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111 Cards in this Set
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for the following oncogenes know the associated tumor and gene product. how many alleles need to be knocked out |
oncogone mutations are gain of function, only one allele needs to be damaged
1. abl- CML, tyrosine kinase 2. c-myc- burkitts lymohone, TF 3. bcl-2: follicular/undifferentiated lymphoma, anti apoptotic 4. erb-B2: breast, ovarian, gastric, tyrosine kinase 5. ras: Colon Carcinoma, GTPase 6. L-myc: Lung Tumor, TF 7. N-myc: Neuroblastoma, TF 8. ret: MEN type II & II, tyrosine kinase 9. c-kit: GI stromal tumor, cytokine receptor |
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for the following tumor suppressor genes list the tumor and gene products that are assocaited. how many alleles need to be damaged
1. Rb (13q) 2. p53 (17p) 3. BRCA1 (17q) 4. BRCA2 (13q) 5. p16 (9p) 6. APC (5q) 7. WT1 (11p) 8. NF1 (17q) 9. NF2 (22q) 10. DPC (18q) 11. DCC (18q) |
this is a loss of fx so BOTH alleles need to be damaged
1. Rb (13q): retinoblastoma, isteosacoma, Rb gene product blocks G1--> S phse 2. p53 (17p): most, LiFraumeni, p53 gene product blocks G --> S phase 3. BRCA1 (17q): breast, ovarian. DNA repair 4. BRCA2 (13q): breast, DNA repair 5. p16 (9p): Melanoma 6. APC (5q): Colorectal, associated with FAP 7. WT1 (11p): Wilms Tumor 8. NF1 (17q): NF 1, 9. NF2 (22q), NF1 10. DPC (18q): pancras 11. DCC (18q): colorectal |
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most cacners arise form...
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1 single malignanct cell
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what are the 4 classes of genes implicated in cancers
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1. DNA repair
2. Tumor Suppressor (LOF, 2 mutations) 3. Oncogenes, growth: (GOF, 1 mutation) 4. Apoptosis **for cancer we need mutations in multiple classes over time. we will have anaplasia and angiogenesis as the tumor grows. MUST have BV |
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whats malignant trasnformation
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1, the tumor needs to have its own growth signals and not respond to anti growth signals from us
2. evade apoptosis 3. defective DNA repair 4. can replicate like none other 5. angiogenesis 6. metastasis 7. escape immune we need everyhing, not JUST defect in DNA repair we also need tumor suppressor, oncogenes, and failure of apoptosis |
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real quick, review the cell cycle
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1. GF binds to cell membrane
2. R is activated and activates signal transduction 3. 2 messenger as TF 4. Entry/Progression into the cell cycle resulting in cell division |
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whats a protooncogene
whats an oncogene |
1. Proto- the normal, its what we have to regulate proloforation
2. Onco- the mutated form. it CANT control proliforation **oncogenes need only 1 mutation bc they are GOF |
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wehats the mech of oncogene activation
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1. Mutation
2. Amplification 3. Overexpression of gene product 4. translocation for activation |
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ok so how many alleles need to be lost for oncogenes adn tumor suppressor genes
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Oncogenes: one allelic mutation lets proliforation occur, its a GOF. ONE
Tumor SUppressor: TWO, its a loss of fx so BOTH copies need to be lost |
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The 2 oncogenes that are GROWTH FACTORS are...
what are their gene products what cancer is associated with it how many alleles are knocked out |
1. PDGF, cis gene, glioblastoma
2. FGF, HST gene, KS, gastric cacner its an ONCOGENE so 1 mutation |
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what type of R are GF R
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tyrosine kinase
**oncogenic R dimerize and activate wo binding to GF **oncogene so only 1 allele needed |
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the oncogenes for GF were PDGFb and FGF. what are the oncogenes for GF RECEPTORS
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1. ERB B1: epidermal growth factor receptor (EGFR). associated with lung, head, neck carcinoma. Tx with monoclonal AB against EGFR and tyrosine kinase inhibitors
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what cancers are associated with EGFR? whats tx? whats the oncogene
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lung carcinoma
head neck Goal of Tx: AB against the EGFR and RTK inhibitors. the problem is the R so target it Oncogene is ERB B1 |
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what are the 2 oncogenic GF receptor genes
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1. ERB B1: EGFR, lung, neck, head carcinoma. tx with monoclonal AB and RTK inhibitor
1. ERB B2- Her 2 neu. overexpressed in breast cancer. POOR PROGNOSTIC marker. Tx with monoclonal AB (trastuzamab) |
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what is her 2 neu
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its a GF receptor that is overexpressed in some breast cancers.
