cancer Flashcards
why are intestinal cells lined with villi
increase their surface area
villi vs microvilli?
intestinal lining has villi. each individual cell has microvilli. both serve to increase surface area
where would you find stem cells?
Between villi in little ‘crypts’ . Stem cells start at very bottom. sitting there maintaining the population of all the cells
how do stem cells produce cells for differentiation?
As they divide, they produce a cell for differentiation. Push those cells up. Eventually go up high enough to stop dividing.
why are cancer cells said to have transformed phenotypes?
they are doing different things, taking on new shapes than they were before.
malignant vs benign
Malignant: ones that will worsen, can lead to death
Benign: enlarging but should not be invasive/dangerous
what do we mean when we say cancer cells are immortal?
grow and divide in agar, and never stop dividing. ex:HeLa cells
De-differentiation of cancer cells
return to fetal state
- Alpha-fetoprotein- only made at time of birth. However in cancer cells, damaged liver starts regenerating itself, produces AFP again
- Also, if liver develops a cancer, they start developing AFP. Allows you to detect a cancer.
- Colon cancer has one too- CEA. Prostate: PSA. (lots of false positives tho) Present in blood is sign of a cancer
Angiogenesis
signal for new blood vessels. As tumor grows, calls for new blood vessels. increase in this is sign of a tumor
factors contributing to cancer
genetic + environmental
of those with lung cancer, __% are smokers
96
latency period for smoking
30 years
does the rate of cancer/death by cancer increase with age?
yes
oncogenes and tumor suppressor genes
oncogenes: acts like a dominant gene. Only need a mutation in ONE copy. This gene says Divide, divide divide! Unregulated cell division.
tumor suppressor genes: Loss of function mutation in one copy of gene-> no effect. But second mutation knocks out other copy- whatever genes were doing is lost. Then, more chance of having a cancer develop
ways to convert proto-oncogene to oncogene
mutation in coding sequence (mutation in coding sequence , produces broken protein, could tell it to divide)
gene amplification (take normal gene, divide wrong, get several copies of it- if each one produces final product, 3x as much of it, increases signal for cell division- just too much of a normal gene)
chromosome rearrangement (weird inversions)
or: virus could disrupt normal regulation or intorduce extra copy of a gene
normal cell signal pathway leading to division
Hormone/ growth factor binds. Changes shape of receptor- causes phosphorylation of some protein factor.
When that is phosphorylated, causes another to be phosphorylated, etc- ‘cascade.’
how do you get an error in cell signaling pathway that could lead to signaling for unlimited division?
Many signaling pathways. Many multistep pathways. A mutation in any of these genes would screw up this process.
Many genes that could be mutated in this process and start to signal for cancers. Could lead to incidence of so many types of cancers
what can happen with retinoblastoma and what is it an example of?
Rb gene- acts like a recessive gene. Both copies need to be mutated or shut off in order for tumor to grow
how does retinblastoma protein normally work and what goes wrong in the case of a cancer?
normally, inactive growth factor receptor, only activates to signal ‘divide’ when a growth factor arrives.
Mutatnt form: protein active 100% of the time! So for people with mutation , whether or not growth factor is there or not, you’re signaling DIVIDE
p53- normal, abnormal
P53 protein: monitors the DNA to see if there is damaged.
Normal: if sees damage, calls in repair enzyme, fixes. If cant fix it, signals for apoptosis (cell death process).
Abnormal: if you lose this function, damaged DNA is going through replication. produce aneuploidy, broken chromosomes, translocations. mutant p53 is found in MANY (70%) of cancers.
___ protein is a suppressor of cell division when DNA is damaged
p53
cell cycle checkpoints
G1, G2, metaphase
Cell in G1: when it wants to go to S, division, there is a G1 checkpoint. Is enviroment favorable? Is cell large enough? Is there DNA damage?
G2: another checkpoint before mitosis. Is all DNA replicated? Undamaged? Environment still good? Ok, enter mitosis
During metaphase: are all chromosomes attached to spindle?
p53/Rb both act like (dominant/recessive) genes
recessive
colon cancer: what does it tell us about multistep cancer
Cancer arises slowly in multiple steps.
Polyps: can be precursors of cancers. When you convert normal epithelium into a hyper prolifitive epithelium, pile up tissue, form polyp, get intermediate polyp- loses its shape, becomes a carcinoma, and then metastasis.
Association between mutation in APC gene – when it get sa mutation, that’s when epithelium becomes a polyp. K-ras converts to intermediate polyp
potential therapeutic targets in cancer
target cell surface protein that is the receptor for cancer, shut it off
OR:
Prevent angiogenesis
OR:
Prevent migration to matrix
treatement for CML / philadlephia chromosome issue
Gleevec: Competitively inhbits this oncogene
chemo vs radiation
- Goal of radiation- eliminate the cancerous area only
- Chemo- blunt force- eliminate growth of ALL dividing cells . Lose hair, intestinal upset as well.
monoclonal antibody therapy
Lung cancer- test for more than 100 different mutations that tend to occur in 13 known genes. Based on that try and tailor the treatment. If you see a particular cell marker, can make a monoclonal Antibody that sticks only to that particular target molecule (some messed up receptor or enzyme) and nothing else
how do you create monoclonal antibodies
- Isolate target molecule and inject it into mice
- Mice will make an immune response
- Isolate mouse immune cells (making antibodies against that molecule)
- Fuse immune cells w/ myeloma cell- type of bone marrow cancer- makes the immune cells be able to permanently grow. “immortal” in culture. Stil producing the antibodies that target our bad guy.
- Then , harvest the antibodies from the culture medium, use those to attack the tumor
- May want to ‘humanize’ the antibodies by recombinant DNA procedure- take off parts of molecule that are mouse specific, keep the binding part. The individual won’t reject the antibodies.
monoclonal atnibody vs gene therapy
•Monoclonal antibody therapy is NOT gene therapy; in gene therapy you’re editing your genes , here you’re training your immune system to attack a target
testing for viruses and cancer
If dealing with a virus causing cancer- test for virus. If virus not present, not likely to die. Example: HPV. Pap smears used to test for HPV. If HPV negative, don’t have to worry about getting cervical cancer
BRCA1, BRCA2: __ of cancers.
10%
BRCA- what is it and why does it cause cancer
•2 separate genes that work along with tumor suppressor activities, also have DNA repair effects- a mutation here inhibits ability to do DNA repair.
HER2: __ % of cancers
20%
. Immune targeting:
isolate some of the cancer , isolate T-CELLS FROM CANCER. CULTURE THE T CELLS, grow millions. Put T cells back w/ interleukin-2. (white blood cells) stimulate them to divide , hopefully will have an effect on that type of cancer. Pioneered by steven rosenberg, NIH.
Car T
chimeric antigen in receptor T cells. Make cells bind even more rapidly than normal targeted cancer therapies. Still not considered gene therapy.
