Exam 3 Flashcards
(125 cards)
1
Q
what is the progression of tumors
A
normal –> hyperplasia –> dysplasia –> neoplasia –> metastasis
2
Q
hyperplasia is characterized increases in what
A
GF and transcription factors
3
Q
what is more influential for carcinogens to cause cancer
A
cumulative exposure rather than age
4
Q
what could decrease cancer incidences
A
removal of potentially cancerous cells
5
Q
give an example of decreasing cancer incidence by removing cancerous cells
A
removing polyps in colorectal cancer
6
Q
give an example of cumulative exposure to a carcinogen that is linked to cancer
A
cancer related to smoking is parallel to the average number of ppl smoking 30 years later
7
Q
give two examples of tumor progression
A
colorectal cancer can be stopped by removing polyps
pancreatic cancer is one of the most orderly cancers
8
Q
explain what colonal succession means
A
one cell obtains a proliferative mutations that takes over an area. The pattern continues to make growths and allows for treatment resistance
9
Q
are tumor stem cells real stem cells? Explain
A
no because relatively few cells from a tumor can form a new one
10
Q
explain clonal diversification in tumors
A
cells mutate indifferent ways and form multiple parallel clonal expansions that may be benign or cancerous
11
Q
What is comparative genomic hybridization (CGH)
A
gives an idea for reason behind duplications or deletions
12
Q
How does comparatice genomic hybridization work
A
hybridize DNA from normal tissues and from cancerous tissues and label them differently. if things in clone not in tumor= deletion. if things in higher levels in clone= amplification
13
Q
how many mutations does transformation require
A
more than 1
14
Q
what does the k-ras oncogene do
A
gives hyperplasia
15
Q
what are the four key pathways to alter to make cancer and what do they affect
A
Ras- mitogenic signaling and cell cycle
pRB- eliminates suppression of cell cycle
p53- disrupts apoptosis
telomeres- stablize for immortality
16
Q
what are some toxic/mitogenic agents that can act as tumor progressors
A
ethanol, inflammation, hormone fluctuations such as the menstrual cycle
17
Q
how does inflammation lead to tumors
A
preserves stressed and damaged cells
18
Q
what is NSAID
A
non-steroidal anti-inflammatory drugs
19
Q
how can NSAID decrease colorectal cancer
A
decreases inflammation
20
Q
what happens when TNF-alpha is inhibited to release NF-KB
A
TNF-alpha leads to more inflammation
cyclin D1 and Myc lead to mitogenesis
anti-apoptotic genes
21
Q
What does TUNEL assay do
A
looks for chromosomal ends
22
Q
What does PCNA staining do
A
looks for proliferating cells
23
Q
What does enabling COX-2 do
A
leads to prostaglandin productions which causes loss of contact inhibition, independent proliferation, and increased cell proliferation
24
Q
What does LT inhibit
A
pRB and P53
25
What happens when pRB is transformed
resistance to growth inhibition
| immortilization
26
What happens when p53 is transformed
resistance to growth inhibition
apoptosis evasion
immortilization
27
What happens when sT is transformed
mitogenic independence
metastasis
28
What happens when hTERT is transformed
immortilization
29
What happens when Ras is transformed
apoptosis evasion
mitogenic independence
angiogenesis
metastasis
30
characteristics of transit-amplifying cells
divide the most
turn into differentiated cells
31
characteristics of stem cells
rarely divide
kept safe deep in the tissues covered in vili and mucous
when divide make one stem cell and one transit amplifying cell
32
ways to limit mutations in stem cells
apoptotic hair trigger
highly active MDR proteins that pump bad tings out
asymmetric strand allocation
33
how does asymmetric strand allocation work
preserve original DNA strand to serve as template for stem cell then use nonconserved strand for transit ampmlifying cells
34
what happens if we lose a stem cell
symmetric division-- make two stem cells, one with conserved and one with non-conserved and then non picks up a cons. and then divides as normal
35
what is mismatch repair
the DNA polymerase degrades and renews the strand nucleotides
36
What are ways DNA proofreads itself
if theres a wrong nucleotide a buldge occurs becuase it won't connect
DNA polymerase is constantly doubling back to check its work
37
What are two types of damage that can occur when not replicating
endogenous and exogenous
38
what are examples of endogenous damage
depurination
depyrimidation
deamination
ROS
39
what is depurination
endogenous
| loss of a purine (G or A)
40
What is depyrimidinaiton
loss of a pyrimidine (C or T)
41
Which is more common depurination or depyrimidination
