Models of disease Flashcards
(25 cards)
cancer
3-6 mutations to epithelial cells -> increase proliferation and decreased cell death.
escape immune system, grow blood vessels, move and metastasise
in vitro
cell culture
in vivo
animals
in vitro cancer model
grow cell lines from humans/animals (grow indefinitely)
use nutrients and serum from cow foetuses
Chou-Talalay method
statistic analysis to see how it interacts with older drugs
additive - 1
synergistic - less than one = more than additive effects
antagonistic - over one
cytotoxicity study
add drug and wait 4 days to assay IC50
mechanism of action (cancer)
how kills cells = stain with fluorescence to see change in shape
problems with cell lines
not physiologically accurate
doesn’t take into account other cell types involved in cancer (blood cells, fibroblasts, stroma, etc) = microenvironment
co-culture
direct mixing of cells (use fluorescence to differentiate)
Boyden Chambers = liquid environment and migration
3D spheroids
3D deformable structure with scaffold of extracellular matrix
difference in proliferation, metabolism and matrix in layers (necrotic pit)
in vivo cancer models
mice can model primary and metastatic tumours
consider tumour type, genetics, location, microenvironment, vasculature, immune system
predict ADME, efficacy, resistance, toxicology
tropic (subcutaneous) or naturally (genetics)
nude mice
inbred, inject human tumour cells (xenografts) subcutaneously
lack thymus (no T cells, no immune system, SCID)
can measure tumour and easily extract
however, different development and incomplete stroma
syngeneic mouse model
normal mouse with special tumour
same genetics from mouse strain
no immune response
orthotopic model
surgery into organ
better representation of microenvironment and development
humanised mouse model
immune cells from human (T cells, NK cells, Ag primed DCs, HSC) into mouse with no immune system
PDX = patient derived xenograft
conditional models
genetic disease model
K-ras mutation = lung cancer
mice die early on
can add removable transcription termination element (removed by virus)
studying tumours
growth rate and tumour size/weight
remove tumour and graph against time
look for metastases - fluorescence markers or staining
neurology animal models
produce neuropathy or similar symptoms
quality = valid representation of human disorder (prove and measure) and reproducible
behavioural assay
normally on a scale (observer or patient)
final test done via this (not cell culture or computer)
anxiety disorders
PTSD, GAD, panic disorder, phobias, OCD
developed over time and has triggers
PTSD and GAD easier to model
anxiety drugs
benzodiazepines, zopiclone, triazolam, antidepressants, beta blocker
elevator plus maze
measures acute anxiety
most common
rats don’t like open space
two closed arms and two open arms = measure time in each
validate method
use control short term vs long term optimal conditions (eg no ambient noise) variable results = not statistically significant
dose translation equations
GD = AD x animal Km/human Km
