Tumor Angiogenesis

Front 1

Steps in physiological angiogenesis

Back 1

Stimuli such as hypoxia (exercise)-->established perfusion-->incr and PDGF,Ang and TGFbeta1 and a decrease in VEGF

Front 2

Steps in pathological angiogenesis

Back 2

Oncogene-induced tumor angiogenesis-tumor driven (GF secretion increase in VEGF-->chemoattactants and immune cells, fibroblasts; continously in a hypoxic state

Front 3

Rip-Tag model of Islet Cell Tumor Progression

Back 3

<5 weeks 100% normal islets; 5-7 weeks 50% hyperlastic islets; 7-12 weeks angiogenic islets; 12-14 weeks 2-4% tumors

Front 4

Angiogenic activators

Back 4

VEGF-A,B and C; FGF1 and 2

Front 5

Angiogenic inhibitors

Back 5

Thrombospondin 1 and 2; interferon alpha and Beta; angiostatin; endostatin; collagen IV fragments

Front 6

HIF1alpha are released in what environments?

Back 6

Hypoxia and VHL disease

Front 7

Tumor associated macrophages

Back 7

Critical in secreting growth factors; matrix metalloproteinases; disrupt ECM (therefore vessels can infiltrate into tumor)

Front 8

Anti-Angiogenic Therapy

Back 8

Targeting a genetically stable population and NOT genetically unstable tumor cell- ability to generate resistance minimal; most therapy uses naturally occurring proteins in the body-high tolerance/less side effects; easy accessibility for drugs-circulatory system

Front 9

Lymphatic vessels in a solid tumor

Back 9

Leads to high interstitial pressure

Front 10

metalloproteinases (MMP-9)

Back 10

degrage ECM and basement membrane-->soluble active VEGF leads to the angiogenic switch

Front 11

High microvessel density

Back 11

lower probability of disease free survival

Front 12

HIF-1 regulation

Back 12

pVHL takes it out of the system with ubiquination; either Hypoxia or VHL disease counteract this

Front 13

VEGF other function

Back 13

originally discovered as a potent permeability factor

Front 14

Tyrosine kinase inhibitors

Back 14

Help both prevent and regress tumor volume

Front 15

Pericytes

Back 15

Provide survival functions to endothelial cells; inhibitors of PDGF signaling

Front 16

Endothelial cells

Back 16

very sensitive to VEGF-R inhibition and chemotherapy