Cancer Flashcards
1
Q
How do tumour cells degrade ECM
A
secrete metaloproteases to break down collagen
2
Q
what treatments target the tumour cells genome instability and mutation
A
PARP inhibitors
2
Q
Staging system of tumours
A
TNM T - T0-T4 = indicates increasing size and/or local extent of the primary tumour N - N0-N3 = regional lymph node metastases M - Mo-M1 = absence or presence of distant metastases X - unable to be assessed or unknown
3
Q
the tumours microenvironment is important for what?
A
- important for establishment and growth of metastases
3
Q
how do mutations in cells occur for cancer
A
- carcinogenic agents: microbes, radiation, chemicals - inherited - normal mistakes in normal DNA replication that is not repaired - sustained cell proliferation from any cause can increase risk
3
Q
once a diagnosis of malignancy is made, we need to know what extra stuff?
A
specific tumour type and subtype (cell lineage) grade stage presence of lymphovascular invasion
4
Q
What is the general function of p53
A
regulates the expression of cell cycle factors (the guardian of the genome)
5
Q
what histological feature is typical of epithelial tumours
A
keratinization
5
Q
a mutation in an oncogene leads to
A
uncontrolled accerlerated growth
5
Q
What does p53 specifically do?
A
Responds to mutations/cellular stress and directs the cell to: - undergo apoptosis - arrest cell cycle - DNA repair - differentiation - sequescence
5
Q
mechanisms that regulate TSG expression
A
- miRNA - methylation
5
Q
What treatment targets the replicative immortality of tumour cells
A
Telemoerase inhibitors
6
Q
death often results from malignant tumour due to:
A
- cachexia - secondary infection related to poor nutrition, effects of treatment - damage to vital organ or system by either primary or secondary tumour
7
Q
What class of genes are BRCA1 and BRCA2
A
DNA repair genes
7
Q
Difference between mutation and polymorphisms
A
Mutation - change in DNA away from normal (rare and abnormal varient) Polymorphism - sequence variation that is common in the population (no single allele is recognised as the standard sequence)
7
Q
Telomeres and cancer?
A
Some tumour cells reactivate telomerase - thus starving off mitotic catastrophe and achieving immortality
8
Q
definition of neoplasia
A
excessive and unregulated cell proliferation
8
Q
adeno: squamous: leiomyo: osteo:
A
adeno: glandular squamous: squamous cell Leiomyo: Smooth muscle Osteo: osteoblastic
8
Q
Questions you must ask yourself when diagnosing a lesion
A
Neoplastic or non-neoplastic Begnign or malignant Epithelial, mesenchymal? Primary versus metastatic
9
Q
which cancers can lead to inappropriate ADH syndrome
A
SCC
9
Q
how can lung cancer predispose to lung infection
A
cancer blocks the bronchus –> leading to pneumonia, collapse or bronchiectasis in the distal lung as you cannot clear the alveoli
10
Q
what is the difference between histopathology and cytology
A
cytology - don quite see the relationship between cells as easily
12
Q
6 main hallmarks of cancer
A
- sustaining proliferative signaling - evading growth suppressors - activating invasion and metastasis - enabling replicative immortality - inducing angiogenesis - resisting cell death
12
Q
What treatments target the tumour cell resistance of cell death
A
pro-apoptotic BH3 mimetics
13
At what stage of tumour growth is the rate of growth the fastest
when the tumour is vascularised but with no necrosis
13
main types of lung cancer in order
adenocarcinoma, Small cell carcinoma, squamous cell carcinoma, large cell carcinoma
15
where does neoplasia normally start?
in stem cells or progenitor cells
17
suffix for a benign tumour
oma
17
what is a premalignant lesion?
