Tumours Flashcards
Define a tumour?
A tumour is an abnormal growing mass of tissue.
What is the difference between this growth of a tumour and the growth of normal tissue?
Tumour growth continues even after the stimulus is removed. It is uncoordinated.
Name the two types of tumour?
Benign
Malignant (cancer)
What is a cancer?
malignant tumour that can invade into adjacent tissue and metastasise and grow at other sites within the body.
Give some general features of cancer?
Major causation of death in UK
Incidents of cancer are increasing
Genetic and environmental factors contribute to causation.
It is a multi-step process of development that is progressive.
What factors affect the classification of tumours?
The tissue that they originate from
Where do germ cell tumours originate and what are they referred to?
Known as teratomas.
Tumours composed of various tissues.
Develop in ovaries and testis
Give some features of benign tumours?
Non- invasive growth pattern Encapsulated No evidence of invasion or metastases. Cells similar to normal cells. Rarely cause death Function not normally affected.
Give some features of malignant tumours?
Invasive growth pattern No capsule or capsule breached by tumour cells Loss of normal function Abnormal cells Cancers are poorly differentiated Often metastases Frequently causes death.
Give some properties of cancer cells?
Loss of tumour suppressor genes Gained function of oncogenes Altered cellular function Abnormal morphology (size/shape) Capable of independent growth No singe one feature unique to all cancer cells Mitoses present and often abnormal.
What causes spreading of cancers?
The loss of cell to cell adhesion and cell to matrix adhesion leads to spreading and cancerous cells can easily break off and deposit elsewhere in the body.
What are tumour biomarkers?
Proteins produced by cancer cells that are related to tumour production. E.g Growth factor receptors, oncogenes, immune checkpoint inhibitors.
In what way can tumour biomarkers be useful?
Used in screening and early diagnosis of patients. Abnormal levels of these proteins can indicate a patient has a tumour before symptoms would be visible. e.g oestrogen receptor is tested in females for breast cancer.
What is tumour angiogenesis?
New blood vessel formation by tumours
What is the function of tumour angiogenesis?
Required to sustain tumour growth and provides a rout of release for tumour cells into the circulation.
What regulates tumour cell growth?
Apoptosis
Can have a negative effect if healthy cells are programmed to be killed.
Describe secondary invasion of cancer and metastasis?
It is a multi-step process and can take different routes - via lymphatics, blood, nearby tissues. It involves the increased degradation of the matrix by proteolytic enzymes and altered adhesion.
What is Trans-coelomic spread?
Special form of local spread.
Metastases across a body cavity e.g pleural or peritoneal
Name some common sites for metastasis?
Liver Lung Brain Bone (axial) Adrenal gland Omentum
What are some uncommon sites of metastasis?
Heart
Spleen
Kidney
Skeletal muscle.
What tissues would these tumours commonly metastasise
- Breast
- Prostate
- Colorectal
- Ovary
- Bone
- Bone
- Liver
- Omentum
What are the local effects of benign tumours?
Pressure and Obstruction.
What are the local effects of malignant tumours?
Pressure Obstruction Tissue destruction - ulceration and infection Bleeding - haemorrhage and anaemia Pain Effects of treatment.
What are the systemic effects of malignant tumours?
Weight loss (cancer cachexia)
Secretion of hormones - Normal/Abnormal
Paraneoplastic syndromes
Describe normal production of hormones by tumours?
Produced by tumours of the endocrine system but there is still abnormal control of its secretion and production.
Describe abnormal production of hormones by tumours?
Produced by a tumour from an organ that does not normally produce hormones. e.g certain lung cancers can produce ADH.
What are paraneoplastic syndromes?
Cannot be explained by local or metastatic effects of tumours. They have misleading symptoms and are therefore difficult to recognise and diagnose.
When is it best to detect cancer?
Early detection, at dysplasia (pre-invasive stage)
What is dysplasia?
