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;
92 Cards in this Set
- Front
- Back
- 3rd side (hint)
|
Are most cancers somatic or germ line?
|
Somatic
|
|
|
|
What is an example of an inherited cancer?
|
xeroderma pigmentosa
|
|
|
|
Objectives:
1. list 5 steps of oncogenesis 2. explain multi-hit model of cancer 3. list 6 types of genes that contribute to carcinogenesis 4. distinguish between oncogenes and tumor suppressors and list examples presented for each 5. explain the 2 hit model for retinoblastoma 6. descrive the 2 carcinogenic tranlocations that are explained 7. Describe the 2 types of carcinogenic gene amplification 8. define chromosome instability syndromes |
here we go
|
|
|
|
What are the stages of the oncogenic transformation?
|
1. cancer is a progressive thing
2. uncontrolled cell cycle progression****EXAM (bell ding ****) 3. Growth factor insensitivity - independence from induction and resistance to inhibition 4. Immortalization - unlimited replication and division**** by pass signals, p53 and telomers associated 5. Evasion of Apoptosis - programed cell death 6. Escape from immunity - immune system can detect 7. Angiogenesis - 2nd half of cancer - interact with environment and change cells - such as increase blood vessels 6. |
|
|
|
Multiple Hit Model of Carcinogenesis
***EXAM (Bell ding) |
Multiple genes must be mutated!***
one mutation is not enough to the cell need to bypass several problems |
|
|
|
there are multiple checkpoints in the cell cycle:
what are the 2 most important checkpoints you need to know and will be responsible for on EXAM ***EXAM |
p53
Rb |
|
|
|
cell cycle regulation is important and has many factors to control what 2 things?
|
Cell replication
or Apoptosis |
|
|
|
What are the 2 MAJOR cancer genes?
***EXAM (bell ding) |
Oncogene
& Tumor Suppressor |
|
|
|
What are oncogenes?
|
PROMOTES THE CELL CYCLE
|
|
|
|
What is a Tumor Suppressor gene?
|
INHIBITS THE CELL CYCLE
|
|
|
|
Would an oncogene be a gain or loss of function mutation?
|
gain of function
|
|
|
|
Would a tumor suppressor gene be gain or loss of mutation?
|
loss of funciton
|
|
|
|
Are oncogenes dominant or recessive?
|
dominant
|
|
|
|
Are tumor suppressor genes dominant or recessive?
|
recessive
|
|
|
|
What gene is involved with immortalization?
|
Telomerase
|
|
|
|
What is the function of telomerase?
|
Limited cell life
|
|
|
|
What is a mutation of telomerase?
|
gain of function
|
|
|
|
What is the inheritance pattern of telomerase?
|
somatic
|
|
|
|
For Cancer gene "DNA repair"
What is the: Wild type function? Mutation type? Inheritance pattern? |
Wild type function?
corrects mutations Mutation type? loss of function Inheritance pattern? recessive |
|
|
|
For the Apoptotic Genes
What is the: Wild type function? Mutation type? Inheritance pattern? |
Wild type function?
Programmed cell death Mutation type? both gain and loss of function Inheritance pattern? both dominant and recessive |
|
|
|
For the gene: Cadherins
What is the: Wild type function? Mutation type? Inheritance pattern? |
Wild type function?
Cell adhesion Mutation type? loss of function Inheritance pattern? somatic |
|
|
|
You need to know oncogenes and tumor suppressor genes
|
.....so review it ok
|
|
|
|
What is a viral oncogene?
|
an oncogene carried by a virus
|
|
|
|
What is Proto-oncogene?
|
an oncogene before its mutated
|
|
|
|
What is a cellular oncogene?
|
an oncogene carried on a cellular chromosome
|
|
|
|
Oncogenes not on exam
|
just know them
|
|
|
|
What is an example of a oncogene?
|
Ras signaling pathway
not on exam |
|
|
|
What do most or all cancers have mutations in what 2 tumor suppressor genes?
