Before the exam Flashcards
What cell in cancer is not affected by radiation
Muscle cell and nerve cells
Name an example of a tumour suppressor gene
APC and TP53
Dysfunction in cell receptor to anti-growth signals is what hallmark is this?
Insensitivity to antigrowth signals
VEGF causes endothelial cells to migrate and proliferate into new blood vessels what
hallmark is this?
Sustained angiongenssi
Loss of APC causes what event in colon cancer?
Hyperplastic epithelium
G2 and M phase are to identify double strand breaks in DNA. What is there when the cell
cycle continues?
Cell cycle adaption leading to genomic aberration.
T(14:18) follicular lymphoma what does this mean, why does it happen?
IGh bcl2, option:
BCR-abl
Trastuzumab resistance to HER2?
answer was resistance
occurs because change in extracellular domain, causing truncated receptor thing?
What is the last stage of a tumour
Distant metastasis
what is the definition of complete loss of morphology features
anaplasia
What one of these small molecules is most common?
Tryosine kinase inhibitor options: Fcr
Fcr cell binding
- What happens when a cell can produce telomerase?
Limitless reproductive potential
What drug can be used to target cell, maybe cause apoptosis of the cell?
– no immune
checkpoint of cell lenalidomide was an option BH3 mimetic inhibitorSomething about
ABT-737 and ABT-263?
ABT199 – small molecule bcl2 inhibitor
define
- anaplasai
- dysplasia
- hyperplasia
- metaplasia
Anaplasia = the loss of the mature or specialized features of a cell or tissue, as in malignant tumours.
dysplasia = the presence of cells of an abnormal type within a tissue, which may signify a stage preceding the development of cancer.
hyperplasia = the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells, often as an initial stage in the development of cancer.
metaplasia = Metaplasia is the conversion from one type of normal adult cell to another type of normal adult cell
What radiotherapy type is used for skin cancer, skin and rib mets and keloids?
Superficial Xrays
What does Tis mean?
Tumour in situ
What route of administration is used in leukaemia to prevent contamination of meninges?
Intrathecal
What are the 3 different types of mAbs?
Unconjugated (complement mediated lysis), coupled to immunotoxins or coupled to radioimmunoconjugates
What are three proposed mechanisms of action for mAbs? Briefly describe each of them.
1) Antibody-dependent cell-mediated cytotoxicity (ADCC): Fc region of CD20-bound mAb binds to Fc receptor on phagocytic cells (NK cells, macrophages and neutrophils) which release mediators that damage and destroy B cells that are then phagocytosed
2) Complement-dependent cytotoxicity: sequential activation of remaining complement components leads to incorporation into MAC (membrane attack complex) which forms a pore through target cell membrance causing osmotic cell lysis
3) Apoptosis: mAbs binds to CD20 and induces transmission of intracellular signals that trigger cell cycle arrest and apoptosis
What are the extracellular and intracellular effects of Trastuzumab?
Extracellular: inhibition of cleavage of HER2
Intracellular: induction of apoptosis, decreased cell proliferation, decreased VEGF production, HER2 downregulation, potentiation of chemotherapy
What is CAR?
Chimeric Antigen Receptor, combine antigen recognition domain of antibody with intracellular signaling domain into single chimeric protein
How is gene for CAR transferred into T cells?
