Easter Term

Question 1

What are nonspecific probes for?

Answer 1

Physiology eg) blood volume

Question 2

What are target probes for?

Answer 2

Protein location and structure

Question 3

What are smart sensor probes for?

Answer 3

Enzyme location and function

Question 4

What are anapleurotic fluxes and which is common in cancer?

Answer 4

Other ways into the Krebs cycle - eg alphaKG (glutamine to glutamate) in cancer

Question 5

What is HIF-1?

Answer 5

Hypoxia inducible factor

Question 6

How does HIF1 affect glycolysis and oxy phos?

Answer 6

Upregulates glycolysis, suppresses oxy phos

Question 7

What stabilises HIF1?

Answer 7

VHL/p53/PTEN

Question 8

What stimulates HIF1?

Answer 8

PI3K, ERBB2, EGFR

Question 9

What can upregulated glycolysis cause in surrounding tissues?

Answer 9

Upregulated H+ transport out of cells so may kill surrounding tissues

Question 10

Why is glycolysis upregulated in tumours?

Answer 10

Increases flux to pentose phosphate pathway for NAPDH synthesis for lipid synthesis, provide carbon for amino acid and nucleotide synthesis

Question 11

What is used to look at hexokinase in cancer metabolism?

Answer 11

[18F] FDG-PET

Question 12

What is used to look at LDH in cancer metabolism?

Answer 12

hyperpolarised MRI of [1-13C] pyruvate

Question 13

What is used to look at fatty acid synthase in cancer metabolism?

Answer 13

[11C] acetate-PET

Question 14

How does PET work?

Answer 14

Biomolecule tracer with positron emitter, annihilation with electron, gamma rays detected and traced back

Question 15

What are the three types of coincidence in PET detection?

Answer 15

True, scatter, random

Question 16

Which length half life is ideal in imaging?

Answer 16

A long one for longer measurements

Question 17

How does SPECT work?

Answer 17

NUclei admit gamma rays only in one direction, 3D images, slits for detection

Question 18

What do smaller or larger slits in SPECT do to the image?

Answer 18

Smaller = clearer/accurate, wider = more sensitive

Question 19

What are some common isotopes for SPECT?

Answer 19

99mTc, 111In

Question 20

What is a Larmor frequency?

Answer 20

The frequency the nuclei “precess” at - when they return to normal spin after the field is turned off. Different in different tissues.

Question 21

What is MRI?

Answer 21

Static magnetic field (can be in gradient across body), fire radio waves and detect response

Question 22

How are relaxation rates used in MRI?

Answer 22

Tissue specific so MRI pulses can be adapted to give contrast between tissues

Question 23

Which kind of metal shortens relaxation rates so can be used as a contrast medium?

Answer 23

Transition metals

Question 24

What is T1 relaxation?

Answer 24

Spin-lattice, slower, return to resting energy levels

Question 25

What is T2 relaxation?

Answer 25

Spin-spin, faster, spins create own magnetic fields and start to move at different times

Question 26

What is the NIR window?

Answer 26

The wavelengths where light has its maximum penetrance in tissues

Question 27

How can luciferin test gene expression?

Answer 27

Fluoresces under luciferase so will fluoresce where a gene has been expresses

Question 28

What is photoacoustic tomography?

Answer 28

Laser excites tissue and creates a temperature and pressure gradient, tissue expansion creates an ultrasound picture

Question 29

What does fMRI look at?

Answer 29

Blood flow in brain

Question 30

Why does oxygen affect relaxation parameters?

Answer 30

Paramagnetic

Question 31

What is BOLD?

Answer 31

Blood oxygen level-dependent MRI

Question 32

What recyles glutamate and what is this linked to?

Answer 32

Astrocytes, glucose metabolism

Question 33

If a water molecule moves, what happens to the coherence of the signal?

Answer 33

Decreases

Question 34

How can you look at possible increased fatty acid synthesis in a tumour?

