L34: Neoplasia II

Question 1

True or False: Cancer is the second leading cause of death in males and females

Answer 1

True

Question 2

True or False: Chronic inflammatory disease of the GI (UC, pancreatitis, hepatitis, H. pylori) can increase cancer risk

Answer 2

True

Mechanisms
- ROS cause genomic damage
- Increased stem cell pool
- Compensatory proliferation
- Maladative immune response

Question 3

What are the 7 mechanisms that form molecular basis of cancer?

Answer 3

1. Defects in DNA repair
2. Self-sufficiency in growth signals
3. Insensitivity to growth inhibition (loss of TS genes)
4. Evasion of apoptosis
5. Limitless replication potential
6. Sustained angiogenesis
7. Ability to invade and met

Question 4

Which condition is associated with increased chance of UV-induced skin cancer due to defects in nucleotide excision repair pathway?

Answer 4

Xeroderma Pigmentosum

Question 5

Activation of ____ allows for self-sufficiency in growth signals in cancer

Answer 5

Oncogenes (proto-oncogenes that have been mutated)

Question 6

True or False: Increased growth factor production is NOT enough to cause neoplastic transformation

Answer 6

True

Question 7

True or False: EGF/ERBB2 (HER2) is amplified in 25% breast cancers

Answer 7

True

Question 8

Which oncogene is the most common abnormality of proto-oncogenes?
A. RAS
B. HER-2

Answer 8

A. RAS

Question 9

Melanomas, colon/lung/pancreatic/kidney/bladder tumors involve which proto-oncogene?
A. Cyclin D
B. MYC
C. RAS/RAF

Answer 9

C. RAS/RAF

Question 10

Burkitt Lymphoma, small cell lung carcinoma, and neuroblastoma are associated with which proto-oncogene?
A. Cyclin D
B. MYC
C. RAS/RAF

Answer 10

C. RAS/RAF

Question 11

____: A gene that, when mutated, causes a decrease or LOF

Answer 11

TS Gene

Question 12

What does Knudson’s 2 Hit Hypothesis of Oncogenesis state?

Answer 12

1) Need to lose both functional alleles of a TS gene
2) Loss of a single allele of a TS - “Haploinsufficiency”

Question 13

True or False: There is a sporatic and familial form of Rb

Answer 13

True

Question 14

___, the most common TS gene and most common target for genetic alterations in tumors

Answer 14

p53

Question 15

Mutated p53 has ___ activity over WT p53 (does not need to lose both alleles - one is enough)
A. recessive
B. dominant

Answer 15

B. dominant

Question 16

If a mutation is inherited with p53 mutation, what is the condition known as? In this case, p53 has dominant activity over WT, meaning?

Answer 16

Li-Fraumeni Syndrome
- do not need to lose both alleles – one is enough

Question 17

True or False: p53 can lead to G1 arrest, DNA repair, and apoptosis

Answer 17

True

Question 18

Which apoptotic pathway is mediated by death receptor? Which is mediated by stress, radiation, and chemicals?

Answer 18

Extrinsic: death receptor
Intrinsic: stress, radiation, and chemical mediated

Question 19

ok

Answer 19

Question 20

Cancer cells increased levels of the enzyme ___, which prevents telomere shortening, leading to “limitless” replicative potential

Answer 20

telomerase

Question 21

All tumors consists of which two components?

Answer 21

1. Parenchyma - clonal neoplasic cells
2. Stroma - CT, B. vessels, macrophages, lymphocytes

Question 22

True or False: Cancer cells can stimulate neoangiogenesis (new vessels sprout from existing capillaries) and vasculogenesis (endothelial cells from b. marrow)

Answer 22

True

Question 23

What does angiogenesis provide cancer cells?

Answer 23

1. Nutrients and endothelial cells secrete GF
2. Access to vasculature

Question 24

____ are enzymes made by cancer calls that promote angiogenesis. Results in remodeling of ECM

_____ results in increased production of pro-angiogenic GF’s (FGF and VEGF)

Answer 24

Protease; Hypoxia

Question 25

In cancer, cytokines increase endothelial growth and attract new ___ towards the tumor

Answer 25

vessels

Question 26

How does cancer invade and metastasize?

Answer 26

1. Invades ECM
2. Vascular dissemination, homing, colonization

Question 27

Steps by which invasion/met occur?

Answer 27

1. Tumor cells detach from each other due to decreased E-Cadherin
2. Enzymes secrete from tumor and stromal cells degrade BM
3. Binding of tumor cells to proteolytically generated binding sites
4. Tumor cell migration

Question 28

What is the first hit and second hit in evolution of colorectal cancers (adenoma-carcinoma sequence)?

Answer 28

First - germline or somatic mutation of cancer TS genes
Second - methylation abnormalities

Question 29

ok

Answer 29

Question 30

What are two examples of inherited predispositions to cancer?

Answer 30

1. Autosomal dominant inherited cancer syndromes
   - point mutation is a TS
2. Autosomal recessive
   - defects in DNA repair leads to DNA instability

Question 31

CA-125 is a tumor marker for ___ cancer while MYCN is a tumor marker for ___ cancaer

Answer 31

ovarian; neuroblastoma

Question 32

True or False: PSA and CA-125 are biomarkers found in the blood while HER-2 and ER are biomarkers found in the tumor itself

Answer 32

True

Question 33

BRAF V600E activating mutations are found in melanoma patients. Which drug type is best for treating these patients?

Answer 33

BRAF Inhibitors

Question 34

Which two biomarkers can be used to stage the disease?
A. MYCN
B. Neuroblastoma
C. PSA
D. BRCA1/2

Answer 34

A. MYCN/ B. Neuroblastoma

Question 35

True or False: Bcr-Abl and CML are biomarkers that can be used to dx

Answer 35

True