define cancer
disorderly growth of epithelial cells which invade adjacent tissue and spread by the lymphatics and blood vessels to other parts of the body
What is the characteristics of cancer cells
loss of contact inhibition
Increase in growth factor secretion
increases in oncogene expression
loss of tumour suppressor gene
What initiates cancer growth
chemical
physical
viral
Give example of chemical carcinogens
smoking
alcohol
nitrogen mustard - leukemia
aniline dyes - bladder
What is a physical carcinogen
ionising radiation
What is the mechanism of ionising radiation
chromosome translocation
gene amplification
oncogene activation
Give example of viral carcinogens
Herpes virus
Papillomavirus -cervical cancer
reterovirus - leukaemia/lymphoma
Hepatitis B - liver cancer
How do growth factors promote cancer
bind to cell membrane and regulate cell growth and function by promoting signal transduction pathway
What are growth factors composed of
polypeptide molecules
Growth factor stimulation is either
autocrine - GF produce acts on its self
or
paracinre - GF produced act locally or o neighbouring cells
What is an example go a growth factor
VEGF: vascular endothelial growth factor
What do oncogens do
promote growth
In folicular lymphoma what is the oncogenes
BCL2
What induces tumour suppressor genes
DNA damage and hypoxia
What is the most common mutated gene in tumours
P53
What is the normal function of tumour suppressor genes
DNA repair,
promote apoptosis
What promotes tumour growth
Increase in growth factor secretion
increases in oncogene expression
loss of tumour suppressor gene
How do tumours progress
metastasis
What is the pathway of metastasis
nvade basement membrane, moves into surrounding cells/tissues, invade blood vessels, tumours cells arrest in distant organ
What process must occur for tumour to surpass 2mm
angiogenesis - New blood vessel formation
What enzymes are involved with metastasis in the ECM
Matrix metalloproteinases (MMPs) eg gelatinases
Plasmin
Cathepsin
What is matrix metallaproteinases responsible for
degradation of most extracellular matrix proteins
What is plasmin responsible for
degrading blood plasma proteins
what is a cathespin
protease
Loss of what adhesion mechanisms causes metastasis
Cahedrins - transmembrane protein
Integrins - attaches cytoskeleton
CD44 - antigen
What is necessary for new blood vessel formation
degradation of ECM
What does a Anti VEGF antibody prevent
Growth factor interacting with receptors prevent transduction signal being sent, therefore tumour lies dormant
Why does our immune system not recognise cancer cells
PD1 present on T cell binds with PDL-1 ligand on tumour cells and suppress T cell action
What may high levels of PD1 or PDL1
protein expression inhibit
immune response
What kind of process is metastasis
organised
