Neoplasia 4 Sept28 M2 Flashcards
main characteristics of normal stem cells
capable of self-renewal
asymmetrical replication
two main types of normal stem cells
adult and embryonic
charact of embryonic stem cells
present in inner cell mass of blastocyst: unlimited potential
charact of adult stem cells
- less undifferentiated. differentiate into cells of particular tissue or ogan
- difficult to find and isolate. quiescent.
function of normal embryonic stem cells
give rise to all cells in organism
function of normal adult stem cells
homeostasis of cell populations, especially in organs with high turnover
2 ways cancer stem cells arise
- from normal stem cells
- from differentiated tissue cells
considerations in treating cancer of stem cells (2)
resistant to therapy because
- low rate of replication (can’t target rapidly dividing cells with chemotherapy)
- express factors like multiple drug resistance 1
3 types of genes in affected in cancer
oncogene, tumor suppressor gene, DNA repair gene
3 main hallmarks of cancer
- evasion of cell death
- unlimited replicative potential
- sustained angiogenesis
regulation of normal cell proliferation: steps
growth factor-receptor-transfuction to cytoplasm protein or mt bcl2 proteins.
cyto proteins affect nuclear TFs which lead to advance in cell cycle, proliferation.
bcl2 regulate apoptosis so get either survival or apoptosis
how oncogenes disrupt normal cell proliferation cascade
give sustained proliferative signals
how tumor suppressor genes disrupt normal cell proliferation cascade
loss of sensitivity to growth inhibitory stimuli. No more restriction to proliferation
how defects in DNA repair genes disrupt normal cell proliferation cascade
lead to genomic instability, facilitate mutations in proto-oncogenes and tumor suppressor genes
example of proto-oncogene or oncogene
RAS
Normal function of RAS
growth factor-EGFR-RAS activated-RAF activated-MEK activated-MAPK activated-cell cycle proliferation
Treatment to colonic cancer if RAS working and its limit
Anti-EGFR antibody. If wild RAS, never activated so no cell proliferation
If RAS mutated, constant prolif signals
5 things oncogenes can be and examples for each
- Growth factors: PDGF
- Growth factors receptors: HER2-NEU
- Signal transducing proteins (RAS)
- Nuclear TFs (MYC)
- Cyclins and CDKs
example of tumour suppressor gene
TP53
normal function of TP53
- arrest cell cycle in late G1
- assist in DNA repair
- apoptosis if DNA can’t repair
- angiogenesis inhibition
angiogenesis definition
blood vessel neoformation from preexisting vasculature
vasculogenesis def
blood vessel formation from endothelial progenitor cells (mesenchyme)
arteriogenesis def
growth and remodelling of collateral preexisting arterioles to form large well-muscularized conductance arteries and arterioles to compensate on closed arteries
how tumor angiogenesis occurs
disruption of the balance between angiogenic factors (VEGF**) and angiogenic inhibitors
stimuli for angiogenesis
ischemia, hypoxia, injury, inflammation, shear stress
5 steps of neovascularizition
- BM degraded
- chemotaxis of endothelial cells to angiogenic stimulus
- elongation and alignement of endothelial cells
- endothelial cell proliferation
- BM produced
how endothelial cells of tumor vessels are different from normal vessels
more fenestrations, more permeable, A-V shunts, loops, abnormal architecture, 50x rate division, express surface integrins (VEGF-R), secrete growth factors and cytokines (autocrine and paracrine loops)
mistake when thinking about tumour vessels
Mistake is to think they have mutations
Examples of DNA repair genes that can be defective in neoplasm
MSH2, MLH1, PMS1 and PMS2
