Cancer

Question 1

Embryonic Differentiation

Answer 1

The process whereby early cells that are identical to one another become different, specialised cells

Question 2

Post embryonic differentiation

Answer 2

Occurs at the level of cells. Whereby stem cells in tissue proliferate and differentiate into mature functional cells. Eg. basal cells in epidermis become keratinised squamous epithelial cells. Involves activation of functional genes and inactivation of proliferation genes.

Question 3

De-differentitation

Answer 3

Whereby cells that are undergoing differentiation no longer move on and become mature, they are stuck in the proliferative phase whereby tissue is formed that is incompletely differentiated. This is what happens in neoplasia’s.

Question 4

Disorders of growth in post embryonic tissues can lead to?

Answer 4

Abnormalities of tissue function

Abnormalities of tissue mass

Question 5

Hyperplasia

Answer 5

Increase in number of cells

Question 6

Hypertrophy

Answer 6

Increase in size of cells

Question 7

Metaplasia

Answer 7

Change in type of cell from one to another

Question 8

Agenesis

Answer 8

Total absence of a tissue type/organ

Question 9

Hypoplasia

Answer 9

Congenital reduction in size

Question 10

Atrophy

Answer 10

An acquired reduction in size (e.g. if an organ has reduced blood supply)

Question 11

Mechanism of skin cancer related to sunburn

Answer 11

UV light is a complete carcinogen, UVB is the initiator and UVA the promotor. With exposure to UV light the p53 tumour suppressor gene is mutated. You start as homozygous p53 wild type, when sunburn occurs p53 mediates apoptosis and peeling of the skin occurs, with repeated exposures you get a mutation to one allele. Reduced function of p53 mediated apoptosis, mutant clones expand with each exposure to sunlight. With numerous exposures you become homozygous for p53 mutant allele and loss of apoptosis occurs, malignant change.

Question 12

Main carcinogen in tobacco smoking

Answer 12

Benz[a]pyrene (PAH).

Question 13

RAS

Answer 13

A proto oncogene that is involved in cell signalling facilitating cell proliferation and division and survival. When it’s switched on you get excessive growth/ division that is uncontrolled.

Question 14

Cell biology of epithelial to mesenchymal transition

Answer 14

Carcinoma cell migrate from their tissue of origin
Convert to motile mesenchymal stem cells cells loosely embedded in the ECM.
This process is called Epithelial to Mesenchymal transition a process that occurs in cancer and in embryological development.

Question 15

What do polar epithelial cells types require?

Answer 15

The polar (normal) epithelial cell phenotype requires adherents junctions. These are constituted by E-cadherin, beta and alpha catenins.

Question 16

In diffuse type cancers what is the biological pathology?

Answer 16

Loss of E-cadherin mediated adhesion and adherens junction. Or loss of alpha catenin. Process is irreversible

Question 17

In non-diffuse cancers what is the biological pathology?

Answer 17

Fibroblast growth factor, secreted by mesenchymal cells, acts on FGFR in endothelial cell walls causing the RAS port oncogene to be activated (growth and proliferation). Also activates expression of snail protein that causes migration of cells through repressing expression of e-cadherin

Question 18

Reasons why HGFR is often over expressed in cancers

Answer 18

• Over expression as a result of altered regulation in high grade tumours
• Gene amplification
• Missense point mutations
• Co-expression with HGF autocrine, self stimulatory loops

Question 19

Mechanism of cancer invasion

Answer 19

Hydrolytic enzymes allow cancer cells to break out of tissue compartments. There are complexes of cell adhesion molecules as well as proteolytic molecules in cancer cell membrane protrusions called podosomes or invadopodia.

Question 20

MMP

Answer 20

Present in cancer cells Matrix metalloproteins (proteolytic system) breaks down ECM

Question 21

Blood supply and cancer. What mediates production of blood vessels into the tumour

Answer 21

Metabolic stress (hypoxia, low pH, hypoglycaemia)
Inflammation
Activation of oncogenes (e.g. RAS) or loss of tumour suppressor genes.

Question 22

Non-coding RNA. tRNA’s

Answer 22

Most tRNAs are found in the mitochondrial genome so mutations only heritable through mothers, function to carry amino acids to mRNA to translate to protein thus a mutation messes up the protein.

Question 23

snoRNA

Answer 23

Function in the cell to modify the ribosomes which help to create proteins. A cluster of snoRNAs sits in a region of chromosome that is lost in Pradar Will and Angolan syndromes. The loss of these snoRNAs is thought to be why some features of these disorders eventuate (obesity and cognitive disability)

Question 24

microRNA

Answer 24

Target specific mRNA and either suppress their translation or alter stability. So regulates mRNA. e.g. in cancer microRNAs regulate oncogenes and tumour surpressor genes.

Question 25

Two important proteolytic systems in cancer invasion

Answer 25

uPA; cancer cells up regulate this enzyme that then binds with its receptor and cleaves plasminogen to plasmin. This can then cleave ECM proteins.
MMPs; degrade components of the ECM

Question 26

Describe cancer cachexia

Answer 26

Characterised by the breakdown of skeletal muscle and abnormalities in fat and carbohydrate metabolism despite normal intake. It is mediated by the inflammatory response.

Question 27

Alterations in metabolism in cancer

Answer 27

Increased protein catabolism
Increased protein loss
Glucose intolerance
ABnormal insulin resistance
Increased lipolysis
Increases in overall energy expenditure

Question 28

INsufficient dietary intake

Answer 28

Suppression of appetite mediated by cytokines
Depression
loss of taste sensation
Nausea etc from treatments
Physical impairment e.g. tumour

Question 29

Treatment of malnutrition

Answer 29

Supplemental feeding- increasing energy/protein content of meals
Enteral feeding (ng tube)
Parenteral nutrition
Pharmacological agents 
Nutraceutical agents

Question 30

Signals that trigger angiogenesis

Answer 30

Metabolic stress- Hypoxia, low pH, hypoglycaemia
Inflammation
Activation of oncogenes or loss of tumour suppressor genes

Question 31

Mechanisms for angiogenesis

Answer 31

Angiogenic sprouting- hypoxic cells express VEGF (especially cancer cells that have lost p53) this causes sprouting of leaky capillaries from existing ones.
Co-option of existing blood vessels- where a tumour grows around a blood supply.
Intussusception- IN which the tumours grows and expands against the lumens of pre-existing vessels forcing them to remodel and expand
Capilliary formation by cancer cells- trans differentiation