Outline of Disease Processes Flashcards
What is cancer
A carcinoma or disorderly growth of cells (80% originate from epithelial cells and 20% in connective, musculoskeletal or nervous tissue) which invade adjacent tissue and spread by the lymphatics and blood vessels to other parts of the body
Most cancers are…
Monoclonal
How do cancer cells divide
Mitosis
State the features of cancer cell growth
Loss of contact inhibition Increase in growth factor secretion Increase in oncogene expression Loss of tumour suppressor genes Frequent mitoses
State the features of normal cell growth
Few mitoses
Oncogene expression is rare
Intermittent or coordinated growth factor secretion
Presence of tumour suppressor genes
Why is cancer sometimes diagnosed late
It cannot be detected until there is 10^9 cancer cells present
What are the causes that initiate cancer cell growth
Chemical
Physical
Viral
What are the causes that promote cancer cell growth
Growth factors
Oncogenes
What are the causes of cancer cell progression
Metastasis
Give examples of chemical carcinogens
Aniline dyes in bladder cancer
Aflatoxin in liver
Nitrogen mustard in leukaemia
Alcohol and smoking in lung, head, neck and gastrointestinal cancers
Give examples of physical carcinogens
Ionising radiation
Mecanisms (e.g. chromosome translocation, gene amplification and oncogene activation)
give examples of viral carcinogens
Herpes virus - Burkitt’s lymphoma
Papillomavirus - Cervical cancer
Retroviruses - Adult T-cell leukaemia/lymphoma (HTLV1), Hairy cell leukaemia (HTLV2)
Hep B - Liver cancer
What are oncogenes
Transforming genes
Positive regulators of growth
Represent a gain in function to transformed cells (e.g. in follicular lymphoma, BCL2 activation prevents apoptosis and p53 a tumour suppressor gene).
What are growth factors
Polypeptide molecules which regulate cell growth and function by binding to cell membrane receptors to stimulate the activation of intracellular signal transduction pathways.
How do growth factors and oncogenes work together
Growth factor attaches to the growth factor receptor
Triggers a post receptor signal transduction pathway
Activates oncogenes which promote growth factor and receptor synthesis.
Receptors produced will move to the cell membrane and the receptors can either cause autocrine stimulation (self-stimulating) or paracrine stimulation (adjacent cells)
What is autocrine stimulation
When the cell carries the receptor and secretes the growth factor to escape the normal control mechanism
What is paracrine stimulation
When the growth factors acting on a cell are produced locally by the cell or its immediate neighbours
What is p53
The most commonly altered tumour suppressor gene in human tumours (37% but higher in lung and colon cancers)
What is p53’s normal function
Act as a transcriptional regulator
Promote DNA repair
Apoptosis
Differentiation
How is p53 induced
By DNA damage
Hypoxia
What checkpoint does p53 control
G1/S checkpoint
State 4 details of metastasis
Its not random
Has a cascade of limited sequential steps
Involves tumour-host interactions
‘Survival of the fittest’ pertains
How does a tumour metastasise
Tumour invades through basement membrane
Moves into the extracellular matrix/connective tissue/surrounding cells
Invades blood vessels allowing tumour cells to be ‘arrested’ in distant organs
Which enzymes in the process are present in the ECM
Matrix metalloproteinases (MMPs) which has several subclasses e.g. gelatinases
Plasmin
Cathepsin
