Cancer II 3

Question 1

PKb (Akt) phosphorylates

Answer 1

Bad - inhibits it

Question 2

Draw out the Pi3K pathway

Answer 2

pg 102-103

Question 3

PTEN is a (tumor suppressor or proto-oncogene)

Answer 3

tumor suppressor gene

Question 4

what is the second most commonly lost tumor suppressor gene in cancer

Answer 4

PTEN

Question 5

in protate cancer there is often loss of what

Answer 5

PTEN

p53

Question 6

males with BRCA2 have increased risk for what

Answer 6

breast & prostate cancer

Question 7

what is overactive in prostate cancer

Answer 7

PSA is increased

Question 8

loss of function of BRCA genes in prostate cancer & increased expression of PSA, what specfically is the increased expression of PSA telling you

Answer 8

AR signaling pathway is overactive,

Question 9

active PKB phosphorylates BAD and results in

Answer 9

increased cell survival

Question 10

besides phosphorylating bad what does active Akt do

Answer 10

more acetyl CoA

Question 11

cancer cells take up massive amounts of

Answer 11

glucose

Question 12

how do cancer cells show up on PET scan

Answer 12

a lot of glucose in cancer cells

Question 13

Warburg effect

Answer 13

somethign that happens in cancer cells
thorught to be early event in cancer progression
cells underoing lots of glycolysis but they aren’t using the oxygen even though they have enough. thought that in the initial stages, the cells do become hypoxic b/c they haven’t stimulated growth of own blood vessles yet
then they stimulate angiogenesis and oxygen and nutrients is restored, but they still undergo anaerobic glycolysis

Question 14

lactic acid produced via whe warburg effect is thought to be

Answer 14

toxic to the surrounding cells

Question 15

warburg effect & wound healing

Answer 15

it happens during initial stages of wound healing but then the cells revert again. so cells take up huge amount of glucose during wound healing to thelp them with the very rapid proliferation. also angiogenesis in wound healing

Question 16

Patient was a 24-year-old woman with a nonmetastatic infiltrating ductal carcinoma of the breast.

Hx: Identical triplet sister developed breast cancer, previous year.
3rd identical triplet had bilateral prophylactic mastectomy at age 24.
Patient’s mother had cancer of uterine cervix at age of 22.
Both maternal grandparents had died of colon cancer in their sixties.

Patient underwent a mastectomy with gross resection of primary tumour
what is running in the family?
Does mother having cervical cancer have anything to do with the breast cancer?
grandparents with colorectal cancer have anything to do with the breast cancer?

Answer 16

BRCA mutation
No - cervical cancer major risk factor is HPV
No

Question 17

mutation in BRCA1 gene - have they inherited one or two loss of function mutations

Answer 17

one

Question 18

what has to happen for pt to inherit a BRCA1 mutation to have a tumor

Answer 18

second mutation/second hit

Question 19

abnormal BRCA1 have high risk of

Answer 19

breast & ovarian cancer

Question 20

when is herceptin given

Answer 20

overexpression in Her2 receptor for breast cancer

Question 21

IKK is a

Answer 21

kinase

Question 22

IKK inhibts

Answer 22

kapa B kinase

Question 23

IkB when active what does it do

Answer 23

inhibtis NF-kB

Question 24

when IKK is active

Answer 24

phorphorylates IkB

Question 25

what is overactive in multiple myeloma

Answer 25

IKK pathway

Question 26

NF-KB is

Answer 26

proto-oncogene | it increases expression of different genes involved in surival and proliferation of cell

Question 27

NF-kB trascribes

Answer 27

- so transcribes IAPs, BCL-XL & BCL-2

Question 28

NF-kB increases what genes

Answer 28

invovled in survival

Question 29

IkB inhibits

Answer 29

NF-kB

Question 30

what does IKK do when active

Answer 30

phorphorylates IkB

Question 31

velcade is a

Answer 31

drug, proteasome inhibitor

Question 32

how does velcade work

Answer 32

there is overactivation of IKK signaling pathway in cancer. phosphorylation of ikb and will get poly-ubiquinated b/c of that but the drug blocks the proteasome so it can't et destroyed in the proteosome because the drug blocks the proteosome! so it's still not releasting NF-kB

Question 33

what need to happenf or tumor cells to keep replciating

Answer 33

reactivation of telomerase | angiogenesis

Question 34

vasculogenesis

Answer 34

forming new vessels from scratch

Question 35

angiogenesis

Answer 35

new blood vessels from existing bessels

Question 36

in wound healing what occurs

Answer 36

angiogenesis

Question 37

when cells are hypoxic they secrete

Answer 37

vegF

Question 38

vegF does what

Answer 38

binds to nearby endothelial tissue and cause those endothelial cells to proliferate and migrate in toward the hypoxic tissue

Question 39

when does angiogenesis normally happen

Answer 39

Embryonic development Menstrual cycle & pregnancy Wound healing (macrophages release VEGF, FGF, PDGF) Vascularisation of ischaemic tissue

