CSIM 1.6 Neoplasia 3 Flashcards
What is transformation?
What is carcinogenesis?
The cellular changes that enable a cell to form a tumour, carcinogenesis is the molecular process underlying this
What are the three types of cells with regard to replication
Which of these are most likely to develop neoplasms?
Permanent cells
Quiescent cells
Continuously cycling cells
Continuously cycling cells
What are cyclins?
Cyclin-dependent kinases (CDK) - these fluctuate in a cyclical manner and have difference concentrations in different parts of the cell cycle
What happens to cyclins in cancer?
They become abnormally activated due to transformation of cyclin genes into oncogenes
What is retinoblastoma protein?
A protein which is a negative regulator of the cell cycle: binds to transcription factors which regulate the genes controlling cyclin levels throughout the cell cycle
It is therefore a tumour suppressor gene
What behavioural differences are seen in tumour cells?
- Loss of contact inhibition (most epithelial cells’ division is inhibited when they come into contact with other cells in the layer)
- Reduced cohesion
- Reduced GF requirement
- Immortal (no hayflick limit)
What is ‘tumour clonality’?
Genetic hypothesis of cancer which states that a tumour mass arises from a single progenitor cell which has incurred repeated genetic damage, therefore most tumours are MONOCLONAL (but still heterogeneous when detectable)
What is the evidence for tumour monoclonality?
In women, where one of their two X-chromosomes (let’s say Xa and Xb) is always deactivated randomly, yet all tumours always have only Xa OR Xb chomosomes active
This is tested for by looking at glucose-6-phosphate dehydrogenase isoenzymes, of which there are many variants, all X-linked
What factors determine the growth rate of tumours
Cell production speed Cell loss: • Shedding • Lack of cohesion • Differentiation • Reversion to G0
What is ‘growth fraction’?
What are the implications of a high and low growth fraction
The proportion of cells which remain in the proliferating pool
High = rapid course and growth of tumour
Low = slower growth
Which growth fraction tumours are often more easily treated?
High growth factor tumours, as chemotherapy is targeted at rapidly dividing cells, and these fast tumours have less time to mutate in more harmful ways
What host factors can affect hormone growth?
- Hormones
* Vascular supply
The growth of which cancers is affected by host hormones? Which hormones affect each
Breast cancer • Oestrogen Prostate cancer • Androgens Uterine leimyosomas • Oestrogen Endometrial cancer • Oestrogen
Which tumours require vascularisation for further growth?
What does this vascularisation allow the tumours to do?
Those over 1-2mm
- Gain oxygen and nutrients
- Metastasise
Through which process can tumours generate their own blood vessels? How do they do this?
Tumour angiogenesis:
• Tumour cells and infiltrating inflammatory cells make angiogenic growth factors
> VEGF
> bFGF
Describe what is meant by tumour heterogeneity
Tumours form ‘subclones’ as different cells within the tumour which are genetically unstable acquire different mutations
How many cells are there in the following tumours, and how many divisions is needed to reach each?
1) 1g tumour
2) 1kg tumour
1) 10^9 cells, 30 divisions
2) 10^12 cells, 10 further divisions (after 1g tumour)
What may occur due to mutations resulting from genetic instability in some subclones
Apoptosis of cells with mutations which make cellular survival inviable (IMG 28)
What is the implication of heterogeneity?
Any given treatment is unlikely to treat all subclones of a tumour
What do mutations leading to tumours do?
Describe if a mutation in each is dominant or recessive
Activate growth-promoting oncogenes
• Mutations dominant over the normal allele
Inactivate tumour suppressor genes
• Recessive - mutations in both alleles needed for this inactivations
Alterations in genes regulating apoptosis
• Can be recessive or dominant
Changes in DNA repair genes can also occur
• Recessive
What viral oncogenes are introduced by cancer-causing retroviruses?
Retroviral transformation gene
Where do viral oncogones come from/ how are the developed by the virua?
When a virus infects a host cell, and inserts its DNA into a gene, some of the host’s DNA is incorporated into the protein product, and thus the genetic information of the daughter viruses. If this gene happens to be an oncogene, these viruses may infect another cell and ‘deliver’ that oncogene, thus spreading it around
This is an issue, as cellular oncogenes are usually very tightly controlled, however this process may activate them inappropriately
What do cellular oncogenes normally do?
Regulate normal growth and differentiation (but can become inappropriately ‘activated’)
Why are cellular oncogene mutations dominant?
They ADD a function (through their inappropriate activation), so only one copy needs to be present
