Outline of Disease Process CANCER Flashcards
What does “cancers are mostly monoclonal” mean?
Mainly arise from one cell
Whats different about cancer cells?
Increased growth factor secretion
Increased in oncogene expression
Loss of tumour supressor genes
Loss of contact inhibition
What are the 5 steps of carcinogenesis?
Carcinogen
Initiation
Promotion
Tumour Growth
Progression
What is a diagnostic threshhold?
Size at which a cancer becomes clinically detectable
What are the 3 types of carcinogens?
Chemical
Physical
Viral
What chemical carcinogen causes liver cancer?
Aflatoxin (in mouldy peanuts)
Most common chemical carcinogens?
Smoking & alcohol
Physical carcinogen?
Ionising radiation
How does ionising radiation cause cancer?
- Translocate chromosomes
- Amplify certain Genes
- Activate Oncogenes
What viral carcinogen causes burkitts lymphoma?
Herpes virus
What viral carcinogen caues liver cancer?
HEP B
What 3 things are involved in the promotion stage?
Oncogenes
Tumour suppressor genes
Growth factors
How do oncogenes promote the progression stage?
Positive growth regulators, stimulate tumour growth
How do growth factors stimulate cell growth?
Bind to cell-membrane receptors & activate intracellular signal transduction pathways
Whats the difference between autocrine & paracrine signalling?
Paracrine signalling - signals act on nearby cells
Autocrine - signals acting on the same cell that produces them
Whats the normal function of tumor suppressor genes?
Promoting:
DNA repair
Apoptosis
Differentiation
What normally induces tumor suppressor genes to act?
Hypoxia & DNA damage
Name a tumor supressor gene
P53
How does progression (metastasis) occur?
Tumour invades through basement membrane
Invades ECM/CT/other cells
Invades blood vessels
Cells arrested in distant tissue
Describe the progression stage
Series of limited sequential steps involving host-tumour interactions
At what point is angiogenesis vital for continued tumor growth?
New vessels must form for a tumour to grow beyond 2mm in diameter
How does angiogenesis affect the ECM?
Enzymes degrade ECM to allow for new vessel growth
How is angiogenesis related to cancer severity?
Higher density of blood vessels, more severe tumour malignancy/metastasis
How is angiogenesis inhibited?
Avastin (anti-VEGF antibody) binds to VEGF
Prevents VEGF-receptor interaction
(VEGF = Vascular endothelial growth factor)
What is the ultimate effect of anti-VEGF treatments?
Vascular regression & dormant tumours
What is the purpose of T cell inhibition receptors?
Maintain self-tolerance & protect tissue during immune responses
How do tumours blind T cells?
Express specific ligand and bind to T cell inhibition receptors
What ligand/receptor combo is used by cancers to blind T cells?
ligand on cancer cell = PDL-1
Receptor on T cell = PD1
Explain therapeutic options to bypass T cell blindness to cancer cells?
Block PDL-1 on cancer cell or PD1 on T cell
Modified artificial T cells - CAR T cells (chimeric antigen receptors)
What is Epithelial Mesenchymal Transition (EMT)
Conversion of connected epithelial cells to
independent mesenchymal cells
Enables the ability to move and invade local environment
Reversible
Occurs in Embryogenesis, cancer metastasis
What is the function of integrin
Allows cells to become mobile
What is the function of proteases in cancer
Creates Pathway through ECM
Matrix Metalloproteins
Contributes to loss of cell junctions
