Unit III Week 1

Question 1

Two major types of tumor initiation mutations

Answer 1

Activation mutation in oncogene

Inactivation mutation in tumor supressor gene

Question 2

Importance of heredity in cancer

Answer 2

Cancer is not inherited (as single Mendelian) but accumulated over time with age.
Susceptibility to development can be inherited

Question 3

Knudson’s Two Hit Hypothesis

Answer 3

Inherit one bad gene copy (hit 1)

Mutation/recombination/chr loss over life causes LOH (hit 2)

Question 4

Familial retinoblastoma inheritance

Answer 4

Recessive disorder (dominant inheritance), but inheriting one bad copy generally results in cancer due to high LOH

Question 5

Sporadic retinoblastoma inheritance

Answer 5

Recessive disorder, not strongly inherited

Question 6

Functions of APC, BRCA1, BRCA2

Answer 6

Tumor suppressor genes
APC: prevents ß-catenin from entering nucleus
BRCA1/2: function in cell cycle checkpoints

Question 7

Function of p53

Answer 7

Tumor suppressor gene
Transcription factor
DNA mutation repair in cell cycle (cell cycle arrest)
Apoptosis stimulating

Question 8

Mutations of p53

Answer 8

Hotspot point mutations

Dominant negative mutations

Question 9

RNA genome segments

Answer 9

gag: internal virion proteins
env: membrane glycoproteins
pol: virus polymerase
v-onc: necessary for malignancy
(v-src, v-erb, v-abl, v-myc)

Question 10

Oncogene function: v-erb-B

Answer 10

Codes for protein similar to EGFR
Increases change of growth simulating properties
Tyrosine kinase activity

Question 11

Oncogene function: v-abl

Answer 11

BCR-ABL
CML
Tyrosine kinase activty

Question 12

Li-Fraumeni criteria

Answer 12

Autosomal dominant
~70% have p53 mutation
Hereditary and sporadic

Question 13

Li-Fraumeni and Knudson’s Hypothesis

Answer 13

Hit 1: p53 point mutation
Hit 2a: amplification of HER2
Hit 2b: EFGR mutation
Hit 2c: changes to oncogene
(Hit 2 can be on different gene)

Question 14

Von Hippel-Lindau

Answer 14

Autosomal dominant
VHL gene = tumor suppressor
Penetrance >95% at 65 y/o (variability in severity)
Cystic and highly vascularized tumors in organs

Question 15

Therapies to treat ccRCC

Answer 15

Majority are sporadic
Local vs. metastatic
Surgical resection/nephrectomy
VEGF-R and MTOR inhibitors
Immunotherapies

Question 16

SREBP

SCAP

Answer 16

Cholesterol regulator
Binds bHLH transcription factor for LDLR and all 30 synthesis proteins (released by two step proteolysis RIP)
SCAP escorts SREBP to Golgi to trigger nuclear receptors

Question 17

Under high cholesterol conditions, SCAP will be ________ with Insig

Answer 17

Bound to/associated with

Question 18

Plasma volume

Answer 18

3 liters

Question 19

ECF/ICF/3rd space volume

Answer 19

13/27/5

Question 20

High concentration in ECF

Answer 20

Na+, Cl-
H2O equal
No A (large molecules)

Question 21

High concentration in ICF

Answer 21

K+, A

H2O equal

Question 22

Forces that determine gating properties

Answer 22

Temperature
Mechanical
Chemical
Electrical

Question 23

Mechanisms to keep cell from bursting

Answer 23

Membrane impermeable to water
Cell wall (brute force)
Osmotic balance

Question 24

Molarity

Answer 24

standard measure of concentration

Question 25

Osmolarity

Answer 25

molarity of all solute

Question 26

Tonicity

Answer 26

how cell reacts to given ECF solution

Question 27

Hypotonic/hypertonic

Answer 27

swell/shrink

Question 28

SNARE proteins

Answer 28

Syntaxin - sits on PM, TM domain and H domain SNAP-25 - sits on PM, no TM domain and 2x H domains VAMP - sits on vesicle, TM domain and H domain *amphipathic a-helices conserved b/t families*

