11 Molecular Basis of Cancer 2

Question 1

Apoptosis typically looks like?

Answer 1

• nuclear condensation
• cell shrinkage
• scattered

Question 2

necrosis typically looks like?

Answer 2

karryorhexis, karryolysis, pyknosis, inflammation, group

Question 3

T/F apoptotic cells cut their DNA into specific chunks?

Answer 3

T (unlike necrosis)

Question 4

T/F p53 activates apoptosis?

Answer 4

T

Question 5

What is the mechanism of p53 action?

Answer 5

working p53 catches DNA damage-> transcribe p21 to arrest cell cycle, bax to apoptosis, or GADD45 for DNA repair

Question 6

What creates hair loss, GI crypt death, bone marrow death in radiation treatment?

Answer 6

p53

Question 7

T/F BOTH p53 and Rb must be lost to allow tumor development?

Answer 7

T

Question 8

2 genes at the same Ink4 locus encode what?

Answer 8

• p16 activates Rb (p16 inhibits cyclin D which inhibits Rb)
• p14 activates p53 (p14 inhibits MDM2 which inhibits p53)

Question 9

knocking out Ink4 would lead to?

Answer 9

cancer! (Rb inactivation)

Question 10

activation of Rb leads to?

Answer 10

cell cycle shutdown at G1/S

Question 11

T/F p53 is usually found in high levels in tumors?

Answer 11

T. (p53 in mutated form which can’t feedback to MDM2 to say “degrade me!”)

Question 12

bcl2 does what?

Answer 12

stops apoptosis (present in follicular B cell lymphomas!)

Question 13

t14:18 translocation should ring a bell for?

Answer 13

-Ig heavy chain enhancer stuck next to Bcl-2 (b-cell lymphomas)

Question 14

how many doublings in a normal cell till senescence?

Answer 14

~60

Question 15

T/F telomere shortening creates genetic instability when p53 is dead?

Answer 15

T

Question 16

Telomerase dose?

Answer 16

lengthen telomeres

Question 17

PML-retinoic acid receptor gene product sounds like what disease?

Answer 17

acute promyelocytic leukemia

Question 18

acute promyelocytic leukemia: treatment?

Answer 18

all-trans-retinoic acid (induces terminal differentiation of leukemia cells) thus also reducing DIC (disseminated intravascular coagulation)

Question 19

limit of tumor growth distance from blood vessel?

Answer 19

1 mm

Question 20

angiogenesis is acquired early in tumor development?

Answer 20

F, late

Question 21

What factors promote angiogenesis?

Answer 21

VEGF

Question 22

What inhibits angiogenesis?

Answer 22

angiostatin, avastatin (anti-VEGF-Ab)

Question 23

What is thalidomide good for?

Answer 23

treating multiple myeloma (anti-angiogenic) and creating birth defects

Question 24

VERY important. Review don’t memorize: metastasis process? (11)

Answer 24

• metastatic subclone
• loosen intercellular junctions
• adhere to basement membrane (fibronectin receptor, laminin receptor)
• Invade basement membrane (type 4 collagenase)
• pass thru ECM
• intravasation
• interact w/ lymphoid cells-> embolus
• adhere to basement membrane
• extravasate
• deposit
• angiogenesis
• grow

Question 25

E-cadherin does what in tumors?

Answer 25

decreases, loosening intercellular junctions (esp gastric cancer!)

Question 26

What is a rule for metastasis end location? 3 classic examples?

Answer 26

often to first tissue encountered - sarcoma to lung - lung carcinoma to brain - colorectal cancer to liver

Question 27

Tumor tropism classic examples?

Answer 27

- breast cancer to ovary | - clear cell carcinoma of kidney to thyroid

Question 28

Which HPV has greatest cervical cancer risk?

Answer 28

HPV 16

Question 29

Which HPV makes condylomas? (worts)

Answer 29

HPV 11

Question 30

How will you remember what E6 and E7 do?

Answer 30

-E6 inactivates p53 -E7 inactivates Rb [6 before 7, p before r. NEITHER affects the actual gene.]

Question 31

4 steps of cervical cancer?

Answer 31

- Rb, p53 loss (live longer) - HGSIL/CIS changes and angiogenesis - invasion - mets

Question 32

length of cervical cancer premalignant phase?

Answer 32

13 yrs

Question 33

Gardasil blocks what HPV types?

Answer 33

- 16 - 18 - 6 (warts) - 11 (warts)