EMS Flashcards
(135 cards)
1
Q
What is a nucleosome?
A
200 base pairs of double stranded DNA wrapped around a histone core octamer
2
Q
Describe the mitochondrial genome
A
Circular, cytoplasmic material inherited via oocyte cytoplasm
3
Q
What its satellite DNA?
A
Large blocks of repetitive sequence heterochromatin, tenderly repeated sequences with possible polymorphic blocks
- alphoid DNA 171bp repeat unit required for centromere assembly
4
Q
What are interspersed repeats?
A
Alu repeats
- Scattered around the genome, individual copies at many locations
- Short interspaced nuclear element
- Dispersed into retro transposition
5
Q
What is a de novo mutation?
A
A new mutation which has occurred during gametogenesis - parents are not affected and do not have the mutation in their somatic tissue
6
Q
What is anticipation?
A
Symptoms of a genetic disorder becoming more severe as the gene is passed on through each generation
7
Q
What is Mocaicism?
A
A new mutation occurrence post-zygotically
- distribution of mutant cells is unpredictable and could involve lethal mutations if non-mosaic
8
Q
Describe Sanger sequencing
A
- Use PCR as a template DNA in the reaction
- Template DNA, nucleotides and polymerase to reaction (+primer)
- Add dye terminator nucleotides (ddNTPs) to terminate the sequence reaction labelled with fluorescent dyes
- cycle through denaturing, annealing and extension 35 times
- DNA will be different lengths due to random incorporation of terminator bases and separate as they leave the capillary based on their size
- Excited with a laser and each dye gives off a different signal which can be collected and decoded
9
Q
Describe next generation sequencing
A
- Clonal sequencing machines which sheer the DNA wanted and make small clones using PCR onto a flow cell
- Similar to Sanger
- Sequencing reads are small (150bp)
10
Q
Describe whole exome sequencing
A
- Generate an exam library - sheer genomic DNA, amplify, tag, hybridise it with a library of probes matching axons in the genome
- have small magnetic bead on the end so we can pull out the sequences that have hybridised
- Go into standard ilumino ex gen sequencing to produce the sequencing reads
11
Q
Describe comparative genome Hybridisation (aCGH)
A
- Standard reference DNA and patient DNA
- Cut and label with patient DNA green fluorescent dye and reference DNA with red dye
- Hybridise it to an array - lots of probes and expand genome
- if equal red and green = yellow
- can see different quantities of DNA but not where it is in the genome
12
Q
What is the dosage effect?
A
Copy number variation, CNV - loss usually worse phenotype than gain
Types:
- Aneuploidy, polyploidy
- Chromosome structure - deletion/duplication
- Mosaicism
13
Q
What is the position effect?
A
Gene in a new chromosomal environment functions inappropriately - unmasking of a recessive disorder
14
Q
What are the three viable trisomy’s?
A
Trisomy 13 - patau syndrome
- microcephaly, holoprosencephaly, cleating, polydactyly
Trisomy 18 - Edward’s Syndrome
- microcephaly, growth retardation, rocker-bottom feet, clenched hands and cardiac abnormalities
Trisomy 21 - Down’s syndrome
- Aneuploidy, resulting from meiotic errors, strong maternal age effect, little or no paternal effect
15
Q
Describe Polyploidy
A
- Errors at fertilisation, most usually triploidy
- Parental origin effect
16
Q
Describe reciprocal translocation?
A
- Breaks and exchanges of chromosomes
- Stem from meiotic errors in segregation and can produced unbalance gametes
- Pachytene cross
17
Q
Describe Robertson Translocation
A
- Whole arm fusion
- Acrocentrics - short arm loss
- No phenotype, reproductive risk
- Full genetic makeup just 45 chromosomes not 46
18
Q
What are 4 types of normal genetic variations?
