1
Q
What are the 2 types of autopsy?
A
Hospital autopsies
Medico-legal autopsies
2
Q
What can medico-legal autopsies be classified into?
A
Coronial and forensic autopsies
3
Q
What are the 3 reasons for deaths being referred to a coroner?
A
Presumed natural, presumed iatrogenic, presumed unnatural
4
Q
Why would a presumed natural death be investigated?
A
Cause of death not known, not seen a doctor in last 14 days
5
Q
Why would a presumed iatrogenic death be performed?
A
Concern that patient’s care led to death
6
Q
Who performs autopsies and what sort of autopsy does each perform?
A
Histopathologists (coronial and hospital autopsies) and forensic pathologies (coronial autopsies)
7
Q
What questions does a coronial autopsy answer?
A
- Who was the deceased?
- When did they die?
- Where did they die?
- How did they die?
8
Q
What are 4 main laws during autopsy?
A
- Coroners Act 1988
- Coroners Rules 1984
- Amendment Rules 2005
- Coroners and Justice Act 2009
9
Q
Which law comes into place when coroner has finished with body?
A
Human Tissues Act 2004
10
Q
What does an autopsy consist of?
A
- History/scene
- External examination
- Evisceration
- Internal examination
- Reconstruction
11
Q
Describe acute inflammation
A
A reaction to injury or infection involving cells like neutrophils and macrophages
12
Q
What is inflammation?
A
A local physiological response to tissue injury
13
Q
How is acute inflammation classified?
A
Initial and often transient series of tissue reactions to injury. Sudden onset, short duration and usually resolves.
14
Q
How is chronic inflammation classified?
A
Subsequent and often prolonged tissue reactions following initial tissue response. Slow onset or sequel to acute, long duration and may never resolve.
15
Q
Which cells are involved in acute inflammation?
A
- Neutrophil polymorphs
- Macrophages
- Lymphocytes
- Endothelial cells
- Fibroblasts
16
Q
Which cells are first to present in acute inflammation?
A
Neutrophil polymorphs
17
Q
How do neutrophil polymorphs kill bacteria?
A
Cytoplasmic granules full of enzymes
18
Q
How do macrophages kill bacteria?
A
Phagocytosis
19
Q
Which cell type presents antigens to lymphocytes?
A
Macrophages
20
Q
What is the function of lymphocytes?
A
Immunological memory for past infections and antigens
21
Q
What cell type becomes sticky in areas of inflammation?
A
Endothelial cells, so inflammatory cells adhere to them
22
Q
What is the function of fibroblasts?
A
Form collagen in areas of chronic inflammation and repair
23
Q
What are the steps of acute inflammation?
A
- Initial reaction of tissue to injury
- Dilation of blood vessels
- Vascular leakage of protein-rich fluid
- Neutrophil polymorphs recruited to tissue
24
Q
What are the causes of acute inflammation?
A
- Microbial infections
- Hypersensitivity reactions
- Physical agents
- Chemicals
- Bacterial toxins
- Tissue necrosis
25
What infections is hypersensitivity important in?
Parasitic infections and TB inflammation
26
Give 3 examples of physical agents causing inflammation
Physical trauma, UV, burns, excessive cooling
27
What are the clinical manifestations of acute inflammation?
1. Rubor - redness
2. Calor - heat
3. Tumor - swelling
4. Dolor - pain
5. Loss of function
28
What is a granuloma?
An aggregate of epithelia histiocytes
29
What cells are involved in chronic inflammation?
1. Plasma cells
2. Lymphocytes
3. Multinucleate giant cell
4. Capillary endothelium
5. Macrophage
6. Fibroblast
30
What are the causes of chronic inflammation?
1. Primary chronic inflammation
2. Transplant rejection
3. Progression from acute inflammation
4. Recurrent episodes of acute inflammation
31
What are the clinical manifestations of chronic inflammation?
