Outline of Disease Processes Flashcards
What are most cancers (in terms of how many cells they arise from)?
Monoclonal (arise from a single cell)
What does monoclonal mean?
Arise from a single cell
How do cancer cells divide?
Using the mitosis stages just like normal cells
What are the stages of mitosis in cancer cells?
1) Interphase
2) Prophase
3) Metaphase
4) Anaphase
5) Telophase
6) Daughter cells
Why do cancer cells have uncontrollable growth?
They have no regulation
What are some properties of cancer cell that is different to normal cells?
Loss of contact inhibition
Increase in growth factor secretion
Increase in oncogene expression
Loss of tumour suppresor genes
What can you say about tumour suppresor genes in relation to cancer?
Cancer is caused by a loss of tumour suppresor genes
What can you say about cancer and oncogene expression?
Increase in oncogene expression leads to cancer
What are properties of normal cells that are different to cancer cells?
Oncogene expression is rare
Intermittent or co-ordinated growth factor secretion
Presence of tumour suppressor genes
What is carcinogenesis?
The initiation of cancer formation
What are the 2 stages of carcinogenesis?
Pre-clinical cancer
Clinical cancer
What are the steps of pre clinical cancer in carcinogenesis?
Initiation
Promotion
Tumour growth
What happens during clinical cancer in carcinogenesis?
Tumour progression
When are cancers detectable?
Only after a certain amount of cells are present
What are the causes of cancer seperated into?
Initiation
Promotion
Progression
What can initiate cancer?
Chemical
Physical
Viral
What is related to the promotion of cancer?
Growth factors
Oncogenes
What is related to the progression of cancer?
Metastasis
What are some chemicals that can initiate cancer?
Hydrocarbons such as soot and tarts
Analine dyes (cause bladder cancer)
Aflatoxin (causes liver cancer)
Nitrogen mustard (causes leukaemia)
Alcohol and smoking (causes lung, head and neck, and gastrointestinal cancers)
What are physical causes of cancer?
Ionising radiation
Mechanisms (chromosome translocation, gene amplification, oncogene activation)
What are some mechanisms that are considered a physical cause of cancer?
Chromosome translocation
Gene amplification
Oncogene activation
What are some virus causes of cancer?
Herpes virus (causes Burkitt’s lymphoma-cervical cancer)
Hepatitis B (causes liver cancer)
Papilomavirus (causes adult T cell leukaemia/lymphoma)
What do oncogenes do?
Promote cells to become cancerous
How do oncogenes promote cells to become cancerous?
Transformation genes
Positive regulators of growth
What are growth factors that promote cancer growth?
Peptide molecules that:
Regulate cell growth and function
Bind to cell membrane receptors
Stimulate activation of intracellular signal transduction pathways
What do polypeptide molecules that are growth factors promoting cancer do?
Regulate cell growth and function
Bind to cell membrane receptors
Stimulate activation of intracellular transduction pathways
What do oncogenes cause in the surrounding cells?
The cells to undergo growth by paracrine stimulation
What does not happen in oncogene expression that normally happens?
The feedback loop that stops growth at a certain point
What is the most common altered tumour suppresor gene?
P53
What is the normal function of P53?
Transcriptional regulator
Promotes DNA repair
Apoptosis
Differentiation
What induces P53 to become altered?
DNA damage
Hypoxia
What is hypoxia?
Deficiency in the amount of oxygen reaching the tissues
Why is metastasis not random?
It is a cascade of tumour-host interactions in sequential steps
What is the process of invasion and metastasis?
1) Tumour invades through basement membrane
2) Moves into extracellular matrix/connective tissue/surrounding cells
3) Invades blood vessels
4) Spreads to distant tissues/organs
What are some enzymes involved in metastasis and what do they do?
Matrix metalloproteinases (MMPs which degrade the extracellular matrix)
Cahedrinks, integrins and CD44 (stop cell ahesion so the cancer cell can break away)
What is matrix metalloproteinases (MMPs)?
Enzymes that degrade the extracellular matrix
What are cahedrins, integrins and CD44?
Enzymes which stop cell adhesion so the cancer cell can break away
What is angiogenesis?
The formation of new blood vessels
What is angiogenesis a key factor in?
The maintanance and progression of malignant tumours
What must happen for a tumour to exceed 2mm in diameter?
New blood vessels must form
What is required for new blood vessels to form?
Degradation of the extracellular matrix
What are clinical correlations seen in relation to angiogenesis and cancer?
Vessel density
Tumour malignancy
Metastasis
What can prevent tumour growth?
Drugs that can inhibit growth factors
What is an example of a growth factor which can be inhibited by drugs?
Vascular endothelial growth factor (VEGF)
How does the inhibition of growth factors like vascular endothelial growth factor (VEGF) work?
Drugs block receptors on epithelial cells and prevent binding of VEGF
Prevents formation of new blood vessels so the tumour cannot grow
Why do immune cells not recognise cancer cells?
They are self
In terms of receptors, why do immune cells not kill cancer cells and how can we change this?
PD1 (programmed cell death receptor) is present on T cells
Ligand (PDL-1) is on tumour cells
Interaction of these two suppreses T cell activation, therapeutic opportunity to block either receptor
