Unit III Week 1 Flashcards

1
Q

Two major types of tumor initiation mutations

A

Activation mutation in oncogene

Inactivation mutation in tumor supressor gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Importance of heredity in cancer

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Knudson’s Two Hit Hypothesis

A

Inherit one bad gene copy (hit 1)

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Familial retinoblastoma inheritance

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Sporadic retinoblastoma inheritance

A

Recessive disorder, not strongly inherited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Functions of APC, BRCA1, BRCA2

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Function of p53

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Mutations of p53

A

Hotspot point mutations

Dominant negative mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

RNA genome segments

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Oncogene function: v-erb-B

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Oncogene function: v-abl

A

BCR-ABL
CML
Tyrosine kinase activty

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Li-Fraumeni criteria

A

Autosomal dominant
~70% have p53 mutation
Hereditary and sporadic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Li-Fraumeni and Knudson’s Hypothesis

A
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Von Hippel-Lindau

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Therapies to treat ccRCC

A
Majority are sporadic
Local vs. metastatic
Surgical resection/nephrectomy
VEGF-R and MTOR inhibitors
Immunotherapies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

SREBP

SCAP

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Under high cholesterol conditions, SCAP will be ________ with Insig

A

Bound to/associated with

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Plasma volume

A

3 liters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

ECF/ICF/3rd space volume

A

13/27/5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

High concentration in ECF

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

High concentration in ICF

A

K+, A

H2O equal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Forces that determine gating properties

A

Temperature
Mechanical
Chemical
Electrical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Mechanisms to keep cell from bursting

A

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

24
Q

Molarity

A

standard measure of concentration

25
Q

Osmolarity

A

molarity of all solute

26
Q

Tonicity

A

how cell reacts to given ECF solution

27
Q

Hypotonic/hypertonic

A

swell/shrink

28
Q

SNARE proteins

A

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

29
Q

Steps of vesicle/membrane fusion

A

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

30
Q

Dissociation of SNARE proteins

A

NSF - twists apart SNARE complex with ATP

nsec1 - binds syntaxin to stabilize and re-fold

31
Q

Viral membrane fusion

A

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

32
Q

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

A

pH (lysosome)

33
Q

Electric forces are _____ than osmotic forces

A

stronger

34
Q

Two forces that act on ion movement

A

concentration

electrical gradient

35
Q

Nernst equation

A

E=RT/ZF * log(Cout/Cin)

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

36
Q

When Vm≠Eion

A

Membrane is either impermeable or has a pump

37
Q

When Vm=Eion

A

Happy! Diffusion without pump - equilibrium

38
Q

[H+] * [OH-] =

A

1x10-14

39
Q

The lower (higher) the pKa the _____ the acid

A

stronger (weaker)

40
Q

HH equation

A

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

undissociated/dissociated

41
Q

HH equation for bicarb buffer

A

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

42
Q

Normal arterial (venous) blood pH

A

7.34-7.44 (7.28-7.42)

43
Q

Normal [HCO3-] in blood

A

24mM

44
Q

Normal PCO2 in blood

A

40mmHg

45
Q

Normal [CO2] in blood

A

1.2mM

46
Q

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

A

10x

47
Q

Smoking and IBD

A

Current smokers at greater risk for Crohn’s

Previous smokers/nonsmokers at greater risk for ulcerative colitis

48
Q

Fistulas and IBD

A

Crohn’s: fistulas common (GI to GI or GI to surface)

Ulcerative colitis: fistulas uncommon

49
Q

Crohn’s vs UC

A

Crohn’s: upper GI, ileum, rare blood in stool

UC: lower GI, rectum, common blood in stool

50
Q

Extraintestinal manifestations of IBD

A
Erythema nodosum (~25%)
red rash that doesn't have to be on shin
51
Q

IBD Etiology

A
inappropriate inflammatory response to intestinal microbes
NOD2, Th17 pathways/autophagy genes
Rising prevalence (diet, abx use, tobacco etc)
52
Q

Straightforward DKA symptoms

A
increased deep respirations
n/v
thirsty
high urine output
elevated glucose
low venous pH
high K+ levels in blood
53
Q

Major metabolic disturbances in DKA

A

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)

54
Q

Three target sites of insulin

A

glucose into cells
inhibit formation of glucose by liver
synthesize glycogen

55
Q

Risk for cerebral edema in DKA tx

A

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