Why do cells divide?
- Healing and tissue repair
- Growth
- Reproduction of unicellular organisms
What are the 4 phases of the cell cycle?
M - Mitosis
G1 - Primary growth
S - Synthesis phase (DNA replicated)
G2 - Secondary growth
What happens in the G1 phase?
- Cells grow in preparation for DNA replication in S phase
- Organelle duplication
- Duration is variable - short in embryonic and cancer cells
- Cells that remain in G1 for a long time = G0 (permanent tissues, such as neural tissue)
What happens in S phase?
- DNA and centrosome replication
- Cells committed to go through cell division once the S phase starts
What happens in G2 phase?
- Cell growth continues
- Enzymes and proteins for cell division are synthesised
- Cell division machinery begins to assemble
How is the cell cycle regulated?
- External regulation eg. growth factor signalling
- Internal checkpoints
What are the internal checkpoints in the cell cycle?
- G1 checkpoint - DNA integrity, cell size and protein levels assessed
- G2 checkpoint - successful chromosome replication and no DNA damage
- M checkpoint - correct attachment of sister chromatids to spindle microtubules
What are some positive regulator molecules of the cell cycle?
Cyclins and cyclin-dependent kinases
Cyclin-dependent kinases are activated by interacting with the regulatory subunit cyclin
What are some negative regulator molecules of the cell cycle?
Rb, p53 and p21
What happens at the G1 checkpoint?
- Main checkpoint that commits a cell to division
- Sensitive to: cell size, nutrients, growth factors and DNA damage
- Cyclin D-cdk complex drives cell through G1 to S phase
What happens at the G2 checkpoint?
- Checks to see whether DNA replication is completed
- If any unreplicated DNA is detected, cells held at G2
- If damaged DNA detected, cells held in G2 until DNA
What is a mitotic promoting factor?
Cyclin B/Cdk1
What happens at the spindle assembly checkpoint (M checkpoint)?
- Prevents cells entering anaphase until all chromosomes are properly attached to the spindle
- Sensor for correct chromosome attachments are in the kinetochores
What does p53 do?
p53 is a tumour suppressor gene
- p53 introduces a temporary cell cycle arrest to allow DNA damage to be repaired
- If damage cannot be repaired –> programmed cell death (apoptosis)
- Mutation in p53 –> cell checkpoint no longer works –> cells replicate damaged DNA and acquire many mutations
What are the two basic components of tumours?
1) Parenchyma: neoplastic cells. Determines the biological behaviour of the neoplasm and the name of the neoplasm.
2) Reactive stroma: connective tissue, blood vessels, the supporting tissue. Determines growth and spread of tumour
What is a carcinoma?
Epithelial neoplasm
What is a sarcoma?
Connective tissue neoplasm
What are the differences between a benign tumour and a malignant tumour?
Benign:
- No local invasion
- No metastasis
- Retain function
- Variable growth rate, often low
Malignant:
- Locally invasive, infiltrate
- Frequently metastasise
- Lose function
- Variable growth rate, grow more rapidly
What does differentiation (in cancer cells) mean?
- Refers to the extent to which the neoplasm looks and functions like the parenchymal cells they are differentiating towards
- Most malignant neoplasms are graded as well (grade 1), moderately (grade 2) or poorly (grade 3) differentiated.
- Undifferentiated (anaplasia) reflects a total lack of differentiation and absence of specialisation
What are the sampling approaches for diagnosis of tumours?
1) Excision
2) Biopsy: needle core/punch
3) Fine-needle aspiration
4) Cytologic smears (blood/bone marrow/ascitic & pleural fluid/ urine/ stool)
What is the tumour regression grade used for?
Determines prognosis after treatment
TRG1 - TRG5
What cancers are people with Lynch syndrome more at risk of developing?
- Colorectal cancer
- Endometrial cancer
- Stomach cancer
- Ovarian cancer
What is relative risk reduction?
The reduction of risk in the intervention group relative to the risk in the control group
What is absolute risk reduction?
The difference between risk in the intervention and control group