Answer 34

Look at lipid synthesis using [11C]-acetate PET

Question 35

How can the tracer FLT be used?

Answer 35

Replace thymidine with 18F, gets phosphorylated and trapped in tumour cell by thymidine kinase I (lots of this in tumour cells)

Question 36

What does labelled annexin bind to?

Answer 36

Phosphatidylserine which is expressed by cells undergoing apoptosis

Question 37

What can be put in nanoparticles to change relaxation times?

Answer 37

Iron oxide

Question 38

How can you change the NMR T term?

Answer 38

Lower temp using another superconducting magnet with 13C in liquid helium

Question 39

Which tumours are the most difficult to diagnose and treat?

Answer 39

Epithelial

Question 40

Which areas is radiotherapy less effective on?

Answer 40

Hypoxic areas of tumour

Question 41

What do copy number alterations in tumours cause?

Answer 41

Alterations in gene products

Question 42

What affects tumour behaviour?

Answer 42

Interaction between cancer and mesenchymal cells

Question 43

An ideal curative cancer therapy must:

Answer 43

Act on mechanisms vital for viability or growth of cancer cells, permeate tumours at effective concentrations, spare normal cells, eliminate sufficiently to prevent recurrence

Question 44

WHy can't antibodies be used for cancer therapy?

Answer 44

Intracellular targets are inaccessible

Question 45

What does Gleevec bind to?

Answer 45

Inhibits Abl kinase activity

Question 46

What does Vemurafenib inhibit?

Answer 46

Activated BRAF kinase

Question 47

What does ipilimumab do?

Answer 47

Prevents T cell inactivation

Question 48

What do homozygous BRCA2 inactivation do?

Answer 48

Sensitizes cells to agents that stall DNA replciation

Question 49

Which inhibitors can be used to treat BRCA-deficient tumours?

Answer 49

PARP-1

Question 50

What does SH2 bind to?

Answer 50

Phosphorylated tyrosine

Question 51

What does SH3 bind to?

Answer 51

Polyproline

Question 52

What do kinases phosphorylate?

Answer 52

OH groups (Tyr, Thr or Ser)

Question 53

Why is Philadelphia chromosome oncogenic?

Answer 53

SH3 domain can't inhibit kinase and there's two kinase domains now

Question 54

What inhibits kinase activity in ABL?

Answer 54

SH3 domain

Question 55

What changes Bid to tBid and what does it do?

Answer 55

Caspase, activates Bak/Bax

Question 56

Why use Warburg metabolism?

Answer 56

G6P can make purines or pyrimidines and DHAP can make lipids

Question 57

What does myc use to always be switched on?

Answer 57

Antibody promoter

Question 58

What do MHC and TCR do?

Answer 58

MHC presents the antigen, TCR recognises it

Question 59

What do CD80/86 and CDT8 do?

Answer 59

CD80/86 on APC recognised by CDT8 on cell

Question 60

How can you prevent CTLA4 binding?

Answer 60

Use anti-CTLA4 antibody

Question 61

How is T cell apoptosis signalled?

Answer 61

CD80/86 and CDT8 signal CTLA4 production on T cell which binds CD80/86 better which signals T cell apoptosis

Question 62

What does PARP1 do?

Answer 62

Repairs single strand breaks

Question 63

What does BRCA2 do?

Answer 63

HR

Question 64

What is the tumour suppressor for G1/S phase?

Answer 64

Rb

Question 65

Which cyclins are for S phase?

Answer 65

E and A

Question 66

What do Rb and E2F do?

Answer 66

Use E2F to transcribe S phase genes, Rb prevents this

Question 67

What do CDK 4 and 6 do?

Answer 67

Phosphorylate Rb to prevent S phase inhibition

Question 68

What does e-Cadherin do?

Answer 68

Makes cells stick together, tumour cells don't do this and spread

Question 69

What are HGF and CMET?

Answer 69

Growth factor and RTK