin drugs.  In the textbox below, explain the significance of early diagnosis in treating ovarian cancer.

7.What alternative strategies would you suggest in treating ovarian cancer? How would you model them here?  Describe two below.