Question 29

Steps of vesicle/membrane fusion

Answer 29

Nucleation - removal of nsec1 (bound to syntaxin) Zippering - coil-coiled trimer of a-helices *squeeze out H2O and overcome charge repulsion* Fusion

Question 30

Dissociation of SNARE proteins

Answer 30

NSF - twists apart SNARE complex with ATP | nsec1 - binds syntaxin to stabilize and re-fold

Question 31

Viral membrane fusion

Answer 31

Only one protein with hairpin and multiple helical domains Several on surface of virus bind membrane (PM or inner) Ratchet via helical domains to squeeze out H2O etc

Question 32

Influenza depends on a drop in _____ to trigger fusion to membrane

Answer 32

pH (lysosome)

Question 33

Electric forces are _____ than osmotic forces

Answer 33

stronger

Question 34

Two forces that act on ion movement

Answer 34

concentration | electrical gradient

Question 35

Nernst equation

Answer 35

E=RT/ZF * log(Cout/Cin) | E (mV)= 60/Z * log(Cout/Cin)

Question 36

When Vm≠Eion

Answer 36

Membrane is either impermeable or has a pump

Question 37

When Vm=Eion

Answer 37

Happy! Diffusion without pump - equilibrium

Question 38

[H+] * [OH-] =

Answer 38

1x10-14

Question 39

The lower (higher) the pKa the _____ the acid

Answer 39

stronger (weaker)

Question 40

HH equation

Answer 40

pH=pKa + log([A-]/[HA]) | undissociated/dissociated

Question 41

HH equation for bicarb buffer

Answer 41

pH=6.1 + log([HCO3-]/(.03*PCO2))

Question 42

Normal arterial (venous) blood pH

Answer 42

7.34-7.44 (7.28-7.42)

Question 43

Normal [HCO3-] in blood

Answer 43

24mM

Question 44

Normal PCO2 in blood

Answer 44

40mmHg

Question 45

Normal [CO2] in blood

Answer 45

1.2mM

Question 46

Amount of A-/HA necessary to move pH of buffer by 1?

Answer 46

10x

Question 47

Smoking and IBD

Answer 47

Current smokers at greater risk for Crohn's | Previous smokers/nonsmokers at greater risk for ulcerative colitis

Question 48

Fistulas and IBD

Answer 48

Crohn's: fistulas common (GI to GI or GI to surface) | Ulcerative colitis: fistulas uncommon

Question 49

Crohn's vs UC

Answer 49

Crohn's: upper GI, ileum, rare blood in stool | UC: lower GI, rectum, common blood in stool

Question 50

Extraintestinal manifestations of IBD

Answer 50

``` Erythema nodosum (~25%) red rash that doesn't have to be on shin ```

Question 51

IBD Etiology

Answer 51

``` inappropriate inflammatory response to intestinal microbes NOD2, Th17 pathways/autophagy genes Rising prevalence (diet, abx use, tobacco etc) ```

Question 52

Straightforward DKA symptoms

Answer 52

``` increased deep respirations n/v thirsty high urine output elevated glucose low venous pH high K+ levels in blood ```

Question 53

Major metabolic disturbances in DKA

Answer 53

hyperglycemia (no insulin) acidosis (accumulation of ketone bodies) K+ depletion (despite high levels in blood, H+/K+ exchanger) dehydration (excess glucose leaks into urine and takes lots of H2O with it)

Question 54

Three target sites of insulin

Answer 54

glucose into cells inhibit formation of glucose by liver synthesize glycogen

Question 55

Risk for cerebral edema in DKA tx

Answer 55

After insulin, brain takes glucose much faster H2O follows -> swelling Tx: mannitol - raises ECF concentration, can't cross BBB