its a BAD prognostic marker tx with monoclonal AB, trastuzamab, (cardiotoxic, balance) its an oncogene, 1 mutation required |
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what are the 2 oncogenes that are signal transduction molecules
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1. RAS
2. abl |
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Ras Oncogene
1. Actions 2. activation? 3. Cacners 4. how many alleles |
1. Actions: GTP binding protein, active with GTP and signals transduction. RAS is inactivated by intrinsic GTPase, GAPs and NF1. When we get that point mutation RAS wont turn off and we get LOTS of cell signaling to promote growth
2. Activation: point mutation due to chemical injury, prevents RAS from turning off. 3. Cancers: colon,pancreas adenocarcinoma 4. one mutation, its an oncogene |
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whats NF1
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its a tumor supressor gene, 2 mutations
*it is the brakes on RAS (recall RAS is a signal transduction when bound stim signaling. associated with colon/pancreas adenocarcinoma) **NF1 is a GAP, GTPase activating protein, it makes GDP on RAS and turns if off *NF1 mutation leads to neurofibromatosis |
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whats ABL
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a signal transduction oncogene (same category as RAS), onco so 1 mutation needed
*no signal needed *activated by a 9, 22 translocation, philadelphia translocation at break point location **BCR, ABL philadelphia chromosome **seen in CML, ALL |
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if my pt has CML what am I looking for
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t (9,22)
philadelphia chromosome, fusion of ABL with BCR **its a signal transduction oncogene, 1 mutation |
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jak stat is associated with what cancer
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oncogene, signal transducation
MYELOID cells in BM, talk about in winter |
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what are the TF oncogene we need to know
how many alleles are mutated whats it fx how is it activated cacners detection |
MYC- TF that binds to DNA and gets transcription going, OVEREXPRESSION is oncogenic
1. Allels: 1 mutaiton, oncogene 2. Fx: it binds to DNA and activates transcriptionbu 3. Activation: 4. cacners: Burkitts Lymphone t(8:14) and many others. N-MYC in neuroblastoma means poor prognosis. L-MYC in lung 5. Detection FIST- translocation (8,14) in burkittes. or look for double minutes or homogenous staining region for neuroblastoma |
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ingeneral what do the oncogenes that are TF do
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control entry into and progression through cell cycle
MYC is the example |
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whats t(8,14) associated with
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MYC overexpresstion. MYC is the TF that gets DNA transcription going. so when its mutated such that it is overexpressed we have TONS of transcroption- ONCOGENIC (1 allele)
associated with Burkitts N-MYC- poor prognosis in neuroblastoma L-MYC in lung |
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detection of MYC depends on...
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the cancer that it gives, but in both cases uses FISH
Burkitts: t(8,14) Nueroblastoma (N-MYC) look for homogenous staining region, indicative of amplification |
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burkits lymphoma is associated with what
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MYC overexpression (TF that activated DNA transcription)
t(8,14) N-MYC is also seen in neuroblastoma with HSR (homogenous stainging region) |
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what are CDK's
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Cyclin Dependent Kinases, regulate cell cycle.