***EXAM |
Retinoblastoma (Rb)
p53 |
|
|
|
What does retinoblastoma gene control?
|
controls G1 to S transition
|
|
|
|
What does p53 tumor suppressor gene control?
|
Blocks G1 to S
Blocks G2 to M Induces Apoptosis in response to DNA damage Induces Apoptosis in repsonse to certain oncogenes |
|
|
|
Incase the picture does not show how does Rb control G1 to S transition
|
increase in cycline -->
cyclines phosphoylate Rb --> hyperphos of Rb causes a conformation chnage of Rb --> Rb then activates E2F --> E2F activated transcription factors to control cell cycle progression E2F also has positive feedback and activated itself and cyclins to to promote G1 to S transition |
Thus if you have a mutation in Rb
E2F is always on which increases G1 to S cell cycle progression |
|
|
How does p53 work?
|
p53 is always being expressed
labile protein - expressed and then degraded if cell thinks it is damage there are things that will stabilze the p53 p53 is a transcription factor |
|
|
|
What does p53 transcribe?
|
p21
|
|
|
|
What does p21 do?
|
inhibits G1 and G2 cyclins
prevents G1 to S and G2 to M |
|
|
|
p53 also causes apoptosis
|
know these
|
|
|
|
Is the 2 hit model the same as multiple hit model?
|
NOPE
|
|
|
|
If on exam for a child you see a tumor
developing on the retina for a child what is this? |
Retinoblastoma
See white on eye exam |
|
|
|
What # hit model is retinoblastoma?
|
2 hit model
|
|
|
|
What are the 2 forms of retinoblastoma?
|
inherited
sporadic |
|
|
|
What is the difference between inherited and sporadic retinoblastoma forms
|
inherited:
bilateral multifocal early age of onset autosomal dominant reduced penetrance |
|
|
|
Sporadic is......
|
Aymmetric
isolated tumor later in life NO inheritance pattern |
|
|
|
Explain the 2 hit model of retinoblastoma
****EXAM |
BOTH Rb alleles MUST BE mutated
|
|
|
|
Why is familial Rb more likely to get cancer?
|
bc every retinoblast begins with a mutated Rb allele
every mutation of the other allele results in a tumor |
|
|
|
How do cells become metastatic?
|
Detachment
basement membrane invasion migration deposition angiogenesis tumor growth |
|
|
|
What is E-cadherin?
|
common in cancer genes
involved in metastasis detachement mediates intercellular signaling as well as adhesion |
|
|
|
What factors are released by the metastatic tumor cell that allow it to deposit at a new location
said imp on audio |
Metastatic cells often alter the local environment at their target site by secreting:
growth factors, proteases and extracellular matrix proteins |
|
|
|
Where does CML
chronic Myelogenous Leukemia translocation occur? |
T(9;22)
|
|
|
|
What is the CML chromosome called?
|
Philadelphia chromosome
|
|
|
|
what happens in CML?
|
Produces a fusion protein between the:
abl oncogene and the Breakpoint Cluster Region (BCR) gene overactivates "abl" and causes leukemia know this |
|
|
|
What happens in Burkitt's Lymphoma?
|
Translocation link!
T(8;14) Translocation links immunoglobulin enhancer on chromosome 14 with c-myc oncogene on 8 |
|
|
|
Where is Burkitt's lymphoma expressed?
|
in WBCs
|
|
|
|
What happens to the regulation of c-myc with Burkitt's lymphoma?
|
Up regulation of c-myc
chromosome 14 Ig Enhancer switches with chromosome 8 myc |
|
|
|
What is Neuroblastoma an example of?
|
Gene amplification
double minutes leads to overexpression forms these circular thing |
|
|
|
What is Homogeneous Staining Regions? (HSR)
|
regions of the DNA that have been over duplicated and now if cancer gene is duplicated more likely to cause cancer
|
|
|
|
What are chromosome instability syndromes a result of?
|
cannot repair DNA enzymes
|
|
|
|
What disease results from defective:
UV specific endonucleases & Thymine Dimmer Repair enzymes |
Xeroderma Pigmentosa
|
|
|
|
What is an example of stem cell therapy?
|
Bone Marrow
Umbilical Cord Peripheral Blood |
|
|
|
What are 3 main challenges we face for stem cell therapy?
|
1. seed threshold
2. cell culture expansion 3. controlling differentiation |
|
|
|
What is seed threshold?
|
Stem cell transplantations fail if the quality isn't high enough
|
|
|
|
What is cell culture expansion?
|
The quantity of stem cells can be increased by propagating them invivo
However.... many cells will differentiate as they grow so you may start with a pure population of stem cells and end up with a small fraction remain in culture |
|
|
|
What is controlling differentiation?
|
Growth factors can potentially be used to control differentiation
prevent premature differentiation and induce differentiation into a desired cell type |
|
|
|
What are 3 more challenges of stem cell Rx?
|
4. Immunogenic Rejection***
5. Autologous 6. Allogenic |
|
|
|
Why is immunogenic rejection a problem?
|
The treatment will fail if the pts immune system
rejects the transformed cells |
|
|
|
what is autologous?
|
Autologous cells were originally extracted from the pt
ex: umbilical cord minimize the risk of immunorejection |
|
|
|
What is allogenic?
