Neoplasia 2

Question 1

Proto-oncogenes

Answer 1

regulate cell growth/differentiation

Question 2

Driver mutations

Answer 2

involve tumor suppressor genes

Question 3

3 steps of neoplasia

Answer 3

1. Initiation = IRREVERSIBLE mutation
2. Promotion = REVERSIBLE change that selects outgrowth of initiated cells (benign tumor)
3. Progression = IRREVERSIBLE transition from benign to malignant

Question 4

What are the 4 preneoplastic changes?

Answer 4

1. hypertrophy
2. hyperplasia
3. metaplasia
4. dysplasia

Question 5

Procarcinogens are often metabolized by

Answer 5

Cytochrome p450

Question 6

Squamous cell carcinoma progression

Answer 6

1. Initiator and promoter = UV light
   - Creates pyrimidine dimers
2. Preneoplastic changes = hyperplasia and dysplasia

Question 7

Which 3 tumor types are UV-induced?

Answer 7

1. Squamous cell carcinoma
2. Cutaneous hemangioma
3. Hemangiosarcoma

Question 8

What causes urinary bladder neoplasia in cattle?

Answer 8

Bovine papillomavirus with bracken fern (chronic toxicity)

Question 9

Which virus uses the host’s DOMINANT ONCOGENES?

Answer 9

Feline Leukemia Virus

Question 10

Infection with which virus leads to insertional mutagenesis?

Answer 10

Avian Leukosis Virus

Question 11

Name an example of a “hit-and-run” virus (i.e. a virus that does not remain part of a tumor)

Answer 11

Bovine p;apillomavirus

Question 12

Which viruses alter immune surveillance?

Answer 12

Shope virus

Marek’s disease

Question 13

List the 10 hallmarks of cancer and their mediators

Answer 13

1. Sustained proliferation
2. Evading growth suppressors
3. Avoiding immune system
4. Replicative immortality
5. Tumor-promoting inflammation
6. Invasion and metastasis
7. Angiogenesis
8. Genome instability (failure to repair DNA)
9. Resisting death
10. Disregulating energetics

Police Get Immediately Reprimanded If Investigative Agents Get Damning Evidence

Question 14

Mutation in ____ enables sustained proliferation of tumors

Answer 14

RAS

Question 15

_____ activates RAS while _____ deactivates it.

Answer 15

GEF activates

GAP inactivates

Question 16

Phosphorylation of retinoblastoma by cyclin-dependent kinases releases ____, which promotes the cell cycle.

Answer 16

E2F

Question 17

Warburg effect

Answer 17

tumor cells exhibit increased glucose uptake and conversion to lactose

Question 18

What are 4 possible functions of the Warburg Effect?

Answer 18

1. Microenvironment: Enhance disruption of tissue architecture/immune cell avoidance
2. Cell signaling
3. Rapid ATP synthesis
4. Biosynthesis flux

Question 19

BCL2

Answer 19

Anti-apoptotic protein that opposes p53

Question 20

Telomere shortening does not lead to apoptosis in cancer cells because:

Answer 20

1. Some cancer cells possess telomerase
2. Some cancer cells inhibit p53; in this case, uncorrected telomere shortening results in fusion of two chromatids and chromosome breakage during mitosis

Question 21

Which enzymes fix single nucleotide mismatches?

Answer 21

MLH1 and MSH2

Question 22

Aside from supplying nutrients and contributing to metastasis, what is the third function of tumor-induced angiogenesis?

Answer 22

Stimulates growth of adjacent tumor cells by secreting growth factors such as IGF and PDGF

Question 23

Which factors up-regulate VEGF-mediated angiogenesis?

Answer 23

1. Hypoxia -> HIF1a

2. RAS

Question 24

Thrombospondin-1

Answer 24

Angiogenesis inhibitor promoted by p53

Question 25

List the steps of invasion/metastasis

Answer 25

1. Loosening of cell-cell contacts by E-cadherin inactivation 2. Degradation of ECM 3. Attachment to new ECM 4. Migration to 1st capillary bed encountered 5. Adhesion of tumor cells and activation of coagulation cascade/embolus formation

Question 26

Tumor specific antigens include

Answer 26

Viral antigens Altered cellular products Embryonic antigens

Question 27

Name 3 ways that tumors avoid the immune system (aside from tolerance)

Answer 27

1. Altered Major Histocompatability Complex (MHC) expression 2. Masking antigens w/ glycocalyx/fibrin 3. Immunosuppressive agents - TGF-a: Inhibits lymphocyte proliferation - FAS L: lymphocyte apoptosis