Growth, Cell Death and Neoplasia Flashcards
1
Q
define apoptosis
A
programmed cell death
2
Q
define necrosis
A
traumatic cell death - unintended cell death in response to cellular injury
3
Q
why do we need apoptosis?
A
for continuous renewal of cells, working alongside mitosis
4
Q
name some inhibitors of apoptosis
A
growth factors
extracellular cell matrix
sex steroids
some viral proteins
5
Q
name some inducers of apoptosis
A
growth factor withdrawal loss of attachment of ECM glucocorticoids some viruses free radicals ionising radiation DNA damage
6
Q
give some examples of when apoptosis is crucial for normal growth - and what occurs if apoptosis fails
A
separating of fingers - interdigital cell death - syndactyl (webbed fingers)
removal of redundant epithelium on fusion of palatine processes in roof of mouth - cleft palate
7
Q
what is coagulative necrosis?
A
most common.
dead tissue is swollen and firm, then later becomes soft - digestion of macrophages
8
Q
what is colliquative (liquefactive) necrosis?
A
occurs in brain due to lack of supporting stroma - necrotic tissue liquefies
9
Q
what is caseous necrosis?
A
dead tissue is completely structureless. histology shows amorphous eosinophilic area with haematoxyphilic nuclear debris.
seen in TB.
10
Q
what is gangrene?
A
necrosis with putrefaction of tissues. tissues appear black.
11
Q
what is fibrinoid necrosis?
A
occurs in malignant hypertension - increased arterial pressure results in necrosis of SM wall.
eosinophilic and fibrinous deposits seen.
12
Q
what is fat necrosis?
A
focal adipose tissue destruction due to direct trauma, or enzymatic lipolysis (seen in acute pancreatitis)
13
Q
define hypertrophy
A
increase in size of a tissue caused by increase in SIZE of the constituent cells
14
Q
define hyperplasia
A
increase in size of a tissue caused by an increase in NUMBER of constituent cells - decrease in apoptosis
15
Q
define atrophy
A
decrease in size of a tissue caused by a decrease in NUMBER or SIZE of constituent cells - apoptosis
16
Q
define metaplasia
A
change in differentiation of a cell from one fully-differentiated type to another
17
Q
define dysplasia
A
morphological changes seen in cells in the progression to becoming cancer
18
Q
give some examples of physiological hypertrophy/hyperplasia
A
muscle hypertrophy in athletes - in limbs and LV of heart.
hyperplasia of breast tissue at puberty and in pregnancy/lactation.
hypertrophy and hyperplasia of uterine smooth muscle at puberty/pregnancy.
19
Q
give some examples of conditions involving pathological hypertrophy/hyperplasia
A
RVH/LVH.
gynaecomastia.
prostate hyperplasia.
follicular epithelial hyperplasia e.g. in Graves’ disease (thyroid)
20
Q
define congenital
A
present at birth - not necessarily inherited, foetus is affected by environmental factors in womb (eg FAS)
21
Q
give some examples of changes to the body that are typical of ageing
A
loss of dermal elastosis osteoporosis cataracts senile dementia sarcopaenia (loss of skeletal muscle mass/strength) deafness
22
Q
define carcinogenesis
A
transformation of normal cells to neoplastic cells through permanent genetic alterations or mututations
- malignant tumours
23
Q
define oncogenesis
A
formation of benign and malignant tumours
24
Q
define carcinogen
A
agents known/suspected to cause cancer - malignant tumours.
act on DNA - mutagenic
25
define oncogenic
agents known/suspected to cause tumours - benign or malignant
26
what problems are presented by attempts to identify carcinogens?
latent interval may be decades.
environment is complex - difficult to isolate one factor.
ethical constraints - can't deliberately give people a suspected carcinogen as part of a study
27
list the classes of carcinogen
```
chemical
viral
ionising/non-ionising radiation
hormones, parasites and mycotoxins
misc.
```
28
define neoplasm
lesion resulting from autonomous (or relatively autonomous) abnormal growth of cells which persists after the initiating stimulus has been removed
A NEW GROWTH
29
what are the features of neoplasia?
autonomous
abnormal
persistent
new growth
30
what makes a neoplasm malignant?
if they invade surrounding tissues, and are able to metastasise/spread to other tissues
31
describe the structure of solid tumours
neoplastic cells + stroma
32
what induces stroma formation in a tumour?
connective tissue fibroblast proliferation is induced by growth factors produced by tumour cells
33
why is angiogenesis needed in tumours?
to perfuse the tumour, allowing it to grow - without angiogenesis, tumour may only grow to 1-2mm diameter
34
what induces angiogenesis in tumours?
vascular endothelial growth factor (VEGF) - secreted by tumour cells
35
describe the features of a neoplastic cell
derived from nucleated cells, usually monoclonal.
growth pattern relates to parent cell.
synthetic activity relates to parent cell - production of collagen/mucin/keratin/hormones etc
36
describe the features of a benign neoplasm
localised, non invasive.
slow growth rate, low mitotic activity.
closely resembles normal tissue.
necrosis/ulceration rare.
