Oncology Flashcards
Define adenocarcinoma.
Cancer arising from ductal or glandular structures
Define anaplasia.
Absence of cell differentiation
Define cancer
Malignant tumor
Define carcinogens
Substances that can cause changes in structure or function of a cell that can result in cancer
Define carcinogenesis
The production of cancer
Define carcinoma
Cancer arising from epithelial tissue
Define leukemia
Cancer arising from blood-forming cells
Define lymphoma
Cancers of the lymphatic tissues
Define neoplasm
New cancer growth
Define oncogenesis
Production or causation of cancer
Define oncogene
Occurs when mutations to proto-oncogene present = results in excessive and uncontrolled cell growth
Define proto-oncogene
Normal gene that promotes cell growth
Define sarcoma
Cancer arising from connective tissue (includes muscle and bone)
Define tumor suppresor gene (TSG)
Normal gene that inhibits cell replication
What are the cell characteristics of malignant neoplasms?
Have little resemblance to the normal cells of that tissue
What are the mode and rate of growth of malignant neoplasms?
Mode - infiltrate and destroy surrounding tissue
Rate - rapid growth/replication
What are other characteristics of malignant neoplasms?
- Will metastasize
- Tend to recur when removed
- Cause extensive tissue damage
- Have the ability to cause death unless growth is controlled
What are the general effects of malignant neoplasms?
Anemia, weight loss, fatigue
What are the 3 basic units of DNA that make up nucleotides?
- Pentose sugar molecule (deoxyribose)
- Phosphate molecule
- Nitrogenous bases
What are the 4 types of nitrogenous bases and their complementary base pairs?
- adenine
- guanine
- thymine
- cytosine
Complementary: A&T, G&C
What is the codon?
The protein coding DNA = are successive triplets of bases
What is the malignant transformation of cells?
An accumulation of mutations in a particular class of genes
What are the 2 gene classes that when mutated account for most controlled cell proliferation seen in cancer?
- Proto-oncogenes
- Tumor suppressor genes
Describe the characteristics of cancer cells.
- Lose shape & boundaries
- stop responding to growth-inhibiting signals
- replicate uncontrollably
What does a tumor descend from?
A single precursor cell that has been transformed
What are the categories of ‘hits’ or carcinogens that can cause normal cells to transform?
- Hormonal
- Viral
- Occupational
- Environmental
- Behavioural
- Other/unknown
What are the 4 types of gene mutations that can occur to result in cancer?
- Point mutation
- Chromosome translocation
- Gene amplification
- Frame-shift mutation
What is a point-mutation?
A single change to one base group
What is chromosome translocation?
A piece of one chromosome that is relocated to or swapped with a different part of the chromosome
What is an example of chromosome translocation?
Burkett’s lymphoma
Occurs when the Ig gene on chromosome 14 and the MYC proto-oncogene on chromosome 8 are translocated
Results in high rate of B cell proliferation = increases change of transcription error = cancer development in B lymphocytes
What is gene amplification?
The over expressing or duplication of a piece of a chromosome
* instead of having 2 copies of a gene, you have LOTS
What is an example of gene amplification?
Breast cancer
Human epidermal growth factor receptor 2 (HER-2) gene becomes over expressed = cells in breast ducts grow and replicate outside of their normal boundaries
What are the 2 types of frame-shift mutations?
Addition or deletion of a base group which shifts the whole reading frame resulting in an inappropriate number of bases
What occurs with addition frame-shift mutations?
An extra base is inserted into a base group
What occurs with deletion frame-shift mutations?
A singe base is removed from a codon
What occurs when a frame-shift mutation results in an inappropriate number of bases?
Codon ‘sentence’ isn’t finished so more bases will continue to be added = doesn’t stop
Now have an abnormal cell which +/- be destroyed by the immune system
What 3 genetic factors contribute to gene mutation?
- Hereditary genetic error
- Exposure to carcinogen
- Exposure to a virus
What is a hereditary genetic error and what are the 2 types?
An inheritance of an altered gene of an offspring from parents that passes on an increased risk of developing cancer but doesn’t guarantee cancer
1. Autosomal dominant inheritance
2. Autosomal recessive inheritance
What is autosomal dominant inheritance?
There are no carriers involved - person is either affected or not affected
** only 1 copy of the allele needs to be mutated for the condition to result
What is autosomal recessive inheritance?
A person can be a carrier but not be affected ** this is the main difference between recessive and dominant
What are examples of viruses that can contribute to genetic mutations?
- Epstein Barr - burkitt’s lymphoma
- HPV - cervical cancer
- Hep B - liver cancer
- Human T-cell leukemia virus
What are the 2 basic control systems or checkpoints that help to prevent a single cell from becoming cancer?
- Promotion of cell growth
- Safeguard systems
Describe the ‘promoting cell growth’ system and what occurs with failure of that system.
proto-oncogenes: normal genes that encode proteins with promote cell growth and development
when these become damaged or mutated = oncogenes which flood cells with signals to keep inappropriately dividing
What are the 4 safeguard systems that help to prevent single transformed cell from becoming cancer?
1) tumor suppressor gene
2) mismatch repair gene
3) apoptosis
4) immune system
Describe what occurs with the inactivation with the TSG.
Normal TSG: inhibit cell growth
When TSG damaged - controls that prevent inappropriate cell growth are lost
** TSG is a recessive gene = both copies need to be mutated for this to occur
What occurs with inactivation of the mismatch repair gene?
