Exam 3 Flashcards
what is the progression of tumors
normal –> hyperplasia –> dysplasia –> neoplasia –> metastasis
hyperplasia is characterized increases in what
GF and transcription factors
what is more influential for carcinogens to cause cancer
cumulative exposure rather than age
what could decrease cancer incidences
removal of potentially cancerous cells
give an example of decreasing cancer incidence by removing cancerous cells
removing polyps in colorectal cancer
give an example of cumulative exposure to a carcinogen that is linked to cancer
cancer related to smoking is parallel to the average number of ppl smoking 30 years later
give two examples of tumor progression
colorectal cancer can be stopped by removing polyps
pancreatic cancer is one of the most orderly cancers
explain what colonal succession means
one cell obtains a proliferative mutations that takes over an area. The pattern continues to make growths and allows for treatment resistance
are tumor stem cells real stem cells? Explain
no because relatively few cells from a tumor can form a new one
explain clonal diversification in tumors
cells mutate indifferent ways and form multiple parallel clonal expansions that may be benign or cancerous
What is comparative genomic hybridization (CGH)
gives an idea for reason behind duplications or deletions
How does comparatice genomic hybridization work
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
how many mutations does transformation require
more than 1
what does the k-ras oncogene do
gives hyperplasia
what are the four key pathways to alter to make cancer and what do they affect
Ras- mitogenic signaling and cell cycle
pRB- eliminates suppression of cell cycle
p53- disrupts apoptosis
telomeres- stablize for immortality
what are some toxic/mitogenic agents that can act as tumor progressors
ethanol, inflammation, hormone fluctuations such as the menstrual cycle
how does inflammation lead to tumors
preserves stressed and damaged cells
what is NSAID
non-steroidal anti-inflammatory drugs
how can NSAID decrease colorectal cancer
decreases inflammation
what happens when TNF-alpha is inhibited to release NF-KB
TNF-alpha leads to more inflammation
cyclin D1 and Myc lead to mitogenesis
anti-apoptotic genes
What does TUNEL assay do
looks for chromosomal ends
What does PCNA staining do
looks for proliferating cells
What does enabling COX-2 do
leads to prostaglandin productions which causes loss of contact inhibition, independent proliferation, and increased cell proliferation
What does LT inhibit
pRB and P53
What happens when pRB is transformed
resistance to growth inhibition
immortilization
What happens when p53 is transformed
resistance to growth inhibition
apoptosis evasion
immortilization
What happens when sT is transformed
mitogenic independence
metastasis
What happens when hTERT is transformed
immortilization
What happens when Ras is transformed
apoptosis evasion
mitogenic independence
angiogenesis
metastasis
characteristics of transit-amplifying cells
divide the most
turn into differentiated cells
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
ways to limit mutations in stem cells
apoptotic hair trigger
highly active MDR proteins that pump bad tings out
asymmetric strand allocation
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
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
what is mismatch repair
the DNA polymerase degrades and renews the strand nucleotides
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
What are two types of damage that can occur when not replicating
endogenous and exogenous
what are examples of endogenous damage
depurination
depyrimidation
deamination
ROS
what is depurination
endogenous
loss of a purine (G or A)
What is depyrimidinaiton
loss of a pyrimidine (C or T)
Which is more common depurination or depyrimidination
depurination
What is deamination
loss of an amine
what is ROS
oxidizes bases
DNA breaks causing abasic sites
What are examples of Exogenous DNA damage
x-rays
UV-radiation
Chemical agents
Liver decontammination
What are ways X-rays damage DNA
breaks sugar phosphate backbone
what are ways UV-rays damage DNA
creates pyrimidine dimers
What are ways chemicals damage DNA and give an example
Mustard gas, benzo(a)pyrine
alter pairing
attach methyl groups to bases
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
What are adducts in DNA damage
they prevent DNA nucleotides from pairing normally
What are some DNA damages that are seen in cancer
transversion
transiton
What is transversion
switching purine with a pyrimidine
What is transition
Switching purine with a dif purine or a pyrimidine with a dif pyrimidine
What are some ways to protect DNA
physical protection shields, scavenging for ROS, inactive electrophilic compounds
what is a way to physically protect DNA
depositing melanin into keratinocytes
What are ways to repair DNA
direct repair base excision repair nucleotide excision repair error-prone repair BRCA1 and 2 proteins
How does Direct repair work
direct removal of ethyl group by MGMT
How does base excision repair work
excision of altered base which can then be repaired individually or with a new strand segment
how does nucleotide excision repair work
DNA is cut out and a new stand is synthesized
explain short vs long patch repair
short puts in a new pair
long makes a new strand
how do BRCA 1 and 2 proteins work to repair DNA
plays a role in dsDNA break repairs at replication forks
What is aneuploidy
