Principles of Oncogenesis Flashcards Preview

Oncology > Principles of Oncogenesis > Flashcards

Flashcards in Principles of Oncogenesis Deck (35)
Loading flashcards...
1
Q

Which breed is specifically predisposed to neoplasia? Which types?

A

Boxers - lymphoma, MCT and others

2
Q

What neoplasia are flat coated retrievers predisposed to?

A

Soft tissue sarcoma

3
Q

What neoplasia are irish wolf hounds predisposed to?

A

OSteosarcoma

4
Q

What neoplasia are GSDs predisposed to?

A

Haemagniosarcoma

5
Q

How may hormones impact neoplasias?

A
  • male v female
  • oestrogens and progesterones affect mammary tumours
  • androgens drive prostate tumours and perianal adenoma
6
Q

What is the difference between mutagens and mitogens?

A
  • mutagens or carcinogens induce mutatiosn

- mitogens stimulate cell proliferation and increase the risk of a random mutation

7
Q

Which viruses are assicated with neoplasia?

A
  • retro virus eg. FeLV

- pox virus eg. BPV and equine sarcoids

8
Q

Which bacteri are associated with neoplasia?

A

Helicobacter pylori and gastric ulcers -> carcinoma

9
Q

How do proto-oncogenes differ to oncogenes?

A
  • proto-oncogenes are normal and stimulate cell division
  • oncogenes are abnorma and result from a loss of control following mutation (some viruses contain oncogenes in their genome)
10
Q

What molecules are potentially oncogenic?

A

Any proteins in the normal cell growth control pathway

11
Q

Give 2 tumour suppressor genes

A

p53 and Rb

- cell cycle arrest and programmed cell death

12
Q

What kind of mutations must happen to oncogenes and tumour suppressor genes respetively to cause neoplasia?

A
  • gain of function to oncogenes

- loss of function to tumour supressors

13
Q

What are the 3 stages of the mutli stage model of neoplasia?

A

Initiation, promotion, progression

14
Q

What are the 6 traditional “hallmarks” of cancer?

A
  • ressiting cell death
  • sustaining proliferative signalling
  • evading growth supressors
  • activating invasion and metastasis
  • enabling replicative immortallity
  • inducing angiogenesis
15
Q

How many copies of the tumour suppressor genes must be mutated before their function is lost?

A

Both

16
Q

How may neoplastic cells become self sufficient in sustained proliferative signalling?

A
  • sectrecting endogenous growth factors -> autocrine/paracrine
  • mutating growth factor receptors so they are active in the abscence of any ligand or overexpressed to make them more sensitive eg. KIT mutation in canine MCT
  • mutating intracellular signalling pathways eg. activating mutations in Ras and Raf
17
Q

How does the KIT gene mutation affect dogs?

A
  • ^ severity of MCT diseaese with KIT mutation which allows receptor to autophoshorylate
  • stem cell factor acts on KIT-R, and is required for mast cell survical
18
Q

What mutation are bull mastiffs predisposed to?

A

p53 -> ^ risk lymphoid neoplasia

19
Q

Hoiw does Rb work?

A

transduces growth-inhibitory signals that originate outside of cell
- can stop cell cycle progression

20
Q

How does p53 work?

A

input from intrcellular operating systems

- can stop cell ccycle and trigger apoptosis

21
Q

How does apoptosis ultimately occour?

A

Caspase cascade

22
Q

What two pathways may lead to cell death and how do neoplastic cells avoid these pathways?

A
  • Intrinsic and extrinsic pathways
  • neoplastic cells downregulate “death receptors” to ignore extrinsic pathway
  • upregulate Bcl-2 family [why??]
23
Q

What is responsible for replicative senecence?

A

Telmomeres

24
Q

What enzyme adds telomeres onto chromosomes? What type of enzyme is this?

A
  • Telomerase
  • a DNA polymerase
  • absent in healthy tissue but upregulated in malignant cells
25
Q

Eg. of an angiogenic factor

A

VEGF (vascular endothelial growth factor)

- supplies tumour with oxygen and nutrients and ^ risk metastasis

26
Q

How may RTK inhibitors work on tumours other than MCTs?

A

inhibiting VEGF

27
Q

How do neoplastic cells invade and metastasise?

A
  • local invasion using matrix metalloproteinases
  • intravasation -> nearby LNs or blood vessels by atering cel adhesion molecules to ^ metastatic potential eg. loss of E-cadherin by carcinoma cells.
  • dissemination via lymphatics or haematogenous
  • extravasation into other tissues
28
Q

What are the 4 emerging hallmarks and enabling characteristcs?

A
Emerging hallmarks 
- deregulating cellular energetics
- avoiding immune destrcution
Enabling characteristics
- genome instability and mutation 
- tumour promoting inflammation
29
Q

How do neoplastic cells deregulate cellular energy metabolis?

A
  • re-programme glucose metabolism
  • use glycolysis only (cf. oxidative phosphorylation)
  • upregulation of GLUT1 receptors for more efficient glucose uptake
30
Q

Which cells are cpable of destroying neoplasia?

A
  • antibody and CD8+ T killer cells (not-self antigen)

- NK cells (upregulated MHC)

31
Q

How do neoplastic cells ensure genome instability and mutations occour at a high rate?

A
  • ^ sensitivity to mutagenic agents

- breakdown of genome maintainance machinery

32
Q

What paradoxical response of the body actually aids neopalstic growth?

A

Inflammation - provides growth factors, angiogenic cytokines and immunosupressive mediators

33
Q

How do tumours evade the immune system?

A
  • downreg immunogenic antigens
  • kill infiltrating lymphocytes
  • produce immunosupressive mediators
  • induce tolerance
34
Q

Which NSAIDs can be used therapeutically as anti-cancer?

A
  • peroxicam (COX-2 blocker) for bladder cancer

- Aspriin for bowel cancer

35
Q

What is oncept and oncept IL2?

A
  • oncept canine melanoma vax

- oncept IL2 - immune modulator for injection iste fibrosarcoma