A
- Single nucleotide polymorphisms
- INDEL’s - insertion or deletion of one or more nucleotides
- SNP + INDEL’s - target site for nuclease enzymes - restriction fragment length polymorphisms RELPs
- CNVs - large indwells change copy number of sequence greater than 100 nucleotides in length
19
Q
Describe allelic heterogeneity
A
Different pathogenic variants in a single gene leading to multiple different phenotypes
20
Q
Describe a point mutation
A
Mutation that effects a single nucleotide
- most common cause of disease
21
Q
Describe variant consequences
A
Protein effect: - No effect - Exchange for reference amino acid for alternate - Null effect - complete absence of the genes protein product People Effect: - No effect - Contribution to individual variation - Cause of mendelian disease - Contribution to normal disease
22
Q
Describe missense mutation
A
- DNA change
- Incorporation of different amino acid at that position substitution
- effect on protein depends on the degree of difference between the reference and substituted amino acids
- Conservative - substitution within the same group
- Non-conservative - amino acid substitution to one in a different group
23
Q
Describe Null Variants
A
- Nonsense
- Frameshift
- Canonical splice site variants - occur at the boundary of an exon and intron impacting splicing
- Loss of start codon
- Single exon or multiexon deletion
24
Q
Describe Atheroma
A
intimal lesion that protrudes into vessel wall
- Raised lesion with soft core of lipid (Mainly cholesterol and cholesterol esters) covered by a fibrous cap
Commonly affected vessels:
Bifurcations, abdominal aorta, coronary arteries, popliteal arteries, carotid arteries, circle of wills
25
Describe atherosclerosis formation
Starts with damage or injury to the inner layer of an artery
- Development of a chronic inflammatory response of the arterial wall to endothelial injury
- Lesion progression through interactions of modified lipoproteins, monocyte-derived macrophages, T-lymphocytes and normal cell constituent of artery wall
- Fatty Streak - earliest lesion in atherosclerosis composed of lipid filled foamy macrophages - begins as multiple flat yellow spots and begin to form in adolescence
- Intermediate lesion
- Atheroma
- Fibroatheroma
- Complicated lesion
26
Describe a thrombus
- Solid mass of blood constituents formed within the vascular system in vivo
- Commonly superimposed on atheroma
- Venous thrombosis commonly caused by stasis
27
Describe Virchow's triad
Endothelial Damage
Hypercoagulability - Heredity (Factor V Leiden, prothrombin G2021OA, Protein C and S deficiency) or acquired
Stasis
28
Describe an embolus
A mass of material in the vascular system able to become lodged in the vessel and block its lumen
- Most derived from thrombi
29
What is ischaemia and Hypoxia?
Ischaemia = interruption of blood flow to cells and tissues reducing oxygen supply
Hypoxia - when the oxygen supply to tissues is impaired
ischaemia always results in hypoxia
30
Describe the mechanisms of ischaemic cell injury
- Decreased oxidative phosphorylation
- Switch to anaerobic respiration
- Failure of Na pump
- Membrane damage and leakage of intracellular proteins - enzymatic digestion of cell
- Failure of Ca pump
- Decreased protein synthesis
31
Describe detection of ischaemic cell injury
Increased lactate
Creatine kinase, troponins - cardiac muscle damage
Transaminases, alk phosphate - liver damage
32
What are the 6 causes of ischaemia?
1. Vascular occlusion
2. Vasospasm
3. Vascular Damage
4. Extrinsic compression
5. Mechanical interruption
6. Hypoperfusion
33
What are the 5 factors for ischaemia outcome dependence?
1. The nature of the blood supply - alternative?
2. The duration of ischaemia
3. The rate of vascular occlusion
4. Tissue vulnerability - brain takes 3-4 mins for irreversible damage, heart takes 20-30mins
5. The blood oxygen content
34
Describe necrosis and the two types
Coagulative - denaturation, basic outline of cell is preserved but DNA and internal material is lost - eosinophilic ghost cells
Liquifactive - enzyme digestion from inside out
35
What are the types of shock?