1. Chronic ulcer
2. Chronic abscess cavity
3. Thickening of wall of a hollow viscus
4. Granulomatous inflammation
5. Fibrosis
32
Describe the microscopic appearance on chronic inflammation
1. Cellular infiltrate [lymphocytes, plasma cells, macrophages, eosinophil polymorph]
2. Granulation tissue becomes fibrous tissue, tissue damage & necrosis
33
What are the systemic effects of acute inflammation?
1. Pyrexia
2. Weight loss,
3. Lymphadenopathy
4. Increased WBC count 5. Amyloidosis
34
What does healing involve?
Regeneration and migration of specialised cells
35
What are the features of repair?
Angiogenesis followed by fibroblast proliferation and collagen synthesis which forms granulation tissue
36
What regulates the cell proliferation processes in repair?
Growth factors
37
What 2 cell types are in lymphocytic tissue?
B lymphocytes and T lymphocytes
38
What happens when B lymphocytes contact antigens?
They transform into plasma cells
39
What is the function of plasma cells?
Antibody production
40
What happens when T lymphocytes contact antigens?
They produce cytokines
41
How do macrophages kill organisms?
Lysosomal enzymes
42
What happens when macrophages particulate in hypersensitivity reactions?
They die leading to necrosis
43
What is the mononuclear phagocyte system also called?
Reticuloendothelial system
44
What is a granuloma?
An aggregate of epithelioid histiocytes
45
Give an example of granulomatous disease
TB, leprosy
46
Describe epithelioid histiocytes
Large vesicular nuclei, plentiful eosinophilic cytoplasm, elongated
47
How are epithelioid histiocytes arranged?
In clusters
48
What is a secretory product of epithelioid histiocytes?
Angiotensin converting enzyme (ACE)
49
How is the appearance of granulomas augmented?
Presence of caseous necrosis or by conversion of histiocytes into multinucleate giant cells
50
What can association of granulomas with eosinophils indicate?
Parasitic infection
51
What is a feature of stimuli which induce granulomatous inflammation?
Indigestibility of particulate matter by macrophages
52
What could cause histiocytic giant cells to form?
Inert minerals e.g. silica, bacteria e.g. tubercle bacilli
53
When may histiocytic giant cells form?
When foreign particles are too large to be ingested by one macrophage, and 2+ fuse and unite
54
What histiocytic giant cell forms in TB?
Langhans' giant cells
55
What histiocytic giant cell are seen in particulate foreign body material?
Foreign body giant cells
56
What histiocytic giant cell are seen in dermatofibromas of skin?
Touton giant cells
57
When is acute inflammation involved in CVS?
In response to acute MI and some of its complications e.g. cardiac rupture
58
How is chronic inflammation involved in carcinogenesis?
Has a role in initiation and propagation of cancer and its progression
59
When is chronic inflammation involved in CVS?
In myocardial fibrosis following MI
60
Name a neurodegenerative disorder of the CNS which inflammation is involved in
Multiple sclerosis - perivascular cuffing by plasma cells and T lymphocytes is seen in zones of white matter where macrophages break down myelin
61
What is resolution?
Where a tissue is undamaged or able to regenerate, and the initiating factor has been removed
62
What is repair?
The initiating factor is still present, tissue is damaged and unable to regenerate
63
What happens when the liver is persistently damaged?
1. Cirrhosis
2. Fibrous scarring
3. Regenerative nodules
64
What can cause persistent damage to the liver?
Alcohol, hepatitis B/C
65
What is lobar pneumonia?
Acute inflammation of one lobe of the lungs full of neutrophil polymorphs
66
Describe abrasion
1. Heals well as haven't removed all of the epithelium
2. Scab forms over surface
3. Epidermis grows out from adnexa
4. Sweat glands and hair follicles remain intact
67
Describe healing by 1st intention
Looks white as collagen is present which is made by fibroblasts
68
Give an example of how healing by 1st intention occurs
Surgical wound
69
Describe healing by 2nd intention
1. Hair follicles removed
| 2. Fibroblasts make collagen so get bigger scar
70
Describe granulation tissue
1. Very big wound which looks granular as blood vessels grow up
2. Big scar with pale fibrous tissue
71
What is repair?
Replacement of damaged tissue by fibrous tissue
72
What produces collagen?
