Cancer Flashcards
What is highest incidence of cancer in males and females?
Main cause of cancer death?
Highest incidence- Prostate- men; breat- female
major cause of death= lung cancer in both male and femal
Top 4 incidence for male? Female?
Male
- Prostate
- Lung and bronchi
- Colon
- Urinary bladder
Female
- Breast
- Lung and bronchi
- Colon and rectum
- uterine corpus
Top 4 Cancer deaths by site male? female?
Male
- lung and bronhus
- prostate
- colon
- pancreas
Female
- lung and bronchus
- breast
- colon
- pancreas
lung and pancreas fairly virulent/fatal
prostate/breast are very common, but not likely to cause death
What is the cell source for the majority of cancers?
Epithelial
What areas of body typically don’t have cancer? Why?
Skeletal, cardiomyocytes, neurons
there’s post-mitotic and don’t divide
Cancer incidence increases markedly with ___
age
- childhood Ca very rare and usualyl devleop in utero
What are stroma/stromal cells?
support cells in tissue
(Connective tissue, blood vessels)
What are parencyhma/parenchymal cells?
special cells uniquely adaped to perform function of organ
(ie hepatocytes, cardiomyocytes, etc)
What are mesenchyme/mesenchymal cells
cells of mesodermal or neural crest orgiin
give rise to connective tissue, blood, and muscle
what does- oma mean?
benign tumoe
What does -carcinoma mean?
malignant tumor of epithelial origin
What does- adenocarinoma mean?
malignant tumor of glandular tissue
What does -sarcoma mean?
malignant tumor of mesenchymal origin (connective tissue tumor)
What does -blastoma mean?
malignant tumor of precursor cells (more common in children)
ex-neuroblastoma
How does a ell become a neoplasm?
- normal tissue has one cell that becomes dysplastic
- not Ca yet
- picks up superpower of growth and becomes a neoplasm
- not yet a Ca
- Now invades other tissue
- now Ca and invasive neoplasm
big picture- it starts as one of your cells! Why it’s hard to kill cancer
What does well differentiated/undifferentiated mean?
Assigns grading to tumor
- Well differentiated- Can still detect origin of cell based on where it came from (hepatocyte still looks like hepatocyte)
- Undifferentiated- does not look like origin site
- genes randomly turn on/off
*
- genes randomly turn on/off
What doe TNM stand for?
- T= Tumor
- T0- no penetration into basement membrane
- T1) through basement membrane, but still local
- T4) invasion into other organs/neighboring tissue
- N= lymph node
- N0) no lymph node involvement
- N1) local lymph node involvement
- N4) extensive lymph node involvement
- M= metastasis
- M0) No metastasis
- m1) metastasis
Characteristics of benign tumor?
- Small
- Well demarcated
- slow growing
- noninvasive
- nonmetastatic
- well differentiated
Characteristics of malignant tumor?
- Large
- poorly demarcated
- rapidly gorwing with hemorrhage and necrosis
- locally invasive
- metastatic
- poorly differentiated
Stages of cancer progression?
- Transformation- carcinogen induced change in a normal cell
- Progression
- growing more tumor cells
- makes multiple mutations
- Proliferation of genetically unstable cells
- tumor cell variants heterogeneity
What are proto oncogenes?
- better termed “pre” oncogene
- gene with some normal function
- usually associated iwth growth
- easily mutated to make oncogene
- the oncogene encourages tumor development
-
only need one mutation<– big point
- mutate either one (either gene) and you have a problem
- “over activity mutation”- gain of function
What is a tumor suppressor gene? Examples?
- suppresses tumors
- regulates cell cycle
- if it is inactivated or defective, the cell can proceed to rapid division
- 2 copies of each
- lose 1- inactivates tumor suppressor gene
- NO effect if mutation only in one copy
- lose 2- eliminates the tumor suppressor gene, stimulating cell proliferation
- lose 1- inactivates tumor suppressor gene
- Examples:
- p53- various ~70% of cancer
- BRCA 1, BRCA2- breast and ovrian cancer
- APC- colorectal (adenomatous polyposis coli)
- RB1- various (retinoblasoma)
- MSH2- colorectal, endometrial, gastric
- NF1, NF2- neuroblastoma, etc (neurofibromin)
BOTH GENES MUST BE DEFECTIVE!