Hypovolaemic - haemorrhage and non-haemorrhagic
Cardiogenic - myopathic, arrhythmia related, mechanical, extra-cardiac
Distributive - anaphylactic, septic, TSS, neurogenic
Obstructive
36
Symptoms of peripheral Arterial Disease
- Hairloss of legs and feet
- Numbness or weakness in the legs
- Brittle slow growing toenails
- Ulcers on feet and legs - non-healing
- Skin colour changes
- Shiny skin
- Painful numb limb
- Wounds and ulcers
- Gangrene
37
What is ischaemic heart disease and its syndromes? (4)
```
Cardiac muscle dysfunction due to inadequate blood supply to the myocardium
Syndromes:
Angina pectoris
Acute coronary syndrome
Sudden cardiac death
Chronic ischaemic heart disease
```
38
Describe MI gross morphology
< 24h - normal
1-2 days - pale, oedematous, myocyte necrosis, neutrophils
3-4 days - yellow with haemorrhage edge, myocyte necrosis, macrophages
1-3 weeks - red-grey to grey-white, pale, thin, granulation tissue then fibrosis
3-6 weeks - dense fibrous scar
39
Describe NSTEMI (Subendocardial MI)
- Can infarct without any acute coronary occlusion
- Normally relatively poorly perfused
- Need for oxygen cannot be met
40
What are the blood markers for cardiac myocyte damage (Cardiac enzymes) (5)
Troponins T&I
- detectable 2-3 hours after, peaks at 12-48 hours - detectable for 7 days post MI
Creatine Kinase MB - 2-3 hours after, peaks 10-24 hours and detectable up to 3 days
Myoglobin - peak at 2 hours and also released from damaged skeletal muscle
Lactate Dehydrogenase Isoenzyme 1 - peaks at 3 days detectable to 14 days
Aspartate Transaminase - also present in liver so less useful for cardiac damage
41
Describe MI Treatment
- M.O.N.A - Morphine, oxygen, nitrates and aspirin
- Reperfusion
- Ace-1, anti platelets and anticoagulation
- Anti-arrhythmics, beta-blockers
- Statins
42
What are some complications of MI?
- Arrhythmias, ventricular fibrillation
- Sudden death
- Myocardial rupture
- Cardiac mural thrombus and emboli
- Pericarditis
43
Describe familial hypercholesterolaemia
- Mutation in genes involved in cholesterol metabolism
- LDL receptor gene
- Apolipoprotein B
44
Describe left and right sided heart failure
Left - problems with pumping of blood outside the main circulation
Right - problems coming from the central circulation and pumping into the lungs
45
Describe Alzheimers disease and the two dominant genes
- Familial clustering 3 to 10 relative risk to second sibling
- Two genes dominant for Alzheimers - PSEN1 and PSEN2
- 95% multifactorial
- Most implicated because of heart disease gene APOE which has three alleles
E2 - protective effect
E3 - low risk
E4 - increased risk to 90%
- Mean age of consent decreases with increased risk from 84 to 68
46
Describe Linkage disequilibrium
- Most disease bearing chromosomes in populations are descended from a few ancestral chromosomes
- Can detect association <2-3 cM
- Careful selection of control groups in GWAS
47
What are the causes of cell death? (6)
```
Hypoxia
Physical agents - temperature, trauma, radiation
Chemical agents
Immunologic agents
Genetic rearrangements
Nutritional imbalance
```
48
What are the types of cell injury?
Reversible
- cell swelling, pallor, hydropic change, vacuolar degenerations
Irreversible
- mitochondrial swelling, lysosomes swells, damage to membranes and leakage of enzymes
Ischaemic Reperfusion Injury
- New damage on repercussion mediated by free oxygen radicals
49
What are the factors determining the outcome of injury?