Fibroblasts
73
Which cells can regenerate?
1. Hepatocytes
2. Pneumocytes
3. All blood cells
4. Gut epithelium
5. Skin epithelium
6. Osteocytes
74
Which cells can't regenerate?
1. Myocardial cells
| 2. Neurons
75
What is laminar flow?
Cells travel in centre of arterial vessels and don't touch sides
76
What happens when the endothelium is damaged?
Platelet aggregation: platelets stick to epithelium and each other, releasing aggregating factors causing a positive feedback loop
77
What happens when laminar flow is disrupted?
RBC may get trapped into platelets
78
How is a fibrin mesh formed?
Fibrin deposition occurs as platelets release chemicals causing fibrinogen to form fibrin. This holds cells together in a fibrin mesh and can trap RBC
79
What is thrombosis?
The formation of a solid mass of blood constituents formed within intact vascular system during life
80
What are the components of the thrombosis triad?
1. Change in vessel wall
2. Change in blood flow (laminar to turbulent)
3. Change in blood constituents
81
How do thrombus form in veins?
If the endothelium becomes sticky, slow blood flow can cause thrombus formation when blood constituents touch the sticky endothelium
82
Why are pulmonary embolisms common in hospital?
Venous thrombus are common as people are bed bound
83
What is thrombus formation in veins called?
Stasis, due to slow blood flow
84
What is the prevention for thrombosis?
Exercise, stockings, aspirin
85
Why is aspirin prescribed to over 50s?
It inhibits platelet aggregation so a smaller embolism will form
86
What is an embolus?
The formation of a mass of material in vascular system able to become lodged within a vessel and block it
87
What is ischaemia?
Reduction in blood flow
88
What is infarction?
Reduction in blood flow with subsequent death of cells
89
What is a reperfusion injury?
When a patient has had ischaemia and blood is let back in, superoxide radicals are also let in which causes damage to cells
90
How can reperfusion injuries be prevented?
Keep patients in an induced coma when they are adjusting to having blood
91
Which organs have dual blood supply?
Lungs, liver, some parts of brain
92
Why is the heart more susceptible to infarction?
It is at the limit of 2 different blood supplies (watershed areas)
93
When does atherosclerosis tend to arise?
40-50 years old
94
What is the early stage of atherosclerosis?
Fatty streak - when macrophages fill with lipids
95
Where is atherosclerosis commonly found?
High pressure systems e.g. aorta and systemic arteries
96
What is in a plaque?
1. Fibrous tissue
2. Lipids - cholesterol
3. Lymphocytes
97
What are the common risk factors for atherosclerosis?
1. Smoking
2. Hypertension
3. Diabetes
4. Hyperlipidaemia
5. CHD in men
6. More deprived industrial areas of UK
98
What is the pathogenesis of atherosclerosis?
1. Endothelial cells are delicate, metabolically active and produce NO
2. Endothelial cells are damaged
3. Recurrent injuries to endothelial cells causes micro-haemorrhages which burst
99
What is the mechanism of damage from smoking?
Free radicals, nicotine, CO
100
How does hypertension cause atherosclerosis?
Shearing forces on endothelial cells esp. at bifurcation points
101
How does diabetes cause atherosclerosis?
Superoxide anions, glycosylation products
102
How does hyperlipidaemia cause atherosclerosis?
Direct damage to endothelial cells
103
What are some complications of atherosclerosis?
1. Cerebral infarction
2. Carotid atheroma
3. MI, cardiac failure
4. Acute aneurysms
5. Peripheral vascular disease with intermittent claudication
6. Gangrene
104
Why are blood clots rare?
1. Laminar flow
| 2. Endothelial cells aren't sticky when healthy
105
What is the first stage of thrombosis?
Platelet aggregation
106
What can be an embolism?
A thrombus break off, air, cholesterol crystals, tumour, amniotic fluid, fat
107
Where will the embolus travel if it enters the venous system?
To the vena cava, through the RHS of the heart and will lodge in pulmonary arteries
108
Where can the emboli travel if it enters the arterial system?
