Neoplasia 2 Flashcards
What are some important genes in carcinogenesis?
- Oncogenes (accelerators)
- Tumour suppressor genes (brakes)
- DNA repair genes
- miRNA’s (non-coding, controlling factor over the rest of genes
- many others
What are proto-oncogenes?
Normal genes which regulate cell division
Give some examples of proto-oncogenes?
- Growth factors
- Growth factor receptors
- Signal transducers
- Control of gene expression
What are abnormal variants of proto-oncogenes?
- Oncogenes
- They produce oncoproteins
How many genes need to be mutated for oncogenes to cause malignancy?
1
What does mutated growth factor cause?
Increasing the amount of growth factor encourages cells to divide at a greater rate than they normally would do
What is enhanced transcription?
- Translocation
- Chromosome rearrangement
- During cell division parts of the chromosomes break off and attach themselves to the same chromosome or a different chromosome - when this happens sometimes genes become fused with each other ‘hybrid’ gene - product of their expression is different genes
How many genes need to be mutated for tumour suppressor genes to cause malignancy?
2
What happens if tumour suppressor genes are mutated?
The brakes mechanism is lost so there is nothing stopping cells from growing and proliferating at a faster rate
What do tumour suppressor genes do?
- Act to inhibit cell division and suppress growth
- Act as ‘anti-oncogenes’ and act by a variety of mechanisms
What are inherited cancer syndromes (Inherited factors)?
- Single mutant genes, often tumour suppressor genes
- Retinoblastoma, some colon cancers
What is familia cancer (inherited factor)?
- Family clusters
- genes and patterns of inheritance not clear
- breast, ovary, colon
What is defective DNA repair (inherited factors)?
- Increased sensitivity to carcinogens and general increased cancer risk
- Xeroderma pigmentosum
What is P53’s function and where does it act?
- Acts just before the restriction point (at the restriction point the cell cycle stops)
- 2 main functions in response to DNA damage:
- Stops the cell cycle to allow DNA repair
- Apoptosis (if repair not possible)
What systems are affected by cancer?
- other cell division controls
- DNA repair mechanisms
- Apoptosis inhibited
- Stimulation of blood vessel formation
- Destructive enzymes activated
- Cell motility increased
What are the characteristics of cancer?
- Growth rate - must divide quickly
- Growth potential - must be able to detach from surrounding abnormal cells
- Differentiation
- Invasion/destruction
- Avoid apoptosis
- Angiogenesis (formation of new blood vessels)
- Evasion of host defences
- Cell surface change (tumour antigens)
- many others…
What are the 6 main hallmarks for cancer?
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
- Evading apoptosis
What are the malignant tumour modes of spread?
- Local spread
- Lymphatic spread
- Blood spread
- Transcoelomic spread
- Intraepithelial spread
What is metastasis?
Spread of the malignant cells to distant organs forming secondary tumours
What is metastases?
Patterns of spread of cancer cells
How are carcinomas spread?
- Lymphatic
- Blood
How are sarcomas spread?
- blood (lymphatic spread rare)
What are some examples of predictable patterns of spread?
- Lung to local nodes, liver, bone and brain
- Tongue to neck nodes, later lung and spine
What is involved in the ‘metastatic cascade’?
- All steps brought about by all different factors that help tumour cells in invasion
- Tumour cells interact with cells and molecules in the local environment
- Motility is often enhanced
- Tumour cells may:
- Alter adhesion molecules
- Make poor basement membrane
- Increase protease production or reduce inhibitors
- Alter extracellular matrix
What is tumour grading?
Biological nature of the tumour (histopathology)
- Dependent on the changes of the tissue
- The more like the original tissue the better it will respond to treatment
What is tumour staging?
Extent of spread - clinical
- By observation or by imaging
In tumour grading what is assessed?
- Invasion into the underlying tissue
- Cellular atypia (do the cells look like the original cells?)
Various methods to do this:
- Numerical grades e.g. 1, 2, 3
- Low, intermediate, high
- Degree of differentiation e.g. well differentiated, moderate and poor
What does cancer staging describe?
The EXTENT or SEVERITY of a person’s cancer. Knowing the stage of the disease helps planning treatment and estimating the person’s prognosis
What tests are used to determine cancer staging?
- Physical exams
- Imaging procedures
- Lab tests
- Pathology and surgical reports
What is the TNM system?
- Used for staging oral cancer
- Tumour size (T)
- Lymph node involvement (N)
- Presence of metastases (M)
What are the clinical effects of lung cancer?
- Cough
- Haemoptysis
- Chest pain
- Pneumonia
What are systemic effects often caused by cytokines or hormones released by tumour cells or dysfunction of the organ?
- Fever
- Anorexia
- Extreme weight loss
- Neurological problems
- Endocrine syndromes
- Metabolic effects
What is the treatment of malignant tumours?
- Depends on type, grade and stage
- Surgery
- Chemotherapy
- Radiotherapy
- All 3 approaches may be used at different stages
What is tumour immunology?
Using a patients own immune system to attack malignancies
How does the immune system recognise tumour cells?
Tumour associated antigens
- Products of mutated genes
- Overexpressed proteins
- Viral proteins
- Oncofoetal antigens
- Others
What is elimination in the body’s immune response to tumour antigens?
- Cytotoxic T-lymphocytes (CD8+)
- NKC - first line defence against tumour cells
- Macrophages - mechanisms similar to anti-microbial killing
Escape: How do tumour cells evade the immune response?
- Alter tumour antigen expression. Lack of T cell recognition
- Activation of immunoregulatory pathways leading to T cell unresponsiveness and apoptosis
- Immunosuppressive factors e.g. cytokines. Inhibit T cell response
What are the possible methods of immunotherapy?
- Active immunization
- Reversal of immunosuppression
- Adopted cell transfer
- Strengthening natural immune responses
When is immunotherapy generally used?
- In advanced stages of the disease
- However more research is needed