activated by Pi C-D binds/activated CDK4 in G1 C-E regulates S phase, initiation of DNA replication others regulate DNA production, mitosis |
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what are the really important cell cycle check points
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G1- S transition, stop to check for DNA damage
G2- M transition, make sure repair happened **one or more of these regulators is not working in human cancer |
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what cell cycle regulators are dyxfx in cancer
where do cell cycle oncogenes act what are the forms of dysregulation? |
1. Cyclin D- overexpression in breast and more
Cyclin D1- translocation CDK4- amplification in glioblastoma, melanoma 2. Act: G1-S, when you check DNA for damage 3. |
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what happens to these cell regulators in cancers
Cyclin D Cyclin D1 CDK4 |
Oncogenes! 1 mutation
1. Cyclin D- overexpression in breast carcinoma 2. Cyclin D1- translocation in lymphoma 3. CDK4- amplification in glioblastoma |
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so one thing we need for cancer to grow is the ability to NOT listen to what
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INHIBITORY growth factors
tumor suppressor genes!!! need BOTH alleles mutated |
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what is a gatekeeper gene
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regulate cell growth, brakes on cell proliforation
tumor suppressor gene, need loss of fx mutation (loose 2 alleles) |
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when do we have a cacner that wont listed to stop growing signals
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when we have tumor suppressors
"escape from senescence" 2 mutations must happen, loss of heterozygosity seen in familial cacners |
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what are some familial cancers that have loss of heterozygosity
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a pt is born with one copy mutated and then they get somatic mutation of another.
Rb- familial retinoblastoma WT1- Wilms, nephroblastoma VHL: vonHippel Lindau: clear cell renal carcinoma |
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whats CpG island methylation (CIMP), whats the normal fx, whats the fx in cancer
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areas of hypermethylation that are common in promoter regions
normal fx is to shut off an X in females BUT can contribute to cancer by silencing tumor suppressors, pro apaptotic, DNA repair, and anti angiogenesis genes Rb, VHL, BRCA1, mismatch rapair genes are all shut off with CIMP |
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ok so we learned about familial Retinoblastoma, wilms tumor, and von hippel lindau. what do they all have in common
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they are all familiar cancers that are associated with loss of heterozygosity.
RB WT1 VHL *the genes responsible are tumor suppressors and all are mutated in the person but they also have one good copy so are "norml" when they loose the 2 copy they get cancer |
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ok so what in the workd turns off our good genes, genes like:
tumor suppressors Pro Apototic DNA repair Anti Angiogenesis |
CpG islant hypermutation turns them off
**normally they are found in promoter regions of the X chromosomes to turn one copy off in gilrs |
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what tumors do you get with CDK inhibitor dysfunction
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ok... so the inhibitor cant be shut off so we get cancer
Inhibitor p16: inhibits Rb. leads to HPV, familial melanoma. |
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p21 induced by
p27 responds to p16 inhibits **these are cell cycle inhibitors |
p53
TGFb Rb- this is a tumor suppressor, so we dont want p16 inhibiting it!! can lead to fimilial melanoma, HPV- E7, Adenovirus EIA polymavirus, RETINOBLASTOMA, osteosarcoma **cell cycle inhibitors. so if CDK4 and cyclin D, stop the cell cycle to look for DNA damage the INHIBITOR wont allow the cycle to stop and damaged DNA is treplicated- bad news |
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whats the fx of Rb
what cell cycle inhibitor acts on it |
its a tumor suppressor that slows the tansition from G1 to S, its active when it is HYPOphosphorylated. Rb inhibits Transcroption of E2F
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what happens with Rb has little Pi on it
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its active and will SLOW the cell cycle by slowing transtion btwn G1 and S
Rb when active then acts to decreases TF for E2F, E2F makes S phase genes when Rb is hyperphosphorylated is active and it will transcribe S phase genes via E2F |
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what inactivates Rb fx
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1. Rb mutaiton, deletion
2. Gene Silencing via hypermethylation 3. Cyclin D, CDK4 activation (pi RB to turn it off) 4. p16INK4a inactivation (turns cell cycle on so Rb is off) |
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whats the interplay btwn Cyclin D and CDK4 and Rb
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Cyclin D and CDK4 will Pi Rb so that it is OFF!!!
