Biology of Neoplasm 2

Question 1

inducers of apoptosis

Answer 1

injury
withdrawal of growth hormones
receptor ligand interactions
t cells

examples: chrmo, X-rays, hypoxia, genetic damage, growth factor/cytokine withdrawal, loss of cohesion/adhesion

Question 2

substrates for the caspase cascade

Answer 2

cytoskeleton and DNA

Question 3

how does the apoptosis go wrong?

Answer 3

dysregulation of anti-apoptotic signals (Bcl-2)

loss of pro apoptotic signals

mutations in these pathways result in resistance to chemotherapy and radiotherapy

mutated p53 is more difficult to treat

Question 4

limitless replicative potential

Answer 4

usually cells stop growing- senescence- after a certain number of doubling

can be circumvented via disabling Rb and p53

immortalization- can multiply endlessly

Question 5

telomeres

Answer 5

brackets of several thousand repeats on chromosomes that shorten w/ every replication cycle

attributed to inability of DNA polymerase to completely replicate of 3’ end

erosion of telomeres causes them to fuse end-to-end- signal that “time is up”

Question 6

telomerase

Answer 6

creates telomeres

not present in normal cells

most cancers have it overexpressed

Question 7

angiogenesis

Answer 7

blood supply necessary above 1mm size

dependent on ratio of VGEF to anti-angiogenetic agens

angiogenic switch- switch of ratio to pro angiogenesis

Question 8

VGEF inhibitors

Answer 8

treatments utilize VGEF inhibitors to prevent angiogenesis

Question 9

metastasis

Answer 9

millions are shed, but fewer than 1/10000 cells survive

steps include:
dyscohesion
matrix degradation
motility
adherence
extravasation
angiogenesis/proliferation

Question 10

cadherins and integrins

Answer 10

loss of cadherins (cell to cell junctions) associated w/ increased metastatic potential

loss of integrins or integrin swithcing removes tumor cells from basement membrane and their preference is for ECM

Question 11

matrix degradation

Answer 11

proteolytic enzymes- metalloproteases and collegenase to degrade membrane

Question 12

soil and seed hypothesis

Answer 12

distant site may have a receptor or binding site on the surface of the tumor that acts as a homing mechanisms

helps explain why cancers have patterns of metastasis

Question 13

therapeutic targets for metastasis

Answer 13

anti adhesive agents

martix metalloproteinase inhibitors

anti motility agents

Question 14

ideal drug target

Answer 14

drives tumor growth
turns on key mechanisms of cancer progression
reversible
dispensable
measureable