B9 Week 6 Flashcards
Side effects of radiotherapy
Sore and pink skin, intestinal discomfort, fertility issues
Microsatellite instability
Prescence of alternate sized repetitive DNA sequences not present in corresponding germline DNA
Endogenous mutations of p53
Methylation and deamination of the CpG site
Microsatellite instabilityfeatures
Right sided, poorly differentiated, chromosomal diploidy, lymphocytic infiltration, better prognosis when adjusted for stage
Late side effects of radiotherapy
Fibrosis, hair loss, dryness, lymphaedema
Small kinase inhibitors
Inhibit EGFR tyrosine kinase on the cyptoplasmic side
Xeroderma pigmentosum
Caused by mutation in nucleotide excision repair enzymes
Effect of aflatoxin
Addition of epoxide group which causes DNA damage by liver cancer tp p53 in the codon 249 due to metabolism by cytochrome P450
Location of alkyl lesions
O6-methylguanine
Endogenous cancer causes
Oxygen, water, reactive metabolic intermediates
Cancers linked to EGFR
Anal cancer, glioblastoma, squamous cell lung carcinoma, epithelial tumours of the head and neck
Effect of EGFR inhibitors
Papulopustular rash across the face and neck
HNPCC
Colorectal cancer which is inherited caused by a microsatellite instability which has no polyps. There is an early onset and it increases risk of further colorectal cancers
Non -homologous joining
Repair for double stranded DNA break where there is rejoining of two broken ends with the loss of some information.
Xerostomia
Oral dryness with decreased saliva production due to radiotherapy or chemotherapy
Effect of pyramidine dimers
Prevents base pairings which lead to mutations
Cause of familial adenomatous colorectal cancer
Mutation in APC which is a caretaker protein that downregulates beta catenin along with AXIN for the control of Wrt cell proliferation. Results in the formation of polyps due to hyperproliferation of bowel cells
Sporadic colorectal cancer
Occurs due to accumulation of mutations part of the aging proces. This leads to chromosomal instability or microsatellite instabliity.
How do immune checkpoint inhibitors work?
Monoclonal antibodies attach to CTL-4 on malignant tumours and prevent activity of immune suppression
Pyramidine dimers
Lesions from cytosine or thymine base due to photochemical reactions
Neoadjuvant
Given before primary treatment to shrink the tumour
Direct reversal
Used for alkylation damage with a transfer to cysteseine residue
Curative chemotherapy for…
Acute leukaemia, Hodgin’s lymphoma, Non-Hodgkin’s lymphoma, small cell lung cancer
Which protein accumulates in DNA damage?
p53
Neoadjuvant can be used for..
Bladder, breast cancerk, head and neck, oesophageal
Which organs are affected in chemotherapy?
Lungs, heart, CNS, endocrine system and skin
How does radiotherapy work?
Photon displaces electron and the electron causes DNA damage
Cause of HNPCC
DNA mismatch repair genes hMSH2 and hMLH1
Glutathione
Reducing agent which reverses radical formation before cell damage occurs such as with aflatoxin
Primary drug resistance
On first dosage, there is no response to treatment
Secondary drug resistance
Resistance develops to drug over the course of treatment
DNA mismatch errors
Errors in DNA replication which results in mismatching alternating DNA sequences to corresponding germline DNA
Log-kill hypothesis
Relationship of number of tumour cells to chemotherapy dose in order to determine diagnosis time, treatment and survival
Stereotactic radiotherapy
Curative treatment for non-small cell lung cancer and small tumours
Cancers caused by exogenous p53 mutation
Skin cancer, liver cancer, lung cancer
What causes AP sites to spontaneously appear?
Reactive oxygen species
Somatic evolution
Accumulation of mutations which is an important part of the aging process
What causes resistance to EGFR inhibitors?
T980 mutation, MET oncogene
How do angiogenesis inhibitors work?
Antibodies, tyrosine kinase inhibitors
O-6 methylguanine transferase
Causes direct reversal of alkylation damage from modified base to cystosine residue
Aflatoxin
Found in moulds on decaying vegetation