Proto oncogene vs oncogene protein product?
Proto oncogene
- normal cellular gene
- can be converted into cancer-promoting oncogene by mutation
Oncogene protein
- Abnormal activity or
- is expressed at abnormal levels
- leads to cell death or gives rise to cancer
What are some examples of proto-oncogenes?
- bcl-2 - bcell lymphoma
- HER2/neu- breast cancer, ovarian cancer, others (epidermal growth factor receptor)
- n-myc- neuroblastoma
- c-myc- burkitt lymphoma, others
- Ras- various, 20-30% of all cancers
only one gene needs to be defective to cause issue!
How are chromosomal translocations oncogenic?
- Change in transcriptional control elements
- During crossover process, the regulatory domain of the gene expressed at high levels was attached to gene normally expressed at low levels, we have a problem
- now overproducing something that should be produced at low level, causes issues
- During crossover process, the regulatory domain of the gene expressed at high levels was attached to gene normally expressed at low levels, we have a problem
- Synthesis of a novel fusion protein
- combine two random axons causing new protein formation
- might give us a superpower, most of times, it’s bad
- combine two random axons causing new protein formation
What is the germline mutation of tumor suppressor gene?
- If mom already defective RB1 (tumor suppressor gene) in egg, then every cell in offspring has one bad tumor suppressor gene
- Only need 1 more mutation and then you have issues
What are six hallmarks of cancer?
- Self sufficiency in growth signals
- can’t wait for someone to tell it to grow
- Insensitivity to antigrowth signals
- needs to do it’s own thing
- cancer has to be a self-starter
- Evading apoptosis
- don’t die
- limitless replicative potential
- turn telomerase back on
- sustained angiogenesis
- need blood as you grow
- tissue invasion and metastasis
How does RAS affect self-sufficiency in growth signals?
- RAS has GTPase mutation (can’t hydrolyze the GTP–> GDP and stop pathway to encourage growth for cell)
- Typically, RAS inactivated by GTP–> GDP, however in this mutation, GRP does not get hydrolyzed
- now, when gorwth factor binds, the cell keeps being stimulaed to grow
- RAS stays in active form, leading to overgrowth
If you have 2 RAS genes, and the one from dad is mutated (during your life), what can happen?
- RAS is protooncogene, so it only needs one mutation (one bad gene) and then the growth pathway stays active
- GTPase is then mutated and cell will continue to activate MAP kinase pathway for cell growth
Examples of how cells maintain insensitivity to anti-growth signals?
- Rb (tumor suppressor gene) is like a gatekeeper for mitosis
- letting people go through if it is appropriate
- We have 2 copies of Rb (one mom, one dad)
- since Rb is like a guard, one is as good as two
- BUT if 2nd Rb is mutated, then anybody can go through
- So, if we lose both Rb, we’ve lost a major contorl of the cell cycle and tumor can replicate indefinitely.
What is the likelihood of developing retinoblastoma if you start with normal genes and have mutation vs inheriting mutation?
- If you inherit normal genes from parents, then you need 2 spontaneous mutations in the same cell in your livelihood
- this is VERY unlikely 1/50,000 incidence. Usually when you’re 60/70 yo
- If you inherit a mutant Rb gene, you only need one more mutation in any cell in order to cause issues
- nearly 100% incidence of retinoblastoma, and probalby before you’re 1 yo
Mutation in one cell throughout life is likely HOWEVER 2 mutations in the same cell is very unlikely!
What is p53 and how does a mutation affect the cell?
- p53 is guardian of DNA. Good p53;
- asks if you’ve replicated DNA properly?
- if answer no, p53 will stop process and allow you to fix DNA. If you can’t, p53 will tell you to die or survive, but can’t replicate again
- asks if you’ve replicated DNA properly?
- If p53 bad
- nothing to safeguard the cell DNA
- no cell cycle arrest, no DNA repair, no senesene
- causes mutant cell to expand and add additional mutations
How do cells accomplish limitless replicative potential?