To anywhere downstream of its entry point
109
What usually causes infarction?
Thrombosis of an artery
110
What is apoptosis?
Programmed cell death
111
What happens in apoptosis?
1. Enzymes are released with a cell that cause it to shrink
2. Nucleus shrivels up
3. Organelles enter vesicles which are engulfed by macrophages
112
What is a common cause of apoptosis?
DNA damage e.g. UV in skin
113
What is the gatekeeper of the genome?
p53
114
What does p53 do?
Detects DNA damage and produces chemicals that may switch on apoptosis
115
What are caspases?
Enzymes which chew up things and are effectors of apoptosis
116
What caspase turns off apoptosis?
Bcl2
117
What caspase stimulates apoptosis?
Bax
118
Wha receptor and ligand are involved in switching on caspases?
Fas ligand and Fas receptor
119
Why is apoptosis needed in development?
Needed to make things work e.g. webbed fingers becoming digits
120
Why is apoptosis needed in normal function?
To remove cells at end of useful life in tissues with high cell turnover
121
What disease has a lack of apoptosis?
Cancers due to p53 mutation for example
122
What disease has too much apoptosis?
HIV/AIDS
123
What is necrosis?
Traumatic cell death affecting large areas of cells
124
Give clinical example of necrosis
1. Toxic spider venom
2. Frostbite
3. Cerebral infarction
4. Avascular necrosis of bone
5. Pancreatitis
125
Describe coagulative necrosis
Thick and gooey
126
Describe liquefactive necrosis
Thin and liquid
127
Describe caseous necrosis
Has multinucleate giant cells, looks like soft cheese and is linked with TB
128
What proportion of conceptions survive 1 month and why?
25%
| Chromosomal abnormalities
129
What are the degrees of exposed spinal cord at birth?
1. Spina bifida
2. Meningocele
3. Myelomeningocele
130
What causes heart murmur?
Ventricular spinal defect
131
What is a congenital condition? Give an example
Present at birth - could be genetic or not
| Club foot
132
What is an inherited condition? Give an example
Caused by an inherited genetic abnormality and may not manifest until later in life
Huntington's disease
133
Give an example of a chromosomal abnormality
Down's syndrome
134
What type of inheritance is linked to Mendelian inheritance?
Autosomal inheritence
135
What type of inheritance is linked to most genetic diseases?
Polygenic inheritance (multiple genes influence)
136
What is an acquired disease? Give an example
Caused by non-genetic environmental factors but may be congenital
Foetal alcohol syndrome
137
What genes can cause dwarfism?
COL2AI (type 2 collagen)
| Fibroblast growth factor receptor 3 gene
138
What is hypertrophy?
Increase in size of a tissue caused by an increase in size of constituent cells
139
What is the function of myostatin gene?
Forms a protein that stops muscles growing once they reach a certain size
140
What is an example of hypertrophy?
Making biceps bigger
141
What is hyperplasia?
Increase in size of a tissue caused by an increase in the number of constituent cells
142
Give an example of hyperplasia
Increase in number of smooth muscle cells in prostate
143
What is atrophy?
Decrease in size of a tissue caused by a decrease in number of constituent cells or a decrease in their size
144
Give an example of atrophy
Loss of brain tissue in Alzheimer's, muscle atrophy after bone breaks
145
What is metaplasia?
Change in differentiation of a cell from one fully differentiated type to a different fully differentiated type
146
Give an example of metaplasia
Ciliated columnar epithelium to squamous epithelium in bronchi of smokers
147
What is dysplasia?
Imprecise term for morphological changes seen in cells in progression to becoming cancer
148
Give an example of dysplasia
Focal cortical dysplasia
149
What allows DNA replication?
Telomeres
150
What happens to telomeres over time?
They shorten with each division so cells eventually stop dividing
151
What is progeria?
Premature ageing of children with short telomeres as cells can no longer divide prematurely
152
What causes damage?
