Neoplasm Flashcards
Neoplasm definition
An abnormal growth of cells that persists after the initial stimulus is removed
Malignant neoplasm definition
An abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue with potential to spread to distant sites
Cancer definition
Malignant neoplasm
Metastasis definition
A malignant neoplams that has spread from its original site to a new non contiguous site
Dysplasia definition
Pre neoplastic alteration in which cells show disordered tissue organisation. It is not neoplastic because the change is reversible
Benign tumour appearance
Grow in a confined local area and so have a pushing outer margin
Malignant tumour appearance
Have an irregular outer margin and shape and may show areas of necrosis and ulceration
Benign neoplasm under the microscope
Cells that closely resemble the parent tissue, i.e. are well differentiated
Malignant neoplasm under the microscope
Range from well to poorly differentiated. Cells with no resemblance to any tissue are called anaplastic. (Malignant tumours ccan be well differentiated)
Worsening differentiation under the microscope
Increasing nuclear size, increased nuclear to cytoplasmic ratio, increased nuclear staining (hyperchromasia), more mitotic figures, increasing variation in size and shape of cells and nuclei (pleomorphism)
High grade means
Poor differentiation
What are initiators ands promoters?
Initiators are mutagenic agents
Promoters cause cell proliferation
Invasion into surrounding tissue by carcinoma cells requires:
Altered adhesion, stromal proteolysis, motility
Industrial carcinogen used in dye manufacture
2-napthylamine
What did malignant neoplasms caused by 2-napthylamine show?
1) There is a long delay between carcinogen exposure and malignant neoplasm onset
2) The risk of cancer depends on total carcinogen dosage
3) There is sometimes organ specificity for particular carcinogens
What does the Ames test show
Initiators are mutagens, while promoters cause prolonged proliferation in target tissue
How can mutagenic chemical carcinogens be classifies?
- Polycyclic aromatic hydrocarbons
- Aromatic amines
- N nitroso compounds
- Alkylating agents
- Natural products
What are pro-carcinogens?
Chemicals that are only converted to carcinogens by cytochrome P450 enzymes in the liver
What are complete carcinogens?
Carcinogens that act as both initiators and promoters
How do infections affect tissue growth?
- Directly affect genes
- Indirectly by causing chronic issue injury where the resulting regeneration acts either as a promoter for any pre existing mutations or causes new mutations from DNA replication errors
How does HPV cause neoplasia?
- Direct carcinogen
- Expresses E6 > inhibits p53
- Expresses E7 > inhibits pRB
- Both are important in cell proliferation
- HPV strongly linked to cervical carcinoma
How do Hep B and C cause neoplasia?
Indirect carcinogens that cause chronic liver cell injury and regeneration
Which bacteria and parasites increase the risk for the development of carcinomas?
- Helicobacter pylori (chronic gastric inflammation)
- Parasite flukes (inflammation in the bile ducts and bladder mucosa)
How does HIV increase risk of neoplasia?
Acts indirectly by lowering immunity and allowing potentially carcinogenic infections to occur
First human oncogene discovered
RAS
- Mutated in a third of all malignant neoplasms
- Encodes a small G protein that relays signals into the cell that eventually pushes the cell past the cell cycle restriction point
- RB inhibits passage through restriction point
What do proto-oncogenes encode?
- Growth factors
- Growth factor receptors
- Plasma membrane signal transducers
- Intracellular kinases
- Transcription factors
- Cell cycle regulators
- Apoptosis regulators
(Tumour suppressor genes encode proteins in the same pathways but with anti growth effects)
Xeroderma pigmentosum
- Autosomal recessive
- Due to a mutation in one of the 7 genes that affect DNA nucleotide excision repair
- Patients very sensitive to UV damage and develop skin cancer at a young age
Hereditary non-polyposis colon cancer (HNPCC) syndrome
- Autosomal dominant
- Associated with colon carcinoma
- Germline mutation affects one of several DNA mismatch repair genes
BRCA1 AND BRCA2
Important for repairing double strand DNA breaks
Nucleotide excision repair: Inherited syndrome, effector genome
Xeroderma pigmentosa
Nuclear instability
Mismatch repair: Inherited syndrome, effector genome
Hereditary non polyposis colon cancer (HNPCC)
Microsatellite instability
Double strand break: Inherited syndrome, effector genome
Breast/ovarian cancer
Chromosomal instability
Cancer progression
- Early adenoma
- Intermediate adenoma
- Late adenoma
- Carcinoma
- Metastasis
Six hallmarks of cancer
1) Self sufficiency in growth signals
2) Resistance to growth stop signals
3) No limit on the number of times a cell can divide
4) Sustained ability to induce new blood vessels
5) Resistance to apoptosis
6) Ability to invade and produce metastases
