Hall 21 - Model Tumor Systems

Question 1

What are tumor growth measurements?

Answer 1

Physical measurements of tumor size in control and irradiated animals

Question 2

What does a tumor cure (TCD50) assay determine?

Answer 2

The radiation dose to achieve 50% tumor control

Question 3

What causes local recurrence after radiation?

Answer 3

Cancer cells with unlimited proliferative potential (cancer “stem cells”)

In theory, only one surviving cancer stem cell is needed

Question 4

How do the bulk of cancer cells respond to RT?

Answer 4

Tumor shrinkage and growth delay

Question 5

What does the radiation response of cancer stem cells define?

Answer 5

Probability of permanent local tumor control

Question 6

What clonogenic assay technique involves determining the number of tumor cells required to transmit tumor from donor animal to a recipient 50% of the time (TD50)?

Answer 6

Dilution assay technique

Surviving fraction = TD50 controls / TD50 irradiated

Question 7

What is a lung colony assay?

Answer 7

Irradiate tumor cells in donor animal, harvest, inject into tail vein of recipient mouse, then count number of tumor colonies formed in the lungs

Question 8

What is a done for an in vivo/in vitro assay?

Answer 8

Irradiate cells in vivo, harvest, plate, count number of colonies that grow in vitro

Question 9

What is a xenograft?

Answer 9

Transplant a human tumor into a lab animal for growth and study

Requires an immunodeficient host (nude mouse, SCID mouse)

Question 10

What are drawbacks of a xenograft?

Answer 10

• Some rejection still possible
• Change in kinetics and cell selection
• Tumor stroma still mouse origin
• Lack of host immune system is artificial (can’t study IO based approaches)

Question 11

What are patient-derived xenografts?

Answer 11

Use NRG mice (B/T cell deficient from lack of RAG1, NK cell deficient from lack of IL-2), and introduce CD34+ hematopoietic stem cells to “humanize” them

Question 12

What are spheroids?

Answer 12

Spherical clumps of tumor cells grown in suspension

Mimic cell-cell contacts, diffusion limitation, waste buildup, and hypoxia of in vivo tumors

Question 13

What are the 5 layers/ 3 populations of a spheroid, which have varying radiosensitivity?

Answer 13

1. Asynchronous
2. Aerobic cycling cells (outer layer)
3. Aerated noncycling G1 like cells (intermediate)
4. Noncycling G1 like hypoxic cells (inner layer)
5. Possible necrotic core

Question 14

What are organoids?

Answer 14

Resected tumor tissue grown in an extracellular matrix gel

More physiological than spheroids (recapitulates complexity of tumor architecture)

Question 15

What are positive regulators of angiogenesis?

Answer 15

VEGF, bFGF, PDGF

Question 16

What are negative regulators of angiogenesis?

Answer 16

Angiostatin, endostatin, thrombospondin

Question 17

How does anti-angiogenic therapy work?

Answer 17

Transiently restores balance of pro/anti-angiogenic factors (in abnormal tumor vasculature) > vascular bed becomes less leaky, dilated, tortuous > increased tumor oxygenation and drug penetration

Question 18

What is angiogenesis?

Answer 18

Sprouting of endothelial cells from nearby blood vessels

Question 19

What is vasculogenesis?

Answer 19

Formation of blood vessels from circulating endothelial progenitors (bone marrow)

(vs angiogenesis which uses existing capillary structure)

*After anti-angiogenic treatment and after RT when local angiogenesis is abrogated

*Local recurrence relies on vasculogenesis