Week 5 - Angiogenesis and Cancer Treatment Flashcards
What is angiogenesis?
Angiogenesis is the formation of new blood
vessels from pre-existing vessels
What are the normal functions of angiogenesis? (2)
Blood vessels supply oxygen, nutrients, remove
waste and allow immune surveillance
Angiogenesis is essential for organ growth in the embryo and repair of wounded tissue in the adult
What diseases does insufficient vessel growth cause?
Insufficient vessel growth
(stroke, myocardial infarction, ulcerative disorders and neurodegeneration
What diseases does excessive vessel growth?
Cancer, inflammatory disorders, pulmonary
hypertension, blindness
Name the 3 types of angiogenesis.
Development/Vasculogenesis - Organ Growth
Normal Angiogenesis - Wound Repair placenta during pregnancy cycling ovary.
Pathological Angiogenesis - Tumour angiogenesis ocular and inflammatory disorders.
What is the difference between vasculogenesis and angiogenesis?
Vasculogenesis:
Progenitors - Primitive Vascular Network
PC/SMC - Mature vascular network (Including artery, veins, capillary and lymph vessels)
Who created the Angiogenesis Hypothesis in 1971?
Judah Folkman
What is the angiogenesis hypothesis?
Idea that tumour growth dependent on new blood vessel growth.
“If a tumor could be held
indefinitely in the non - vascularized dormant state….it is possible that metastases will not arise”
Give 3 examples of pro-angiogenic factors and 3 examples of anti-angiogenic factors
Pro-Angiogenic: VEGF, PDGF, TGF-alpha, TGF-beta.
Anti-angiogenic: TIMP’s, Thrombospondin 1 and 2, Angiostatin
What does the angiogenic shift refer to?
An imbalance between stimulators and inhibitors resulting in excessive stimulus.
What is Hypoxia?
Low Oxygen Tension - <1% O2
Why is Hypoxia important in angiogenesis?
It activates genes involved in angiogensis, tumour cell migration and metastasis.
Examples of the target gene activation include: VEGF, GLUT-1, u-PAR and PAl-1
What is the difference between vessel structure of healthy tissue and vessel structure of tumour tissue?
Tumour vessel: Immature vessel pericyte detachment, tumour cell intravasation due to leaky vessel from a lack fo pericyte coverage. Obstruction of blood flow due to stacked activated EC’s.
Why does tumour hypoxia mean poor response to therapy?
Chemotherapy: Reduced drug delivery and hypoxic cells do not proliferate
Radiotherapy - Free O2 radicals required.
What is the main transcription regulator/factor in tumour angiogenesis?
HIF - Hypoxia Inducible Factor