37
how might benign neoplasms cause problems?
```
pressure on adjacent structures.
obstruction of flow.
production of hormones.
transformation to malignant neoplasm.
anxiety.
```
38
describe the features of a malignant neoplasm
invasive.
metastases.
rapid growth rate.
variable resemblance to normal tissue - closer resemblance = better prognosis.
poorly defined/irregular border.
hyperchromatic nuclei, increased mitotic activity.
necrosis/ulceration common.
39
how might malignant neoplasms cause problems?
```
destruction of adjacent tissue.
metastases.
blood loss from ulcers.
obstruction of flow.
hormone production.
paraneoplastic effects.
anxiety.
```
40
what is a papilloma?
benign tumour of non-glandular, non-secretory epithelium.
| prefix with cell type of origin.
41
what is a squamous cell papilloma?
benign tumour of squamous cell (non-glandular, non-secretory) epithelium
42
what is an adenoma?
benign tumour of glandular or secretory epithelium.
| prefix with cell type of origin.
43
what is a colonic adenoma?
benign tumour of colonic epithelium
44
how would you refer to a benign tumour of thyroid epithelium?
thyroid adenoma - benign, secretory/glandular epithelium
45
what is a carcinoma?
malignant tumour of epithelial cells.
| prefix by name of epithelial cell type.
46
what is an adenocarcinoma?
malignant tumour of glandular epithelium
47
how are benign connective tissue neoplasms named?
cell of origin, suffix -oma
48
what is a lipoma?
benign neoplasm of adipocytes
49
what is a chondroma?
benign neoplasm of cartilage
50
what is an osteoma?
benign neoplasm of bone
51
what is an angioma?
benign vascular neoplasm
52
what is a rhabdomyoma?
benign neoplasm of striated muscle
53
what is a leiomyoma?
benign neoplasm of smooth muscle
54
how are malignant connective tissue neoplasms named?
'sarcoma' prefixed by cell type of origin
55
what is a liposarcoma?
malignant tumour of adipose tissue
56
what is a rhabdomyosarcoma?
malignant tumour of striated muscle
57
what is a leiomyosarcoma?
malignant tumour of smooth muscle
58
what is a chondrosarcoma?
malignant tumour of cartilage
59
what is an osteosarcoma?
malignant tumour of bone
60
what is an angiosarcoma?
malignant tumour of blood vessels
61
what does anaplastic mean?
cell-type of origin of a carcinoma/sarcoma is unknown
62
how are carcinomas/sarcomas further classified, apart from by cell type of origin?
according to degree of differentiation
63
what is screening?
process of identifying apparently healthy people who may be at risk of a disease or condition - then offering info, tests and/or treatment
64
what are the four principles of screening to be considered in developing a screening programme?
1. knowledge of disease - important condition, recognisable early/latent stage, course of disease understood.
2. knowledge of test - suitable and acceptable test. continuous case finding.
3. treatment for disease - acceptable, available
4. cost considerations - cost of screening balanced by savings
65
what is meant by the "sensitivity" of a screening test?
how successful was the test at identifying all those with cancer/condition screened for?
true positives divided by true positives + false negatives
66
what is meant by the "specificity" of a screening test?
how well did the test identify all those without cancer/condition screened for?
true negatives divided by false positives + true negatives
67
what is meant by the "positive predictive value" of a screening test?
how accurate was the selection of cases believed to have the condition screened for?
true positives divided by sum of true and false positives
i.e. what percentage of positive results were accurate
68
what is the incidence rate of a disease?
the number of new cases per population at risk in a given time period
69
what is the mortality rate of a disease?
measure of the number of deaths due to a specific cause in a population, per unit of time
70
describe some limitations of screening
1. reduces risk of developing condition, but doesn't offer guaranteed protection.
2. false positives/negatives
3. misinterpretation/false results leading to false sense of security
4. cost to society/individuals - funds directed away from other services
71
what cancers commonly spread to bone?
breast, prostate, lung, thyroid, and kidney
72
what sort of cancers are treated well by conventional chemotherapy? list some.