Cell cycle progresses Rb like to put the brakes on the cell cycle but when its hyper Pi it cant!!!! |
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whats the interplay btwn p16INK4a inactivation and Rb
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well p16 will turn ON Cyclin D and CDK4 so that the cell cycle is on Rb is Pi (OFF) (when p16 is inhibited it leads to cacner, so the inhibitor is OFF)
**cell cycle progresses **Rb malfx in Retinoblastoma, HPV, Osteosarcoma |
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what are the fx of p53
whats the gene, what chromosome |
Gate keeper! regulated cell growth, puts the brakes on proliferation 2 alleles for cacner,
Gene: Tp53, 17 Ok so here is the story, anoxia, oncogene expression, DNA damage triggers p53 path which will: 1. arrest cell cycle, p21 2. permanet cell arrest, (senescense) 3. apoptosis, BAX |
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what familial syndrome is assocated with p53 mutaion
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LiFraumeni Syndrome
heterozygous germ line mutaiton, increased risk of cacner by 25x all kinds of cancers |
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what gene is mutated in 50% of all cacners
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p53, chromosome 17. homozygous loss
its a gate keeper |
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p53 is activated by...
and causes... |
Activation:
anoxia, oncogene expression, DNA damage Causes 1. Arrest cell cycle, p21 2. Permanet cell arrest, 3. Apoptosis, BAX (BAX kills BAD cells) 50% of ALL tumors have p53 mutation |
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when p53 is mutated what happens
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we cant repair the damage or kill the cell so we get anaplasia, malignant cells
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tell me about p53 and sensing DNA damage, how is the cell cycle approached, is DNA repaired, what happnes if it is, what if its not
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ATM, Rad3 sense DNA damage and upreg p53
1. p53 arrests cell cycle via p21 (CDKI) 2. p53 binds to DNA to control repair genes 3. If repaired happy cell 4. If NOT repaired p53 can make BAX to kill the cell OR put the cell into PERMANENT cell cycle arrest |
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the p53 family member p73 does what
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apoptosis in cancer cells damaged by chemo
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how are p53 and p21 related
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when p53 is high it makes p21 which then arrests the cell cycle at G1 (p53 can now bind to and check the DNA will either repaair, kill, or perm arrest)
p21 is a CDKI |
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what happens with a homozygoius loss of p53
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promotes malignant transfrmation
the cell can no longer use p52 to... 1. Upreg p21 and put cell cycle in arrest 2. bind to and repair/sense DNA damage. ATM 3 make BAX to kill kill cell 4. permamnetly arrest it |
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what are some ways p53 can be mutated
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1. tobacco- benzopyrene
2. HPV 3. Hep B 4. Aflotoxin 5. UV light |
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what is cellular snescence
what genes are involved |
Senescene: can no longer complete mitosis
p53, Rb induce senescence in cells that are bad but but cant be repaired |
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what are the gene products and functions of APC
what sporadic neoplasm i sassociated, what familial is associated |
5q21
APC degrades B catenin b catenin: monitors cell adhesion via E cadherin and participates in WNT **when APC is mutated b catenin is ALWAYS on and cells proliforate SPoradic Colon Cancers FAP (familiar polyp) |
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talk to me about APC
chromosome what does it regulate |
chromosome 5q21
APC, degrades b catenin b cetenin then... 1. maintains cell cohesion via E cadherin 2. WNT signaling **when APC is mutated b catenin is ALWAYS on and cells proliforate |
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what is the problem in FAP, what about some sproradic colon cancers
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APC mutation
b catenin is NOT shut off and so can go wild adn do lots of proloforation B catenin is involved with cell cohesion via e cadherin and WNT |
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E cadherin
whats the fx of the gene product and the related neoplasm |
Growth Inhibitory Signal: glues epithelial cells together, when they arent connected malignancy is favored