- Ability of cells to replicate
| - Ability to rebuild complicit architectural structures
50
Describe labile cell populations
- High normal turnover
- Active stem cell population
- Excellent regenerative capacity
51
Describe stable quiescent cell populations
- Low physiological turnover
Turnover can massively increase if needed
- Good regenerative capacity
52
Describe the permanent cell populations
- No physiological turnover
- long life cells
No regenerative capacity
53
Describe organisation of cells (scar formation)
- The repair of specialised tissue by formation if a fibrous scar
- basic stereotyped pathological process
- Production of granulation tissue - acting as a scaffold of fibrin and removal of dead tissue by phagocytosis
- Granulation tissue contracts and accumulates collagen forming a scar - type 1 + 3
- organisation is a common consequence of pneumonia and infarction
Organised area = firm and puckered
54
Describe healing by first and second intention
```
First
- Clean surgical wounds
- Good haemeostasis
- Edges opposed with sutures or staples
Second
- Wound edges are not opposed
- Extensive loss of tissue
- More florid granulation tissue reaction
- More extensive scaring
```
55
Describe control of healing
- Blood coagulation and platelet degranulation releases growth factors which are chemotactic for macrophages
- Macrophages migrate into the wound and phagocytose bacteria and necrotic debris
- Growth factors are also released by platelets and activate basal epidermal cells
- Growth factor released forms dermal myofibroblastic cells, epidermal cells and saliva
- Nutrients, oxygen, hormones and growth factors diffuse in from blood supply and contribute to epidermal growth
- Lack of nutrients, inhibitors factor presence - infection, steroids, or poor blood circulation inhibit wound healing
56
Describe fracture healing
- Haemorrhage around and within the bone
- Haematoma is organised
- Removal of necrotic fragments
- Osteoblasts lay down disorganised woven bone (callus)
- Remodelling according to mechanical stress
- Replacement by more orderly lamellar bone
57
Describe healing of the brain
- Neurones are terminally differentiated
- Supporting tissue is glial cells rather than collagen and fibroblasts which can proliferate
- Damaged tissue is removed and often leave cyst
- Gliosis rather than scarring
58
Describe acute inflammation
- Initial response to injury
- Can last minutes, hours or days
- Characteristic is cell neutrophil polymorph
59
Describe the physical characteristics of acute inflammation
Rubor, calor, tumor, dolor, laesa
60
What are the major components of acute inflammation?
1. Change in vessel calibre
2. Increased vascular permeability and fluid exudate formation
3. Cellular exudate formation
61
What is fluid exudate?
Extravascular fluid with a high protein concentration containing cellular debris
62
What is a transudate?
Low protein, little or no cellular component
63
What is pus?
Inflammatory exudate rich in neutrophils dead cell debris and microbes
64
Describe chronic inflammation
Inflammation of prolonged duration, concomitant tissue destruction and repair
65
Describe granulation/granulomatous tissue
- Collection of activated epithelioid macrophages
- Surrounded by mononuclear leukocytes
- May contain multinucleate giant cells
66
What is the treatment of paracetamol overdose?
- Activated charcoal
| - N-acetyl cysteine - L-cysteine Glutathione
67
What is suppuration?
Formation of pus in abscess
| - usually staphylococcus, streptococcus or gonococcus
68
What are prions?
Misfloded protein, no genetic material, can be inherited spread via contaminated material or occur spontaneously
69
What is cell wall of fungi made of?
Chitin
70
What is the cycle of infection?
```
Encounter
Entry
Spread
Evade Defence
Multiply & Damage
Disperse
```
71
Describe pneumococcal surface protein A
- Prevent complement mediated killing IgA protease
- Secretory immunoglobulin A found in mucosal secretions of respiratory and urogential tract
- Bind to pathogens to prevent them adhering to host tissues
72
What is Pneumolysin?
- Secreted by S.Pneumoniae
- Multiple monomers come together and bind to cholesterol in host plasma membrane
- Pore formation, host cell releases internal contents and dies
73
Describe Hyaluronidase & Neuraminidase's
- Enzyme capable of degrading hyaluronic acid, silica/neuraminic acid
- Both targets are components of interstitial cement in connective tissue or epithelial cells
74
Describe type 1 hypersensitivity
- IgE antibody mediated mast cell and basophil degranulation
- Degranulation causes histamine, proteases and chemotactic factors to be released
- Hayfever, asthma, hives etc
75
Describe type 2 hypersensitivity
- IgG mediated cytotoxic
- Directed against cell surface antigens mediates cell destruction via complement
- Blood transfusion reactions
76
Describe type 3 hypersensitivity
- Immune complex mediated
- IgG/ IgM against soluble antigen immune complex deposition
- Vasculitis
- Traditional cause of serum sickness
- Arthus reaction
77
Describe type 4 hypersensitivity
- Antigen specific T cell mediated cytotoxicity
- Sensitised Th1 cells release cytokines which activate macrophages or Tc cells which mediate direct cellular damage
- Contact dermatitis, tubercular lesions and graft rejection
78
What is an ulcer?
