An outline of cancer process Flashcards
What does a monoclonal cancer mean?
Arises from a single cell
Which stage of the cell cycle can give rise to non-proliferating cells?
G1
Describe the activity of cancer cells
Frequent mitosis
Increase in growth factor secretion
Loss of contact inhibition
Describe the structure of cancer cells
Lots of blood vessels
Increase in oncogene expression
Loss of tumour suppressor genes
What are the initiation causes of cancer?
Chemical
Physical
Viral
Give an example of chemicals which cause cancer
Nitrogen mustard gas - leukaemia
Aninline dyes - bladder cancer
Alcohol and smoking - Lung, head and neck, GI
Give an example of physical carcinogens
Ionising radiation - Radon source is mainly in buildings, risk increased by smoking, ventilation reduces risk
What is the mechanism of ionising radiation to cause cancer?
Chromosome translocation
Gene amplification
Oncogene activation
Give an example of Viral carcinogens
Papillomavirus - cervical cancer
Hepatitis B - Liver acncer
Herpes Virus - Burkitt’s lymphoma
What are growth factors and what are their effects?
Polypeptide molecules
Regulate cell growth and function, bind to cell membrane receptors, stimulate activation of intracellular signal transduction pathways
Define autocrine stimulation
Cell carries the receptor and secretes growth factor
Cell escapes normal control mechanism
Define paracrine stimuation
GF’s are produced by local neighbour
Describe the process of invasion and metastasis
Tumour invades through basement membrane
Moves into extracellular matrix/connective tissue/surrounding cellsInvades blood vessels
Tumour cells ‘arrested’ in distant organ
What is the effect of Matrix metalloproteinases, Plasmin and Cathepsin on Invasion and metastasis?
Increase the likelihood of the cell coming into the extracellular matrix and metastasising
What is the role of enzymes involved in cell adhesion (cahedrins, Integrins, CD 44) on Invasion and metastasis?
makes the cell less sticky so it is more likely to invade other cells
What is the cost of angiogenesis in the maintenance and progression of tumours?
Degradation of the extracellular matrix - necessary for new blood vessel formation to occur
What is the most commonly altered gene in human tumours?
P53 which is a tumour suppressor gene
What is the normal function of the p53 gene?
Transcriptional regulator, promotes DNA repair, apoptosis, diffrerentiation
It is the G1/S checkpoint control gene
What stimulates p53?
Induced by DNA damage and hypoxia
Give an example of a growth factor
Vascular endothelial growth factor VEGF - leads to the growth, proliferation, migration and survival of endothelial cells
What is the effect of Anti-VEGF?
Prevents the action of VEGF on receptors.
Reduces microvascular growth, inhibits the progression of metastatic disease and reduces intratumoral pressure, which may improve the delivery of cytotoxic agents.
What is the function of the PD-1 protein?
Expressed on T cels and pro-B cells.
Plays an important role in down-regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promotes self-tolerance.
What is the effect of the binding between PDL-1 (found on the surface of cells in various tissues) and PD-1?
Promotes immunosuppression to various mechanisms including apoptosis
How can a PD-1 inhibitor treat cancer?
Prevents the binding interaction between PD-1 and PDL-1 and so activates the immune system to attack tumours
How does the presence of PDL-1 in cancer cells affect survival?
PDL-1 stops the immune system recognising the cancer cells - reduced survival rates.