cells that are not yet malignant but there is a reasonable chance of them becoming malignant
18
how do cancer cells evade apoptosis
- reduced CD95 level (Fas receptor) - inactivation of death-induced signaling complex by FLICE protein - up-regulation of BCL2 - reduced levels of pro-apoptotic BAX resulting from loss of p53 - loss of APAF-1 - upregulation of inhibitors of apoptosis
20
mutations that cause cancer occur in which types of genes (broadly)
cell proliferation apoptosis DNA repair
20
definition of a malignant tumour
locally invasive, destructive growth, often poorly circumscribed
20
which cancers can lead to hypoglycaemia
ovarian cancer fibroma
21
EGFR mutations are particularly present in which population
young, non or light smoking female Asians with low-stage disease
22
What treatment targets the sustained proliferative signalling of tumour cells
EGFR inhibitors
24
What are the 2 hallmarks of emerging tumour development
deregulating cellular energetics Avoiding immune destruction
25
What are the 2 characteristics enabling tumour formation
Genome instability and mutation Tumour-promoting inflammation
27
main defining features of a benign tumour
- well circumscribed - local - usually well differentiated cells (look similar to mature cells) - unable to metastasise
28
Leading cancer that causes death in Victoria
Lung cancer
29
alternative names for premalignant lesion
dysplasia intraepithelial neoplasia
29
What are the oncogenic factors that can result in abnormal cell proliferation
the growth factor The receptor The proteins involved in signal transduction Cell cycle regulators
31
what does anaplastic mean
completely undifferentiated cell
33
examples of TSGs
P53 Rb APC PTEN
35
common sites of metastases
brain, liver, lung, colon
37
how does metastases spread
- lymphatics - haematogenous - transcoelomic (along pericardial, pleural or peritoneal cavities)
37
What is a homogenous stained region of a chromosome
Where there is many copies of the same gene on one chromosome leading to amplification of the expressed protein
37
order of the histopathological changes seen up until invasive lung carcinoma
- goblet cell hyperplasia - reserve cell hyperplasia - squamous metaplasia - squamous dysplasia - carinoma in situ - invasive carcinoma
38
clinical presentation of lung tumour
Cough Haemoptysis Wheeze Dyspnoea Pneumonia Pancoasts syndrome
40
a mutation in a TSG leads to
Uncontrolled continuous growth
40
histopathological features of squamous cell carcinoma
shows stratified squamous and keratinized whirls, often with a lot of eosinophilic cytoplasm
41
how is grading of a tumour decided
determined by the extent to which the tumour cells resemble their normal counterparts histologically (well differentiated, moderately differentiated, poorly differentiated, aplastic)
42
histopathological features of adenocarcinoma
cells try and form a lumen like gland
43
function of shortened teleomeres
eventually activate cell cycle checkpoings, leading to senescene and placing a limit on the number of divisions a cell may undergo
44
what does tumour stroma consist of?
fibroblasts, ECM, endothelial cells, immune cells, soluble molecules
44
definition of loss of heterozygosity
loss of normal function of one allele of a gene in which the other allele was already inactivated
45
Function of miRNA
Non coding ss RNA that function as negatie regulators of genes
47
main defining features of a malignant tumour
- frequently induce desmoplasia in stroma as they invade - sometimes necrosis (from tumour outgrowing blood supply) - variable differentiation: well, moderate, poor or anaplastic - potential to metastasise
48
what do traditional chemotherapy drugs aim to do
interfere with cell division - including normal cells
49
features of cytological atypia
- larger nuclei - pleomorphic nuclei - coarser nuclear chromatin - hyperchromatic nuclei - larger more prominent nucleoli - more mitotic activity with abnormal mitotic figures
51
definition of a benign tumour
local expansile, generally slow growing, often (not always) well circumscribed (+- encapsulated)
52
Definition of oncogene
mutant versions of proto-oncogenes that function autonomously without requirements for normal growth-promoting signals
53
Which hormone imbalance leads to cushings syndrome
ACTH
55
Definition of proto-oncogene
Normal cellular genes whose products promote cell proliferation
56
histopathological features of small cell carcinoma
cells are small (not particularly pleomorphic), very different looking to normal cancer cells
57
what do targeted therapies for cancer do?
