Edmead - The future Flashcards
Cancer Vaccines:
Active immunisation involves administration of _____ and ____. Tries to get immune system to attack cancerous cells. Take proteins of tumour cells - mix with ____ to stimulate the immune system which leads to activation of tumour infiltrating _____ that attack the tumour cells!
Antigen and adjuvant
Adjuvant
lymphocytes
Therapeutic vaccines:
Uses appropriate ____ that stimulate the anti tumour response. These are derived from degradation and processing of unfolded intracellular proteins that are shuttled to the surface of _____ cell or from damaged or dying ____ cell. ____ cells acquire the ____ and processes them so they display them to _ cells using MHC. The T cell then recognises the ____ on the tumour membrane and kills the cell by releasing cytotoxic granules or inducing apoptosis.
Antigens Tumour Tumour Dendritic Antigen T cells Antigen
Prophylactic vaccines:
Useful in cancers that are caused by ______ carcinogens (e.g. viruses) e.g. ___ is the causative factor of cervical cancer so vaccines against ___ strains have been produced
pathogenic
HPV, HPV
Bioinformatics:
Individual ____ profiling. Could subject tumour to ____ analysis upon detection during and after treatment. Pool data from thousands of locations and clinical trials to build a ____ of tumorigenic changes and responses. So the molecular _____ of an individual patients tumour can be compared to selective the best therapy available.
Genomic
Genomic
Database
Profile
Biomarkers:
Early detection of cancer is crucial for a good _____. Biomarkers used in diagnostics and prognostics.
What do biomarkers indicate?
Prognosis
Whether levels are normal or abnormal to help suggest a diagnosis/prognosis.
Future: new and improved biomarkers.
Eg in prostate cancer detection:
What do we currently use as a biomarker?
What are the issues?
Diagnostics based on genomics can be used. E.g a gene has been identified as a prostate specific cancer gene that is only _______ in prostate tissue in over 95% of prostate tumours. _____ can detect the RNA using __-____. This is non _____ and reduces the need for unnecessary biopsies.
Currently use serum PSA levels but this is non specific and raised levels can increase simply with age, benign prostatitis and BPH. So lots of false negatives and positives as not all PC has raised PSA either!
Overexpressed
Urinalysis
RT-PCA
Invasive
In the future it is possible that we could have an implantable ____ chip under our skin that measures changes in _____ of genes to speed up diagnosis. This could be feasible as circulating DNA from ____ cell death is released into the blood stream. Detecting over expression of genes/mutations early could speed up treatment.
Gene chip
Expression
Tumour
Hyper_____ of gene _____ is characteristic of specific tumours. e.g. _____ regions of the genes P___ and M____ is frequently mutated in ___ cancer. ____ specific PCR can be used to detect aberrant _____ of these 2 genes in sputum of patients at the time of ____ cancer diagnosis. They can also be detected in blood and exhaled breath of patients. This could be another non _____ molecular diagnostic marker!
Hypermethylation Promoters Promoter P16 and MGMT Lung Methylation Methylation Lung Non invasive
Pharmacogenomics:
‘Influence of ____ on individuals response to drug’
e.g. Iressa (______) is a ____ _____ inhibitor targeted against the _____ receptor. This prevents it’s activation. It is used in ____ _____ ____ ____ cancer but has mixed clinical responses. Patients who respond have a specific mutation in the ____ gene which occurs in the coding region of the ____ ____ ____ active site near the binding site of _____. This results in increased activation of the ____ receptors and these mutations also make the tumour more susceptible to _____. SO knowing the molecular characteristics of the tumour e.g. mutation in ____ gene is important for selecting the most appropriate treatment.
Genome (Gefitinib) tyrosine kinase EGFR Non small cell lung cancer EGFR receptor tyrosine kinase Iressa (gefitinib) EGFR Iressa EGFR
It is useful to carry out genetic screening of tumours to identify the most appropriate treatments. For example treating a cancer with a drug that blocks activation of _____ e.g. Gefitinib is no use if there is a mutation further down the same signalling pathway e.g. in ___ (___ gene).
EGFR
RAS (KRAS)
M_____ and F_____ imaging (MFI) can be used to investigate ____ pathways (e.g. receptor overexpression, gene expression) and tissue _____ (angiogenesis, permeability, hypoxia). This can impact on the diagnosis and monitoring of the progression of disease and can reduce number of invasive ___ taken in clinic. Can also match the tumour to appropriate therapy. BUT ____.
Molecular and functional molecular tissue funciton invasive biopsies EXPENSIVE
Microarrays are a detection mechanism: The _____ of up to thousands of genes can be analysed and matched to certain types of cancer. What does this enable?
Looks at ____ levels to give an idea of protein _____. They can also be used in the identification of gene _______.
Expression
This enables more precise diagnosis and selection of appropriate treatment.
MRNA
Protein expression
Expression arrays: define
Functional arrays: define
Expression arrays tell us the amount of the gene expressed but don’t tell us about whether the protein is functional or not. The antibodies are fixed to a support and bind the protein in the sample.
Functional arrays provide us with info on protein interactions and function. Requires attachment of protein to support using biotinylated tag. This ensures the proteins are functional if they bind with the correct folding and spacing. e.g if P53 is functional it’ll bind and fluoresce if not it wont bind or fluoresce.
