Cancer Physiology; Disease and Symptoms Flashcards Preview

B33CAN - Pharmacology & Therapeutics > Cancer Physiology; Disease and Symptoms > Flashcards

Flashcards in Cancer Physiology; Disease and Symptoms Deck (28)
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1
Q

What is cancer? What is it characterised by?

A
  • A GROUP of diseases (many different aetiologies)
  • Characterised by abnormal cell growth, where cells may acquire the potential to metastasise from the primary tumour (site of origin) to other sites in the body; secondary tumours
2
Q

What is tumour growth dependent upon?

A
  • Delivery of nutrients and oxygen via increased vascular supply
  • Thus, angiogenesis (initiation of growth of blood vessels towards tumour)
3
Q

What are the two different types of tumour, and how are they characterised?

A

Benign:

  • Cells well-differentiated (look like normal cells)
  • Slow growing
  • Encapsulated; cells are self-contained
  • Does not metastasise “not trying to escape”
  • Can remove via surgery

Malignant:

  • Cells poorly differentiated
  • Frequent cell division; fast growing
  • Loss of capsule
  • Capable of intravasation (breaking through any capsule and pushing through, e.g. endothelial lining, travelling around the body via blood vessel), arrest at distant site, metastasis (90% capable of metastasis)
4
Q

What is a carcinoma?

A
  • Solid tumour, most common type of cancer
  • Arising from cells of embryonic endoderm (interior layer, which develops into interior lining of GIT and lungs) or ectoderm (exterior layer, giving rise to epidermis of skin cells, neurons of brain etc.)
  • Covers external and internal body surfaces e.g. lung, breast, colon
5
Q

What is a sarcoma?

A
  • Cancer arising from cells of embryonic mesoderm (middle layer)
  • Of the supporting tissues of the body such as bone, cartilage, fat, connective tissue and muscle
  • Slightly less common
6
Q

What is a lymphoma?

A
  • Cancer that arises in the lymph nodes and tissues of the body’s immune system
  • Lymph = lymphatic; body’s drainage system, related to the immune system
  • “Liquid cancer”
7
Q

What is a leukaemia?

A
  • Cancer of the immature white blood cells that grow in the bone marrow, and accumulate in large numbers in the blood stream
  • “Liquid cancer”
8
Q

What are some causes of cancer?

A
  • Tobacco
  • XS body weight
  • Physical activity
  • Diet
  • Hormones (reproductive factors; late age at first pregnancy is a factor in breast cancer)
  • Sunlight (UV radiation)
  • Occupational carcinogens (asbestos, benzene, pesticides)
  • Infectious agents: viruses (HPV in cervical cancer), bacteria (H. Pylori cause gastric ulcers, sometimes cancer)
  • Medical treatment (radio/chemo-therapy increases risk later on)
  • Pollution (diesel exhaust, xenoestrogens)
  • Genetic factors
9
Q

What are the symptoms of cancer?

A
  • They are disease-specific

- Often none in early stages; metastases happens v early on, often asymptomatic

10
Q

What are the typical symptoms of lung cancer?

A
  • Cough haemoptysis (coughing up blood)
  • Chest pain
  • Breathlessness
  • Tiredness
11
Q

What are the typical symptoms of pancreatic cancer?

A
  • Weight loss
  • Stomach/back pain (rule out other back pain sources)
  • Jaundice
  • Development of diabetes
12
Q

What are the typical symptoms of breast cancer?

A
  • Lump or thickening (90% of such abnormalities are benign)
  • Change in breast size
  • Discharge
  • Bleeding
  • Weight loss
13
Q

What makes a cell metastatic?

A

Mutagenic initiation:
> Chemicals, radiation, viruses, spontaneous changes
> Changes that are positively selected

Point mutations:
> Missense, nonsense, or silent

Chromosomal alterations:
> Deletion, insertions, aneuploidy (abnormal normal no. of chromosomes in a cell), translocation

Epigenetic alterations (nongenetic influences on gene expression):
> Acetylation, methylation
14
Q

What are the properties of metastatic cells?

A
  • Local invasion into vasculature
  • Survival in a blood vessel
  • Arrest at distant site (integrins)
  • Extravasation
  • Growth of secondary tumour, angiogenesis.
15
Q

What things allow metastatic cells to invade the vasculature?

A
  • Loss of cell adhesion; cadherins normally keep endothelial wall of vasculature nice and tight
  • Gain of alternate adhesion; integrins, allows cancer cells to cling on to outside of vessel (at secondary site?)
16
Q

What factors allow metastatic cells to survive in a blood vessel?