A pre-malignant change that is the earliest possible change in the process of malignancy that can be visualised. There is no invasion but it can progress to cancer.
What are some features of dysplasia?
Disorganisation of cells - increased nuclear size, mitotic activity and abnormal mitoses.
Grading of dysplasia - high or low throughout normal tissue
No invasion.
How is dysplasia currently used in the detection of cancer?
Used in cervical screening. Dysplastic cells are detected in the squamous epithelium of the cervix.
What is an adenoma?
A benign tumour of glandular epithelium
What is an Adenocarcinoma?
Malignant tumour of glandular epithelium
Which biomarker would you monitor for the recurrence of an adenocarcinoma of the colon?
Carcinoembryonic antigen
How is genetic fidelity ensured in daughter cells?
Quality control checkpoints - each cell must receive a full chromosome complement.
Mutations in DNA sequences must not pass on.
What are some external factors to cell cycle control?
Hormones
Growth factors
Cytokines
Stromas
What is the quiescence phase?
G0- Resting phase: cell has left the cycle and stopped dividing. (quiet phase).
What factors cause G1 and G2 cycle arrest?
If cell size inadequate
If DNA damage is detected
What factors cause only G1 arrest?
If nutrient supply inadequate
Essential external stimulus lacking
What factor causes S phase arrest?
If the DNA is not replicated
What factor causes M phase arrest?
Chromosome mis-alignment
What are the checkpoints?
System of cyclically active and inactive enzymes
Catalytic sub-unit activated by a regulatory sub-unit.
catalytic subunits are called cyclin-dependent kinases (CDKs)
Regulatory sub-units are called cyclins.
What do active CDK/cyclin complexes do?
Phosphorylate target proteins.
Phosphorylation results in activation/inactivation of that substrate.
Substrates regulate events in the next cycle phase.
What are CDK inhibitors?
The cell cycle brakes. E.g INK4A inhibits kinase.
What is carcinogenesis?
Failure of cell cycle control
Balance between proliferation and apoptosis are disrupted.
Uncontrolled proliferation leads to tumours.
What are chemical carcinogens?
Chemical carcinogens or their active metabolites react with DNA forming covalently bound products (DNA adducts).
Adduct formation at particular chromosome sites causes cancer.
What regulatory pathways are frequently disrupted by cancer?
- The cyclin D-pRb-E2F pathway
2. p53 pathway
What is the role of p53?
Maintains the integrity of the genome.
Induced cell cycle arrest at G1
Facilitates DNA repair.
Can induce apoptosis.
What happens when the p53 pathway is disrupted?
Mutated p53 doesn’t arrest at G1 so the damaged DNA is not repaired.
What is a retinoblastoma gene?
An anti-oncogene (tumour supressor)
What is the inherited form of anti-oncogene mutation?
One defective inherited copy of pRb
Somatic point mutation of other copy
What is the sporadic form of anti-oncogene mutation?
Both hits occur in a single cell.
Takes longer to develop than inherited.
What are some examples of inherited cancer syndromes?
Familial retinoblastoma Familial adenomatous polyposis of colon- 1000s of polyps Multiple Endocrine Neoplasia Neurofibromatosis Von Hippel-Lindau Syndrome
How are proto-oncogenes activated to form oncogenes?
Point mutation.
Chromosome rearrangements + translocations.
Name some active oncogene products?
Growth Factors Growth Factor Receptors Proteins involved in Signal Transduction Nuclear Regulatory Proteins Cell Cycle Regulators
What are the mechanisms of viral carcinogenesis?
Virus genome inserts near a host proto-oncogene.
Viral promoter or other transcription regulation elements cause proto-oncogene over-expression.
Retroviruses insert an oncogene into host DNA causing cell division.
What are some DNA viruses that are known to cause cancer in humans?
HPV (cervical cancer)
Hepatitis B (liver cancer)
EBV (Burkitt lymphoma)
