Lecture 16: Cancer Flashcards
What is the significance of cancer?
- is a significant disease
- about 25% of UK deaths
- Cancer is MOSTLY a disease of old age
- 5 year survival improving but is not 100%
Tissue repair: small air ways (bronchioles)
Damage results in loss of basal stem cells –> dedifferentiated of clara cells.
-Process of repair has to be controlled to replace just the tissue (cells) required
adult stem cells: asymmetric division
stem cell = 1 stem cell, 1 progeny
Stochastic or Directed division:
stem cell = 2 stem cells (or 2 progeny)
Exactly half of the progeny of a stem cell must stay as a stem cell: less & more
Less = regenerative capacity of the tissue is compromised
MORE - CANCER?
Hypertrophy:
increase in cell size
Hyperplasia:
increase in cell number
Metaplasia:
change in cell differentiation (mature 4 mature)
Dysplasia:
change in cell differentiation (mature 4 less mature)
whats the difference between hypertrophy, hyperplasia, metaplasia , dysplasia + Neoplasia
NEOPLASIA IS IRREVERSIBLE BECAUSE IT IS AUTONOMOUS.
Neoplasia
CANCER
chronic irritation from cigarette smoke leads to
METAPLASIA reversible to dysplasia reversible also.
But on its way to neoplasia - IRREVERSIBLE
What is Cancer?
1) uncontrolled cell proliferation i.e. mitosis
2) Aberrant differentiation
3) uncontrolled cell interaction -invasion&metastasis
4) Cancer cell host interactions
Aberrant differentiation:
Normally there is a balance between cell proliferation & differentiation
Cancer cell host interactions:
- Angiogenesis
- -tumour cells need blood supply
- Hormone dependency
- hormone production
- immune response
- immune response
- protection can be damaging
2 types of tumours
benign + malignant
benign =
confined, well defined structures
malignant tumours:
(Early)
- dsyplasia
- anaplasia (sever dysphasia)
- invasion
- metastasis
(late)
ALL IRREVERSIBLE
what causes cancer?Major carcinogenic factors
- chemical (smoking)
- Parasites
- Radiation
- Viruses
what causes cancer? Genetic changes
- oncogenes
- loss or inactivation of RECESSIVE inhibitory genes (tumour suppressor genes)
- need multiple mutations to cause cancer
A general model for cancer
- Stochastic model
ALWAYS:
1 becomes 3, 2 survive. join become 2, divide & become 4, join
-All cancer cells are potential tumour initiating cells but have a low probability of proliferation in clonogenic assays
tumour heterogeneity
- display high degree of heterogeneity
- tumours contain lots of differentiated cells
- this extends to virtually all measurable properties of cancer cells
implications oh tumour heterogeneity
- not every cell in a tumour is the same
- only some cels can give rise to cells with higher proliferative capacity
- only some cells appear to be capable of re-initiating the tumours, i.e. are TUMOUR INITIATING CELLS
“Cancer stem cell” model?
- Only a small definable subset of cancer cells are tumour initiating cells that have the ability to proliferate indefinitely.
- heterogeneity is from differentiation (i.e.stem cell)
- only some these cells are tumour-initiating & therefore can be targets for anti-cancer treatments
- BUT remember that further mutation & selection will be happening