Mismatch repair gene normally - reads DNA sequence and repairs errors that occur during replication = if damaged, doesn’t occur = errors aren’t fixed
What occurs with the failure of apoptosis?
Apoptosis = normal process of removing old + damaged cells
When apoptosis doesn’t occur = end up with more abnormal cells bc old and damaged cells are allowed to continue replicating
What occurs with immune system dysfunction?(3)
aka - cell-mediated immunity that gets rid of abnormal cells
- cancer outpaces the immune system
- cancer cells can change their appearance (MHC1)
- cancer cells lose contact inhibition
What 3 factors influence the local manifestations of cancer?
- location of the tumor
- size + distensibility of the space the tumor occupies
- surrounding structures
What factors influence the systemic manifestations of cancer?
depends on if the cancer is a systemic type or a local type
What is hyperplasia?
Increased number of transformed cells
What is dysplasia?
Change in size and appearance of cells
What are the steps of tumour spread?
- Transformation of cell
- Growth of transformed cell
- Local invasion - mechanical pressure, lytic enzymes, motility
- Dissemination into lymphatics + bloodstream
- Metastasis
What is replicative immunity?
Transformed cell can shut off systems that normally maintain normal cell life cycle via telomerase enzyme
- telomere caps on chromosomes tell cells to go through apoptosis when caps get worn down
- telomerase enzyme stops wearing down = extends the life of the cell
What are the 3 tactics of local invasion?
- Mechanical pressure
- Lytic enzymes
- Motility
Explain how the basement membrane functions and how it’s involved in tumor spread
Basement membrane: delineates tissue boundaries & is involved in cell-to-cell communication
– if cells detach from ECM, it sends a cytokine message to the cell to go through apoptosis
** this doesn’t occur with cancer cells and they grow where they want
(unruly teen and worn-down mom analogy)
How does mechanical pressure facilitate tumor spread?
Cancer cells will grow through the path of the least resistance
How do lytic enzymes facilitate tumour spread?
Cancer cells secrete lytic enzymes to digest physical barriers and facilitate movement within an organ/tissue
- type 4 collagenase
- plasminogen activator
What are the 2 lytic enzymes secreted by cancer cells and what do they do?
- Type 4 collagenase - digests type 4 collagen in ECM, esp. epithelial and vascular basement membranes
- Plasminogen activator: converts serum proenzyme plasminogen into protease plasmin = breaks down ECM
How does motility facilitate tumour spread? (2)
Cancer cells can move via 2 methods:
1. Autocrine motility factor enzyme
2. Invadopodia - finger like projections that grab onto proteins in ECM (laminin + fibronectin)
What methods do cancer cells use to facilitate movement/dissemination into lymphatics + bloodstream? (2)
- Cancer cells clump together = makes them more difficult to phagocytose
- Cell clumps cover themselves in platelets so they don’t appear foreign
What are challenges cancer cells face when relocating via lymphatics and bloodstream? (2)
- Circulatory = turbulent blood flow (why cells clump together)
- Lymphatics = contains lots of immunity cells
What tactics do cancer cells use to facilitate metastasis?
Same as local invasion tacts = allows cancer to leave the blood/lymph system
What facilitates angiogenesis?
Vascular endothelial growth factor (VEGF)
** once tumour is larger than 2cm, requires its own blood supply
How do metastasized tumours get nutrition? What condition is the result of this?
Tumour takes from body’s fact and nutrient stores to feed self
** anorexia-cachexia syndrome = tumour-induced starvation
what causes cancer patients to lose weight
What is the grading and staging of tumours?
Every type of cancer is graded + staged differently
It sets the parameters of the clinical gravity (aka severity) of the disease
How are tumours graded?
Based on the degree of cell differentiation **not the tissue of origin
What does cell differentiation mean?
Differentiation: the process of the cell becoming more specialized in structure + function
Explain what it means when cells are poorly differentiated. (3)
- Mutation occurs early in cell division resulting in cells that have little resemblance to the tissue of origin
- They’re harder to treat and more unpredictable
- Usually more aggressive types of cancer
Explain what it means when cells are well differentiated. (3)
- Mutation occurs later in cell division so it looks more like the tissue of origin
- Cancer is more predictable
- Usually easier to treat
What system is used to staged cancers? What is important to note about this system?
Cancers are staged 1-4 using the TNM system
**it’s a basic framework - each type of cancer has more detailed staging within this system
What is the T category within the TNM system used to assess?
T: the primary tumour & it’s extent or size
T0 = no tumour
T1-4 - based on measured tumour size (bigger # = bigger tumour)
TX = cannot be assessed
Tis = tumour in situ
What is the N category within the TNM system used to assess?
N: regional lymph node involvement
N0 = no node involvement
N1-3 = based on increasing number + range of node involvement
Nx = cannot be assessed
What is the M category within the TNM system used to assess?
M: if metastasis has occurred
M0 = no mets present
M1 = mets present
MX = cannot be assessed
What is the A & B category used to assess?
If patient is symptomatic
A = symptoms present
B = no symptoms present
Explain what tumour markers are. What is important to note about tumour markers?
Proteins, enzymes, or antigens that can be present in the blood and are cancer specific
** not all cancers have tumour markers
What situations are tumour markers used for? (4)
- Screening high-risk people for presence of cancer
- Diagnosing/determining primary source/origin of cancer
- Monitoring effectiveness of treatment (TM should drop with effective treatment)
- Detecting reoccurrence of cancer