By lentivirus vector
Give some examples of an oncogene
BCL-2, C-MYC, VEGF, TGF alpha, EGFR, VEGFR, B-Raf
give an example of photo-oncogenes and what cancers they cause
- Translocation = t(14;18)(q32;q21) Bcl-2= follicular lymphoma
- Amplification in ERBB2 or HER2 breast cancer
- c-Fos (transcription factor)Skin/endometrial = point mtuations
- c-H-ras (Gly)GGC- (Val)CTG = bladder = point mtuations
Describes examples of
- Single strange breaks (spontaneous mutations)
- Damage DNA bases – cause of mismatch errors
- UV light
- Replication errors
- Interstrand breaks within the DNA
Single strange breaks (spontaneous mutations)
- reactive oxygen species
- x rays
- oxygen radicals
- spontaneous reactions
Damage DNA bases – cause of mismatch errors
- alkylating agents (usually methylation)
UV light
- UV light
- Causes the Addiction of bulky adducts
- Or causes pyrimidine dimers
- Polycyclic hydrocarbons – see from tobacco smoke
- Specific DNA remair mechanism within the cell to repair this
Replication errors
- Replication errors such as depurination
- Occur normally during the cell cycle s, G1, and G2 phases
Interstrand breaks within the DNA
- UV lights
- Hydroxyurea
- X rays
- Anti -tumour agents
Describe what the normal prostate gland look like
Tubuloalvolar glands
basal cells
describe what BPH looks like
- Crowded tubules
- columnar arrangement near gland
- nucleoli not typically seen
describe the difference between a high grade and low grade PIN - (Prostatic intraepithelial neoplasia)
Low grade PIN
- Nucleoli not prominent
- Tissue appears almost normal
- Intact basal layer
High grade PIN
- Large nuclei,
- hyperchromasia
- prominent nucleoli,
- scattered basal cells periphery
What does a malignant prostate gland look like
- note size of nucleus: cytoplasm = high nuclei to cytoplasm ratio
- prominent nucleoli
- absence of basal cell layer
- hyperchromasia
What is the 9 criteria for the Wilson criteria of screening
- the condition should be an important health problem
- the natural history of the condition should be understood
- there should be a recognisable latent or early symptomatic stage
- there should be a test that is easy to perform and interpret, acceptable, accurate, reliable, sensitive and specific
- there should be an accepted treatment recognised for the disease
- treatment should be more effective if started early
- there should be a policy on who should be treated
- diagnosis and treatment should be cost-effective
- case-finding should be a continuous process
what are the nationally used screening test and how do you test them
- retinoblastoma = Newborn and 6 week check for red reflex
- Bowel Cancer = scope at 55yrs and faecal occult blood(FOB)/ (FiT) faecal immunoflurence test 60-74 = 2 yearly
- Cervical cancer = tested in 25-49 = 3 yearly, tested in 50-64 = 5 yearly
- Breast cancer = 50-70 3 yearly and pilots to extend.
What things do you look for in assessment of the risk to benefit ratio before surgery
Nutritional status - have to increase there nutritional status, can do this by PEG or PN feeding
Co-mordbities –Hypertension –Diabetes –Congestive heart failure –Liver or renal insufficiency –Immunosuppresion
What is staging
Staging is the clinical or pathological assessment of the extent of tumor spread
what does clinical and pathological mean in staging
Clinical = stage at onset
pathological = microscopic biopsy diagnosis and more specific stage
How do you control recurrence of cancer
Adjuvant Treatment – additional treatment after potentially curative surgery
Neo-adjuvant Treatment - additional treatment before potentially curative surgery - therefore this is surgery and chemo or radiotherapy
What is the grey
• The Gray: the unit of absorbed dose.
What is 1 gray
• 1 Gray: deposit of one joule of (radiation) energy in one kg of matter or tissue.
what does 1 gray exposure cause
• 1 Gray: exposure in cells causes:
o >1000 damage DNA bases
o ~1000 single stranded DNA breaks
o ~40 double stranded breaks.
What are the side effects of chemotherapy
Tiredness
Nausea
Vomiting
Hair loss
Risk of infection requiring hospitalisation
Infertility
Long term 2ary malignancies
Hazard to staff
cardiotoxicity
How long is chemotherapy given for
6 months duration , 3-4 weekly cycles
What is the PI3K pathway important for
- cell growth
- proliferation
- agniogensis
- metabolism
What is the MAPK pathway important for
Cell proliferation
What does Cetuximab do
– binds to the Epidermal growth factor receptor and inhibit binding so we don’t get activation of the growth pathways
- inhibit dimerisation and therefore inhibit activation
What is cetuximab used to treat
2017 NICE recommended (EGFR)-expressing, RAS wild-type metastatic colorectal cancer/ recurrent or metastatic squamous cell cancer of the head and neck
How does VEGF protect the endothelial cells from death
Protects endothelial cells from death via activation of PKC pathways and up-regulation of anti-apoptotic proteins such as Bcl-2
What is bevacizumab approved for
- Recurrent or metastatic cervical cancer,
- Third line treatment of low grade gliomas (children)
- First line treatment of advanced epithelial ovarian,
- funded by the cancer drugs fund
What are the activating mutations in tyrosine kinase domain of EGFR in lung cancer