|
if health cells from the pt are no available
they must be taken from SOMEONE ELSE these are called allogenic cells are subject to immunorejection must find a histocompatabile donor |
|
|
|
What are 2 more challenges of stem cell Rx?
|
7. Development of 2nd cancer
8. Infection |
|
|
|
How can you develop 2nd cancer?
|
stem cells proliferate rapidly
there is risk of cancer if they divide out of control |
|
|
|
How can you get infection?
|
contaminated stem cells
can produce life threatening infections |
|
|
|
What are Adult Stem Cells?
|
Stem cells from Non-hematopotetic tissues
1. Mesenchymal cells: infiltrate most tissues and are a source of adult stem cells 2. Undifferentiated although these will differentiate into specific cells types they are more differentiated than embryonic cells so their potential is more restrictive |
|
|
|
How do you get Embryonic Stem cells?
|
Isolated from inner cell mass of the
MORULA stage of embryo Cells are then purified by centrifugation and propagated on collagen |
|
|
|
What is the advantage of embryonic stem cells?
|
Pluripotent!
Can develop into any type of tissue Much more powerful but ethical issues |
|
|
|
What is gene therapy?
|
introduce genes into a pt for Rx uses
|
|
|
|
What are 2 strategies under investigation for gene therapy?
|
1. Somatic Transformation
2. Germ Line Transformation |
|
|
|
What are somatic transformations?
|
deliver a wild type gene to somatic cells of an adult or child
w/out eliminating the mutant allele |
|
|
|
Important for exam about somatic transformations
|
all Rx trials investigate somatic transformation
germ line transformation is powerful but not efficient or predictable enough for humans |
|
|
|
What is Germ Line Transformation?
|
replace a mutant gene with a wild type allele in the germ line
|
|
|
|
What is in vivo gene Rx?
|
transformation of cells within the body
|
|
|
|
What is Ex vivo Rx?
|
Transformation of extracted cells which are then re implicated back into the body
|
In vivo strategies deliver genes directly
ex vivo combine stem cell and gene Rx |
|
|
Compare Direct and Indirect Gene Therapies
|
Direct - are used for specific mutations
such as Cystic Fibrosis and Duchennes Indirect - Used to target cancers |
|
|
|
What are 2 examples of direct gene therapies?
|
Gene reconstitution: add wild type
gene to cells with mutant genes RNAi: Inhibits expression of a spefiic gene |
|
|
|
What are 3 examples of Indirect gene therapies?
|
Immune Response: antigenic genes - tranformed cells cleared
Suicide Genes: Gene expression kills transformed cells Tumor Suppressor Genes: genes that inhibit tumorgenesis, ex p53 |
|
|
|
What is the main therapy problem for gene therapy?
|
transformation stability
transient due to degradation of DNA vector as an antiviral mechanism the nucleus automatically degrades DNA that is free of a chromosome therefore extrachromosomal transformations are transient Chromosomal integration - stable and passed to daughter cells |
A transformation is stabilized if the vector is inserted into a chromosome
the cell will propagate the inserts with the chromosome |
|
|
How is Immunogenicity a problem with gene Rx?
|
Transformed cells cleared, often increases with repeated treatments
This results in transient transformations similar to extrachromosomal vectors exceots that the pt becomes non-responsive to further treatments |
|
|
|
What are multifactorial traits?
|
numerous genes contribute to a multifactorial trait.
Its not practical to transform a pt with a wild type allele for each. It may be possible to cure a pt by transforming him or her with a few critical genes |
|
|
|
What is transgene size?
|
vectors can accept limited insert sizes
this becomes a issue with very large genes |
|
|
|
What is a major complication of gene therapy?
|
immunologic reactions
allergic reactions |
|
|
|
What is a bad consequence of horizontal transformation?
|
prevent transformation from spreading to uninteded cells
consequences unpredictable e.g. somatic to germ line cells |
|
|
|
Insertional mutagenesis
|
When a gene inserts into a chromosome
it can disrupt expression of adjacent genes occured with XSCID trial |
|
|
|
What does most gene therapy target?
|
Mosts gene therapy targets cancer
|
|
|
|
What are viral vectors?
|
Viral vectors advantage make them useful for gene therapy
|
naturally infect host cells - viruses carry therapeutic gene
cell type specificity - target specific type of tissue Genetic Engineering |
|
|
What are retroviral vectors?
|
RNA viruses - the greatest successes have used retroviral vectors!
chromosomal integration require dividing cells small transgene capacity |
|
|
|
SCIDS trial - has been cured in several clinical trials
|
Severe combined immunodeficiency
must live in a sterile environment bubble boy x-linked |
|
