Cellular and Environmental Basis of Malignancy

Question 1

12 warning signs of cancer

Answer 1

Excessive hair growth that is coarse and dark
Abnormal period cycles
Backpain
Belly bloat
Pelvic/abdominal pain
Constipation
Difficult eating
Nausea
vom
Fatigue
Increased gas
Urinary symptoms
painful sex

Question 2

What are the three main ISSUES of cancer

Answer 2

1. Too many cells
   - dysregulated cell cycle/uncontrolled proliferation
   - response to proliferative signals
   - ignoring anti-proliferative signals
   - avoiding cell death
   - evading the immune system
2. Cells doing the wrong ‘job’ at the ‘wrong’ time
   - de-differentiation
3. Cells in the wrong place in the body
   - angiogenesis, invasion, metastasis -> cells in search of nutrients,
   oxygen and to evade the immune system

Question 3

Smoking and cancer

Answer 3

Chemicals in the cigarette smoke cause DNA adducts e.g. Nicotine Derivative
Nitrosaminoketone (NNK) and Polycyclic Aromatic hydrocarbons (PAH e.g.
benz[a]pyrene)

Initiates via G->T and G->A transitions (mutations in the DNA)

Promotes via cell signalling -> stimulates acetylcholine receptors (nAChRs) causing cancer on lung epithelium and angiogenesis on endothelial cells

Question 4

Cancer and UV exposure

Answer 4

UVB -> direct DNA damage
-> C to T transitions
-> CC to TT tandem repeats
-> strong initiator and promoter

UVA -> Reactive Oxygen Species
-> indirect DNA oxidation + damage
-> weak initiator, strong promoter

Lecture Slide

Question 5

Viruses that cause cancer

Answer 5

Human Papillomavirus (HPV)
Hepatitis B and C (HBV, HBC)
Kaposi’s sarcoma Herpesvirus (KSHV)
Human T-Lymphotrophic (HTLV)
Merkel Cell Polyomavirus (MCPyV)
Epstein Barr (EBV/ HHV-4)

Question 6

How does Hep B cause cancer

Answer 6

Aflatoxin B1 -> consumption -> Liver -> metabolised -> product binds DNA covalently -> DNA damage characterised by G->T transversions
= initiator

AND

HBV -> virus liver infection -> production of oncogenic proteins (HBX) -> cell death, chronic inflammation, proliferation, interference with DNA repair proteins, production of ROS
= progressor

Question 7

Tumour Invasion and Metastasis process

Answer 7

1. Acquisition of invasive potential
   - TSGs/Metastatic supressor genes
2. Expansive growth and invasion of the basement
   membrane
   - Enhanced protease activity (e.g. MMPs)
   - Enhanced cell motility and interactions with ECM/stroma
   - Decrease integrity of cell-cell contacts (e.g. E-cadherin)
3. Angiogenesis, intravasation and transport
   - Migration/interaction through ECM
   - Interaction with vascular cells
   - Invasion into blood vessel
   - Survival in circulation/immune evasion
4. Arrest and extravasation at secondary site
   - Interaction with vascular cells
   - Invasion into secondary tissue
5. Invasion of secondary tissue and formation of metastasis
   - Invasion/migration into secondary tissue
   - Interaction and adaptation to tissue microenvironment
   - Establisment of new blood vessels
   - Secondary tumour establishment or dormancy

Question 8

Define tumor

Answer 8

Tumour = malignant cells + stroma

Question 9

Stroma in Malignant Melanoma
- why is the first option to cut blood supply to tumor?

Answer 9

Angiogenesis inhibitors cut blood supply to tumor which it needs for
- Oxygen
- Nutrients
- Pathway to spread/metastasise

Question 10

3 responses that T cells have for cancer cells

Answer 10

UV light = DNA Mutations = Wrong/new peptides = Neoantigens

Elimination
Escape (no recog)
Escape (stop signals from cancer cell)