ONCOLOGY Flashcards
HPV and Cancer
Select the most correct answer
a. HPV-18 is the associated with H&N cancers
b. HPV proteins E6 and E7 target tumour suppressor genes
c. HPV transforms mesenchymal cells
d. HPV is a non-enveloped ssRNA virus
B is correct - E6 degrades p53 and E7 binds and inhibits Rb
Incorrect Answers
A - HPV 16 & 18 are associated with cervical cancer but only HPV 16 is associated with H&N cancers
C - HPV transforms epithelial cells
D - HPV is a non-enveloped dsDNA virus
Neoplasm Nomenclature
A pituitary adenoma is classified as a:
a. Benign mesenchymal neoplasm
b. Malignant mesenchymal neoplasm
c. Benign epithelial neoplasm
d. Malignant epithelial neoplasm
C is correct - Benign epithelial neoplasm that forms glandular tissue = Site + Adenoma
Name four features to distinguish benign vs malignant neoplasms.
Benign:
- Slow growing
- Non invasive
- Displace adjacent tissue
- Mobile/encapsulated
- Soft
- No necrosis, haemorrhage, pain
Malignant:
- Invasive
- Fast growing
- Replace adjacent tissue
- Fixed/unencapsulated
- Indurated
- Necrotic, haemorrhagic, pain
What are the four classes of mutations that result in neoplasms?
Growth promoting genes/Oncogenes
Tumour suppressor genes
Apoptosis regulation genes
DNA repair genes
What are the three types of carcinogens?
- Chemical
- Direct-acting initiators → Chemical itself causes DNA mutation
- Indirect-acting initiators → Chemical must be metabolised before it become carcinogenic
- Chemical Promotors: Can cause proliferation of cells direction and kill normal cells and allow initiated cells to proliferate more quickly - Radiation
E.g. UV light and ionising radiation - Oncogenic microbes
E.g. HPV, Hep B, EBV
What are the two defences against pre malignancy?
- DNA repair genes
- Direct DNA repair
- Indirect DNA repair - Immune surveillance - APC to t cells
List 3 ways cancers escape from the immune system?
- Immunosuppression by tumour - release of cytokines that prevent antigen recognition and prevents co stimulation required for t-cell activation
- Glycocalyx hides antigens
- Ligand expression cause lymphocyte apoptosis
- PD1 expressed on tcells bind with PDL-1 on cancer cells resulting in inactivation and apoptosis of t cells
What are paraneoplastic syndromes? Define the following:
- Endocrinopathies
- Neuromyopathic paraneoplastic syndrome
- Hypertrophic osteoarthropathy
Paraneoplastic syndromes: rare disorders triggered by abnormal production of hormones or cytokines by tumour or immune cells
- Endocrinopathies: production of bioactive substances from neoplastic cells
- Neuromyopathic paraneoplastic syndrome: muscle weakness due to immune cells attacking nerves
- Hypertrophic osteoarthropathy: abnormal proliferation of skin and periosteal tissues in extremities (clubbing of fingers)
What are the five clinical signs of OSCC?
- Induration
- Fixation
- False ulceration
- Fungation
- Lymphadenopathy
Nodular fasciitis are large tender nodules associated with trauma.
A. True
B. False
B. False - they are small nodules associated with trauma and are locally infiltrative but self-limiting
What are the three checkpoints in cell cycle?
- G1 Checkpoint – Checks for cell size, DNA damage, nutrients, and growth factors
- G2 Checkpoint – Checks if DNA replicated properly
- M Checkpoint – Checks if chromosomes are attached to spindle fibres (ie. alignment of chromosomes)
Which is most correct about p53
A. p53 is involved in direct DNA repair
B. p53 releases E2F once phosphyrlated by activated CDKcyclin
C. p53 detects DNA damage to arrest the G1/S phase for repair or apoptosis
D. p53 senses and repairs DNA double stranded breaks
C is correct.