- there are mutations in exon 18, 19, 21 which occur in 50% of non small cell . lung cancer
- Exon 19 and 21 are particularly important in causing activating mutations (change in ATP sites)
What does a mutation at Exon 19 cause in non small cell lung cancer
- increase in autophopsphorylation
- cell survival via AKT increases
- dimerisation increases
What does a mutation at Exon 21 cause in non small cell lung cancer
dimerisation increases
name the ways in which the cancer cells have evolved to prevent immune rejection
Secretion of inhibitory cytokines
Creation of unique microenvironment - sits and organises in a way that it can grow and become more malignant and is protected from the immune system
Alteration of host immune system locally and systemically
Induction of inhibitory T cell subsets
what are the two molecules that T reg cells express
Most Treg cells express CD4/CD25high and FOXP3
Describe how complement dependent cytotoxicity works (CDC)
- uses a membrane attack complex(MAC) and beta cell lysis
- there is a sequential activation of remaining complement components which leads to incorporation into the MAC
- The MAC then forms a pore through the target cell membrane and causes lysi
give an example of a bi specific monoclonal ab
blinatumomab
What cancers is PD-L1 expressed in
- Non small cell lung cancer (squamous cell carcinoma)
- Non small cell lung cancer (adenocarcinoma)
- colon
- melanoma
- renal
What is the approved treatment used for PD1 (checkpoint inhibitors) today
PD1 inhibitors;
- Nivolumab
- Pembrolizumab
What is a chimeric antigen receptor
The chimeric antigen receptor is then added to immune cells called T cells. This helps the T cells find and kill cancer cells that have the specific protein that the receptor is designed to bind.
what rules are clinical trails performed under
Clinical trials are performed under very strict Research Governance under Good Clinical Practice and require Research Ethics Committee (REC) review
- legal requirements
what is research governance
Research Governance is the term covering the principles and processes by which standards are set in research.
How does research governance improve research and safeguards the pubic
- enhancing ethical awareness and scientific quality
- promoting good practice
- reducing adverse incidents and ensuring lessons are learned
- forestalling poor performance and misconduct
What does the research governance framework entail
Ethics (The dignity, rights, safety & wellbeing of participants must be the primary consideration in any research study)
Science (must ensure only high quality, valid research is conducted as determined by independent scientific review of research proposals)
Health & Safety (research can use potentially dangerous equipment, substances or organisms so patient and researcher safety is paramount)
Information (allow public access to information on research being conducted and the findings from research)
Finance (financial probity, consideration of adequate insurance cover for research, arrangements for intellectual property, contracting)
Quality Research Culture (promotion of excellence in research in the UK)
What is good clinical practise
GCP is an international ethical and scientific quality standard for the design, conduct, recording and reporting of trials that involve the participation of human subjects
What must the sponsor ensure
he research team hold the necessary contracts with the Trust and are appropriately qualified to conduct the research
Arrangements are in place locally to deliver the research as proposed in the research protocol
Through independent peer review the scientific quality of the research is assured
All necessary approvals are obtained prior to the research commencing (REC approval, MHRA approval, all local approvals etc)
Responsibilities for the management, monitoring and reporting of the research are delegated appropriately
How are patients rights protected
Informed consent
Scientific review
Institutional review boards (IRBs)
Data safety and monitoring boards
What are the factors defining a good death
- preference
- pain free
- emotional well being
- family
- dignity
- life completion
- religiosity
- treatment preference
- quality of life
- relationship with health care professional
- other
What are the psychological issues faced by survivors
Living with uncertainty
Recurrence and fear of recurrence
Relief, and open-ended threat
‘You’re on your own now’ / cliff-edge
Annual checkups threatening
Persistent symptoms, endless appointments
Un-coordinated care, GPs out of sync
Developing a “new normal”
- Integrating experiences into new sense of self, body
- New priorities, goals – clarifying personal values
Impact on fertility, sexuality, endurance (fatigue)
Focus on quality & relationships
What is the process of the 3 stages after the end of treatment
Recuperation – recovering from:
- Physical damage/impact of treatment
- Emotional turmoil/upheaval
Convalescence – “build up strength”
- Build up physical and emotional strength
Rehabilitation – finding your “new normal”
- Regaining trust in body
- Regaining trust in yourself
- Living with uncertainty
- Dealing with the world
- Regaining mastery and control
What are the domains of self care
- physical
- professional
- spiritual
- psychological and emotional
