WEEK 5 - Malignancies Flashcards
What is apoptosis?
Natural programmed cell death
What is necrosis?
Cell death due to injury or disease progression
What is the cell cycle and what does it consist of?
The division of one parent cell into two daughter cells
Consists of interphase and the mitotic phase
Describe the three subphases of interphase
G1 = growth phase, new daughter cells grow to adult size and duplicate organelles S = DNA synthesis phase, DNA replicates G2 = 2nd growth phase, cells grow and more organelles are added to the cytoplasm
What is mitosis?
Nuclear division such that each daughter cell has the same DNA as the parent cell
Cancer is characterised by?
Uncontrolled reproduction of cells that can arise from ANY cell type
Why does risk of cancer increase with age?
Incidence of gene mutations via epigenetic and genetic mechanisms increases
What is epigenetics?
Environmental factors that can turn genes on or off - changes how genes are read but does not change the actual gene itself
What is a neoplasm?
A new growth, swelling or tumour, may be benign (well differentiated) or malignant (poorly differentiated)
What is an adenocarcinoma?
A cancer arising from the glandular epithelium
What is a sarcoma?
Cancer arising from connective tissue
What is a lymphoma?
Cancer arising from lymphatic tissue
What is leukemia?
Cancer of white blood cells, proliferation of cancerous WBCs
What are the defining characteristics of cancers?
- Have autonomy, ca produce their own growth factors and blood vessels, survive independently
- Have an unlimited life span - vary in size and shape (pleomorphic), lack apoptosis due to telomerase
- Are anaplastic - loss of differentiation, lack organisation, internal structure is not recognisable
What are neoplastic markers?
Substances produced by neoplastic cells, can also be produced by benign cells.
Describe the four stages of cancer?
- Confined to tissue of origin
- Locally invasive - poorly differentiated cells present
- Spreads to regional structures such as lymph nodes
- Metastasis to distant sites
Define carcinogenesis
The transformation of healthy cells to malignant cells.
Triggered by gene mutations as a result of risk factors, mutations stimulate growth promoting pathways and inhibit host antigrowth signals
What are risk factors for cancer? (x7)
- Chronic inflammation
- Viruses and bacteria
- Smoking
- Alcohol
- Radiation
- Obesity
- Physical inactivity
Symptoms of cancer?
- Pain
- Fatigue - unknown mechanism
- Weight loss - altered metabolism, loss of fat stores and muscle
- Infections - decreased granulocytes and lymphocytes
- Blood dyscrasias - anaemia (chronic bleeding), thrombocytopenia (cancer in bone marrow), leukopenia (cancer in bone marrow)
Describe the physiology of the pain response
Stimulation of nociceptors under the dermis and within deep tissues
Mediated by substance P, PGs, histamines and bradykinin
Arises from actual or potential tissue damage
How is cancer pain managed?
ALWAYS with opioid and narcotic analgesics
MOA of morphine?
Acts on mu-receptors in the CNS = reduces pain transmission, slow onset
Longer duration than fentanyl due to high water solubility
MOA of fentanyl?
Mainly acts on mu-receptors in the CNS, more potent than morphine due to high lipid solubility
Short onset and duration of analgesia
MOA of heroin?
Morphine analogue
Rapidly converted to morphine, greater lipid solubility, can cross the BBB
MOA of bupenorphine?
For terminal cancer pain
Partial agonist of mu-receptors = strong analgesic effects
What three blood abnormalities occur in cancer?
- Anaemia
- Leukopenia
- Thrombocytopenia
How do chemotherapy drugs work?
- Target cell cycle and metabolic pathways = aim to kill cells that are in interphase or that are dividing
- Using more than one chemo drug = synergistic effects
- Chemo drugs have a narrow therapeutic effects and a low therapeutic index
Side effects of antineoplastic agents?
- Bone marrow suppression
- Decreased WBCs
- Nausea and vomiting
- Hair loss
What do alkylating and platinum drugs do?
Interfere with cellular replication (cell cycle)
What does doxyrubicin do?
Inhibits DNA and RNA synthesis
What does bleomycin do?
Inhibits DNA and to a lesser extent RNA synthesis. Also breaks DNA strands via ROS
What do antimetabolites do and what are the three subgroups?
Incorporate into DNA during replication - misreading of DNA = DNA breakage, acts on dividing cells
Subgroups:
- Folic acid analogues
- Pyrimidine analogues
- Purine analogues
Adverse effects of antimetabolites?
- Bone marrow suppression
- N & V
- GI damage
What are the two types of hormonal antineoplastics?
- Antiandrogenic
- Antioestrogenic
How does chronic inflammation cause cancer?
Induces growth factors = gene mutations and cellular proliferation
Induces ROS = increases DNA damage
How do viruses and bacteria cause cancer?
Trigger inflammation
How does smoking cause cancer?
Increases inflammation and induces CRP that isn’t normally present in blood unless there is an inflammatory response
How does alcohol cause cancer?
Increases the concentration of acetaldehyde = induction of cytochrome P450 = increases ROS = causes altered cell cycle
Radiation inducing damage to DNA and thus causing cancer depends on?
Dose
Repair mechanisms
Antioxidants
How does obesity cause cancer?
By increasing:
- Free fatty acids
- Tumour necrosis factors (TNF)
- Insulin resistance
- Insulin-like growth factors (IGF)
By decreasing:
- Sex hormone binding globulins (SHBGs) = unbound hormones able to decrease apoptosis and anti-cancer mechanisms in sex hormone sensitive tissues
How does physical inactivity cause cancer?
By promoting insulin resistance and IGFs, decreasing SHBGs, increasing cytokine and inflammatory mediator production
Regardless of antineoplastic agents used, what should be monitored in cancer patients?
- Blood count
- Renal and liver function