A. p53 is involved in indirect DNA repair as it does not directly repair DNA but arrests the cell cycle for repair/apoptosis
B. Referring to pRb
D. Referring to BRCA1
Provide an example that would induce each of the following DNA repair mechanisms
- Direct repair
- Nucleotide excision repair
- Base excision repair
- Mismatch repair
- Double strand break repair
o Direct repair: UV-induced thymidine dimers, Removal of methyl groups
o Base excision repair (BES): Non-bulky damage to DNA (oxidation, deamination, methylation, or spontaneous loss
o Nucleotide excision repair (NER): Remove bulky DNA lesions (UV irradiation, photo products, chemical adducts, DNA intra-strand cross links and oxidative damage)
o Mismatch repair (MMR): Base-base mismatches, insertion/deletion loops
o Double-strand break repair (DSBR): Breaks on both DNA strand, caused by ionising radiation
What protein complex prevents telomere ends from sticking to teach other (potentially resulting in neoplasia)?
Shelterin
Explain the role of telomerase in neoplasia.
Telomerase = Enzyme that repairs telomeres
o Allows cells to replicate indefinitely
o Usually only expressed in foetal tissue, germ cells, and proliferative cells (shut down in adults)
o Commonly expressed in cancer = Immortalisation
Distinguish familial adenomatous polyposis and hereditary non-polyposis colorectal cancer.
Familial adenomatous polyposis:
- Polyps in colon
- Results from mutation of APC gene
Hereditary non-polyposis colorectal cancer:
- No polyps
- Family history of colorectal cancer < 50 years
- Mutation in 1/4 mismatch DNA repair genes.
Explain the role of the APC gene
- Controls entry of cells in cell cycle
- Regulates e-cadherins for cell adhesion (issues lead detachment = greater susceptibility for invasion and metastasis in neoplasms)
Explain function of Wilm’s tumour-1 gene (WT-1)? What cancer does it lead to when mutated?
- Codes for a zinc-finger class of transcription factor which functions
as a transcriptional repressor, for example, of growth factors such as PDGF and
Insulin-like Growth Factor 2. - Mutation of the gene abolishes the DNA-binding activity
of WT-1, abolishing transcriptional repression and allowing unregulated cell. It can result in nephroblastoma - cancer of the kidney.
Which of the following is false about Rb?
A. Requires a single mutation for development of retinoblastoma
B. Located on chromosome 13
C. pRB upregulates the G1 to S transition in cell cycle
D. Mutations of Rb leading to retinoblastoma is an autosomal dominant trait
A is false. Retinoblastoma requires two mutations for retinoblastoma
• Genetic = One inherited and somatic mutation of other normal gene
• Sporadic case = Somatic mutation of both normal alleles
Which of the following is true regarding p53?
A. Requires two mutations for neoplasia
B. Regulates e-cadherins
C. Located on chromosome 11
D. Mutant p53 will bind and inactivate normal p53 in unaffected allele
D is true.
A. Referring to retinoblastoma
B. Referring to APC
C. Referring to WT-1
List the 8 steps in the metastasis of cancer cells.
- Primary Tumour
- Local Invasion
- Intravasation (into blood stream)
- Survival in circulation
- Arrest at distant organ site
- Extravasation (out of blood stream)
- Micro-metastasis
- Metastatic colonisation
Distinguish amoeboid and mesenchymal invasion.
Amoeboid invasion = Cell restructures cytoskeleton but no change in phenotype
o Cytoskeleton acts as engine
o Cell surface receptors bind and pull cell
Mesenchymal invasion = Cell reverts into mesenchymal cell
o Phenotypic change into highly motile cells
o Inhibition of cell-cell adhesion
Name two factors that allow neoplastic cells in intravasation.
- Angiogenesis at primary tumour site
- VEGF: promotes growth of new blood vessels
Name two factors that allow neoplastic cells to survive in circulation.
- Anoikis inhibitors: anoikis is programmed cell death that occurs when epithelial cells detach from surrounding ECM. Inhibiting this allows survival of the neoplastic cell.
- Formation of embolus with platelets to evade detection by immune system
What are the two theories regarding arrest of neoplastic cells at distant organ site?
- Physical entrapment (passive)
- Receptor-ligand mediated arrest (active)
What are the two theories of metastatic colonisation?