Local defect or excavation of surface of an organ or tissue that is produced by sloughing of inflammatory necrotic tissue
79
What are the causes of leg ulcers?
```
Vascular - Venous most common
Neuropathic
Inflammatory
malignant
Latrogenic
Infection
Metabolic
Traumatic
```
80
What is lipodermatosclerosis?
- Inflammatory skin condition resulting from underlying venous insufficiency
- resulting venous hypertension causing increased leukocytes within veins which migrate to surrounding tissues
- Leukocytes are activated and attract pro inflammatory cells and cytokines inducing a chronic inflammatory state
- Increased collagen production leading to fibrosis of subcutaneous fat
81
Describe pyoderma gangrenosum
- Inflammatory ulcer
| - One of a number of neutrophilic dermatoses
82
Describe pentoxifylline
Licensed for venous leg ulcers - 400mg BD-TDS
| - Increase microvascular blood flow thereby enhancing oxygenation of ischaemic tissue
83
What is the most allergenic drug in the anaesthetic cupboard?
Teicoplanin
84
Describe chlorohexidine anaphylaxis
- Causes 10-15% of all preoperative anaphylaxis
- Severe IgE mediated reactions
- Hidden allergen
85
Describe hyperammonaemia in the liver
- Liver unable to perform urea cycle to convert toxic ammonia to urea for excretion in urine
- Ammonia stimulates the respiratory centre causing hyperventilation and blows off CO2 leading to increased blood pH - respiratory alkalosis
86
Describe mechanisms of disease
1. accumulation of a toxin - hyperammonaemia + porphyrins
2. energy deficiency
3. deficient production of essential metabolite/structural component
87
Describe inborn errors of metabolism (IEM) diagnosis
- Pre symptomatic screening
- Investigations of symptomatic individuals
Test body fluids for abnormal metabolites
measure enzyme activity
Histochemical staining
DNA analysis
88
What are the 9 disorders screen for in newborns and what is screened for?
1. Congenital Hypothyroidism
2. Sickle cell and Hb disorders -
3. CF -
4. PKU - phenylketonuria
5. MCADD - medium chain acyl CoA dehydrogenase deficiency - acylcarnitines urine organic acid for confirmation
6. MSUD - maple syrup urine disease - leucine target for confirmation
7. IVA - isovaleric acidaemia - carnitine C5 for screening target
8. Homocystinuria - non-pyridoxine responsiveness -methionine screening target
9. GA1 - glutaric acuduria type 1 - glut aryl carnitine C5DC for screening target
89
What are porphyrins?
Natural chemicals made of proteins - making of haem for haemoglobin
90
What is treatment for hyperkalaemia?
- Correct the acidosis if this is the cause
- Stop unnecessary supplements/intake
- Give Glucose and insulin to drive potassium into cells
- Ion exchange resins
- Dialysis
91
Describe Base excess
Amount of acid or alkali to titrate blood pH to 7.40
Normal = purely respiratory disorder
Negative BE < -2.3 mmol/L - metabolic acidosis
Positive BE > 2.3 mmol/L - metabolic alkalosis
92
What is hyperplasia?
Increased number of cells caused by cell division - possible in labile and stable cell populations
93
What is atrophy?
- Reduction in size of organ or tissue by decrease in cell size and number
- Reduction in volume of individual cells and death of individual cells
94
What is agenesis?
Complete failure of organ to develop
95
What is aplasia?
Failure to maintain size or function
96
What is dysgenesis?
Abnormal organ development
97
What is hypoplasia?
Underdevelopment of tissue/ lack of cells
98
What is metaplasia?
- Transformation of one differentiated cell type into another
- Trans differentiation of stem cells
- Can affect epithelium and mesenchymal tissue
99
What is dysplasia?
- Earliest morphological manifestation of multistage process of neoplasia
- In-situ disease - non invasive
- Shows cytological features of malignancy but no invasion
100
What is anaplasia?
A neoplasm that is poorly differentiated and highly pleomorphic
101
What does pleomorphic mean?
