Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
32 Cards in this Set
- Front
- Back
|
main signalling molecule in 3 pathways of Ras
|
1. Raf
2. Ral-GEF 3. PI3K |
|
|
Raf pathway
|
Ras -> Raf -> MEK -> MAPK/ERK
|
|
|
PI3K pathway
|
PI3K = docking site for Akt/PKB
which gets activated by PDK downstream of Akt/PKB = mTOR Bad GSK3B |
|
|
mTOR effect
|
growth
|
|
|
Bad effect
|
inhibition of apoptosis
|
|
|
GSK3B effect
|
proliferation
|
|
|
farnesyl and geranyl-geranyl are
|
post translational modifications required for small GTPases
|
|
|
which 2 types of Ras do not need farnesyl (Have geranyl instead)
|
N and K
|
|
|
which type does need farnesyl
|
H
|
|
|
problems with use of farnesyl inhibitors
|
1. other proteins need it
2. only works on H Ras 3. other cell types need H Ras |
|
|
farnesyl inhibitors used in conjunction with
|
Gemcitabine (Cytidine analogue)
|
|
|
Raf inhibitor
|
Sorafenib
|
|
|
monoclonal Ab to VEGF
|
Avastin
|
|
|
PI3K kinase inhibitor
|
GDC0941
|
|
|
downstream targets for inhibitors of Ras
|
1. Pi3K
2. MAPK 3. Akt 4. Raf |
|
|
4 goals of phase 1
|
safe dose range
does it shrink the tumour side effects? how body deals with drug |
|
|
4 goals of phase 2
|
side effects
how to deal with them cancer types ideal dose range |
|
|
phase 3 aims (2)
|
compare with standard treatment
investigate new way of giving old treatment |
|
|
size of phase 2
|
100ish
|
|
|
name of study: metastasis from orthotopic model
|
spontaneous metastasis model
|
|
|
injecting cancer into the blood
|
experimental model
|
|
|
tail vein goes to
|
lung
|
|
|
intracardiac goes to
|
brain/bone
|
|
|
intraportal goes to
|
liver
|
|
|
genetically similar/identical model
|
syngeneic
|
|
|
example of syngeneic
|
4T1
|
|
|
where to inject to colonize brain
|
intracardiac
|
|
|
where to inject to colonize liver
|
intraportal
|
|
|
where to inject to colonize bone
|
intracardiac
|
|
|
where to inject to colonize lungs
|
tail vein
|
|
|
3 pro-angiogenic factors
|
angiogenin
VEGF prostaglandin |
|
|
3 anti-angiogenic factors
|
angiostatin
TIMPs proteolytic fragments from ECM (Collagen fragment) |