A
  • Selectins; cancer cells express sugar ligand which binds to platelets. Platelets end up aggregating to cancer cell, providing a ‘protective duvet’ against immune response. But platelets also express selectins.
    »> Results in platelet-enhanced metastatic spread
17
Q

Describe the metastatic cascade.

A
  • Primary tumour formation
  • Localised invasion
  • Intravasation (into bloodstream)
  • Transport throgh circulation
  • Arrest in microvessels of organs; lungs, bone, brain.
  • Extravasation; breaking down tight junctions of endothelial wall, from vessel to tissue
  • Formation of micrometastasis
  • Colonisation; formation of macrometastasis (secondary tumour), w/angiogenesis.
18
Q

What is vessel formation essential for the cancer cell?

A

For optimal:

  • Gas exchange
  • Nutrient delivery
  • Disposal of metabolic waste
19
Q

What is vasculogenesis?

A
  • Differentiation and activation of endothelial cells (ECs) with subsequent proliferation, migration, alignment, tube formation, branching and remodelling
  • Confined to embryogenesis; new vessel formation as a foetus.
20
Q

What is angiogenesis, and how does it differ to vasculogenesis?

A
  • Formation of new vessels from a pre-existing vasculature (sprouting off)
  • Enables vascularisation of an avascular region
  • Vasculogenesis is during embryogenesis, and is not from pre-existing vasculature.
21
Q

What are the normal reasons for angiogenesis?

A
  • Development
  • Menstrual cycle
  • Wound healing
  • In response to disease; e.g. ischaemia, diabetic retinopathy (in a bid to save tissue)
22
Q

What size will a tumour’s growth be limited to without angiogenesis?

A

Required for tumour growth beyond 1 mm^3.

23
Q

What are the characteristics of pathological angiogenesis, and what is its vessel morphology like?

A
  • Persistent and unresolved
  • Little stability and high cell turnover

Vessel morphology:
> Poorly designed and distributed “ugly”
> Intrinsically leaky, lacking vasoconstrictor tone
> Endothelial cells loosely connected w/inadequate pericyte (vascular smooth muscle cell) coverage
> Vessel lumen = heterogenous mixture of endothelial and tumour cells; doesn’t stitch together well (leaky)

24
Q

How does normal angiogenesis compare with pathological angiogenesis?

A

Normal tissue:

  • Controlled
  • Highly regulated
  • Organised
  • Mature
  • Low interstitial pressure

Tumour “overcooked spaghetti”:

  • Uncontrolled
  • Unregulated
  • Disorganised
  • Immature
  • High interstitial pressure
25
Q

What does the high interstitial pressure of tumour angiogenesis mean for potential drug targeting?

A
  • Not preferable; hard for drug to escape blood vessel to reach the tumour mass due to high pressure
  • Whereas in normal tissue angiogenesis, the pressure outside of the cell is low; favourable for drug targeting
26
Q

What is the process of normal angiogenesis at cellular level?

A
  • VEGF (vascular endothelial growth factor) is upregulated in wound site, (strongly) promotes angiogenesis
  • Some endothelial cells thus stimulated to change from normal cells to TIP ‘leader’ cells; promoting proliferation and migration
  • TIP cells send signals to stalk cells to stay as stalk cells, and ‘follow’ TIP as as new vessel
  • Platelet derived growth factor recruits smooth muscle cells (pericytes)
  • Pericytes temporarily removed from outside of stalk cells to allow stalk cells to move in direction of TIP cells, and are then put back in place for stability
    »> Pericytes are put back perfectly in normal angiogenesis, BUT this is not the case in tumour, pathological angiogenesis (hence poor pericyte coverage)
  • All the while, matrix metalloproteinases degrade extracellular matrix to allow angiogenesis
27
Q

What are the 3 main goals of cancer therapy, and what do they entail?

A

Curative:

  • Main goal to CURE
  • Ideal outcome: clinically and pathologically free of disease, w/similar life expectancy and QoL as healthy individuals of same age

Maintenance:

  • Secondary goal; MAINTENANCE of patient in functional state
  • Prolonging progression-free survival

Palliative:

  • Goal of treatment is pain relief/comfort for patient
  • When clear the patient is unlikely to be cured, w/low chances of prolonged survival.
28
Q

What are the general characteristics of a cancer cell?

A
  • Stop depending on external signals for growth
  • Ignore signals that tell them NOT to grow
  • Avoid cell suicide, which would naturally eliminate damaged cells
  • Grow indefinitely
  • Stimulate angiogenesis
  • Disturb normal metabolism
  • Promote inflammation and activation of an immune response
  • Initiate process of metastasis.
    (Hallmarks)