```
fast dividing tumours:
germ cell tumours of testis;
acute leukaemias;
lymphomas;
embryonal paediatric tumours;
choriocarcinoma
```
73
what are the issues with conventional chemotherapy? what side effects does this commonly cause?
not selective for tumour cells.
hits normal cells which are dividing:
myelosuppression; hair loss; diarrhoea
74
what is targeted chemotherapy?
exploits some difference between cancer cells and normal cells to target drugs specifcally at the cancer cells - more effective, fewer side effects
75
describe the 'two-hit hypothesis' of cancer
first 'hit' is inheritance of a defective allele of a tumour suppressor gene, the other allele being normal.
second 'hit' is acquired mutational loss of function of normal allele - cell has lost all tumour suppressive function.
76
what are tumour suppressor genes? how are they classified?
genes that inhibit carcinogenesis.
| divided into 'gate-keepers' and 'caretakers'
77
describe how caretaker tumour suppressor genes act
maintain the integrity of genome by repairing DNA damage
78
describe how gatekeeper tumour suppressor genes act
inhibit the proliferation of, or promote death of, cells with damaged DNA
79
name some examples of tumour suppressor genes
gatekeepers - p53, APC
| caretakers - BRCA1, BRCA2
80
what is the p53 gene?
gatekeeper tumour suppressor gene.
| transcription factor that responds to DNA damage - mutated in c.50% of human cancers
81
where is the p53 gene located?
short arm of chromosome 17
82
what are the normal functions of p53 protein?
enable repair of damaged DNA before S phase in cell cycle, by arresting cycle in G1 until damage is repaired.
enable apoptotic cell death if there is extensive DNA damage.
83
what is the important consequence of loss of function of p53?
cells with damaged DNA (inc. mutated oncogenes or TSGs) undergo mitosis instead of apoptosis.
84
how are oncogenes classified? (5 groups)
growth factors;
receptors for growth factors;
signalling mediator with tyrosine kinase activity;
signalling mediator with nucleotide binding activity (disrupting intracellular signalling);
nuclear-binding transcription factor oncoproteins - involved in regulation of cellular proliferation
85
how may oncogenes be activated?
by mutation;
| by excessive production of a normal oncoprotein
86
list a few oncogene examples and how they function
sis - growth factor (PDGF)
erb-B - receptor (for EGF)
src - intracellular signalling (protein-tyrosine kinase)
87
define a somatic mutation
mutations that develop after conception in any cell of the body, and are passed down only to daughter cells of that original cell
88
define a germline mutation
germline mutations are present in the germ cells at birth and are passed down from generation to generation
89
list factors that influence tumour invasion
decreased cellular adhesion.
secretion of proteolytic enzymes.
abnormal/increased cellular motility.
90
what is the role of matrix metalloproteinases in neoplastic invasion?
secreted by malignant neoplastic cells, enabling them to digest surrounding connective tissue
91
what counteracts the action of matrix metalloproteinases?
tissue inhibitors of metalloproteinases (TIMPs) - net effect determined by balance of TIMPs and metalloproteinases.
92
what is "pagetoid infiltration"?
invasion within epithelium
93
what is the significance of invasion?
most important criterion for malignancy.
| metastases are a consequence of invasion.
94
what is metastasis?
the process of malignant tumours spreading from the primary tumour to form other, secondary tumours at distant sites
95
define carcinomatosis
extensive metastatic disease
96
what are the 6 steps involved in the metastatic sequence?
1. detachment of tumour cells from neighbours
2. invasion of surrounding connective tissue to reach blood/lymph vessels
3. intravasation into lumen of vessels
4. evasion of host defences (e.g. NK cells in blood)
5. adherence to endothelium at remote location
6. extravasation of cells from vessel lumen into surrounding tissue
97
describe the possible routes of metastasis
1. haematogenous - by blood stream
2. lymphatic - secondary tumours in regional lymph nodes
3. transcoelomic - in pleural/pericardial/peritoneal cavities - neoplastic effusion
4. implantation - accidental spillage of tumour cells in surgery
98
what types of metastatic spread do carcinomas and sarcomas prefer, respectively?
```
carcinomas = lymphatic
sarcomas = haematogenous
```
99
describe what the term "tumour grade" means
an assessment of the degree of malignancy or aggressiveness of a tumour -assessed histologically
100
list the most important features contributing to tumour grade
mitotic activity.
nuclear size, hyperchromasia and pleomorphism.
degree of resemblance to normal tissue (i.e. differentiation)
101
what does the "tumour stage" describe?
the extent of spread
102
what do the letters and numbers stand for in the TNM staging system?
T = primary tumour. number indicates tumour size/local extent. number varies with organ harbouring tumour.
N = lymph node status. number indicates number of lymph nodes/groups of nodes containing mets.
M = anatomical extent of distant metastases
TNM is then used to derive a stage score.
103
what is meant by a "stage 1" or "stage 4" cancer?
varies with type of cancer. derived from TNM status.
stage 1 = confined to organ of origin.
stage 4 = disseminated widely.
