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Flashcards in Disease process of cancer Deck (13):
1

Causes of cancer

- Initiation
- Promotion
- Progression (metastasis)

2

Initiation

- Chemical: alcohol, smoking, tar etc.
- Physical: ionising radiation, mechanism: chromosome translocation, gene amplification, oncogene activation
- Viral: Herpes virus, papillomavirus, hepatitis B

3

Promotion

- Growth factors
- Oncogenes

4

2 methods of stimulation for growth factors

- Autocrine: cell carries receptor and secretes growth factor (GF)
- Paracrine: GFs acting on a cell are produced locally by the cell or its immediate neighbours

5

Growth factors

- Polypetide molecule
- Regulate cell growth and function
- Bind to cell membrane receptors
- Stimulate activation of intracellular signal transduction pathways

6

Oncogenes

- Transforming genes
- Positive regulators of growth
- Represent a gain in function to transformed cells

7

Tumour suppressor genes

- e.g. P53
- Most commonly altered gene in human tumours
- Normal function is as transcriptional regulator, promotes DNA repair, apoptosis, differentiation
- Induced by DNA damage and hypoxia
- G1/S checkpoint control gene

8

Metastasis

- Not random
- Cascade of limited sequential steps
- Involves tumour-host interactions
- 'Survival of the fittest' pertains. So the healthier you are, the better the outcome

9

Invasion and metastasis

- Tumour invades through basement membrane
- Moves into extracellular matrix/connective tissue/surrounding cells
- Invades blood vessels
- Tumours cells 'arrested;' in distant organ
- Enzymes involved from the ECM: plasmin, cathepsin
- Enzyme involved from cell adhesion: integrins and loss of cahedrins correlates with tumour invasion and metastasis

10

Steps of invasion of metastasis

- Primary tumour -> intravasation -> circulating tumour cell in vessel -> extravsation -> metastases

11

Angiogenesis

- Formation of new blood vessels is a key factor in the maintenance and progression of malignant tumours
- For tumour to grow >2mm there needs to be new blood vessels

12

Example of understanding molecular biology can result in improved treatment methods

- Growth factors
- Anti-VEGF antbodies can prevent interaction of VEGF with its receptors
- Can prevent interaction with receptors
- Activation of downstream signalling pathways
- Can lead to vascular regression and a dormant tumour

13

How the immune systems recognise 'foreign' cancer cells

- Cancer cells can 'hide' from T cells
- PD1 (programmed death receptors) is present on T lymphocytes
- Ligand (PGL-1) on tumour cells
- Interaction of these suppresses T cell action
- There is a therapeutic opportunity to block PD1 or PDL-1