visceral cancer, breast cancer **b catenin regulates E cadherin |
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TBGF b
whats the fx of the gene product and the related neoplasm |
stim CDKI's p21 and p15 (CDK will slow the cycle but the INHIBITOR increases cell cycling)
TUMOR SUPPRESSOR: inhibits transcription of CDK, cyclins, MYC via SMAD signaling path Pancreatic cancer, gastric cacner |
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NF1
whats the fx of the gene product and the related neoplasm |
tumor suppressor. its a GAP that turns off RAS
leads to neurofibromatosis I with one germline mutation Loss of 2 alleles leads to sporadic and familial neurofibromas |
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NF2
whats the fx of the gene product and the related neoplasm |
timor suppressor. gene product is involved with cell cell junctions/signaling
germline mutation leads to BL acoustic neuromas Sporadic mutations lead to schwanomas, meningiomas |
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what NFcodes for neurofibromin, what cancers
what NF codes for cell adhesion/signaling, what cacners |
I- germline mutation --> neurofibromatosis I
LOH --> sporadic, familliar neurofibromas. due to RAS activation II- germline mutaiton --> BL acoustic neuroma sproadic --> schwanoma, meningioma |
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VHL WILL be on the test, what is it, what cancers are associated with it
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Von Hippel Lindau syndrome due to VHL mutation
renal cell carcinoma, pheochrytoma (adrenal medulla), hemangioblastomas of CNS **tumor suppressor so 2 alleles are inactive |
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angiosarcoma is common what what organ bc of exposure to what
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liver
arsenic |
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what are the cacners assoaciated with VHL? what indices mutation of VHL
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1. renal cell carcinoma
2. pheochromocytoma 3. hemangioblastomas HIFa- hypoxia induced factor a, when mutated increases VEGF |
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how do we often get renal cell carcoinoma
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SPORADIC mutation of VHL by hypermethylation of the promoter
**when VHL is mutated VEGF is upregulated to make more BV to support cancer |
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whats the tumor suppressor that when working prevent BV growth, what happens when its mutated
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VHL--> HIFa
**we get renal cell carcinoma, oheochromocytoma, hemangioblastomp |
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what are the fx and neoplasms related to PTEN
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its a tumor suppressor so we are thinking...2 gene mutations
Phosphate and Tensin Homologue *dephosphorylates things to turn them off: PI3K/AKT- prosurvival path affects RAS and p53 |
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ok so whats the main thing PTEN acts on
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PI3K/AKT path, this is a prosurvival path. it is turned OFF by PTEN
**when we have mutated PTEN we can no longer turn off the proliforation path, PI3K/AKT and so we get LOTS of proloforation and decreased apoptosis --> **PTEN mutation is 2 most common mutation in cacner **familial mutation leads to cowden syndrome (benign appendages harmatoma, increase risk of cancer). a homozygous mutation leads to endometrial cacner |
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what normally inhibits the prosurvival PI3K/AKT path, what happens when its turned off
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normally inhibited by PTEN
**when PTEN is mutated we can get cacner! common mutation in cancer (2 most common) **Cowden syndrome- familir mutation, breast cacner, benign skin appendages hamartomas **sporadic mutation: endometrial cancers |
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whats Cowden syndrom assocaited with
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PTEN mutation, leads to appendage bening harmaoma in familar mutation
homozygous mutation leads to endometrial |
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what is the fx of WT1, what neoplasm
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Wilms Tumor (nephroblastoma), common RENAL cacner in kids. chromosome 11p13 deletion
**tumor supressor AND Oncogenic Activity |
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chromosome 11 is associated with what
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wilms tumor (nephroblastoma), inactivation of WT1
**tumor suppressor AND oncogene |
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recall teh tumor suppressors!!!
