MBB 446 Lecture 6

Question 1

What is cancer?

Answer 1

• Progressive disorder of signaling transduction leading to uncontrolled cell growth
• Balance of growth stimulators (proto-oncogenes) and growth inhibitors (anti-oncogenes); Tumours due to activation of one and or inactivation of the other.

Question 2

Describe the multistage steps in carcinogenesis

Answer 2

1. Normal cell (Normal cell line)
2. Carcinogenic agent: chemical agent, radiation, virus (DNA damage and cell mutation)
   INITIATION
3. Activation of oncogenes by promoter agent
   PROMOTION
4. Malignant tumor
   PROGRESSION

Question 3

Lifetime probability of cancer in females vs. males?

Answer 3

Lifetime probability 45.4% female

49.4% Male

Question 4

Examples of GENETIC initiators of cancer

Answer 4

1. Mutation
2. Fusion
3. Amplification/Deletion

Question 5

Examples of ENIRONMENTAL initiators of cancer

Answer 5

1. Smoking
2. Radiation
3. Chemicals and environmental materials e.g. Asbestos
4. Sunlight (UV)
5. Infectious Agents

Question 6

Global Cancer Burden Caused by infectious Agents; Developed world vs. developing world?

Answer 6

Developed world ~20%

Developing world ~30-40%

Question 7

Cancers caused by HPV?

Answer 7

Cervical, Anal, Oropharyngeal, Penile, Conjunctival

Question 8

Cancers caused by EBV

Answer 8

Buritt’s Lymphoma, Naso-pharyngeal, Hodgkin’s

Question 9

Cancer caused by F. Nucleatum

Answer 9

Colo-rectal

Question 10

Cancer caused by HCV

Answer 10

Liver

Question 11

What are Koch’s 4 postulates

Answer 11

1. Association and Causation
2. Transforming Ability
3. Presence
4. Activity

Question 12

What are the 5 key cell regulators that are commonly affected in cancer

Answer 12

1. P53 (50% inactivated)
2. Ras (33% constitutively on)
3. PTEN (50% down)
4. pRb
5. NFkB

Question 13

Virus can mediate activation of _____ or inactivation of _____ through direct or indirect mechanisms

Answer 13

Virus can mediate activation of ONCOGENES or inactivation of TS through direct or indirect mechanisms

Question 14

How does polymaviruses drive cell cycle in order to replicate?

Answer 14

1. Large T interferes with p53 and Rb.
2. Causes increases in c-myc and cyclin D1
3. Agnoprotein binds to p53
4. Small t-mitogen, inhibits protein phosphate 2A

Question 15

How does Human T-lymphotropic virus 1 (HTLV-1) promote cancer

Answer 15

** Not insertional mutagenesis like most oncogenic retroviruses**

1. Tax binds to factors leading to gene regulation
2. Binds to IkB leading to NFkB activation
3. Induces prosurvival Bcl-XL
4. Also inactivates INK4A

Question 16

EBV LMP1 gene activates ____ via TRAFs. LMP2-PI3K and Akt

Answer 16

NFkB

Question 17

___ - K1 and vGPCR transforming capacity

Answer 17

HHV8

Question 18

HBV and HCV - HBx binds ___, interacts with DDB1

Answer 18

p53

Question 19

HPV and cancer

Answer 19

1. HPV infection of basal/suprabasal keratinocytes
2. Non-cytolytic virus replication. Expression of “early” orf genes
3. Distal movement of infected cells. “Late” gene expression and capsid formation. Viral DNA linearization. Viral DNA integration into host genome leads to uncontrolled viral oncoprotein production and host cell transformation.
4. Invasive neoplasia