A high number of cells that show variability in cell size and shape
102
Describe tumour stroma
Desmoplastic - stromal cells have different function to normal stoma - tumour stroma has a role in the hallmarks of cancer
103
Describe the effects of primary tumour invasion
- Invasion into and replacement of normal tissues
- Pressure on normal tissue, invade into blood vessel causing bleeding
- Growth into lumen causing obstruction
104
Describe the effects of distant tumour metastases
- Cause the same effects as a primary tumour in an alternative place
105
Describe the effects of paraneoplastic syndromes
- Signs and symptoms that are not related to the local effects of the primary or secondary tumours
- Develop as a result of proteins, hormones and secreted by tumour cells
- Immune cross reactivity between tumour cells and normal tissues
106
Describe the cancer prefix for: smooth muscle, skeletal muscle, adipose, blood vessel, bone, cartilage and fibrous tissue
```
Smooth muscle - leiomyo-
Skeletal muscle - rhabdomyo-
Adipose - lipo-
Blood vessel - angio-
Bone - osteo-
Cartilage - chondro-
Fibrous - fibro-
```
107
Describe homologous recombination in DNA repair
- Type of genetic recombination where genetic information is exchanged between two similar
- Used by cells to accurately repair harmful breaks that occur on both strands of DNA
108
Describe non-homologous end joining in DNA Repair
- Repairs double strands and breaks
- Break hands are directly ligated without the need for a homologous template
- Non-homologous end joining is the primary repair pathway used by cells when the experience DNA damage
- Prior to replication in G1 or early S phase this provides rapid but sometimes imprecise way to maintain genomic integrity
- Preferred repair pathway when cells reach later stages G2 + M phase sister chromatids are used as templates
- Kinases trigger activation of key gate keeper of genome P53
109
What is the key gate keeper of the genome and what activates it?
P53 tumour suppressor activated by kinases
110
What is genomic imprinting?
- Ensures functional non-equivalence of the maternal and paternal genomes
- Non encoded in the DNA nucleotide sequence
- Depends on modifications to the genome during gametogenesis
111
What is the transformation zone?
The area between original and new SCJ where the columnar epithelium has been and/or is being replaced by new metaplastic squamous epithelium
112
What are the risk factors for cervical intraepithelial neoplasms?
Women: HPV, first coitus<17 yrs, multiple sexual partners, long term oral contraception
Men: penile warts, multiple sexual partners, cervical cancer in previous partner
113
What is a colposcopy used for?
To diagnose cervical intraepithelial neoplasia and differentiate high grade lesions from low grade abnormalities
114
Describe Paget's disease in relation to the reproductive system
- 1% of vulval cancers
- Usually seen in 70 +
- Pruitus, burning, eczematous patch
- 30% of patients have synchronous or metachronus internal carcinoma - most common of breast of genitourinary system
115
What is triple assessment of breast lumps and describe each stage?
```
Clinical, Imaging and Pathology
Clinical:
- Mobile or fixed
- Well defined or not
- Smooth or irregular
- Firmness
- Location
- Nipple inversion/rash/discharge
- Tethering/retraction
- Oedema
- Ulceration/fungating lesion
```
Imaging:
- Ultrasound
- Fat - hypoechoic white
- Fibroglandular breast tissue - echogenic black
- Identify lesions: size, solid or fluid filled
- Mammogram
Pathology:
- Core biopsy
- Pathological examination
- Tissue embedded in wax before being cut ready for examination
- Cytology - fine needle aspiration to show some of the cells
116
Describe acquisition of motility and loss of adhesion
- Cell to cell adhesion molecule - cadherins, mutation causes reduced cell-cell adhesion
- Cell matrix adhesion molecule interns, mutation causes expression changes leading to decreases cell-matrix adhesion
117
Describe proteolytic enzymes
- Most important enzyme in neoplastic invasion is matrix metalloproteinases
- Secreted by malignant neoplastic cells
- Can digest 3 surrounding major connective tissue types