1. E Cadherin 2. TGFb, SMAD2, SMAD4 3. NF1, NF2 4. APC/b catenin 5. PTEN 4. Rb 5. p53 6. WT1 7. p16INK4a 8. BRCA1, BECA2 |
1. E Cadherin: anchor cells together, when lost favors malignancy
2. TGFb, SMAD2, SMAD4: stimulate CDKI p21, p15. inhibit transcription of CDK, cyclin (cell cycle regulators) colon, pancreatic, gastric cancer 3. NF1, NF2: NF1 when mutated keeps RAS on. neurofibromatosis. NF2- cell adhesion/signaling --> schwanoma 4. APC/b catenin: b catenin stim cell cycle, APC degrades APC. when APC is degraded we get proliforation (b catenin binds to E cadherin, WNT signaling) familiarl FAP and sporadic colon cacner 5. PTEN: Pi the brakes (PI3K) so when mutated the cell cycle goes wild. Famiilal- Cowden syndrome. Sporadic- endometrial 4. Rb: inhibits cell cycle, HPV, 13q delestion --> retinoblastoma, osteosarcoma 5. p53: gatekeeper, slows cell cycle. chromosome 17. present in 50% of all cancers. Familial LiFraumeni 6. WT1: tumor suppressor and oncogene. Wilms Tumor/Nephroblastoma. Chromosome 11q13 7. p16INK4a: inhibits Rb, familial melanoma. HPV |
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what cancer is assocaited with BCL2 overexpression
what are the effects of p53, PTEN dysregulation on apoptosis |
1. BCL is ANTIapoptotic so when its increased bad cells wont die. B cell follicular lymphoma
2. BAX is PRO apoptosis, with p53 mutation we cant make BAX. PTEN can do alternate killing via autophagy, PTEN upreg BAD |
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if you loose cell adhesion to the basement membrane what happens
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apoptosis
BCL2- anti apoptosis BAX- PRO apoptosis |
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whats involved in the extrinsic apoptosis path
what about intrinsic |
Extrinsic: FAS: FASL
Intrinsic: release of mito cyto C Pro apoptosis: BAX (made by p53) Anti apoptosis: BCL2 |
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name 3 ways cacner evade apoptosis
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1. Decrease FAS, no extrinsic path
2. BCL 2 overexpression, PRO survival (anti apoptotic) est in B cell follicular lymphoma t(14:18) 3. p53 mutation, NO BAX is made (BAX kills BAD cells) |
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what is B cell follicular cell lymphoma associated with
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BCL2 overexpression
t(14:18) |
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what an alternate to apoptosis
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autophagy, increased autophagy with PTEN
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ok so gatekeeper regulated cell growth, put brakes on proliforation. what are caretakers
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DNA replication/repair
Mismatch Repair NER (Nucleotide excision repair) Recombination |
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what inherited and sporadic malignancy is associated with defective mismatch repair
what are the common genes what defects accumulate |
Mismatch: our spell checkers
Familial: nonpolyposis colon cancer Sporadic: colon Genes: MLH1, MLH2 Defect: errors, the spell checker was not on, in tumor supressors and oncogenes |
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what inherited disease is associated with defective nucleotide excision repair, what cancers are associated with this defect
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1. Disease: xeroderma pigmentosum, UV(B) expusure creates dimers that arent repaired
2. squamous cell carcinoma, basal cell carcinoma, malignant melanoma Autosomal R inheritance |
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what gene is involved in DNA repair by homologous recombination
cancer predispositions |
BRCA1 BRCA2 ATM
inherited defects lead to hypersentitive DNA, can get Ataxia Telangiectasia (ATM) or Fanconi Anemia Predisposed to cancer and developmental defects |
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BRCA I BRCA 2 and ATM are associated with a defect in what DNA repair.
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homologous recombination
Breast Ovary ATM Fanconi Anemia z**hypersensitive to e rays and damaging things |
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whats the role of telomerase and telomers in cacner
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no telomerase in cells so we have limited replicative capacity. cancer cells have telomerase so can divide and divide adn divede
p53 mutation **give the cancer limitless ability to divide |
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how can cancer sustain angiogenesis
why is it important what are the vessels like |
Cancer NEEDS BV to support it, even if they are tortous, and leaky
Continuous growth in response to VGEF- VGEF is activated by.. 1. HIFa (recall VHL is the brakes) 2. RAS-MAP, MYC Anti Angiogenesis: cancer therapy. angiostatin nad endostatin |
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what are the things that increase transcription of VEGF, what are some features of the BV that are made
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1. HIFa
2. MYC dilated, tortous, leaky, irregular, not normal location |
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what are angiostatin and endostatin
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antiangiogenesis factors
cancer will eventually make HIFa and MYC to increase angiogenesis by increasing VEGF> this makes dilated leaky BV |
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what gives tumors the ability in invade and metastazise?
