Tannock and Hill

Question 1

What is the Warburg effect?

Answer 1

Cancer cells experience a metabolic shift from oxidative respiration to an energy-efficient aerobic glycolytic profile.

Question 2

Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. The most common alteration in BRAF are point substitutions at:

Answer 2

Valine 600 (V600). In dogs with iUC it is usually V595E

Question 3

Which JAK/STAT inhibitor is used in veterinary medicine?

Answer 3

Oclacitinib

Question 4

What is Knudson’s 2 hit hypothesis?

Answer 4

That most tumor suppressor genes require both alleles to be inactivated (recessively acting cancer gene), either through mutations or through epigenetic silencing, to cause a phenotypic change (cancer development).

This was proven with the Rb1 locus (retinoblastoma tumor suppressor gene). Homozygous loss of the wild-type Rb1 locus correlated with retinoblastoma development.

Question 5

Which virus is associated with the development of Burkitt lymphoma?

Answer 5

Epstein-Barr virus (EBV)

Question 6

What is the Hayflick limit?

Answer 6

The eventual loss of replicative potential (cellular senescence). The time to the cessation of cell division correlates closely with critically eroded telomeres (called telomere signal-free ends).

Question 7

What is the name of the complex that degrades proteins that are tagged with ubiquitin?

Answer 7

26S Proteosome

Question 8

List the stages of apoptosis

Answer 8

1) Rounding up of the cell
2) Plasma membrane blebbing
3) Cytoplasm shrinkage
4) Alteration of membrane asymmetry
5) Condensation and fragmentation of the nucleus

Late stage: fragmented into apoptotic bodies that are eliminated by phagocytic cells without triggering inflammation

Question 9

What is the action of RANKL?

Answer 9

Receptor activator of nuclear factor-kB ligand (RANKL) is released by osteoblasts. It activates myeloid progenitor cells to differentiate into osteoclasts that can digests bone structures, creating space for establishment of metastasis. Denosumab is a monoclonal Ab targeting RANKL, approved for treating patients with bone mets.

Question 10

How many tumor cells necessary for 1g (1cm) of tumor (smallest clinically detectable mass)

Answer 10

1 x 10^9

Question 11

What is the action of DNA methylation?

Answer 11

Covalent addition of a methyl group at position 5 of a cytosine (C) nucleotide (5mC), typically positioned close to a guanine residue (G), occuring mostly in CpG islands (regions dense in adjacent C and G nucleotides) found at the promoter region of genes. Typically results in gene-SILENCING.

Question 12

What is the normal diffusion distance of oxygen from tumor blood vessels?

Answer 12

150 - 200 um

Question 13

Name for the novel hedgehog pathway inhibitor?

Answer 13

Saridegib

Question 14

What is the name of the most common HDAC inhibitor?

Answer 14

Vorinostat

Question 15

What is the name of the most common PARP inhibitor?

Answer 15

Olaparib

Question 16

What are the markers for Cancer Associated Fibroblasts?

Answer 16

a-smooth muscle actin (a-SMA), fibroblast specific protein-1 (FSP-1)/S100, neuron-glial antigen-2 (NG-2), PDGFR-B.