Basic Science Flashcards
What are three consequences of p53 loss
Genomic instability (loss of G1/S checkpoint),
impaired DNA repair
impaired apoptosis
Fibrosis is common after RT. List THREE cytokines/pathways that cause it
TGFB (transforming growth factor beta ) – converts fibroblasts into myofibroblasts; collagen production: I found the most evidence for this
CTGF (connective tissue growth factor) – collagen production
PDGF (platelet derived growth factor)
What are the 4 Phases of Mitosis
Prophase – Chromatin condenses to chromosomes
Metaphase – Spindle fibres align at metaphase plate
Anaphase – Paired chromosomes move to opposite sides of cell
Telophase – Division into daughter cells, chromosome dispersal
Name 3 angiogenic factors produced by tumor cells
Vascular endothelial growth factor (VEGF)
Interleukin-8
tumor necrosis factor (TNF)-α
What type of molecule is HER2?
What are the 2 domains or components of HER2?
Why is trastuzumab humanized?
Receptor tyrosine kinase of the EGFR family.
Extracellular domain: signal transduction is initiated through dimerization with other receptors. Intracellular domain: responsible for phosphorylation and recruitment of proteins
Improves efficacy because humanized monoclonal antibodies (as compared to chimeric [mouse-human] or mouse MABs) are less likely to induce an immune response in the patient.
Explain the mechanism of p53
tumor suppressor gene and checkpoint protein, with many anti-cancer mechanisms:
- recognize DNA damage
- cause cell cycle arrest if damage detected
- initiate DNA repair
- initiate apoptosis or programmed cell death if DNA irreparable
What is Fluorescence in situ hybridization (FISH) and give an example where you would use it
FLUORESCENT LABELLED PROBES COMPLEMENTARY TO SEPCIFIC DNA SEQUENCES. hER-2/NEU. TRANSLOCATION FOR Dx LIKE in double hit lymphoma with C-MYC and BCL2 or BCL6
What gene is amplified in a liposarcoma?
MDM2
CDK4
Name 3 ways the human genome differs between individuals
- Various mutational events
- Genetic drift – insertions, deletions, translocations.
- Epigenetics factors: eg silencing.
Explain the mechanism of: BRCA1
– BRCA1 is a tumor suppressor gene.
interact with RAD51 during repair of DNA double-strand breaks. DNA repair protein in Homologous recombination.
8 modifiable breast cancer risk factors
- Parity
- Time of first pregnancy
- Breastfeeding duration
- Weight loss
- Use of oral contraceptive pill
- Use of hormone replacement therapy
- Use of selective estrogen receptor modulator (raloxifene)
- Choice to have prophylactic oophorectomies
- Choice to have prophylactic mastectomies
- Alcohol
- Physical activity
- Smoking
Prove that HPV causes cervical cancer (from Gunderson)
1) Multiple epidemiologic studies showing HPV infection as the most important risk factor for the development of squamous cell intra-epithelial lesions and cervical carcinomas
2) Detection of HPV DNA in more than 90% of cervical cancers and their precursor lesions
3) Evidence of HPV transcriptional activity in neoplastic tissues
4) Evidence that HPV oncogenes can mediate malignant transformation in transgenic mice
List 3 reasons why a screening study may falsely show improved survival
Lead time bias
Length time bias
Selection bias
Between which 2 active phases is G0? (0.5)
M and G1
List 5 factors that influence relative biological effectiveness:
o Linear energy transfer
o Radiation dose
o Number of fractions
o Dose per fraction
o Dose rate
o Biological system or tissue studied
Abiraterone: How does it work as an anti-androgen?
Why do you prescribe prednisone with abiraterone?
Androgen biosynthesis inhibitor, which inhibits 17α hydroxylase/C1, 20-lyase (CYP-17A1) involved in androgen biosynthesis and mineralocorticoid production. Abiraterone also inhibits DHEA and androstenedione
To replace endogenous steroids
EGFR+ NSCLC, what are two most common point mutations. Does gefinitib work better for one mutation than another. If there is resistance what mutation do you now test for and what medication is health Canada approved to treat with now.
Two most common point mutations: Exon 19 and exon 21
Gefinitib works better than Exon 19
If resistent to Gefinitib, test for T790M and if positive, can use Osimertinib
In personalized medicine what enzymes could be tested for, that would limit efficacy of;
Tamoxifen: tamoxifen is SERM (selective estrogen receptor modulator). metabolizes it to active metabolites.
Capecitabine:
Tamoxifen: CYP2D6 to make the drug effective
Capecitabine: DPD enzyme metabolizes, and deficiency could cause severe toxicity.
8 side effects to monitor for capecitabine
Palmar plantar erythrodysesthesia
Diarrhea
Nausea
Vomiting
Stomatitis
ALT elevation
AST elevation
Neutropenia (also anemia, lymphopenia, thrombocytopenia)
