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Flashcards in Cancer Deck (107):
1

How do tumour cells degrade ECM

secrete metaloproteases to break down collagen

2

what treatments target the tumour cells genome instability and mutation

PARP inhibitors

2

Staging system of tumours

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

the tumours microenvironment is important for what?

- important for establishment and growth of metastases

3

how do mutations in cells occur for cancer

- 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

once a diagnosis of malignancy is made, we need to know what extra stuff?

specific tumour type and subtype (cell lineage) grade stage presence of lymphovascular invasion

4

What is the general function of p53

regulates the expression of cell cycle factors (the guardian of the genome)

5

what histological feature is typical of epithelial tumours

keratinization

5

a mutation in an oncogene leads to

uncontrolled accerlerated growth

5

What does p53 specifically do?

Responds to mutations/cellular stress and directs the cell to: - undergo apoptosis - arrest cell cycle - DNA repair - differentiation - sequescence

5

mechanisms that regulate TSG expression

- miRNA - methylation

5

What treatment targets the replicative immortality of tumour cells

Telemoerase inhibitors

6

death often results from malignant tumour due to:

- cachexia - secondary infection related to poor nutrition, effects of treatment - damage to vital organ or system by either primary or secondary tumour

7

What class of genes are BRCA1 and BRCA2

DNA repair genes

7

Difference between mutation and polymorphisms

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

Telomeres and cancer?

Some tumour cells reactivate telomerase - thus starving off mitotic catastrophe and achieving immortality

8

definition of neoplasia

excessive and unregulated cell proliferation

8

adeno: squamous: leiomyo: osteo:

adeno: glandular squamous: squamous cell Leiomyo: Smooth muscle Osteo: osteoblastic

8

Questions you must ask yourself when diagnosing a lesion

Neoplastic or non-neoplastic Begnign or malignant Epithelial, mesenchymal? Primary versus metastatic

9

which cancers can lead to inappropriate ADH syndrome

SCC

9

how can lung cancer predispose to lung infection

cancer blocks the bronchus --> leading to pneumonia, collapse or bronchiectasis in the distal lung as you cannot clear the alveoli

10

what is the difference between histopathology and cytology

cytology - don quite see the relationship between cells as easily

12

6 main hallmarks of cancer

- sustaining proliferative signaling - evading growth suppressors - activating invasion and metastasis - enabling replicative immortality - inducing angiogenesis - resisting cell death

12

What treatments target the tumour cell resistance of cell death

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