Neoplasia and tumour biology

Question 1

What are all the different growth disorders during life?

Answer 1

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Question 2

What does a normal cell cycle look like? (draw it)

Answer 2

https://s3.amazonaws.com/brainscape-prod/system/cm/173/711/901/a_image_thumb.png?1451232333

Question 3

How does cell proliferation occur?

Answer 3

Growth factors

growth factor receptors

transduction

translation

cell cycle proteins

Question 4

When are the proto oncogenes and tumour suppressor genes involved?

Answer 4

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Question 5

What are proto oncogenes?

Answer 5

They are the pre form of oncogenes before they are switched on. When they mutate usually they then become oncogenes.

Question 6

Can you name some oncogenes?

Answer 6

RAS- involved in kinase signalling pathway- regulating cell growth and differentiation

Src- regulates cell activity

Question 7

What are tumour suppressor genes?

Answer 7

They suppress the tumour at various stages in the cell cycle. This coupled with proto oncogenes is the two hit hypothesis being both need to mutate in order for a tumour to occur.

Question 8

Can you name some tumour suppressor genes?

Answer 8

p53: a transcription factor that regulates cell division and cell death

Rb: alters the activity of transcription factors:::::: side note::::

need to overcome passive and active regression.

rb involved in G0-G1 phase of the cell cycle HDAC etc. research

APC: controls the availability of a transcription factor.

Question 9

Why is p53 so important?

Answer 9

P53 can arrest the cell cycle and send cells into apoptosis. This is important if the cells are going into tumours cells as this could be dangerous and it would need to be stopped.

Question 10

Can you summarise the molecular determinants of cancer?

Answer 10

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Question 11

What is the first step in tumour genesis?

Answer 11

Initiation: Introduction of irreversible genetic change into cells by action of mutagenic intiator.

But have mutations which give them growth advantage. Could be resistant to apoptosis inducing stimuli.

Question 12

What is the second step in tumour genesis?

Answer 12

Promotion: Initiated cells exposed to certain stimuli, which alter gene expression and creates an envrionment which promotes cell growth.

May lead to pre neoplastic lesion of benign tumours

Promoters are non mutagenic their effects can be reversible.

Question 13

What is the third step in tumour genesis?

Answer 13

Progression: Includes conversion of benign tumours into metastatic ones.

Malignant conversion irreversible

complex poorly understood procedure

increasingly tumour cell heterogenity

Question 14

Can you show all three steps of tumour growth in a diagram?

Answer 14

https://s3.amazonaws.com/brainscape-prod/system/cm/173/717/874/a_image_thumb.png?1451240104

Question 15

What are the 6 hallmarks of cancer?

Answer 15

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Question 16

What would the pathologist describe if analysing a neoplastic lesion?

Answer 16

Cell and nuclear characteristics

Mitotic index

Signs of invasion or metastasis

margins

Other features- connective tissues etc. ground substances and ulceration

Question 17

When proliferating what determines how a benign tumour grows and how a metastatic tumour grows?

Answer 17

Benign tumour will tend to grow by expansion and compression.

Malignant tumour will tend to grow by local invasion

Question 18

What is tumour angiogenesis?

Answer 18

Tumours induce host vessels to supply, branches by production of tumour angiogenesis factors.

Tumour lymphangiogenesis similar.

Question 19

What are the routes of metastasis?

Answer 19

Local invasion

Intra vascular blood or lymphatic

serosal spread

intra organ seeding

Question 20

Can you draw a diagram of the metastatic cascade

Answer 20

https://s3.amazonaws.com/brainscape-prod/system/cm/173/718/310/a_image_thumb.png?1451241488

Question 21

What does OPA stand for?

Answer 21

Ovine pulmonary adenocarcinoma which is a cause of chronic respiratory disease in humans.

Question 22

What type of virus is OPA?

Answer 22

Beta retrovirus

Question 23

Can you draw a diagram of retroviral replication?

Answer 23

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Question 24

How can you detect whether this OPA is targetting b or t cells?

Answer 24

IHC. Staining particular b or t cells. For B cells it is most likely CD38 and for t cells it is most likely CD3.

Question 25

Can you show a diagram with the pathogenesis of OPA?

Answer 25

https://s3.amazonaws.com/brainscape-prod/system/cm/173/775/619/a\_image\_thumb.png?1451328206

Question 26

Why is identification of the target cell important?

Answer 26

1. improve the understanding of the early stages of OPA pathogenesis in sheep. 2. Improve the use of OPA as a model to bronchioloalveolar carcinoma (BAC)

Question 27

What goes into the pathology report when describing the neoplasm?

Answer 27

Subgross description Patterns of cells and type of stroma The cells mitotic activity unique features evidence of malignancy clean up

Question 28

How would you describe this? https://s3.amazonaws.com/brainscape-prod/system/cm/173/776/606/q\_image\_thumb.png?1451329717

Answer 28

squamous cell carcinoma: nests, packets and cords of polygonal shaped cells

Question 29

What is tumour grading?

Answer 29

Determines cellular morphology most accurate predictor of tumour behavior. Grading can be based on behavior, invasiveness, mitotic index, necrosis and overall cellularity

Question 30

What are the main sub divisions for tumour grading?

Answer 30

Mast cells Mammary gland Soft tissue sarcomas Synovial sarcomas Lymphomas

Question 31

What is vimentin and cytokeratin and what do they do?

Answer 31

Markers for IHC. They can help distinguish a tumour if it from epithelial origin or mesenchymal origin. Cytokeratin is epithlial +ve. Vimentin is mesenchymal +ve.

Question 32

What markers can you use for round cell tumours?

Answer 32

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Question 33

What is a mast cell?

Answer 33

Normally present in low numbers in the tissue. Cytoplasmic granules containing bioactive substances. Granules are heterochromatic hence the use of various stains. Involved in type 1 hypersensitivity which is usually allergens.

Question 34

Are mast cells common and are any breeds disposed to them?

Answer 34

Yes common tumours, 16-20% of all tumours are mast cell in dogs! Most dog breed so the boxer, etc. Typically in 7-9 year old dogs. HOwever some breeds can have more aggressive mast cell tumours than others.

Question 35

What is the growth fraction?

Answer 35

The relative number of cells actively involved in cell cycle growth at that one point in time.

Question 36

What is generation time?

Answer 36

Rate of cell proliferation or cell doubling in vivo.

Question 37

How do you calculate cellular prolfieration then?

Answer 37

growth fraction x generation time _OR_ Ki67 x AgNor score.

Question 38

What can mast cell tumours (cutaneous) be differentiated into?

Answer 38

Mastocytic- Well differentiated -pleomorphic Histiocytic- (poorly granulated)

Question 39

Are there any prognostic tests for mast cell tumours?

Answer 39

Yes, KIT and C-KIT test. KIT is the protein and is found as a receptor on mast cells. Ligand is a stem factor of KIT. Activation via ligand binding promotes cell survival, proliferation and differentiation. C-KIt is the encoding gene. Determinant whether mast cells have mutated and overall prognosis of the patient. Especially when it comes to determining the time of spread etc.