Cancer II 4 Flashcards
1
Q
drug that blocks VegF
A
Bevacizumab
2
Q
as the tumor grows, the cells in center get
A
hypoxic
3
Q
as cells get hypoxic they accumulate what TF
A
HIF
4
Q
HIF does what
A
transcribes VEGF
5
Q
VEGF goes to
A
VEGF receptors
6
Q
what is function of VEGF
A
goes to endothelial cells to stimulate more growth
7
Q
what drug would you use to block VEGF
A
Bevacizumab
8
Q
mab is
A
monoclonial antibody
9
Q
Sunitinib does what
A
inhibits tyrosine kinase activity
10
Q
What does bevacizumab do
A
monoclonal antibody targets growth factor to block VEGF receptor
11
Q
any cell migrating needs to secrete
A
MMPs - digest and get through tissue
12
Q
besides blocking VEGF how can you stop angiogenesis
A
block MMP activity
13
Q
thrombospondin
A
naturally occuring angiogenesis inhibitor
14
Q
endostatin
A
naturally occuring angiogenesis inhibitor
15
Q
if endothelial cells are exposed to VEGF signaling (proangiogenic) they start proliferating and VEGF will do what
A
activates ras/map kinase acitvity
stimualtes expression of FAS-R
16
Q
what does FAS-R mean
A
fas receptor
17
Q
besides activating ras/map kinase what does VEGF stimulate
A
expression of FAS-R
18
Q
thrombospondin can stimulate cells to secrete
A
Fas ligand (Fas-L)
19
Q
FasL stands for
A
Fas Ligand
20
Q
stimualte expression of Fas-L what happens
A
endothelial cells express Fas-L, it will target only the newly divided endothelial cells so it will bind to FasR and lead to apoptosis
21
Q
When FasL binds to FasR what happens
A
apoptosis
22
Q
can FasL bind to mature endothelial cells
A
no
23
Q
what does FasL target
A
newly devloping endothelial cells that express FasR
24
Q
what is the purpose of new trials that are mimicking FasL
A
stopping angiogenesis - it will bidn Fas R and lead to apopt.
25
endostatin is a protein that helps
stabilize endothelial cell-cell interactions
26
newly formed blood vessels are very
leaky/permeable
27
endostatin could be therapeutic drug in US b/c
endostatin will anchor the endothelial cells and will stabilize the cells so they can't sprout, it would inhibit the vessel sprouting
28
in chronic wounds there are not enough
angiogenesis promoters
| there are too many angiogensis inhibitors
29
after ischaemic stroke the angiogenic response is direclty related to
prognosis for pt
| the quickly we can supply bood to that area of the brain the better the outcome for that pt
30
metastasis is responsible for what percent of cancer death
90%
31
tumor cells are ___clonal & _____geneous
monocolonal
| heterogeneous
32
main difference b/w benign and malignant tumor cells
malignant are invasive and capable of matastisizing
33
angiogenesis is very tightly correlated to
metastesis
34
direct extension of tumor
the cancer invading local tissue
35
lymphatic spread
spread into lymphatic circulation
36
haematogenous cancer spread
spread of cancer into blood spread
37
most common initial dissemination of carcinoma is into
lymphatic circulation
38
most common type of cancer in humans
carcinoma
39
carcinoma is
cancer of epithelial cells
40
anatomical location from primary tumor can tell you where
cancer is likely to spread to first
41
what organ is most commonly infiltrated by tumors
lung
42
what is second most common organ to be infiltrated by tumors
liver
43
what primary tumors are most likely to metastesize to liver
blood from digestive organs
44
steps that need to occur for cancer to be successful at metastasis
break away from primary tumor, invade through connective tissue (MMP), attach to basal lamina surrounding endothelial cells, digest through, intravasate, get into blood stream, survive circulation, bind to endothelial cells of other organ, digest throgh endothelial cells, digest through new tissue, form secondary tumor through restimulatino of angiogenesis
45
is it easy to complete the steps to become metasasis
no
46
growth of secondary tumor is one of the major
rate limiting steps
47
why is growth of second tumor rate limit step for tumor
the new enviornment might not be good for them to be able to grow. the types of stromal cells will be different, the whole enviornment different and the tumor cells might not be adapted to the new environment