name the molecules |
when tumor cells detach
Loss of E cadherins, decreased catenin protein Type 4 collagen BM is degraded with MMP -Type IV collagenase: MMP9 Cathepsin D -Urokinase plasminogen activator **cells loose polarity |
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whats the tranlocation
1. t(8:14) 2. t(9:22) 3. t(14:18) 4. C: 11p13, deletion |
1. Burkitts Lymphoma (MYC)
2. CML, BCR: ABL (signal transduction) 3. BCL2 overexpression, no apoptosis. B cell follicular lymphoma 4. WT1, WIlms Tumor/Nephroblastoma |
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squamous cell lung cencer secretes what
what about small cell carcinoma of the lungs WHAT does renal cell carcinoma secrete |
Parathyroid related hormone, leads to HYPERcalcemia
Squamous Cell Carcinoma: ACTH like EPO, polycycthemia |
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CEA
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ONCOFETAL GENE ASSOCIATED WITH COLON CANCER
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tobacco is assocaited with what cancers
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mouth
larynx esophagous bladder **when combind with asbestos you get bronchogenic cancer |
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ok so once a cancer has degraded the ECM and busted through teh ECM (loose E cadherin and catenin, BM killed with MMP9 cathepsin D nad urokinase plasminogen activatorh)
what is the next step |
1. ATTACHMENT and MIGRATION
loose laminin and fibronectin receptors, loose polaity move via attachment via fibronectin (like lots of little hands that move the cells along) movement is also directed bvy Autocrine motility factor \- chemotatic **CD44 lets it attach to BM of BV |
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how do metastatic cancer cells move
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via attachment to fibrinectin receptors, like sticky hands
Autocrine motility Factor, Chemotacitc **lets the tumor cell move through the ECM and find lymph or BV *movement supported by preseases, MMP, integrins etc |
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what are hte 2 ways a tumor can enter a BV
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1. Tumor Embolus- tumor cells surrounded by platelets
2. single tumor cell |
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whats intravasationo
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when a tumor gets into BV as part of mets
CD44 lets it adhere to BV BM TUmor can enter as an embolus covered in plateles or as a singel cell |
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how will a tumor adhere to activated endo
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CD44
this is what happens when a tume invades BV METS,. bad news. the tumor will then eventually leave the BV and make new ones in a 2 site |
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what determines sites of METS
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1. drainaige, first filter, regionsl nodes
2. Metastatic Site Tropism: chemokines from target tissue can let or inhibit cancer |
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what are the outcomes of METS
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1 can be latent/dormant
2. death |
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where does METS occur
1. Prostate 2. Bronchgenic (smoth and asbestos) 3. Neuroblastoma 4. Breast |
1. lumbar vert
2. adrenals, brain 3. liver, bone 4. bone, liver, lung (lung has chemokines for breast cancer) |
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what are some non permissive sites of METS
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heart
SK mm spleen |
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what does the stroma do for malignant cells
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stroma HELPS the cancer
ECM and tumor corss talk for paracrine GROWTH signals and even genetic changes |
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whats the warburg effect
clinical application |
dominant metabolic path of cancer cells --> AEROBIC GLYCOLYSIS
mutatinos in PTEN, RAS, p53 and MYC help shift metabolism **lets us use PET scan to see glucose uptake |
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whats the metabolism of malignant cancer
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aerobic glycolysis
called warburg effect **make it hypoxic to increase cell division of cacner. mutations in PTEN, RAS, p53, and MYC all alter metabolism **lets us use PET scar to see glucose uptake |
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glucose uptake in cacner cetts via PET is allowed by
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warburg effect, malignancies switch to aerobic glycolysis
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whats the molecular multistep basis of cacner
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each cancer gets accumulations of multiple mutaitons
**NO SINGLE ONCOGENES CAN FULLY TRANSFORM A CELL several onco genes are at least 2 suppressor genes are mutant **mutations are incremental over time and have phenotypic changes assocaited |
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what is the term that ID's cancer as being an accumulation of multiple mutaitons nad not a single oncogene mutaiton
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molecular multistep basis of carcinogenesis
**mutations are incremental over time and are associated with phenotypic changes |
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normal epithelium has an APC mutaiont, there is then hyperproloforative epithelium and abbarent cryptic foci and COX 2 overexpression. the leads to a small adenoma, there is then a K RAS mutation and we get a larger adenoma, then there is a p53 mutation and a DCC mutaiton and we end up with invasive colon adenocarcinoma.
what does this illustrate |
multistep evolution of colon cancer
accumulation of incremental changes over time. no cacners come from a SINGE oncogene mutaiton. mutations are associated with a phenotypic change |