1. Crosslinking proteins
2. Loss of Ca influx
3. Damage to mitochondrial DNA
4. Loss of DNA repair mechanism
5. Peroxidation of membranes
6. Free radical generation
7. Activation of ageing and death genes
8. Telomere shortening
9. Accumulation of toxic by-products of metabolism
10. Crosslinking or mutations of DNA
153
What can stop damage?
Calorific restriction
154
What causes dermal elastosis?
UV-B light protein cross linking causing collagen crosslinks and loss of elasticity
155
What causes osteoporosis?
1. Increased bone resorption
| 2. Decreased bone formation
156
Why is osteoporosis more common in women?
Due to the lack of oestrogen after menopause
157
What causes cataracts?
UV-B light protein crosslinking
158
What causes senile dementia?
1. Atrophy of brain
2. Neuronal loss
3. Plaques
4. Neurofibrillary tangles
159
What causes sarcopaenia?
1. Decreased growth hormone
2. Decreased testosterone
3. Increased catabolic cytokines
160
What causes deafness?
Loss of hair cells
161
Why can basal cell carcinoma of skin be cured?
It only invades locally
162
What causes basal cell carcinoma of skin?
UV light
163
What are the systemic symptoms of leukaemia?
Weight loss
Fever
Frequent infections
164
Name 10 other symptoms of leukaemia
1. Easy SOB
2. Muscle weakness
3. Bone/joint pain
4. Fatigue
5. Loss of appetite
6. Lymph node swelling
7. Spleen enlargement
8. Night sweats
9. Easy bleeding and bruising
10. Purplish patches or spots
165
What 2 types of leukaemia are treated with chemotherapy?
AKL
| AML
166
What type of cancer spreads from blood to bone?
Carcinomas
167
What cancers commonly spread to bone?
1. Breast
2. Prostate
3. Lung
4. Thyroid
5. Kidney
168
How can a breast cancer diagnosis be confirmed?
1. Mammograms
| 2. Core biopsy
169
What happens if breast cancer spreads to the axilla?
Axillary nodes are cleared
170
What would not be seen on scans following a tumour excision?
Micro metastases
171
What is adjuvant therapy?
Extra treatment given after surgical excision to prevent local recurrence
172
What therapy can improve survival and recurrence in breast cancer?
Anti-oestrogen therapy
173
How many breast cancers are HER2 positive?
20%
174
What is a side effect of anti-oestrogen therapy?
Premature menopause
175
What drug is used in HER2 positive breast cancers?
Herceptin
176
What is carcinogenesis?
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
177
What does carcinogenesis apply to?
Malignant neoplasms
178
What are carcinogens?
Agents known or suspected to cause tumours
179
Why are carcinogens known as mutagenic?
They act on DNA
180
What % of cancer risk is environmental?
85%
181
What are the main problems with identifying carcinogens?
1. Latent interval may be decades
2. Complexity of environment
3. Ethical constraints
182
Where is hepatocellular carcinoma common?
In areas with more hepatitis B/C and mycotoxins
183
Where is oesophageal cancer common?
Japan, China, Turkey, Iran
184
What are the risks oesophageal cancer?
Drinking very hot coffee, diet
185
What are the behavioural risks for lung cancer?
Smoking
| Blue asbestos
186
What are the occupational risks or bladder cancer?
Aniline dye in printing, rubber industries
187
What is the risk for scrotal cancer?
Polycyclic aromatic hydrocarbons in chimney sweeps
188
Radioactive iodine is a risk factor for which cancer?
Thyroid cancer
189
Thorotrast is a risk for which cancer?
Angiosarcoma
190
What are the issues with experimental models in cancer?
1. Bacterial mutation may not = carcinogenicity
| 2. Animals/cultures may metabolise agents differently to humans
191
What are the classes of carcinogens?
1. Chemical
2. Viral
3. Ionising and non-ionising radiation
4. Hormones, parasites and mycotoxins
5. Miscellaneous
192
What is the common metabolic conversion for chemical carcinogens?
Pro-carcinogens to ultimate carcinogenic
193
What can the metabolic conversion from pro-carcinogens to ultimate carcinogenic cause?
Cancer in a place different to the exposure site
194
What does exposure to UV-A or UV-B increase risk of?
