AETIOLOGY OF CANCER 2 Flashcards Preview

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Flashcards in AETIOLOGY OF CANCER 2 Deck (63):
1

why are cancer cells called selfish cells?

they have have a selective advantage over normal, regulated cells – a form of natural selection

2

why are tumours said to have a 'life of their own'?

Increase in neoplasm size persists whilst the hosts body is wasting (cachexia)
Ultimately kill themselves by killing the host

3

how do cancer cells and normal cells differ?

Growth control
Contact inhibition
Repair/death mechanisms
Metastatic ability
Appearance
Growth rate
Maturity/differentiation
Immune evasion
Function
Angiogenesis

4

how can you measure tumour growth?

amount of time it takes the cell mass to double in size, and the number of such ‘doublings’

5

what is carcinogenesis?

process of inducing cancer

6

what kind of process is carcinogenesis?

A multistep process

7

what does carcinogenesis involve?

A normal cell evolves progressively to a cancerous state through acquiring a succession of properties
A normal cell acquires a series of molecular changes which result in the cell having new properties

8

what molecular changes does a cancer cell acquire?

changes to its DNA (genetic material) and to the proteins it produces

9

what is a change to DNA called?

mutation

10

define hallmarks

small number of traits

11

what are hallmarks?

traits that are shared by all cancers that govern the transformation of normal cells into cancerous ones

12

what are the 6 original hallmarks?

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

13

what does sustaining proliferative signalling involve?

Normal cells need external signals from growth factors to divide
Cancer cells are not dependent on normal growth factor signalling
Acquired mutations `short-circuit’ growth factor pathways leading to unregulated growth

14

give an example of ustaining proliferative signalling

mutation in Ras oncoprotein disrupts the normal -ve feedback mechanisms that dampen a signalling pathway when a mitogenic signal is hyperactivated

15

what does evading growth suppressors involve?

Normal cells respond to inhibitory signals
Cancer cells do not respond to growth inhibitory signals
Acquired mutations interfere with inhibitory pathways

16

give an example of evading growth suppressors

p53 is a common tumour suppressor gene which is inactivated in cancer cells leading to uncontrolled growth and proliferation

17

what does resisting cell death involve?

Apoptosis
Normal cells are removed by apoptosis, often in response to DNA damage
Cancer cells evade apoptotic signals

18

give an example of resisting cell death

dysregulation of anti-apoptotic BCL-2 family members

19

what does enabling replicative immortality involve?

Normal cells have a finite number of cell divisions after which they become senescent
The `cellular counting device’ is the shortening of chromosomal ends (telomeres) that occur after every round of DNA replication

20

what do cancer cells do in enabling replicative immortality?

Cancer cells maintain the length of their telomeres
Altered regulation of telomere maintenance results in unlimited replicative potential

21

give an example of enabling replicative immortality

Overexpression of telomerase allows tumour cells to overcome finite replicative ability

22

what does inducing angiogenesis involve?

Normal cells depend on established BV to supply oxygen and nutrients
Cancer cells induce angiogenesis, the growth of new BV, needed for tumour survival and expansion

23

give an example of inducing angiogenesis

Tumour angiogenesis is a function of multiple signals from a number of cell types residing in the tumour microenvironment

24

what does activating invasion and metastasis involve?

Normal cells maintain their location in the body and generally do not migrate
Cancer cells can move to other parts of the body and start secondary tumours

25

how does cancer grow?

Cells of malignant tumour duplicate rapidly and invade surrounding tissue (break through basement memb)
triggers angiogenesis through production of (TAFs)

26

how does cancer spread?

Cells compete with normal tissue for space and nutrients and eventually kills them
Some cells detach from primary tumour, enter body cavity or blood and establish secondary tumours

27

what are the 4 modes of tumour spread?

Local invasion
Lymphatic spread
Vascular spread
Trans-coelomic spread

28

what is the difference between malignant and benign tumours?

benign tour cells grow only locally and can't spread by invasion or metastasis
malignant cells invade neighbouring tissues, enter BV, and metastasise to different sites

29

what are the 4 steps in the metastatic process?

Motility and invasion from the primary site – can be as single cells or clumps
Embolism and circulation in blood or lymph system – can also get spread through fluids in a body cavity
Arrest in a distant capillary & adherence to the endothelium
Extravasation into the target organ parenchyma

30

what do tumours need to metastasise?

they need an external stimulus through molecular cross-talk with cells in the neoplastic environment

31

what is EMT?

Epithelial mesenchymal transition

32

what is EMT involved in?

wound repair
metastasis

33

what does genome instability & mutation involve?

Cancer cells generally have severe chromosomal abnormalities, which worsen as the disease progresses
These genetic alterations drive tumour progression

34

how do cancer cells promote genome instability?

they take advantage of mutations in DNA repair pathways

35

what has been found to induce many types of cancer?

local chronic inflammation

36

what do inflammatory cytokines promote?

tumour growth, proliferation and angiogenesis

37

how does tumour-associated inflammation promote tumour growth?

by supplying the microenvironment with growth factors, survival factors, and factors that promote angiogenesis

38

how are cancer cells seen by the body?

they appear to be invisible to the body’s immune system

39

how do cancer cells avoid immune destruction?

by disabling components of the immune system that have been dispatched to eliminate them
recruitment of inflammatory cells that are actively immunosuppressive

40

how do cancer cells generate energy?

use abnormal metabolic pathways

41

how do cancer cells produce energy?

by a high rate of glycolysis followed by lactic acid fermentation in the cytosol

42

what is the warburg effect?

Cancer cells convert available glucose to lactate irrespective of the availability of oxygen

43

what does the warburg effect lead to?

they divert glucose metabolites to useful anabolic processes that accelerate cell proliferation

44

what is the tumour stroma?

Cells co-opted in to supporting the cancer

45

what does the tumour stroma contain?

vascular elements
fibroblasts
macrophages

46

what do vascular elements do?

provide growth factors, blood supply (oxygen, nutrients)

47

what do fibroblasts do?

contribute MMPs for extracellular matrix degradation during cancer cell migration

48

what do macrophages do?

(alternatively activated), may provide defence against immune surveillance

49

what are the causes of cancer?

carcinogens
viral infections
oncogenes

50

what are carcinogens?

chemical agent or radiation that causes cancer eg. hydrocarbons, UV

51

what are oncogenes?

cancer causing cells

52

where are oncogenes derived from?

from proto-oncogenes (normal genes)

53

what do porto-oncogenes do?

regulate normal growth and development

54

what are carcinogenic agents?

chemicals
radiation
microbiologicals

55

what are chemical carcinogenic agents?

Some direct acting but most require metabolic conversion (procarcinogens)

56

what are radiation carcinogenic agents?

Hard uv light, X-rays, ß, gamma

57

what are microbiologicals carcinogenic agents?

RNA viruses-leukaemia
DNA viruses- Kaposi’s sarcoma
Pathogenic species- gastric carcinoma and lymphoma

58

give examples of carcinogens

Percival Pott
Soot
Tobacco smoke

59

give examples of cancers

chronic myelogenous leukaemia
cervical cancer
breast cancer
melanoma
retinoblastoma

60

what are the different treatments of cancer?

Surgery, chemotherapy, radiotherapy, biological - individually or in combination

61

what are the side effects of radiation therapy?

hair loss, nausea and vomiting (destructive effect on hair follicles and lining of stomach and intestine)

62

why does radiation therapy increase susceptibility to infection?

due to slow production of WBCs in bone marrow

63

why is treatment of cancer difficult?

as cancer contains diverse population of abnormal cells varying in their resistance to drugs