48
for tumor cells to invade they have to secrete
MMP
49
to get through basal lamina tumor cells have to secrete
MMP
50
what is first step of cell invasion
cell attachment
51
what is second step of cell invasion
enzymatic degradation of ECM
52
what is 3rd step of cell invasion
cell migration
53
describe the first step of cell invasion
downregulation of cell-cell attachment, then it attaches to basal lamina, then it expresses MMP
54
autocrine motility factor
stimualtes itself to migrate, a lot of cancer cells express this
when it binds to own AMF receptors it triggers rearrangement of cell to start migrating
55
what is a common mutation found in the first step of metastesis (loss of cell-cell adhesion, loosening of intracellular junctions)
loss of e-cadherin
56
what changes do cancer cells go through to have attachment to ECM
change in integrin expression profiles (ex: they might express integrins that are normally found in blood cells that migrate)
increased CD44 hyaluronan-binding proteins
57
CD44 hyaluronan sequesters what to help with digestion
MMP
58
very generally, what happens to cancer cells to allow them to attach to ECM
change the types of cell matrix receptors and start to express cell matrix receptors that are involved in invasion
59
should epithelial cells normally express MMP
no
60
in cancer cells what do they express to allow them to detach
MMP
61
uPA and tPA are normally secreted by what
stromal cells
62
uPA stands for
urokinase plasminogen activator
63
tPA stands for
tissue-type plasminogen activator
64
uPA and tPA do what
convert plasminogen into plasmin
65
what does plasmin do
activate MMPs present in ECM
digests ECM
digests clots
66
in cancer cells to degrade the ECM the cancer cells do what
serine proteases: uPA and tPA
matrix metalloproteinases
they can either make this themself, or stimulate the cells around them to make it
67
uPA and tPA are both
serine proteases
68
upregulation of MMP2 is commonly found in
metastasis cancer
69
as the MMP degrades ECM and other cells what does it release
growth factor - this helps proliferation of cancer cells
70
what is an example of a crytpic site
laminin
71
laminin is a component of what
basal lamina
72
when laminin is degraded by MMP what happens
its cleaved and cleavage product is a motility factor, when cell binds to the digested product it will stimualte the cell to migrating
73
what are the two ways the cell can become mobile
binding to some of the digestive products from digestion of the matrix
tumor secreted motility factor - the cancer cell itself starts to express motility factor
74
what is a major motility factor cancer releases
Autocrine Motility Factor (AMF)
75
binding of cell receptors to the motility factor stimualtes what
Rho GTPases
76
Rho GTPase stimualte what
changes in cytoskeleton resulting in movement
77
besides AMF what are other tumor motility factors
HGF
| EGF
78
AMF is a what
chemokine
79
increased expression of AMF cells in vitro become
motile
80
AMF receptor activation activates what
Rho GTPases to stimualte cell migration
Ras Map kinase pathway
PI3 kinase pathwy
expression of VEGF
81
EGFR signling can activate
Ras Map kinase pathway
Rho GTPases
expression of AMF
82
VEGF signaling is goign to cause endocytosis of
the VE-cadherin receptors
83
vascular endothelial cadherin receptors are responsible for
keeping endothelial cells together
84
with VEGF signaling it activates proliferation of endothelial cell and downregulates
cell-cell adhesions (increases permeability so it's easier for cancer cells to get inside the newly formed vessels)
85
when cancer cell wants to transport what does it need to express
receptors to clump together and be able to bind to platelets to form emboli to better their chance of survival
86
what do cancer cells in order to better their chances of survival when they are being transported down vasculature
emboli
87
cancer cells can influence other cells, how do they hide from the immune system
downregulate the MHC complex
