cancer

Question 1

define retrovirus

Answer 1

their rna genome is reverse transcribed into DNA and inserted in the eukaryotic genome.

Question 2

what is the only retrovirus causing human tumors?

Answer 2

the human T cell leukemia/lymphoma virus

example: Hepatitis virus

Question 3

whats a dna virus?

Answer 3

dna virus can include oncogenes and inorporate them in the host dna
example: HPV

Question 4

how does the microbiota play a role in cancer?

Answer 4

it can have an anti-tumoral effect or a pro-tumoral effect

Question 5

define tumor supressor?

Answer 5

proteins that inhibit cell growth and proliferation which become inactivated by mutation (loss of function mutatioin)

Question 6

how can cancer arise?

Answer 6

when mutation blocks the activity of a tumor suppressor

Question 7

what are the 5 major types of tumor suppressors?

Answer 7

inhibitors of the cell cycle
receptors and signal transducers inhibiting cell proloferation
checkpoint proteins that stop the cell cycle if dna is damaged
activators of apoptosis
dna repair mechanisms

Question 8

what are the checkpoints?

Answer 8

g1 checkpoint
g2checkpoint
metaphase checkpoint

Question 9

how does p53 supress cell division?

Answer 9

by turning on the cdk inhibitor p21

Question 10

what activates p53?

Answer 10

dna damage

Question 11

what does p21 turn off?

Answer 11

S-phase CDK

Question 12

what is micrometastatic?

Answer 12

small collection of cancer cells that have been shed from the original tumor and spread to another part of the body through the blood or lymph nodes

Question 13

the loss of function mutation needs ?

Answer 13

both alleles to be mutated to induce cancer

Question 14

what is loss of heterozygosity mutation?

Answer 14

when person with one mutated allele develops a single mutation of the second allele which is enough to induce transformation.

Question 15

genetic basis of cancer for Rb?

Answer 15

Rb blocks G1 phase of cell cycle. Rb+/- predisposes to retinoblastoma if it mutates to its absence Rb-/-

Question 16

genetic basis of cancer for APC?

Answer 16

APC prevents the expression of proto-oncogene Myc. APC +/- predisposes to colon cancer if it mutates to its absence APC-/-

Question 17

genetic basis of cancer for BRCA-1?

Answer 17

BRCA-1 blocks cell cycle progression. BRCA+/- predisposes to breast cancer if it mutates to its absence BRCA-/-

Question 18

whats hereditary retinoblastoma ?

Answer 18

somatic retinal cell has Rb+/- then a somatic mutation occurs leading to Rb-/- which is a homozygous cell that gives rise to tumors in retina

Question 19

whats sporadic retinoblastoma?

Answer 19

somatic retinal cell first has Rb+ Rb+ then 1st mutation occurs to give heterozygous Rb+/- then 2nd somatic mutation occurs to give Rb-/- leading to tumors in retina

Question 20

what mutation slows down GTPase activity of Ras, which becomes a constitutively active oncoprotein

Answer 20

mutation of glycine at position 12

Question 21

what blocks the activity of Bcr-ABl Protein?

Answer 21

Gleevec binds the kinase domain and inhibits the enzyme which causes no signal and no leukemia

Question 22

what is the cancer therapy of Gleevec?

Answer 22

Treats chronic myelogenous leukemia with philadelphia chromosome. its the first drug targeting a signaling pathway specific of a cancer cell. mutations can make cancer cells resistant to gleevec

Question 23

what is TGFbeta?

Answer 23

an inhibitor of cell growth. can promote apoptosis. when it binds to a dimeric receptor with serine/threonine kinase activity, TGF beta activates intracellular messengers Smad proteins.

Question 24

what are smad proteins?

Answer 24

smads activate expression of cell cycle inhibitors genes like p15
and PAI - inhibitor of proteases

Question 25

what do mutatioins in TGF beta pathway lead to?

Answer 25

increased proliferatioin by blocking p15 | increased risk of metastasis by blocking PAI

Question 26

what are cyclins?

Answer 26

they promote progression through cell cycle which is induced by growth factors. cyclins bind and activate specific cyclin dependent kinases ( CDKs)

Question 27

what do CDK do?

Answer 27

phosphorylate inhibitors of cell cycle like Rb which when Rb is phosphorylated it become inactivated and cells are allowed to proliferate

Question 28

what can inhibit CDK?

Answer 28

p15 and p16

Question 29

what is a common cause of cancer involving mutations?

Answer 29

1) Over production of cyclins which allow cell cycle progression 2) Loss of Rb or p15/p16 (cell cycle inhibitors) which causes excessive proliferation

Question 30

define carcinogen

Answer 30

natural or synthetic chemicals that increase risk of mutations for cancer by DNA mutations grouped in 2 classes 1. direct acting carcinogens on N and O atoms on DNA 2. indirect acting carcinogens - chemicals that become reactive after they are modified by cellular enzymes. addition of OH to make the compound more soluble for exretion.

Question 31

list carcinogens

Answer 31

``` vinyl chloride benzene arsenic asbestos radium ```

Question 32

overcooked meat can cause what cancer?

Answer 32

colon cancer

Question 33

what are caretaker genes?

Answer 33

prevent or repair dna damage. their inactivation increases risk of mutations for tumors

Question 34

how does multidrug cancer therapy help?

Answer 34

treating cancer with 2 drugs at a single time shows resistance and do not cure cancer treating cancer with 2 drugs simultaneously shows cell is not resistant to both drugs and cancer is cured

Question 35

what are the mechanisms of cancer?

Answer 35

carcinogens hormones viruses they all genetically damage the cell and cause excessive proliferation

Question 36

define oncogenesis

Answer 36

progressive development of a cancer

Question 37

define proto-oncogenes

Answer 37

normal regulator of cell growth that becomes an oncogene when a mutation creates excessive activity (gain of function mutation) example: Ras , EGF receptor, Akt

Question 38

benign vs malignant tumor

Answer 38

benign tumor has 1 mutation of epithelial cell | malignant tumor grows and invades other organs

Question 39

what are the 5 types of cancers?

Answer 39

carcinoma - derived from epithelial cells sarcoma - derived from mesoderm (muscle, blood, connective tissue) Leukemia - derived from white blod cells in bone marrow lymphhoma - derived from lymphocytes and plasma cells in lymph nodes Blastomas - cancer cells that lost their differentiation characteristics

Question 40

what are mast cells?

Answer 40

white blood cell found in connective tissue

Question 41

what are the hallmarks of cancer?

Answer 41

deregulating cellular energetics avoiding immune destruction tumor promoting inflammation genome instability and mutation

Question 42

define angiogensis

Answer 42

formation of bew blood vessels to promote the growth of tumor by providing more O2 and open the path to tumor metastasis

Question 43

what gowth factors promot angiogeneis?

Answer 43

beta FGF, TGF alpha, and VEGF

Question 44

what is HIF-1 (hypoxia inducible factor)

Answer 44

activates glucose anaerobic metabolism to increase survival of cancer cell in hypoxic environment

Question 45

what controls movement of tumor cell?

Answer 45

actin cytoskeleton