What is cancer? Flashcards
What is metaplasia?
A change from one mature cell type to another in response to a stimulus
What type of stimulus is the usual cause of metaplasia?
Noxious substances
How does smoking cause metaplasia?
Smoking causes thermal and toxic injury to the epithelium of the lungs
This causes metaplasia of the epithelium to squamous epithelium which is much more resistant to heat and trauma
What is the cause of Barrett’s oesophagus?
Gastric juices burn easily through squamous epithelium in the oesophagus
This causes metaplasia of squamous epithelium into glandular epithelium which releases alkaline mucin
What can constant metaplastic signals cause?
The cells eventually begins to ignore the signals and undergo metaplasia autonomously, even if the stimulus is stopped
What is dysplasia?
The abnormal development of cells
What are dysplastic lesions?
Lesions caused by the many mutation of cells, however is not yet malignant. It cannot yet invade tissue
What is pleomorphism?
The presence of many different shapes and sizes of cells
What is meant by a high nucleus:cytoplasm ratio?
A very large nucleus and little cytoplasm
What is hyperchromasia?
Different colours after staining
What is neoplasia?
New growth (Abnormal mass but unknown malignant potential)
What are the main categories of carcinogens?
Inherited predisposition
Chemicals
Radiation
Infection
Inflammation
Lifestyle factors
Bad luck
What is carcinogenesis?
The development of cancer
What syndrome is caused by mutation of p53?
Li Fraumeni syndrome
Which cancer’s risk is increased by a mutation of the BRCA gene?
Breast and ovarian cancer
What test is used to define chemical carcinogens?
The Ame’s test in which cells are introduced to the stimulus to see if it causes mutation
What compounds are carcinogenic within cigarette smoke?
Polycyclic aromatic hydrocarbons
What is the name of the fungus found on peanuts that can act as a carcinogen?
Aflatoxin
Which carcinogen used to be present in chemical dyes?
ß-naphthylamine
Which carcinogen is found in food preservatives?
Nitrosamines
Which cancer is arsenic a carcinogen to?
Skin cancer
Which type of radiation is a carcinogen?
UV-B
How does UV-B radiation act as a carcinogen?
It causes the formation of pyrimidine dimers (Thymine and Cytosine build up in unpaired lesions on the DNA)
This eventually overwhelms the nucleotide excision repair mechanisms
What occurs in Xeroderma pigmentosa?
A genetic defect that inhibits the nucleotide excision repair mechanism, leading to increased risk of skin cancers
What are 2 examples of viruses that act as carcinogens?
Epstein-Barr virus (Glandular fever/Mononucleosis)
Human Papilloma Virus (HPV16 and HPV18)
How can Human Papilloma Virus cause cancer?
E7 HPV proteins bind to the retinoblastoma protein
This allows for constant release of E2F
This allows constant passage of cells into the S phase
E6 HPV proteins bind to p53 and stop it from stimulating apoptosis or DNA repair
Which cancers can be caused by Epstein-Barr virus?
Burkitt Lymphoma
Hodgkin Lymphoma
What are the 2 routes of carcinogenesis in inflammation?
Constant immune stimulation leading to autonomous production
Adaptive response leads to high turnover of cells, leading to growth and metaplasia
How can coeliac’s disease lead to lymphoma formation?
Persistent immune stimulation during ingestion of gluten can lead to autonomous lymphocyte production
How can obesity lead to increased risk of endometrial cancer?
Cholesterol is analogous to oestrogen
More cholesterol = more oestrogen
Oestrogen stimulates hyperplasia of the endometrium which can lead to cancer
What are some examples of dietary components that act as carcinogens?
N-Nitrosamides in burnt meat
Nitrosamines in preserved meats
Both can cause bowel cancer
N-6-Polyunsaturated Fatty Acids
N-3 Polyunsaturated Fatty Acids
Arachidonic acid
Linolenic acid
All are pro-inflammatory so can increase risk of cancer
What causes Lynch Syndrome?
A mutation in the MMR genes (MisMatch Repair genes) which corrects DNA polymerase errors
What causes Gorlin syndrome?
Mutation of PATCH genes
How can cancers sustain proliferative signalling, meaning they can divide without stimulus?
Mutations in the pathway leading to the activation of growth factors that allow growth
What are the 3 most common mutations in the MAPK/ERK pathway?
EGFR, RAS and BRAF
How can Herceptin (Trastuzumab) prevent the growth of some cancer cells?
It binds to EGFR (EGF Receptor) and prevents the binding of EGF, stopping stimulation of growth
What is the most common mutation in the Wnt pathway?
APC mutation
What are some ways in which cancers can evade growth suppressors?
Mutation of the STAT3 gene causes dysfunction of the p53 protein which allows for cell checking and arrest before mitosis
Mutation of the Retinoblastoma can allow constant release of E2F, which is a potent transcription factor, allowing the cells to move into the S phase
PTEN mutations increases transcription of p27, which inhibits CDK, used in cell cycle checkpoints
How do cancer cells enable replicative immortality?
They can reactivate telomerase, found only in stem cells, meaning many TTAGGG repeats can be synthesised. The number of repeats controls how many times a cell can divide
How do cancer cels resist cell death?
Translocation t(14;18) activates Bcl2 which binds to BAX/BAC to prevent intrinsic apoptosis
What is an NSAID?
Non-Steroidal Anti-Inflammatory Drugs