Seed and Soil Hypothesis
- Tumour cells can adapt to new environments
- Metastasis only develop at sites where tumour cells are adapted for survival and proliferation
Cancer Stem Cells Hypothesis
- Only some cells within tumours have self-renewing ability which can initiate a new tumour
- Cancer stem cells = Tumour cells that have reverted to multipotent mesenchymal cells. Mesenchymal cells have self-renewing ability, thus more likely to metastasise
- Presence of cancer stem cells enable metastasis to secondary tissues → No cancer stem cells = No metastasis even if site is favourable
Which of the following is false?
A. HPV 16 is a leading cause of oropharyngeal cancer
B. E6 and E7 protein binds to and degrades pRb and p53 respectively.
C. HPV is a dsDNA virus
D. Transmission of HPB occurs through contact with infected epithelial cells - conventional and oral sex
B is false - E6 binds and degrades p53 while E7 binds and degrades pRb
What are the three types of biopsies that can used for diagnosing cancer?
- Incisional
- Fine needle
- Brush biopsy
Explain the positive feedback with metastasis in relation to bone resorption.
o Bone metastasis causes bone resorption
o Bone resorption releases growth factors from bone matrix
o Growth factors stimulate tumour growth
o Tumour growth cause more bone resorption
How do tumours cause hypercalcaemia? Name three mechanisms.
- Local release of cytokines by osteolytic metastasis (tumour –> bone resorption –> cytokines released from bone matrix for growth –> tumour growth –> bone resorption –> cycle)
- Inhibit secretion of calcitriol
- Tumour secretion of parathyroid hormone-related peptide which stimulates bone resorption (similar actions to PTH)
What is cancer cachexia and how does it result?
- Cancer Cachexia = Progressive loss of fat and lean muscle mass accompanied by weakness, anorexia, and anaemia
- Cancer patients with metastases become cachexic
Possible Causes: o Widespread infection and haemorrhage o Immunosuppression due to therapy o Poor diet o Depression
What are the common treatment options for early vs advanced oral cancer?
Early (Stage I & II) = Surgery Advanced cancer (Stage III & IV) = Surgery + (Chemo)RT
Radiotherapy is avoided if possible due to significant destruction of H&N structures.
Name four key oral side effects of radiotherapy.
- Mucositis
- Xerostomia; dental caries, difficulty swallowing, oral candidiasis
- Osteoradionecrosis; significantly increased with >65 Gy dose
- Fibrosis of jaw muscles; trismus, restricted jaw opening
Which of the following is most correct?
A. Dental treatments should be carried out at a minimum of 7 days before radiation.
B. Placement of implants are recommended 2 years post radiation.
C. Placement of implants are NOT recommended <6 months post radiation.
C
- Complete all dental treatment >14 days BEFORE radiation if possible.
- Placement of implants recommended 6 – 24 months AFTER radiation therapy recommended.
Distinguish nociceptive and neuropathic pain.
Nociceptive:
- Localised
- Sharp
- Worse with movement
Neuropathic:
- Not well localised
- Burning, shooting, numbness
Which of the following is true?
A. Nociceptive pain should be treated with pregablin.
B. Denosumab is first line of treatment for bone pain.
C. Duloxetine is contraindicated for neuropathic pain.
D. Fentanyl patches are effective for 24 hours after they are removed.
D is true.
A. Pregablin is a gabapentinoid and recommended for neuropathic pain
B. Bisphosphonates are first line treatment as benefits can be seen >6 months.
C. Duloxetine is an SNRI and is recommended for neuropathic pain.
How to calculate dosage for new opioid prescribed?
- Calculate equianalgesic dose
2. Initiate 50-75% of equianalgesic dose
Distinguish incident and breakthrough pain and the treatment options for both.
Incident pain: associated with activity → Treat by modifying activity – NOT opioid dosage
Breakthrough pain: fluctuation of pain not controlled by analgesia → Treat with immediate-release opioid = 1/12 to 1/6 of daily dose
Which of the following is false regarding treatment of pain in cancer patients?
A. Nociceptive pain can be treated with paracetamol, NSAIDs and opioids.
B. Transmucosal fentanyl most commonly used to treat incident bone pain.
C. Gabapentinoids are effective for treating chemotherapy induced peripheral neuropathies
D. Regular opioid dose should be increased if breakthrough pain is experienced 3-4 times a day.
C is false as only duloxetine has been shown to be effective for chemotherapy induced peripheral neuropathies.