depurination
42
What is deamination
loss of an amine
43
what is ROS
oxidizes bases
DNA breaks causing abasic sites
44
What are examples of Exogenous DNA damage
x-rays
UV-radiation
Chemical agents
Liver decontammination
45
What are ways X-rays damage DNA
breaks sugar phosphate backbone
46
what are ways UV-rays damage DNA
creates pyrimidine dimers
47
What are ways chemicals damage DNA and give an example
Mustard gas, benzo(a)pyrine
alter pairing
attach methyl groups to bases
48
how does benzo(a)pyrine damage DNA
cytochrome p450 tried to break it down and if it doesn't then it makes it more toxic and forms an adduct
49
What are adducts in DNA damage
they prevent DNA nucleotides from pairing normally
50
What are some DNA damages that are seen in cancer
transversion
| transiton
51
What is transversion
switching purine with a pyrimidine
52
What is transition
Switching purine with a dif purine or a pyrimidine with a dif pyrimidine
53
What are some ways to protect DNA
physical protection shields, scavenging for ROS, inactive electrophilic compounds
54
what is a way to physically protect DNA
depositing melanin into keratinocytes
55
What are ways to repair DNA
```
direct repair
base excision repair
nucleotide excision repair
error-prone repair
BRCA1 and 2 proteins
```
56
How does Direct repair work
direct removal of ethyl group by MGMT
57
How does base excision repair work
excision of altered base which can then be repaired individually or with a new strand segment
58
how does nucleotide excision repair work
DNA is cut out and a new stand is synthesized
59
explain short vs long patch repair
short puts in a new pair
| long makes a new strand
60
how do BRCA 1 and 2 proteins work to repair DNA
plays a role in dsDNA break repairs at replication forks
61
What is aneuploidy
missing or extra chromosomes
62
what is CIN and what cancer is it seen in
chromosomal instability has a lot of aneuploidy
Breast Cancer
63
what is MIN and what cancer is it seen in
microsatellite instability has little aneuploidy
colorectal cancer
64
what is heterotypic signaling
one cell type tells another what to do
65
tumors are mostly made up of what type of cell
stromal cells
66
stromal support is essential for which type of tumors
carcinomas
67
explain the epithelial to mesenchymal transition
cells turn motile to cover the wound but then don't go through mesenchymal to epithelial transition so then there are changes in the cytoskeleton
68
why are firboblasts important in cancer
they produce response proteins and make it more likely that the cancer will metastasize
69
how are tumor vessels different from normal ones
large, unorganized, leaky
70
How do leaky vessels affect tumors
they create heard lumps from the plasma leaking out and fibrin bundles
71
how do macrophages contribute to tumorigenesis
in hypoxic conditions they produce lots of VEGF and IL-8 which then form new blood vessels
supply EGF for proliferation
secrete proteases to disrupt the ECM
72
what recruits macrophages for tumors
production of CSF-1 and PDGF
73
what happens if tumors can't get a blood supply
they go through necrosis
74
What is the angiogenesis switch
induces blood vessel growth at will
75
how are malignancy and microvessel density related
greater density give more blood supply to tumors and therefore lowers survival rate
76
What is the thrombospondin-1 pathway
controls formation of new blood vessels to maintain order
new blood cells are targeting by Fas die but mature endothelial cell don't produce Fas receptor so they don't die
77
neoangiogenesis
mechanism cancer uses for creation of new blood vessels to supply growths
78
how can we target neoangiogenesis
treat with Avastin antibody that attacks VEGF
VEGF receptor inhibitors
Attack stromal cells
79
define intravasion
cancer cells invade blood vessels
80
define extravasion
the cancer cell gets stuck somewhere and moves out of the blood stream
81
explain the process of metastasis
intravasion, extravasion, micrometastasis, macrometastasis
82
How do EMT and E-Cadherin enable carcinoma cell invasiveness
overexpression of transc. factors can induce EMT without E-cad. E-cad get replaced with N-cad and allows epi cells to talk to stromal cells
83
What does TGF-Beta do
stops the progression of the cell cycle
84
What happens when TGF-Beta is present in a cell
the cells undergo EMT and suppress expression of E-cad and express vimentin
85
how do macrophages assist in stromal signals causing EMT
allow cells to gain access to blood vessels by degrading ECM
86
What happens when MT-1-MMP is expressed by cancer cells
degrades the basement membrane to invade he stroma deeper and frees up GFs