1. Interstitial collagenases - degrade type 1,2,3 collagen
2. Gelatinases degrade type 4 collagen and gelatin
3. Stromelysins degrade type 4 collagen and proteoglycans
118
Describe tumour stage
```
T- extent of tumour spread
T0 - no evidence of primary tumour
T1-T4 - increasing size/invasion of tumour
N - extent of nodal spread
N0 - no regional node metastases
N1-N3 - increasing involvement of nodes
M - presence or absence of distant metastases
M0 - no distant metastases
M1 - distant metastases
```
119
Describe tumour grade
How aggressive a tumour is
1. how much do the cancer cells resemble the normal tissue- differentiation
Well differentiated - low grade
Poorly differentiated - high grade
2. The variation in size and shape of the cancer cells - pleomorphisms
3. How many cells are actively dividing, can count mitotic figures - proliferation
120
Describe the evasion of growth suppressors in carcinogenesis
- Rb protein is key regulator of cell cycle by preventing progression from G1 to S phase
- Negative GFs inhibit progression of cell cycle by activating Rb protein
- Inactivation of Rb gene is common event in tumours and results in resistance to negative growth regulation
121
Describe avoiding of immune destruction in carcinogenesis
Binding of PD-1 and PD-L1 inhibit T cell from killing tumour cell
122
Describe enabling of replicative immortality in carcinogenesis
- Telomeres shrink with each cell cycle
- Telomere shortening in cancers does not follow the path its meant to so cells replicate for a much longer time that they usually would
123
What are the 9 hallmarks of carcinogenesis?
1. Sustaining proliferative signalling
2. Evading of growth suppressors
3. Avoiding immune destruction
4. Enabling of replicative immorality
5. Tumour Promoting inflammation
6. Activating invasion and metastasis
7. Inducing of angiogenesis
8. Resisting cell death
9. Deregulated metabolism
124
Describe proto-oncogenes
Normal genes that promote cell proliferation, survival and angiogenesis
- Encode for protein directly
- Involved in control of cell proliferation
- Allow for checkpoints to be overcome - Ras, myc
- Dominant
125
Describe oncogenes
Mutated versions/increased expression of proto-oncogenes causing increased/uncontrolled activity of expressed proteins
126
Describe 5 tumour suppressor genes
```
Act to maintain checkpoints, control genome stability
P53
Rb
APC
BRACA1/2
hMLH1/hMSH2
```
127
What are the typical investigations for a suspected ovarian tumour?
1. Refer urgently to gynaecology
2. Baseline bloods including LFTs
3. Serum CA125 tumour marker in ovarian cancer
4. Pelvic and abdominal ultrasound
5. CT pelvis and abdomen to confirm previous tests
128
Describe epithelial ovarian cancer and its symptoms
- Responsible for more deaths than any other gynaecological malignancy in the UK
- Presents late
Non-specific symptoms
- Weight loss
- Bloating
- Fatigue
- Urinary frequency increase
- PV bleeding
129
Describe teratomas
- Most common germ cell tumour
- Nearly all are benign
- Arise from oocyte once they have completed the first mitotic division
- Tumour that contains elements of all three germ cell layers
130
What is a dysgerminoma tumour and what can be used as a tumour marker?
Germ Cell tumour
Malignant, very rare
- LDH used as tumour marker, sensitive to chemotherapy
131
What is a yolk sac tumour and what can be used as a tumour marker?
Germ cell tumour
Malignant
- sensitive to chemotherapy
- Alpha-Feto protein used as tumour marker
132
What is a choriocarcinoma tumour?
Germ cell tumour Extremely rare and malignant
- Differentiation towards placenta
produces betaHCG as tumour marker
133
Describe sex cord stromal tumours
1. Thecoma/fibrothecoma/fibroma
- Benign
- Thecoma and fibrothecomas produce estradiol
2. Granulose cell Tumours
- Low grade malignant tumour producing estradiol
3. Sertoli Leydig cell tumours
- Produces androgens - 10-25% malignant
134
What is Meig's Syndrome?
Triad of ovarian tumour (fibroma) right sided pleural effusion and ascites
135
Describe BRAF inhibitors
- 50% of melanomas have somatic mutation in the BRAF gene
| - New target therapy vemurafenib recently showed a 48% response rate compared with 5% for standard chemotherapy