Hamartoma is a;
A. neoplastic lesion
B. haematological lesion
C. controlled tumour-like lesion with contiuous proliferative growth
D. controlled tumour-like lesion with limited growth
D
What are 3 features of a Pseudosarcoma
- Increased growth/proliferation BUT self-limiting
- Hypercellular lesion
- Increased mitotic activity
The local invasion mechanism of a squamous cell carcinoma is most likely;
A. Strand with a lumen
B. Cluster
C. Solid strand
C - Squamous cell carcinoma’s are moderately differentiated epithelial tumours with subreagions after EMT which invade in a solid strand pattern.
A - vascular neoplasias
B - moderately differentiated epithelial tumours
*digram on slide 12 from mechanisms of metastasis lecture
A patient is taking morphine (oral) 42mg bd - what is the breakthrough/incident dose?
Breakthrough/Incident dose is 1/12 ro 1/6 of the daily dose
42mg x 2 = 84mg daily
1/12 - 7mg
1/6 - 14mg
Recomended dose 7-14mg or 10mg
A patient is taking morphine (oral) 40mg bd but due to inadequate anaelgesia you want to switch the patient to Hydromorphone (oral) - what is the starting dose?
hydromorphone is 5x stronger than morphine
equianalgesic dose is 40/5 - 8mg bd
50-75% of this dosage given
50% = 4mg
75% = 6mg
Dose of Hydromorphone is 4-6mg bd or 5mg bd
What is the most correct statement about Duloxetine
A. it is an SSRI
B. it is given to reduce bone pain in cancer patients
C. ADR’s are similar to Opioids
D. it is the only recomended agent in chemo-induced peripheral neuropathies
D is correct
A- its an SNRI
B- it is given for chemo-induced pain, may be confused with denosumab which is given for bone pain in cancer patients
C- ADR’s are that of SNRI/SSRI’s - raised BP and decreased NA
Match the neoplasm with its group/type Neoplasms - pituitary adenoma - oral squamous cell carcinoma - osteoma - fibrosarcoma
Group/Type
- Bening epithelial
- Benign mesenchymal
- Malignant epithelial
- Malignant mesenchymal
Bening epithelial - pituitary adenoma
Benign mesenchymal - osteoma
Malignant epithelial - oral squamous cell carcinoma
Malignant mesenchymal - fibrosarcoma
In the TNM staging system what do the letters TNM relate to?
A- tumour, necrosis, metastasis
B - ten new malignancies
C - tumour, node, metastasis
D - tumour, node, malignancy
C - correct
What are two potential causal relationships between OSCC and its known affected areas (ie. floor of mouth and ventral/lateral borders of the tongue)
- saliva pooling in the floor of the mouth containing carcinogens - increasing contact time between the carcinogens and these anatomical locations
- Lack of keratin in the affected areas
What is the relevance of interphase CDK’s in cancer therapy?
Cancer cell activity is similar to that of embryonic cell activity
Interphase CDK’s are imperative to survival during embryogenesis but become less important as an individual grows
As interphase CDK’s are less imperative to adult cells but significantly affect cancer cells they are a good target in cancer treatment
Which DNA repair mechanism is matched correctly with its intitator (damage) cause
A. Direct repair - UV induced thymadine dimers
B. Double-strand break repair - oxidation, deamination, methylation
C. Mismatch Repair - ionizing radiation
D. Base Excision Repair - insertion/deletion loops, base-base mismatch
A is correct
B. Double-strand break repair - ionizing radiation
C. Mismatch Repair - insertion/deletion loops, base-base mismatch
D. Base Excision Repair - oxidation, deamination, methylation
What are the grades of squamous cell carcinoma and what do the grades refer to?
Mild - lower 1/3rd of epithelium affected
Moderate - lower 2/3rds of epithelium affected
Severe - whole epithelium affected
Which of these statements is the most correct
A. squamous cell carcinoma’s make up 70-80% of all oral cancers
B. The 5 year survival of oral cancer is 75%
C. Oral cancer deaths in Australia account for 1% of all cancer deaths
D. Women are more affected by H&N cancers than men
C is correct
A - SCC make up >90%
B - 5 yr survival is 50%
D - Men tend to be more affected