Easter Term Flashcards
What are nonspecific probes for?
Physiology eg) blood volume
What are target probes for?
Protein location and structure
What are smart sensor probes for?
Enzyme location and function
What are anapleurotic fluxes and which is common in cancer?
Other ways into the Krebs cycle - eg alphaKG (glutamine to glutamate) in cancer
What is HIF-1?
Hypoxia inducible factor
How does HIF1 affect glycolysis and oxy phos?
Upregulates glycolysis, suppresses oxy phos
What stabilises HIF1?
VHL/p53/PTEN
What stimulates HIF1?
PI3K, ERBB2, EGFR
What can upregulated glycolysis cause in surrounding tissues?
Upregulated H+ transport out of cells so may kill surrounding tissues
Why is glycolysis upregulated in tumours?
Increases flux to pentose phosphate pathway for NAPDH synthesis for lipid synthesis, provide carbon for amino acid and nucleotide synthesis
What is used to look at hexokinase in cancer metabolism?
[18F] FDG-PET
What is used to look at LDH in cancer metabolism?
hyperpolarised MRI of [1-13C] pyruvate
What is used to look at fatty acid synthase in cancer metabolism?
[11C] acetate-PET
How does PET work?
Biomolecule tracer with positron emitter, annihilation with electron, gamma rays detected and traced back
What are the three types of coincidence in PET detection?
True, scatter, random
Which length half life is ideal in imaging?
A long one for longer measurements
How does SPECT work?
NUclei admit gamma rays only in one direction, 3D images, slits for detection
What do smaller or larger slits in SPECT do to the image?
Smaller = clearer/accurate, wider = more sensitive
What are some common isotopes for SPECT?
99mTc, 111In
What is a Larmor frequency?
The frequency the nuclei “precess” at - when they return to normal spin after the field is turned off. Different in different tissues.
What is MRI?
Static magnetic field (can be in gradient across body), fire radio waves and detect response
How are relaxation rates used in MRI?
Tissue specific so MRI pulses can be adapted to give contrast between tissues
Which kind of metal shortens relaxation rates so can be used as a contrast medium?
Transition metals
What is T1 relaxation?
Spin-lattice, slower, return to resting energy levels
What is T2 relaxation?
Spin-spin, faster, spins create own magnetic fields and start to move at different times
What is the NIR window?
The wavelengths where light has its maximum penetrance in tissues
How can luciferin test gene expression?
Fluoresces under luciferase so will fluoresce where a gene has been expresses
What is photoacoustic tomography?
Laser excites tissue and creates a temperature and pressure gradient, tissue expansion creates an ultrasound picture
What does fMRI look at?
Blood flow in brain
Why does oxygen affect relaxation parameters?
Paramagnetic
What is BOLD?
Blood oxygen level-dependent MRI
What recyles glutamate and what is this linked to?
Astrocytes, glucose metabolism
If a water molecule moves, what happens to the coherence of the signal?
Decreases
How can you look at possible increased fatty acid synthesis in a tumour?
Look at lipid synthesis using [11C]-acetate PET
How can the tracer FLT be used?
Replace thymidine with 18F, gets phosphorylated and trapped in tumour cell by thymidine kinase I (lots of this in tumour cells)
What does labelled annexin bind to?
Phosphatidylserine which is expressed by cells undergoing apoptosis
What can be put in nanoparticles to change relaxation times?
Iron oxide
How can you change the NMR T term?
Lower temp using another superconducting magnet with 13C in liquid helium
Which tumours are the most difficult to diagnose and treat?
Epithelial
Which areas is radiotherapy less effective on?
Hypoxic areas of tumour
What do copy number alterations in tumours cause?
Alterations in gene products
What affects tumour behaviour?
Interaction between cancer and mesenchymal cells
An ideal curative cancer therapy must:
Act on mechanisms vital for viability or growth of cancer cells, permeate tumours at effective concentrations, spare normal cells, eliminate sufficiently to prevent recurrence
WHy can’t antibodies be used for cancer therapy?
Intracellular targets are inaccessible
What does Gleevec bind to?
Inhibits Abl kinase activity
What does Vemurafenib inhibit?
Activated BRAF kinase
What does ipilimumab do?
Prevents T cell inactivation
What do homozygous BRCA2 inactivation do?
Sensitizes cells to agents that stall DNA replciation
Which inhibitors can be used to treat BRCA-deficient tumours?
PARP-1
What does SH2 bind to?
Phosphorylated tyrosine
What does SH3 bind to?
Polyproline
What do kinases phosphorylate?
OH groups (Tyr, Thr or Ser)
Why is Philadelphia chromosome oncogenic?
SH3 domain can’t inhibit kinase and there’s two kinase domains now
What inhibits kinase activity in ABL?
SH3 domain
What changes Bid to tBid and what does it do?
Caspase, activates Bak/Bax
Why use Warburg metabolism?
G6P can make purines or pyrimidines and DHAP can make lipids
What does myc use to always be switched on?
Antibody promoter
What do MHC and TCR do?
MHC presents the antigen, TCR recognises it
What do CD80/86 and CDT8 do?
CD80/86 on APC recognised by CDT8 on cell
How can you prevent CTLA4 binding?
Use anti-CTLA4 antibody
How is T cell apoptosis signalled?
CD80/86 and CDT8 signal CTLA4 production on T cell which binds CD80/86 better which signals T cell apoptosis
What does PARP1 do?
Repairs single strand breaks
What does BRCA2 do?
HR
What is the tumour suppressor for G1/S phase?
Rb
Which cyclins are for S phase?
E and A
What do Rb and E2F do?
Use E2F to transcribe S phase genes, Rb prevents this
What do CDK 4 and 6 do?
Phosphorylate Rb to prevent S phase inhibition
What does e-Cadherin do?
Makes cells stick together, tumour cells don’t do this and spread
What are HGF and CMET?
Growth factor and RTK
