Neoplasia 3 Flashcards
How do infections induce neoplasms indirectly?
- Chronic tissue injury and regeneration -> mutations
- Reduced immunity e.g. HIV
- Helicobacter pylori
How do infections induce neoplasms directly?
- Directly: affects genes controlling cell growth
- HPV: E6 inhibits p53 (reparative/apoptosis)
E7 inhibits pR6 (cell proliferation)
What link is there between chemicals neoplasms?
- Long delay between carcinogen exposure and malignant neoplasm onset
- Risk depends on carcinogen dosage
- Sometimes organ specific
What is meant by a complex carcinogen?
- It is both an initiator and promoter
- Smoking
What sources of radiation are commonly the cause of some neoplasms?
- Radon gas
- Medical tests
- UV light
- Free radical damage
- Ionising radiation: radioactive (a,b,y)
electromagnetic (y,X,UV)
What types of damage can radiation cause?
- Indirect damage: free radicals
- Direct DNA damage: altered bases, single/double stranded DNA breaks
Why is someone more likely to obtain cancer if they have a family history?
- First hit is inherited via germ line
- Affects all cells in the body
- Easier to obtain cancer with germline mutation already present
What roles do RAS and RB genes have in neoplasia?
- RAS encodes for a small G protein
- This pushes cells past cell cycle restriction point
- Mutation causes this to be constant
- RB restricts cell passage through restriction point
- Mutation = no control
What are the 6 main hallmark cellular behaviours?
- Self sufficient growth signals
- Resistance to anti-growth signals
- Grows indefinitely
- Induces new blood vessels
- Apoptosis resistance
- Invades and produces metastasise
What do Proto-oncogenes do and what happens to them in neoplasia?
- Encode growth factors and receptors
- Plasma membrane signal transducers
- Intracellular kinases
- Transcription factors
- Only one of the POG alleles need to be activated for neoplastic growth
What do tumour-suppressor genes do and how are they affected in neoplastic growth?
- TSG supply anti growth factor effects
- Needs both alleles to be inactivated hence 2 hit theory
Outline the adenoma to carcinoma sequence
- Normal epithelium -> early adenoma -> intermediate adenoma -> late adenoma -> carcinoma -> metastasis