MoD 11 Neoplasia 3 Flashcards Preview

ESA 2 SK > MoD 11 Neoplasia 3 > Flashcards

Flashcards in MoD 11 Neoplasia 3 Deck (37):
1

What is cancinogenesis?

causes of cancer

2

Give examples of some intrinsic and extrinsic factors leading to cancer

Intrinsic- Age, sex (hormonal), heredity
Extrinsic- environment, lifestyle

3

What are the 5 leading behavioural risks leading to cancer?

High BMI
Low fruit and veg intake
Lack of physical activity
Tobacco use
Alcohol use

4

What 3 main categories do extrinsic carcingoens fall into?

Chemicals
Radiation
Infections

5

What three things did malignant neoplasms caused by the dye 2-napthylamine show?

Long delay (sometimes decades) between exposure and malignant neoplasm onset
Risk of cancer depends on total carcinogen dosage
Sometimes organ specificity for particular carcinogens e.g 2-napthylamine causes bladder carcinoma

6

What did the Ames test show?

That initiators are mutagens while promoters cause prolonged proliferation in target tissues

7

What kinds of chemicals are initiators (mutagens)?

Polycyclic aromatic hydrocarbons, aromatic amines, N-nitroso compunds, natural products

8

What is asbestos?

Mutagen originating from a rock which was used industrially due to its fire retardant properties
Inhalation of its needle shaped dust causes cancer as the fibres get into the lung pleura

9

How are N-nitroso ocmpounds formed?

Stomach converts nitrates in cured and pickled food to these

10

What are pro-carcinogens?

Chemicals that become carcinogenic when converted to carcinogens by cytochrome P450 enzymes in the liver

11

What are complete carcinogens?

Carcinogens that act as both initiators and promoters

12

What types of radiation are mutagenic?

alpha and beta particles
gamma rays
x rays
UV rays

13

What is ionising radiation?

Radiation that strips electrons from atoms
Includes x rays and nuclear radiation

14

What comprises nuclear radiation?

Alpha particles, beta particels, gamma rays

15

In what ways can radiation damage DNA?

Directly by altering bases and causing single/ double strand DNA breaks
indirectly by generating free radicals

16

How do infections behave carcinogenically?

Directly affect genes that control cell growth
Indirectly by causing chronic tissue injury where resulting regeneration either acts as a promoter for a pre-existing mutations or else causes new mutations from DNA replication errors

17

How does HPV act as a carcinogen?

Direct carcingoen that expresses E6 and E7 proteins which inhibit p53 and pRB respectively, both of which important in cell proliferation

18

How do hepatitis viruses act as carcinogens?

Indirectly as cause chronic liver injury and regeneration

19

How does HIV act as a carcinogen?

Indirectly by lowering immunity so other potentially carcinogenic infections can occur

20

What is the inheritance pattern of retinoblastoma?

dominant

21

What is the two hit hypothesis?

Two mutations must occur for a cancer to develop. so in familial cancers one mutation is present in the germ-line so one somatic mutation has to occur for cancer to develop whereas in sporadic cancers, both mutations must be somatic mutations in the same one cell

22

How do tumour suppressor gene mutations support the two hit hypothesis?

Tumour supressor gene will have two alleles and both these alleles must be hit and inactivated for neoplastic growth to occur

23

Do both alleles of a proto-oncogene need to be mutated to favour neoplastic growth?

No, just one

24

What is RAS?

First human oncogene to be discovered
Proto-oncogene for RAS encodes a small G protein that relays signals to push cell past cell cycle restriction point/ Mutant RAS is constantly activated so constantly signals cell past restriction point

25

What does RBp do?

Tumour suppressor that inhibits passage through cell cycle restriction point

26

What proteins can proto-oncogenes encode?

Growth factors e.g PDGF, growth factor receptors, plasma membrane signal transducers e.g RAS, intracellular kinases, transcription factors, cell cycle regulators, apoptosis regulators

27

Apart from tumour suppressor and proto-oncogenes, what other genes can be mutated to cause cancer?

DNA repair genes

28

Give an example of a cancer caused by mutation to nucleotide excision repair genes

Xeroderma Pigmentosum (XP)
Inherited, autosomal recessive, with germline mutation to one of 7 genes that affect nucleotide excision repair (NER)
These patients are very sensitive to UV damage and develop skin cancer at a young age
Causes nucleotide instability

29

What is Hereditary non-polyposis colon cancer (HNPCC) syndrome?

Hereditary, autosomal dominant, associated with colon carcinoma with germline mutation of a DNA mismatch repair gene causing microsatellite instability

30

Which genes are familial breast carcinoma associated with?

BRCA 1 BRCA 2 genes that are important in repairing double stranded DNA breaks causing chromosomal instability

31

What is the accelerated mutation rate in malignant neoplasms called?

Genetic instability

32

How does chromosomal segregation affect genetic instability?

Increases it as can be abnormal in malignant cells

33

What is progression?

The steady accumulation of multiple mutations
e.g progression from early adenoma> later adenoma > primary carcinoma >metastatic carcinomas
Time frame typically decades

34

How many mutations is it thought are needed for a fully evolved malignant neoplasm? What does a fully evolved malignant neoplasm exhibit?

10 or less
Must exhibit 6 hallmarks of cancer and one enabling feature

35

What are the 6 hallmarks of cancer?

1. Self sufficiency in growth signals
2. Resistance to growth stop signals
3. No limit on number of times cell can divide
4. Sustained ability to induce new blood vessels (angiogenesis)
5. Resistance to apoptosis
6. Ability to invade and produce metastases
(1-5 also apply to benign)

36

What is an enabling characteristic for a malignant neoplasm?

Genetic instability

37

Summarise the model of cancer pathogenesis

Somatic cells exposed to environmental carcinogens that are either initiators or promoters giving monoclonal pop of mutant cells
By chance some of clones have mutations affecting proto-oncogne or tumour supressor gene whose protein transcripts have crucial role in pathway affecting hallmark changes
During progression cells acquire further activated oncogenes inc those causing genetic instability
Eventually this leasa to a population of cells with all the hallmarks of cancer