Cancer 'The How' Flashcards
What are the 10 hallmarks of cancer
Avoiding immune destruction
Evading growth suppressors
Angiogenesis (make blood supply)
Replicative immortality
Invasion & metastasis
Genomic instability
Resist cell death
Degranulation energetics
Proliferative signals
What is tumour heterogeneity
Different components in every tumour due to genomic instability. Same drug/treatment not work on every tumour
Why do neoplastic cells become immortal
Keep proliferating
Abnormal oncogene expression
Inactivate tumour suppressors
Genes inhibiting apoptosis
what is a tumour suppressor
Genes inhibit neoplastic growth in normal conditions
Genes can be Caretaker or Gatekeeper
What are gatekeeper and caretaker genes
Gatekeeper- Stops damaged cells dividing
Caretaker- Repairs DNA damage
What has gatekeeper and caretaker functions & how does it lose this
p53
Loses function from mutations, binding to oncoproteins of viruses and mutants
What is an oncogene
Genes which drive neoplastic behaviour of cells. Make oncoproteins
What are the 5 groups of oncogenes
Growth factors
Receptors of growth factors
Signalling mediator with- Tyrosine kinase or nucleotide binding activity
Nuclear binding transcription factor
What genomic instability terms are in neoplastic cells
Diploid, Polyploidy or aneuploidy
What is diploid
Normal amount of DNA, 2 copies each chromosome
What is polyploidy
Exact multiples of diploid state in cell tetraploidy=4N octoploidy= 8N
What is aneuploidy
Cell contains inexact chromosome numbers- Translocations
What is a carcinogen
Environmental agent participating in causing tumours
What is a mutagenic carcinogen
Acts on DNA of cells
How are carcinogens identified
epidemiological studies
Direct evidence- Chernobyl
Experimental testing e.g animals + cells
Occupational risks
What cancer did Chernobyl cause
Thyroid carcinoma
What cancer and carcinogen is caused by smoking
Carcinomas- skin, lung and mouth
Aromatic hydrocarbons= carcinogen
What carcinogens cause bladder cancer
Aromatic amines in rubber/dye industry and azo dyes from mutagenic
What carcinogen causes angiosarcoma
Vinyl chloride in PVC maufacuring
What carcinogen causes GI cancers
Nitrosamines in tobacco and cured meats
What is HPV in 5 steps
- Get infected with high risk HPV subtype
- Virus integrates into host genome
- E6 viral oncoprotein acts on TP53 making p53
- E& viral oncoprotein acts on RB coding for retinoblastoma protein
- Neoplastic cells with integrated viral gene keep replicating
What cancers can Epstein Barr Virus (EBV) cause
Lymphomas and carcinomas
What lymphomas are EBV associated with
Burkitt (high grade B cell)
Hodgkin
Primary effusion
What carcinomas are EBV associated with
Squamous cell carcinomas
Nasopharyngeal Carcinoma- combination with smoking/EBV
What cancers can UV light cause
Malignant Melanoma
Basal cell carcinoma
What is a melanoma
Melanocytes are neural derived cells in basal layer of epidermis producing melanin pigment
What is a basal cell carcinoma
Tumour of skin which is 80% of of skin cancers associated with sunburn
What is ionising radiation
Radiation which detaches electrons from atoms/molecules like X-ray, nuclear radiation and gamma
What tissues are sensitive to carcinogenic effects of ionising radiation
Thyroid
Breast
Bone
Why are epithelial origin carcinomas more prominent in >60 years
As increasing somatic genetic mutation and loss of immune competence
Why can diet cause carcinogenesis
Excess adipose tissue has higher levels of growth hormones (oestrogen causes cancer)
Processed meats have nitrosamines (chemical carcinogen)
What inherited mutation predispose to breast and ovarian cancers
BRCA1 and BRCA2
How do neoplastic cells increase chances of invasion
decrease cellular adhesion
Increase cellular motility
Secrete proteolytic enzymes (damage tissue surrounding)
How does metastasis occur
- Detachment
- Invades surrounding tissue
- Intravasation to vessels
- Evasion host defences
- Adhere to other endothelium
- Extravasation of cells from vessel into surrounding new tissue
What is metastasis
Process where tumour cells get from site of origin to secondary site
What are the routes of metastasis
Haematogenous
Lymphatic
Trans coelomic (across body cavity)
