Oxygen Sensing and Angiogenesis Flashcards
What distance does O2 diffusion in multicellular organisms become inefficient?
> 1mm
What does the vasculature provide for the endocrine system?
Tissue communication & co-ordination
What is a hemangioblast?
Progenitor stem-like cell
What is vasculogenesis?
Embryos form all their blood vessels from the hemagioblast
When does true vasculogenesis only occur?
During embryogenesis
Define angiogenesis.
Formation/sprouting of new blood vessels from pre-existing ones
What is arteriogenesis?
The remodeling of blood vessels in order to form arterial collaterals
What are 4 oncogenes that are pro-angiogeneic?
KRAS
SRC
c-MYC
EGFR
What does excessive tumoral angiogenesis promote?
Hypoxia
What does angiogenic vessels provide for cancer cells?
An exit route for invasion & metastasis
What are 3 oxygen sensing pathways promoting angiogenesis?
HIF
mTOR
UPR
What is MTD chemotherapy?
Applying maximum dose possible causing adverse effects & cancer cell killing -> increased hypoxia, therapy resistance leading to recurrence & metastasis
What is LDM chemotherapy?
Splitting chemotherapy into small, frequent doses limiting cell killing with a favorable safety profile
What type of therapy has antiangiogenic agents been effective & well tolerated?
LDM
Why does improved oxygenation lead to better pre-clinical outcomes?
maturation of intratumoral vessels is thought to enhance access of drugs to cancer cells whilst decreasing hypoxia-related resistance
