Outline of disease process

Question 1

what are 4 main terms used to describe cancer?

Answer 1

• mass
• neoplasm
• growth
• tumour

Question 2

what is a carcinoma?

Answer 2

disorderly growth of epithelial tissue/cells which invade adjacent tissue and spread by the lymphatics and blood vessels to other body parts (malignancy, metastasis)

Question 3

are most cancers monoclonal? (arise from a single cell?)

Answer 3

Yes

Question 4

where do most cancers originate from?

Answer 4

epithelial cells (only 20% originate from connective, muscle and nervous tissue)

Question 5

what cancer type makes up almost a quarter of ALL cancer deaths?

Answer 5

lung cancer

Question 6

what are 6 stages of mitosis?

Answer 6

1. interphase
2. prophase
3. metaphase
4. anaphase
5. telophase

Question 7

what are properties of cancer cells in terms of:

1. contact inhibition
2. growth factor secretion
3. oncogene expression
4. tumour suppressor genes

Answer 7

1. LOSS of contact inhibition (don’t stick together well)
2. INCREASE in growth factor secretion
3. INCREASE in oncogene expression
4. LOSS of tumour suppressor genes

Question 8

what are properties of normal cells in terms of:

1. contact inhibition
2. growth factor secretion
3. oncogene expression
4. tumour suppressor genes

Answer 8

1. contact inhibition
2. intermittent or co-ordinated growth factor secretion
3. oncogene expression is rate (proto-oncogenes present instead)
4. presence of tumour suppressor genes

Question 9

what are the 5 stages of carcinogenesis?

Answer 9

1. carcinogen
2. initiation
3. promotion
4. tumour growth
   (pre-clinical cancer, dysplasia)
5. progression (clinical cancer, when diagnosed), metastasis

Question 10

what are the 3 cancer initiation causes?

Answer 10

1. chemical
2. physical
3. viral

Question 11

what are the 2 cancer promotion factors?

Answer 11

1. growth factors

2. oncogenes

Question 12

what are the main chemical carcinogens (cancer initiation)?

Answer 12

1. polycyclic hydrocarbons (in soots and tars)
2. aflatoxin (liver cancer)
3. nitrogen mustard (leakemia cancer)
4. alcohol and smoking (liver, head &neck, GI cancers)

Question 13

what are 2 main physical carcinogens?

Answer 13

1. ionising radiation
   - dose-response relationship
   - radon source
   - risk increased by smoking
   - ventilation reduced risk
2. mechanism (in the body)
   - chromosome translocation
   - gene amplification
   - oncogene activation

Question 14

what cancer can herpes virus cause?

Answer 14

Burkitt’s lymphoma

Question 15

what cancer can papillomavirus cause?

Answer 15

cervical cancer

Question 16

what cancer can HTLV1 retrovirus cause?

Answer 16

adult T cell leukaemia/lymphoma

Question 17

what cancer can HTLV2 retrovirus cause?

Answer 17

hairy cell leukaemia

Question 18

what cancer can hepatitis B cause?

Answer 18

liver cancer

Question 19

what do oncogenes do and what are they?

Answer 19

• they’re transforming genes
• positive regulators of growth
• represent a gain in function to transformed cells

Question 20

what are growth factors?

Answer 20

• polypeptide molecules
• regulate cell growth
• bind to cell membrane receptors
• stimulate activation of intracellular signal transduction pathways

Question 21

what does autocrine substance mean?

Answer 21

cell-produced substance which has an effect on the cell by which it is secreted

Question 22

what does paracrine substance mean?

Answer 22

cell-produced substance which has an effect on the adjacent cells

Question 23

what is autocrine stimulation of growth factors and oncogenes?

Answer 23

• cell carries receptor and secretes growth factor

- cell escapes normal control mechanism

Question 24

what is paracrine stimulation of growth factors and oncogenes?

Answer 24

Growth factors acting on a cell produced locally by the cell or its immediate neighbours (travels short distances)

Question 25

what is an example of a common tumour suppressor gene?

Answer 25

p.53 (most altered gene in tumours)

Question 26

what does p.53 normally do?

Answer 26

- tumour suppressor - transcriptional regulator - promotes DNA repair - apoptosis - differentiation - induced by DNA damage and hypoxia

Question 27

which stages in the cell cycle does p.53 control?

Answer 27

G1/S checkpoint

Question 28

how does the tumour invade? (order of layer it penetrates)

Answer 28

1. invades basement membrane 2. moves into ECM/connective tissue/ surrounding cells 3. invades blood vessels

Question 29

what enzymes are involved in invasion and metastasis in ECM? (3)

Answer 29

1. matrix metalloproteinases *MMPs), several subclasses e.g. gelatinases 2. plasmin; degrades blood plasma proteins e.g. fibrin clots 3. cathepsin

Question 30

what enzymes are involved in invasion and metastasis in cell adhesion?

Answer 30

1. cahedrins (loss) 2. integrins 3. CD44

Question 31

what is angiogenesis?

Answer 31

formation of new blood vessels (key factor in maintenance and progression of malignant tumours)

Question 32

what happens to ECM during angiogenesis?

Answer 32

ECM is degraded

Question 33

what does angiogenesis allow tumours to do?

Answer 33

- allows easier metastasis | - its own blood supply means no blood flow and nutrients

Question 34

what does VEGF do?

Answer 34

- growth factor - stimulates angiogenesis - helps tumours grow and develop

Question 35

what does anti-VEGF antibody Avastin do? (therapeutic option)

Answer 35

- binds to VEGF - prevents interaction of VEGF with receptors - prevents activation of downstream signalling pathways - vascular regression occurs - tumour remains dormant

Question 36

why does our immune system not recognise "foreign cancer cells"?

Answer 36

cancer cells can hide from T cells, because: - PD1 (programmed death receptor) is present on T lymphocytes -Ligand PDL-1 is present on tumour cells Interaction between the two SUPPRESSES T cell action which means lymphocyte cannot identify the foreign body (inhibits immune response)

Question 37

high levels of which two proteins inhibit the immune response?

Answer 37

PD1 and PDL1

Question 38

what would happen if PD1 and PDL1 were blocked?

Answer 38

immune damage to tumours would occur