Oncology-alternate model of tumour formation

Question 1

Chemical exposure resulting in tumourigenesis

Answer 1

Stages:
-Initiation- primary event
-promotion- secondary event

Question 2

Initiation

Answer 2

-primary event
-carcinogens causing irreversible change to cell through a single exposure. Change is fixed by completing a cell cycle

Question 3

Promotion

Answer 3

-secondary event
-proliferation of initiated cells
-reversible non genetic changes to cell
-sustained or multiple exposure required
-results in inflammation and biochemical changes

Question 4

Tumour heterogeneity

Answer 4

-Cell transformed in some way, and when it replicates we know that it has issues with certain aspects and replication is more likely to result in mutations
-Results in different groups of cells that have slightly different genetic backgrounds than others. Sometimes there are mutations of cell groups that result in cell death and can result in tumour regression.

Question 5

Cell group mutations

Answer 5

Most mutations are not a big deal and are irrelevant but sometimes there are variations that make it invasive and are a big deal

> Abilities: metastasis, ability to die, ability to survive different agents, ability to survive in different environments
**Reason why drug therapies for same tumour type can work well on one and not another

Question 6

Metastasis

Answer 6

-occurs when colonies of tumour cells spread to and grow within distant parts of the body
-only malignant tumours

Question 7

Seed and soil hypothesis

Answer 7

-not random
>cells from certain tumours are better adapted to survive in specific microenvironments
**so some tumour cells more likely to spread to certain areas
- not solely explained by blood flow

Question 8

Tumour movement

Answer 8

-transcoelomic
-lymph vessels
-hematogenous

Question 9

Transcoelomic

Answer 9

-spread from seeding of neoplastic cells from serosal surfaces
-ex. gastric or intestinal carcinomas
-ex. mesotheliomas

Question 10

Lymphatic vessel tumour movement

Answer 10

-no basement membrane so easily for tumour to move into lymph nodes
-Visible in lymph nodes
-common in carcinomas

Question 11

Hematogenous

Answer 11

-movement of tumours through blood
>veins most common because thinner walls
-usually sarcomas

Question 12

Common sites of hematogenous

Answer 12

-Liver- portal system (GI tract and Pancreas)
-Lungs- vena cava (skin, soft tissue, bone, thyroid, mammary gland)
-Spinal column (paravertebral plexus develop around spinal columns which allows accumulation)

Question 13

Steps in tissue invasion

Answer 13

1.Detachment of tumour cells
-loosening of intracellular bridges =no E-cadherin expression= inhibits Anoikis (death by apoptosis when alone)
2.Degrades basement membrane
-secretion of proteolytic enzymes which breaks down basement membrane
3.Attachment to basement membrane
-expression of receptors on basement membrane which allows it to attach and move
4.Migration
-expression of fibronectin which allows it to migrate through the basement membranes and between endothelial cells
5. Find location in specific tissue that they can survive. Set up, and find nutrients for metastasis

Question 14

Benign tumour characteristics

Answer 14

-only have progressive growth and vascular supply

Question 15

Malignant tumour characteristics

Answer 15

-can move, grow, found vascular supply and have many mutations allowing it to proliferate and have successful metastasis

Question 16

Neoplasia and host stroma

Answer 16

• Stroma is non neoplastic connective tissue and blood supply that supports, supplies and may be produced by the neoplasm
• -interactions between neoplasm and stroma work both ways (mediated by growth factors, cytokines, hormones)

Question 17

Neoplasms

Answer 17

-produce excess platelet derived growth factor
-stimulates fibroblasts in surrounding tissues to produce desmoplastic tissue reaction
-stimulate macrophages which break down basement membrane

Question 18

Angiogenesis

Answer 18

-to grow beyond 1-2 mm diameter tumours, the tumour must induce new blood vessel formation

Question 19

Angiogenic switch

Answer 19

-formation of abnormal new blood vessels
>from release vascular endothelial growth factor (VEGF)
>also tumour downregulates thrombospondin (which is from p53 to prevent new blood supply)

Question 20

Abnormal Blood vessel formation for tumour

Answer 20

-have gaps
>easier for tumour cells to get inside = prometastatic
>exposure of basement membrane likely results in clot formation but makes tumours more likely to have thrombosis and tissue death.