Question 40

in response to ischemia stroke you wan to

Answer 40

increase angiogenesis

Question 41

what are some conditions with excessive angiogenesisi

Answer 41

``` Psoriasis Rheumatoid arthritis Endometriosis & Menorrhagia Atherosclerosis Cancer ```

Question 42

what are some conditions with insufficient angiogenesis

Answer 42

``` Stroke Heart disease Chronic wounds Venous ulcers Infertility ```

Question 43

angiogenesis normally very tightly

Answer 43

regulated

Question 44

in cancer what happens regarding angiogenesis

Answer 44

too many positive regulators of angiogenesis

Question 45

thrombospondin inhibits

Answer 45

angiogenesis

Question 46

angiostatin inhibits

Answer 46

angiogenesis

Question 47

VEGF stimultaes

Answer 47

angiogenesis

Question 48

thrombospondin

Answer 48

inhibits angiogenesis

Question 49

VEGF stands for

Answer 49

vascular endothelial growth factor

Question 50

when wound is repaired, amount of oxygen cells needs is restored and

Answer 50

angiogenesis will stop

Question 51

as tumor grows cells in middle become

Answer 51

hypoxic

Question 52

when cells become hypoxic they secrete

Answer 52

VEGF

Question 53

VEGF

Answer 53

diffuses in extracellular space and binds to nearby endothelial cells and activates VEGF receptors

Question 54

when VEGF binds to its receptors

Answer 54

activates RAS/MAP kinase pathway in the endothelial cells so they migrate towards the VEGF secretion, they proliferate and migrate into tumor

Question 55

VEGF is normal?

Answer 55

yes, it's a normal response, in cancer it's just on too much

Question 56

newly formed blood vessels are ? | it's relationship to cancer

Answer 56

permeable - haven't been stabilized properly so it's really easy for cancer cells to get into vessels

Question 57

if there's enough oxygen there is low amount of what TF

Answer 57

HIF

Question 58

HIF stands for

Answer 58

hypoxia inducible factor

Question 59

HIF

Answer 59

TF - transcribes VEGF

Question 60

what transcription factor transcribes VEGF

Answer 60

HIF

Question 61

if cells don't have enough O2 they have accumulation of

Answer 61

HIF - starts to transcribe VEGF

Question 62

VE stands for

Answer 62

vascular endothelial cells

Question 63

what happens when cells are migrating?

Answer 63

in order for endothelial cells to migrate they have to secrete MMP to digest path through the surrounding tissue, decrease in cell- cell adhesion so they can move. eventually will have endothelial maturation and stabilization of them by the pericytes

Question 64

any migrating cell will have secretion of

Answer 64

MMP

Question 65

TIMP stands for?

Answer 65

tissue inhibitors of MMP

Question 66

TIMPS do waht

Answer 66

block MMP activity

Question 67

major activator of angiogenesis

Answer 67

VEGF

Question 68

hypoxia

Answer 68

cell doesn't have enough oxygen

Question 69

hypoxia results in accumulation of

Answer 69

HIF

Question 70

HIF binds to

Answer 70

HRE

Question 71

HRE

Answer 71

region in promoter of genes responsive to hypoxia and results in promotion of VEGF

Question 72

HRE stands for

Answer 72

hypoxia response element

Question 73

HIF in presence of normoxia, proline hydroxylase does what to HIF

Answer 73

hydroxylates it

Question 74

normoxia

Answer 74

normal oxygen conditions

Question 75

HIF is always

Answer 75

produced in cells

Question 76

hydroxylated HIF recognized by

Answer 76

PVHL

Question 77

PVHL is part of

Answer 77

ubiquitn ligase complex

Question 78

PVHL

Answer 78

recognizes hydroxylated HIF and degrade it in protosome

Question 79

if cells become hypoxic PVHL cannot

Answer 79

hydroxylate HIF

Question 80

if there's no HIF hyroxylated it wno't

Answer 80

get polyubiquinated, will accumulate in cell

Question 81

VHL stands for

Answer 81

von Hippel-Lindau

Question 82

VHL MOI

Answer 82

AD

Question 83

VHL the pt inherits what

Answer 83

one LOF mutation in PVHL

Question 84

what happens if there is second hit in PVHL

Answer 84

if there is no PVHL, won't get polyubiquinated, so increased VEGF expression even when there is enough oxygen.

Question 85

pts with VHL have what

Answer 85

hemangioblastoma -

Question 86

what is hemangioblastoma

Answer 86

tumor of blood vessel

Question 87

Haemangioma are what kind of tumor

Answer 87

benign

Question 88

Haemangioma within them there are too many

Answer 88

pro-angiogenic facotrs | not enough anti-angiogenic inhibitors

Question 89

when IkB is phosphorylated what does this do

Answer 89

targets IkB for polyubiquination and degradation in protosome - this frees NfkB