block the growth of cancer cells by interfering with the function of specific molecules resulting from genetic alterations that drive carcinogenesis and tumour growth
58
which cancers can lead to hypercalcaemia
SCC breast carcinoma renal cell carcinoma adult T cell leukaemia/lymphoma
60
histopathological features of neoplasia
cytological atypia and architectural disorganisation
61
what histological feature is typical of adenocarcinoma
cells trying to form lumina (look like glands)
62
2 ways cytology can be gained
fine needle aspiration exfoliative cytology
63
what does staging incorporate
- the size or depth of invasion - local extent of primary tumour and location - extent of metastases
64
2 specific mutations that lead to non-small cell carcinomas (primarily adenocarcinoma)
EGFR ALK
66
definition of dysplasia
abnormality of development, alteration in size, shape and organisation of cells
67
What is the cause for familial predisoposition to developing tumours
the individual inherits one defective copy of TSG and loose the second one through somatic mutation
68
small cell carcinoma is an example of what
neuroendocrine carcinoma
70
what is the cause for familial retinoblastoma
Germiline mutation of one allele of the retinoblastoma (RB1) gene, and a mutation of the other allele later gives rise to clinical cancer at very young age
71
What are the 4 classes of normal regulatory genes that are the prinicpal targets of genetic damage leading to tumour formation
-growth promoting proto-oncogenes - growth-inhibiting tumour suppressor genes - genes that regulate programmed cell death - genes involved in DNA repair
72
factors secreted by tumour cells to allow angiogenesis
VEGF
73
what treatments target angiogenesis of tumour cells
inhibitors of VEGF signalling
74
macroscopic look of lung carcinoma
pale mass, irregular, may be associated with a bronchus, may be necrotic
75
suffixes for a malignant tumour
carcinoma: epithelial sarcoma: mesenchymal
76
definition of oncoproteins
proteins encoded by oncogenes
77
which cancers can lead to polycythaemia
renal carcinoma hepatocellular carcinoma
79
main cancers of paediatrics
- certain leukemias - certain brain tumours - neuroblastoma - Wilm's tumor - certain lymphos - rhabdomyosarcoma - retinoblastoma - certain bone cancers
80
what treatment targets the deregulating cellular energetics of tumour cells
Aerobic glycolysis inhibitors
82
Number of alleles needed to be affected with oncogenes and TSGs
Oncogenes - only 1 allele needs to be mutated TSG - both alleles need to be mutated
83
2 main categories of targeted therapy for cancer
- small molecules that inhibit growth factor Rs or tyrosine kinase - monoclonal antibodies that target specific proteins or receptors
84
What treatment targets the activation of invasion and metastasis
inhibitors of HGF/c-Met
85
How does bone pain occur from metastases
Related to hypercalcaemia
86
What treatment targets the tumour promoting inflammation
selective anti-inflammatory drugs
87
which hormone imbalance leads to hypoglycaemia in cancers
insulin
88
which cancers can lead to Cushing's sundrome
SCC pancreatic cancer
89
How many of the major classes of normal regulatory genes need to be involved in the initation of a tumour
All 4 in most cases
90
Staging of a tumour cell refers to
the progression of the malignancy in terms of local spread and metastasis
91
Types of mutations involved in cancer
- errors in DNA replication not repaired - point mutations - amplification of oncogenes - chromosomal rearrangements
93
what is does the grade refer to in malignant tumours
the differentiation of the cells within the tumour
94
a grade 3 tumour usually refers to
in situ carcinoma
96
Examples of oncogenes
Her2-neu Ras Myc
97
4 things that need to occur for metastasis
1. Detachment of tumour cells from each ther 2. Degradation of ECM 3. Attachment to novel ECM components 4. Migration of tumour cells
98
What treatment targets the evasion of growth suppression of tumour cells
cyclin-dependent kinase inhibitors
99
when are polyps associated with cancer
glandular dysplastic lesions arising from lining epithelial often form polyps
100
how does EGFR mutation predispose you to non small cell carcinoma
increase the EGFR tyrosine kinase domain activity leading to hyperactivation of downstream signalling pathways
102
How can polymorphisms increase the risk of cancer
May be associated with differences in cell response to cytotoxicity due to changes in how much of the SNPd protein is expressed, or a change in its stability
103
What treatment targets tumour cell immune destruction avoidance
anti-CTLA4 mAb
104
Which hormone imbalance leads to hypercalcaemia in cancers
PTH related protein
105
histopathological features of large cell carcinoma
large atypical cells, sheets of atypical cells which are not differentiated (no keratinization, glands, mucus), but still epithelial
106
grading of dysplasia
mild,moderate or severe 1, 2 or 3
107
which hormone imbalance leads to polycythaemia in cancers
erythropoeitin
