27 - Oncology 1

Question 1

Describe the genetics component of cancer

Answer 1

• Proto-oncogenes -> normal cellular genes that are important regulators of normal cellular processes
• • Mutation = oncogenes (tumour-inducing)
• Tumour suppressor genes -> suppress growth of tumours
• • Mutations render them inactive, allowing tumours to develop
• DNA repair genes -> mutations allow DNA damage to accumulate over time
• Usually, one mutation isn’t enough to cause cancer; generally, need mutation to proto-oncogenes as well as mutation to tumour suppressor genes

Question 2

Role of immune system in cancer

Answer 2

• Immune system response is to reject or destroy cells perceived as non-self
• Immunologic surveillance
• • Lymphocytes continually check cell surfaces, detect and destroy cells w/ abnormalities
• • Involves cytotoxic T-cell NK cells, macrophages, and B lymphocytes
• Some cancer cells have changes on their surface Ags (tumour-associated Ags/ TAAs)

Question 3

Escape mechanisms by which cancer cells evade immune system

Answer 3

• Weak surface Ags allow cancer cells to “sneak through” surveillance
• Development of tolerance of immune system
• Suppression of immune response to products secreted by cancer cells
• Suppression of killer T-cells
• Induction of suppressor T-cells

Question 4

Properties of cancer cells

Answer 4

1. Cytological changes
   – Increased size and number of nucleoli
   – Increased nuclear/cytoplasmic ratio
   – Altered cytoskeleton
2. Altered cell growth
   – Immortality -> unlimited # of cell divisions
   – “Go” & “stop” signals -> grow w/o “go” signals (growth factors, cell-to-cell adhesion molecules, and extracellular matrix components); ignoring “stop” signals
   – Decreased density-dependent growth inhibition (loss of contact inhibition)
   – Loss of anchorage-dependent growth
   – Loss of cell-cycle control
   – Reduced apoptosis
   3 Changes in cell -> new surface Ags
   - Membrane -> new or altered glycoproteins and glycolipids

Question 5

Desribe telomeres and immortality

Answer 5

• Body cells are not immortal and can only divide a limited number of times due to telomeres
• Telomeres are repeated DNA sequence (TTAGGG x 1000) and protective caps on each chromosome and are held in place and maintained by enzyme telomerase
• Telomeres become smaller and smaller w/ each cell division
• Telomerase is increased in cancer

Question 6

Describe how cancer cells ignore “stop” signals

Answer 6

• Loss of contact inhibition -> invade neighbouring cells, keep dividing
• Loss of restrictive point control -> keep dividing w/o adequate nutrients

Question 7

Describe the phenomenon of density dependent inhibition of growth

Answer 7

• When cells are placed in a flask, cells attach to the bottom of the flask and start dividing
• • Normal cells stop dividing at monolayer stage
• • Cancer cells continue dividing, piling up on one another

Question 8

Describe the phenomenon of anchorage independent growth

Answer 8

• When normal cells are placed in a flask, cells grow well when you allow them to settle and grow poorly when you keep them suspended
• When cancer cells are placed in a flask, they grow well whether they are allowed to settle, or they remain suspended

Question 9

How do cancer cells invade tissue and spread?

Answer 9

• Getting into the bloodstream (altered adhesion and mobility)
• Surviving in the bloodstream (altered anchorage-dependent growth)
• Getting back into tissue (extravasation and attraction to adhesion molecules in metastatic site)
• Angiogenesis is important component

Question 10

Describe the steps of metastasis

Answer 10

1. In situ cancer
2. Cancer invades the tumour border
3. Spreads via lymphatic system
4. Intravasion of the circulatory system; survival and transport
5. Arrest extravasion
6. Solitary dormant cells; occult micrometastases
7. Progressive colonization and angiogenesis

Question 11

What causes cancer?

Answer 11

• External stimuli causing genetic mutation
• Exposure to viruses
• Genetic abnormalities (oncogenes, proto-oncogenes, tumour suppressor genes)
• Chromosomal abnormalities (spontaneous; increased #, deletion, translocation, breakage)
• Immune system abnormalities

Question 12

Risk factors for cancer – external stimuli (carcinogens)

Answer 12

• Diet
• Tobacco
• Bacteria (H. pylori)
• Radiation (basal, squamous cell skin)
• Chemicals (asbestos, vinyl chloride, arsenic, benzidine, aniline dyes, wool, leather, dust)

Question 13

Risk factors for cancer – viruses and immune abnormalities

Answer 13

• Viruses -> most common = hepatitis B
• • Hepatitis C, HPV, Epstein Barr, HTLV-1, HTLV-2
• Immune abnormalities
• • Disorders (HIV/AIDS, lupus)
• • Medications (prednisone, cyclosporine, immuran, etc.)
• • Age-related susceptibility (children, elderly)

Question 14

Risk factors for cancer – inheritable genetic mutations

Answer 14

• BRCA-1 (breast, ovarian, prostate)
• BRCA-2 (breast)
• RB1, WT1
• Hereditary non-polyposis colorectal cancer
• MEN1 and MEN2 (multiple endocrine neoplasia)

Question 15

How to prevent cancer

Answer 15

Up to 50% of cancers could be prevented if Canadians make healthier choices about tobacco, diet, exercise, and sexual practices (HPV, hep B/C, etc)

Question 16

Early warning signs for common cancers that should be acted upon

Answer 16

• Change in bowel or bladder habits
• Sores that won’t heal
• Unusual bleeding or discharge
• Thickening or lump in breast or elsewhere
• Indigestion or difficulty swallowing
• Obvious change in a mole or wart
• Nagging cough or hoarseness

Question 17

Cancer diagnosis

Answer 17

• History and physical
• Blood work
• Tumour markers
• Imaging -> X-ray, CT, MRI, nuclear medicine, ultrasound, PET scan
• Visualization -> endoscopy, cystoscopy
• Biopsy

Question 18

Classifying cancer

Answer 18

• Histopathology (what it looks like under the microscope)
• • Tissue of origin
• • Tumour grade (how aggressive is it)
• • Receptors, chromosomal abnormalities, tumour markers, etc.
• Disease stage (how far has it spread)

Question 19

Describe the classification of cancer based on tissue of origin

Answer 19

• Carcinoma = epithelial tissue
• • Adeno = glandular/columnar
• • Squamous = squamous
• Sarcoma = connective tissue
• • Osteo = bone
• • Blastoma = embryonal origin
• Teratoma = germ cells
• Leukemia, lymphoma = hematologic

Question 20

Describe the classification of cancer based on anatomic site

Answer 20

• Where tumour was found (ex: adenocarcinoma of the breast)
• If disease is found distant from normal location, it is identified as:
• • Breast cancer metastatic to brain
• • Not brain cancer, unless the histology shows brain cancer cells

Question 21

Describe staging of cancer

Answer 21

• TNM classification – one example, there are many staging systems that are disease-specific
• • Tumour size rated as T0 to T4
• • Spread to lymph nodes rated as N0 to N4
• • Metastasis rated as M0 or M1
• • Not used to stage brain or CNS tumours or cancers that affect the blood and lymphatic system
• • Stage 0 = in situ (group of abnormal cells that may develop into cancer at some time in the future but are not yet considered cancer)
• • Stage 1-2 = localized (cancer is relatively small and hasn’t spread into surrounding tissue; sometimes stage 2 means that cancer cells have spread into lymph nodes close to the tumour)
• • Stage 2-3 = regional (stage 3 = large and may have spread into surrounding tissues and lymph nodes in the area)
• • Stage 4 = distant (cancer has spread through the blood or lymphatic system from where it started to a distant site in the body)