missing or extra chromosomes
what is CIN and what cancer is it seen in
chromosomal instability has a lot of aneuploidy
Breast Cancer
what is MIN and what cancer is it seen in
microsatellite instability has little aneuploidy
colorectal cancer
what is heterotypic signaling
one cell type tells another what to do
tumors are mostly made up of what type of cell
stromal cells
stromal support is essential for which type of tumors
carcinomas
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
why are firboblasts important in cancer
they produce response proteins and make it more likely that the cancer will metastasize
how are tumor vessels different from normal ones
large, unorganized, leaky
How do leaky vessels affect tumors
they create heard lumps from the plasma leaking out and fibrin bundles
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
what recruits macrophages for tumors
production of CSF-1 and PDGF
what happens if tumors can’t get a blood supply
they go through necrosis
What is the angiogenesis switch
induces blood vessel growth at will
how are malignancy and microvessel density related
greater density give more blood supply to tumors and therefore lowers survival rate
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
neoangiogenesis
mechanism cancer uses for creation of new blood vessels to supply growths
how can we target neoangiogenesis
treat with Avastin antibody that attacks VEGF
VEGF receptor inhibitors
Attack stromal cells
define intravasion
cancer cells invade blood vessels
define extravasion
the cancer cell gets stuck somewhere and moves out of the blood stream
explain the process of metastasis
intravasion, extravasion, micrometastasis, macrometastasis
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
What does TGF-Beta do
stops the progression of the cell cycle
What happens when TGF-Beta is present in a cell
the cells undergo EMT and suppress expression of E-cad and express vimentin
how do macrophages assist in stromal signals causing EMT
allow cells to gain access to blood vessels by degrading ECM
What happens when MT-1-MMP is expressed by cancer cells
degrades the basement membrane to invade he stroma deeper and frees up GFs
What is cell motility controlled by
Ras-like GTPases
how are filopodia and lemelipodia formed on cells
Ral-GEF activating Cdc42 forms filopodia
Ral-GEF activating Rac forms lemelipodia
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
Where does prostate cancer usually move to
bone marrow, lungs
Where does colon cancer usually move to
liver, lungs
where does breast cancer usually move to
lungs, bone marrow
where does pancreatic cancer usually move to
liver, lungs
what do osteoblasts do
create bone
what do osteoclasts do
break down bone
Explain how osteoblasts balance bone degradation and growth
osteob creates RANKL protein to activate osteoclasts
osteob also creates OPG which inhibits RANKL
How does breast cancer metastasize to bone marrow
can produce PTHrP which tells osteob to produce RANKL and produce more osteoc
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
what do T-cell receptors bind to
major historeceptor proteins
What is the humoral immune response
generates soluble antibodies to bind invaders
helps keep invaders out of cell and targets them for degredation
how do macrophages help the humoral immune response
antigens bind to various domains to notify macrophages to endocytase
explain the cellular immune response
develop specialized cytotoxic cells that attack cell displaying certain antigens
Tcells and CTLs
what do T cells do
directly attack target cell
what do Cytotoxic T lymphocytes do
help trigger apoptosis in cell
Explain the adaptive immune response
requires previous exposure to antigen
MHC class 1 and 2 targeted by T cells
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
How to CTLs kill
secrete perforin to put holes in the membrane to allow granzyme to enter the cell
secrete death ligand FasL
Explain the innate immune response
no prior exposure, automatically recognize abnormal things
NK cells
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
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
What do we use to know when T cells should kill something or not
regulatory T cells
what are some cancers not associated with infectious agents
breast, prostate, colon, rectum, ovary, lung
what are some cancers associated with infectious agents
(non)Hodkins lymphoma, liver, Kaposi’s sarcoma
How do cells distinguish neoplastic cells from normal cells
look at what is expressed on the MHC-c1
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
What are the proteins that signal eat me or dont eat me
eat me- calreticulin
dont eat me- CD47
What are some Tumor cell counterattacks
become resistant to FasL mediated apoptosis
produce IL-10 or TGF-B that are kill lymphocytes
recruit TregS
ways to use the immune system to kill cancer
passive immunization
adaptive immune response
stimulate response or inhibit suppression
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
ways to use adaptive immune response to kills cancer and give an example
preload dendritic cells with antigen– provenge for prostate cancer
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
what are electrophilic compounds
things that can react witht the bases to cause oxidative damage or adducts
What inactivates electrophilic compounds
glutathione
activators of the angiogenic switch
VEGF, FGF
inhibitors of the angiogenic switch
Thrombospondin 1,
ECM proteins