- In cancer, turns back on telomerase enzyme activity
- this allows telomeres to be maintained and allows cancer cell to replicate indefinitely
How do cancer cells sustain angiogensis?
- Tumor needs to secrete tumor agniogenic factors (ie. VEGF- vascular endothlial growth factor)
- uses normal blood vessel and encourages growth of blood vessels
How do tumors invade and metastasize?
- Tumor produces collagenase in order to dissolve basal membrane and separate from neighboring cells
- then, reaches down to grab fibronectin of basement membrane layer, invading surrounding tissue
What is multistep nature of metastasis?
- Primary tumor
- proliferation/angiogensis
- detachment/invasion
- lymphatics, venules, capillaries
- embolism/circulation
- interaction with platelets, lymphocytes and other blood components
- transport
- arrest in organs
- adherence ot vesssel wall
- extravasation
- establishment of microenvironment
- proliferation/angiogenesis
- metastasis
What determine where things metastasize
- Cell needs to be able to survive in new organ environment
- if cell too foreign, then it will die in new organ
- certain cancers favor certain met spots
- ie breat–> bone
Main sites of blood-borne metastasis?
- Lungs, liver have lots of blood flow, lots of mets
- However, not many mets to kidney because it’s a bizarre environment for most cells
- prostate and breast like bone
- Once cancer metastasizes to brain- game over with mets
- Also, mets are like cockroaches- once you have one, you have hundreds.
- mets look like seeds in organ while primary tumors look like one big tumor
When does HPV develop from wart to tumor?
- When there’s accidental integration of viral DNA fragment into host chromosome DNA
- when it’s a benign growth or wart, the viral DNA is still separate from the host DNA
- Involves binding of E7 and E6 protein to tumor suppressor genes
- E7 binds to Rb
- E6 binds to p53
What protein does E7 (from HPV) bind to? E6?
What does this do to the cell?
- E7 binds to the retinoblastoma protein ( a tumor suppressor gene)
- E6 binds to the P53 gene (our most powerful tumor suppressor gene)
- It doesn’t mutate the gene at all, instead it binds and renders it inactive
- This makes the cell most susceptible to mutations at a higher rate
- now cell infected with HPV will more likely become cancerous
HPV is responsible for almost ____ % of cervical cancer
100%
HPV is also responsible for cancers at other sites
- strands of HPV are cell-specific and the ones that cause cancer REALLY like cervical cells
What are the strands of HPV covered by the HPV vaccine?
- 6, 11, 16, 18
- By a certain age, you’ve most likely been exposed to them all
- However, if you’ve only been exposed to say, 18 before the vaccine, then the vaccine will still be effective against 6, 11, and 16
- Vaccine works like all other vaccines. Antigen from virus is presented to body for B/T cells to find, then your body creates a response to the antigen.
- next time you’re body is exposed, your immune system can readily fight the virus
What is the relationship between tumor cell burden and the phases of cancer treatment?
- Typically, most cancer cells are rejected by natural immune mechanisms (if under 1mm mass)
- unsure of the exact rate because there’s cancer cells developing all the time in your body
- When 1 cm mass, then more clinically diagnostic neoplasm. How detectable it is depends on where the tumor is on your body
- can do surgical debulking, try to remove all tumor but if they don’t remove every cell, then cancer can reoccur
- Debulking followed by chemo to continue killing cancer cells left behind
What are some adverse effects of cancer chemoptherapy?
- Gi tract- particularly mucosa of small intestines
- bone marrow- all hematopoietic cells are affected
- anemia, neutropenia- biggest problem
- hair- hair follicles on head most affected
- skin- decreased epidermal renewal rate
- fetus- chemo is strictly contraindicated in pregnancy
- 1st trimester- absolutely don’t do chemo
- 2nd and 3rd- maybe ok if absolutely necessary
What is actually causing the nasty symptoms of cancer?
Immune system response
- Cytokines and chemokines released causing all the same problems as when you have the flu but at a much higher level
- often time, no overt organ failure causes death from cancer but instead usually killed by the immune system