Basal cell carcinoma, melanoma, squamous cell carcinoma
195
What is xeroderma pigmentosum?
Failure in the ability of DNA to repair mutations in skin
196
What does oestrogen increase the risk of?
Mammary/endometrial cancer
197
What do anabolic steroids increase the risk of?
Hepatocellular carcinoma
198
What does aflatoxin B1 (grain mould) cause?
Hepatocellular carcinoma
199
What cancer does Chlonorchis sinensis cause?
Cholangiocarcinoma (bile duct cancer)
200
What does Shistosoma cause?
Bladder cancer (SCC)
201
What are the host factors in carcinogenesis?
1. Race
2. Diet
3. Constitutional factors e.g. age, sex
4. Premalignant legions
5. Transplacental exposure
202
Why is oral cancer is more common in SE Asia?
Reverse smoking, betal chewing, chewing tobacco
203
Why is skin cancer less common in black people?
They have more melanin
204
Give 2 examples of cancers with inherited predisposition
1. Familial polyposis coli
| 2. Retinoblastoma
205
Name a cancer which is affected by gender?
Breast cancer (F:M 200:1)
206
What are premalignant conditions?
Identifiable local abnormalities associated with increased risk of malignancy at that site
207
Name a premalignant condition
1. Colonic polyps
2. Cervical dysplasia
3. Ulcerative colitis
4. Undescended testis
208
What is a tumour?
Any abnormal swelling
209
What can be classed as a tumour?
1. Neoplasm
2. Inflammation
3. Hypertrophy
4. Hyperplasia
210
What is a neoplasm?
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
211
Describe neoplasm
1. Autonomous
2. Abnormal
3. Persistent
4. New growth
212
What proportion of deaths do neoplasms account for?
20%
213
Where is borderline neoplasm commonly found?
Ovary
214
What cancer is often subclinical?
Thyroid cancer
215
Where do neoplastic cells derive from?
Nucleated cells
216
What is the function of stroma?
1. Supportive
2. Mechanical support
3. Nutrition
217
What does success as a neoplasm depend on?
Tumour angiogenesis
218
At what size does a neoplasm need a blood supply?
2mm
219
What drives the growth of tumour blood supply?
Vascular endothelial growth factor
220
Why must neoplasms be classified?
1. To determine appropriate treatment
| 2. To provide prognostic information
221
How can neoplasms be classified behaviourally?
1. Benign
2. Borderline
3. Malignant
222
How can benign tumour causes morbidity and mortality?
1. Pressure on adjacent structures
2. Obstruct flow
3. Production of hormones
4. Transformation to malignant neoplasm
5. Anxiety
223
Describe benign neoplasms
1. Localised, non-invasive
2. Slow growth rate
3. Low mitotic activity
4. Resemble normal tissue
5. Circumscribed or encapsulated
224
How do malignant neoplasms cause morbidity and malignancy?
1. Destruction of adjacent tissue
2. Metastases
3. Blood loss from ulcers
4. Obstruction of flow
5. Hormone production
6. Paraneoplastic effects
7. Anxiety and pain
225
What are the common features of malignant neoplasms?
1. Metastases
2. Invasive
3. Rapid growth rate
4. Poorly defined border
5. Increased mitotic activity
6. Variable resemblance to normal tissue
7. Poorly circumscribed
226
Describe the nuclei of malignant neoplasms
1. Hyperchromatic - darker than normal
| 2. Pleomorphic - different sized nuclei
227
What is histogenesis?
Specific cell of origin of a tumour
228
Where may neoplasms arise from?
Epithelial cells, connective tissues, lymphoid/haemopoietic organs
229
What is the suffix of neoplasms?
-oma
230
What is a papilloma?
Benign tumour of non-glandular non-secretory epithelium
231
What is an adenoma?
Benign tumour of glandular or secretary epithelium
232
What is a carcinoma?
Malignant tumour of epithelial cells
233
What is an adenocarcinoma?
Carcinoma of glandular epithelium
234
How are benign connective tissue neoplasms named?
