Therapy 1

Question 1

What is the unit of measurement of cancer therapy radiation?

Answer 1

Grey (joule/kilogram)

Question 2

Name 4 radioactive elements used in radiotherapy.

Answer 2

Radium 226
Caesium 137
Iridium 192
Gold 198

Question 3

Which radioactive element emits alpha radiation?

Answer 3

Radium 226

Question 4

Why does radium 226 have to be encased?

Answer 4

Decays to radioactive gas radon

Question 5

What is the limitation of caesium 137?

Answer 5

Reacts with water so needs to be encased

Question 6

What is the limitation of Iridium 192?

Answer 6

It has low emission energy so needs to be close to target

Question 7

Why does gold 198 need to be encased?

Answer 7

Decays to mercury (toxic)

Question 8

What is the half life of radium 226?

Answer 8

1664 years

Question 9

What is the half life of caesium 137?

Answer 9

30 years

Question 10

What is the half life of iridium 192?

Answer 10

75 days

Question 11

What is the half life of gold 198?

Answer 11

2.7 days

Question 12

What is an example internal systemic radiotherapy?

Answer 12

iodine 131 injected into the blood - localises to the thyroid because it is the only organ that uses it

Question 13

What are the 3 main types of chemotherapeutics?

Answer 13

1) microtubule interferening agents
2) DNA damaging agents
3) antimetabolites (primarily nucleotide production)

Question 14

How does taxol work?

Answer 14

Binds interior of microtubules and stabilises them to prevent catastrophe - therefore prevents mitosis

Question 15

How does Vincristine (Vinblastine) work?

Answer 15

At low doses - Binds interior of microtubules and stabilises them to prevent catastrophe
AT high doses - binds monomers to prevent formation of microtubules

Question 16

Give an example of a mustard gas like agent?

Answer 16

Mitomycin C

- draw the mechanism if you fancy

Question 17

How does temozolomide function as a chemotherapy?

Answer 17

Prodrug - decays to to active form at physiological pH.
Adds methyl to guanine so it can interacts with thymidine.
MGMT removes methyl - temozolomide would overwhelm MGMT if levels high enough

Question 18

What does cis-platin do?

Answer 18

Cause inter/intra strand crosslinking

Oxygen independant

Question 19

Why can Cis-platin be used in hypoxic cells?

Answer 19

Oxygen independent function

Question 20

What is 5-fluorouracil?

Answer 20

Pyrimidine analogue that inhibits thymidine synthase

Question 21

What does di-phospo difluorodeoxycytidine do?

Answer 21

Inhibits ribonucleotide reductase

Question 22

What does tri-phospo difluorodeoxycytidine do?

Answer 22

Gets incorporated into DNA and terminates replication after one base. Cell is unable to repair because it is one base along.

Question 23

In what way might cells become resistant to chemotherapies?

Answer 23

Upregulate efflux transporters e.g. pgp, ABC

- DNA origami helps bypass problem

Question 24

What is the relevance of cytochrome p450 enzymes to chemotherapy to resistance?

Answer 24

Binds small compounds to toxic compounds

Question 25

How long do chronic, accelerated, blast phases of CML last?

Answer 25

chronic - 4/5 years accelerated - 8/16 months blast - 4/6 months

Question 26

what is the fusion protein responsible for CML?

Answer 26

bcr-abl, tyrosine kinase - constitutive phosphotyrosine | 177 binds GAB/GRB2

Question 27

Which chromosomes are involved in the translocation that causes CML?

Answer 27

chromosome 9 - abl - the kinase chromosome 22 - bcr fusion protein forms on chromosome 22

Question 28

What is the standard treatment for CML?

Answer 28

Gleevec 33 point mutants resist this so use nilotinib which treats 22/33 mutants ponatinib treats the 1/33 resistant T315I - gleevec can;t bind because of a protruding side chain

Question 29

What is the mutation causing constiutively active RAF, BRAF?

Answer 29

V599E. -ve amino acid mimics phosphorylation so T loop moves out of active site so constitutively active MAP kinase pathway

Question 30

What is BRAF treated with ?

Answer 30

PLX470

Question 31

Why is it difficult to determine driver mutations?

Answer 31

Cancer cells are mutation prone, so many exist

Question 32

What is synthetic lethality in tumour suppressors?

Answer 32

Cancer cells may have a loss of function TS and so become more reliant on another pathway than other cells. Block this pathway and kill cancer cell.

Question 33

What is synthetic lethality in oncogenes?

Answer 33

Pathway up regulated by mutant oncogene, block a down stream protein to prevent down stream affects

Question 34

What does bortezomib do?

Answer 34

Proteasome inhibitor

Question 35

What are the 4 methods of gene correction?

Answer 35

Zinc finger Nucleases TALENS Cas9/CRISPR Viral vectors

Question 36

How do you convert MLV to a delivery system?

Answer 36

Remove everything from genome except LTR and packaging sequence. Add GOI behind packaging sequence. Packaging cells encode GAG, POL, and ENV MLV introduced Packaging sequence is required to form GAG capsid and so GOI has to be included in viral particles

Question 37

Why might you use a virus that contains E7 but not E6 as a cancer target?

Answer 37

In normal cells virus will be rejected because p53 is active. In cancerous null p53 cells virus will not be rejected and will replicate and kill the cell