Neoplasia 2

Question 1

What are the 2 key regulator gens in carcinogenesis?

Answer 1

-Oncogenes (“accelerators”)
-Tumour suppressor genes (“brakes”)

Question 2

What are the other Key regulator genes in carcinogenesis?

Answer 2

DNA repair genes
miRNAs
Chromosomal aberrations
Epigenetic mutations

Question 3

What is Proto-oncogenes?

Answer 3

Normal genes which regulate cell division.
– growth factors
– growth factor receptors
– signal transducers
– control of gene expression

Question 4

What is oncogenes?

Answer 4

Abnormal variation, they produce oncoproteins.

Question 5

Oncogenes are under tight regulation, how this may be lost?

Answer 5

• Mutation - increases product activity
• Gene duplication - Excess normal product
• Viral product
• Gene translocation - Enhanced transcription
• Chromosome rearrangement

Question 6

What is the function of Tumour suppressor genes (TSG)?

Answer 6

Act to inhibit cell division and suppress growth

Question 7

Which genes acts as anti-oncogenes?

Answer 7

TSG- Tumour suppressor genes (“Brakes”)

Question 8

What is the gene that can lead to Retinoblastoma?

Answer 8

Mutation in RB gene

Question 9

What is the Key regulator gene that responds to damaged DNA?

Answer 9

TP53 (“Police”)

Question 10

How TP53 response to damage DNA?

Answer 10

TP53 acts just before the Restriction Point (cell cycle)
-stops the cell cycle to allow DNA repair
-apoptosis (if repair not possible)

Question 11

Mention Inherited factors- Genetic susceptibility to cancer

Answer 11

• Inherited cancer syndromes
  single mutant genes, often TSG
  retinoblastoma (Rb gene)
• Familial cancer - Breast, Ovarian, Colon
• Defective DNA repair - Increased cancer risk, e.g.Xeroderma pigmentosum

Question 12

What are the malignant tumours modes of spread?

Answer 12

local spread
lymphatic spread
Blood spread (haematogenous)
transcoelomic spread
Intraepithelial spread (Paget’s disease of the breast)

Question 13

What are the Pattern of metastases?

Answer 13

-Carcinomas typically spread to lymphatics & blood
-Sarcomas typically spread to blood
-Predictable patterns of spread:
Lung → local nodes, liver, bone, brain
Tongue → neck nodes, lung & spine

Question 14

What is grading of tumours?

Answer 14

-Biological nature of tumour (Histopathology)
Involves assessment of:
- Invasion of underlying tissue
- Cellular atypia - abnormal features

Question 15

What are the methods of grading?

Answer 15

• Can be numerical (1.2,3)
• Can be classified by low, intermediate, high
• Measured against degree of differentiation (squamous cell carcinoma)

Question 16

What is cancer staging?

Answer 16

Physical exams. clinical imaging. lab tests, pathology and surgical reports can be used to estimate extent or severity

Question 17

Why is it important to know the stage of diseases?

Answer 17

That is helps planning treatment and estimating the person’s prognosis.

Question 18

What is the staging system that used for oral cancer?

Answer 18

TNM system:
• Tumour size (T)
• Lymph node involvement (N)
• Presence of metastases (M)

Question 19

How does the immune system recognise tumour cells?

Answer 19

• Detection of TAA’s (tumour associated antigens)
• TAA’s present in various forms:
  
  • Products of mutated genes
  • Overexpressed proteins
  • Viral proteins
  • Oncofoetal antigens

Question 20

What are the Cell-mediated immune responses?

Answer 20

• Cytotoxic T-cell attack
• NK cell attack
• Macrophages

Question 21

How do tumour cells evade the immune response?

Answer 21

Molecular changes can drive evasion:
- Altered TAA expression - (Insufficient T cell recognition)
- Activation of immunoregulatory pathways → causing T cell unresponsiveness and apoptosis
- Immunosuppressive factors - Cytokines (TGF-Beta)

Question 22

What is Immunotherapy?

Answer 22

Use of the patient’s own immune response to control and destroy malignant cells

• Active immunisation - HPV, HEP B
• Reversal of immuno-suppression
• Adopted cell transfer (ACT)
• Tumour-infiltrating lymphocytes (TILs)
• CAR T-cell therapy → strengthening natural immune responses