According to the cell of origin and are suffixed by -oma
235
What is a lipoma?
A benign neoplasm of adipocytes
236
What is a chondroma?
A benign neoplasm of cartilage
237
What is an osteoma?
A benign neoplasm of bone
238
What is an angioma?
A benign vascular neoplasm
239
What is a rhabdomyoma?
A benign neoplasm of striated muscle
240
What is a leiomyoma?
A benign neoplasm of smooth muscle
241
What is a neuroma?
A benign neoplasm of nerves
242
How is a malignant connective tissue neoplasm named?
Sarcoma prefixed by cell type of origin
243
What is an anaplastic tumour?
Where the cell type of origin of a tumour is unknown
244
What is a malignant neoplasm of melanocytes called?
Melanoma
245
What is a malignant tumour of mesothelial cells called?
Mesothelioma
246
What is a malignant neoplasm of lymphoid cells called?
Lymphoma
247
What is a carcinoma in situ?
When a membrane is full of cancer cells but they haven't invaded anywhere else
248
How do cancer cells cross the basement membrane?
With proteases
249
What is the function of collagenases in intravasation?
Chew through vessel walls to allow the tumour to enter it
250
How do tumours evade the host immune defence?
1. Aggregation with platelets
2. Shed surface antigens
3. Adhesion to other tumour cells
251
What contributes to extravasation?
1. Adhesion receptors
2. Collagenases
3. Cell motility
252
What is needed to allow vessel growth?
Angiogenesis promotors
253
What are the angiogenesis inhibitors?
1. Angiostatin
2. Endostatin
3. Vasculostatin
254
Where does a tumour in the lower body often metastasise to?
Lungs
255
What is it called when metastases in the lungs break off and metastasise to further sites?
Cannonball metastases
256
What sort of tumour often metastasise to the lungs?
Sarcomas and any common cancers
257
Which tumours commonly metastasise to the liver?
Colon
Stomach
Pancreas
Carcinoid tumours of intestine
258
Which tumours commonly metastasise to bone?
Prostate, breast, thyroid, lung, kidney
259
What are some common side effects of chemotherapy?
1. Myelosuppression
2. Hair loss
3. Diarrhoea
260
Which chemotherapies work by binding directly to DNA to inhibit DNA synthesis crosslinking?
1. Ifosamide
| 2. Cisplatin
261
How does Vinblastine work?
Binds microtubules to stop them contracting
262
How does etoposide work?
Inhibits topoisomerase II so it can't replicate DNA
263
What contribute to tumour size increases?
1. Cell division
| 2. Lack of apoptosis
264
What type of tumour is conventional chemotherapy useful for?
Fast dividing tumours (most)
265
What are the benefits to targeted chemotherapy?
1. More effective
| 2. Less side effects
266
What techniques can be used to differentiate between normal and cancer cells?
1. Gene arrays
2. Proteomics
3. Tissue microarrays
267
What is cetuximab?
A monoclonal antibody against epidermal growth factor receptor
268
What is the effect of tyrosine kinase activity on EGFR?
1. Epidermal GF binds
2. IC signalling proteins released
3. Transcriptional upregulation
4. Proliferation
5. Angiogenesis
6. Cell motility/invasion
269
What is herceptin?
A monoclonal antibody against human epidermal growth factor receptor 2: Her2
270
What is the result of over expression of HER2 in breast cancer?
1. Increased dimerisation
| 2. More IC signalling proteins so more transcriptional upregulation so more proliferation
271
What drug causes endocytosis of Her2?
Herceptin
272
How common is HER2 gene amplified in breast cancer?
20-30% of cases
273
What are the characteristics of a HER2 upregulated tumour?
1. Large size
2. High grade
3. Aneuploidy
4. Negative oestrogen receptor status
5. Independent adverse prognostic factor
274
What is an adjuvant therapy?
When a drug e.g. herceptin is given following tumour removal to eliminate any remaining metastases
275
What is gleevec?
An inhibitor of c-kit tyrosine kinase
276
What can gleevec treat?
Chronic myelogenous leukaemia