87
What is cell motility controlled by
Ras-like GTPases
88
how are filopodia and lemelipodia formed on cells
Ral-GEF activating Cdc42 forms filopodia
Ral-GEF activating Rac forms lemelipodia
89
how can you tell cancer is spreading by looking at the lymph nodes
look at sentinal node where tumor lymph drains because would shoe the cancer first
90
Where does prostate cancer usually move to
bone marrow, lungs
91
Where does colon cancer usually move to
liver, lungs
92
where does breast cancer usually move to
lungs, bone marrow
93
where does pancreatic cancer usually move to
liver, lungs
94
what do osteoblasts do
create bone
95
what do osteoclasts do
break down bone
96
Explain how osteoblasts balance bone degradation and growth
osteob creates RANKL protein to activate osteoclasts
osteob also creates OPG which inhibits RANKL
97
How does breast cancer metastasize to bone marrow
can produce PTHrP which tells osteob to produce RANKL and produce more osteoc
98
list metastasis suppressor genes and what they suppress
NM23 regulates MAPK cascade for cell proliferation and growth
E-cadherin stabalizes cell-cell contact in epithelial cells to prevent EMT and keep them in contact with each other
RhoGD1-2 supresses Rho proteins to reduce cell mobility
99
what do T-cell receptors bind to
major historeceptor proteins
100
What is the humoral immune response
generates soluble antibodies to bind invaders
helps keep invaders out of cell and targets them for degredation
101
how do macrophages help the humoral immune response
antigens bind to various domains to notify macrophages to endocytase
102
explain the cellular immune response
develop specialized cytotoxic cells that attack cell displaying certain antigens
Tcells and CTLs
103
what do T cells do
directly attack target cell
104
what do Cytotoxic T lymphocytes do
help trigger apoptosis in cell
105
Explain the adaptive immune response
requires previous exposure to antigen
MHC class 1 and 2 targeted by T cells
106
What is the difference between MHC-c1 and MHC-c2
c1 display proteins that are being made in the cell and are looked at by CTLs
c2 display oligopeptides and are displayed by dendritic cells or macrophages and are looked at by T helper cells
107
How to CTLs kill
secrete perforin to put holes in the membrane to allow granzyme to enter the cell
secrete death ligand FasL
108
Explain the innate immune response
no prior exposure, automatically recognize abnormal things
NK cells
109
how do NK cells work
recognize cells with low MHC-c1 expression and attacks them
secretes IFN-y to recruit other immunocytes to the area such as B-cells
110
How do regulatory Tcells work
express specific TCRs to stop activation of Tcells
release TGF-B and IL-10 to kill other T lmphocytes and block CTLs actions
111
What do we use to know when T cells should kill something or not
regulatory T cells
112
what are some cancers not associated with infectious agents
breast, prostate, colon, rectum, ovary, lung
113
what are some cancers associated with infectious agents
(non)Hodkins lymphoma, liver, Kaposi's sarcoma
114
How do cells distinguish neoplastic cells from normal cells
look at what is expressed on the MHC-c1
115
How do tumors evade detection of immune response
```
repress expression of MHC-1
Hide stress/repress NKG2D ligands
innactivate immunocytes that target cancer cells
avoid apoptosis
lose B2-microglobulin or TAP proteins
block eat me signal
```
116
What are the proteins that signal eat me or dont eat me
eat me- calreticulin
dont eat me- CD47
117
What are some Tumor cell counterattacks
become resistant to FasL mediated apoptosis
produce IL-10 or TGF-B that are kill lymphocytes
recruit TregS
118
ways to use the immune system to kill cancer
passive immunization
adaptive immune response
stimulate response or inhibit suppression
119
Ways to use passive immunization to kill cancer and examples
supply body with antibodies- herceptin for Breast Cancer
Treat B cells with monoclonal antibodies-- retuxan for Burkitt's
120
ways to use adaptive immune response to kills cancer and give an example
preload dendritic cells with antigen-- provenge for prostate cancer
121
ways to stimulate a response or inhibit supression to kill cancer
enhance antigen presentation by dendritic cells
block immunologic checkpoints
enhance activity of tumor-specific Tcells at metastasis site
122
what are electrophilic compounds
things that can react witht the bases to cause oxidative damage or adducts
123
What inactivates electrophilic compounds
glutathione
124
activators of the angiogenic switch
VEGF, FGF
125
inhibitors of the angiogenic switch
Thrombospondin 1,
ECM proteins
