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Flashcards in Neoplasia 3&4 Deck (49)
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1
Q

What is Retinitis Pigmentosum?

A

An inherited degenerative eye disease due to degeneration of rod photoreceptors cells in the retina.
Causes increased risk of skin cancers when exposed to UV rays in sunlight.

2
Q

What is Ataxia Telangiectasia?

A

An inherited neurodegenerative disease. A defect in the ATM gene causes a defective response to DNA damage due to stress eg. radiation.
Increases susceptibility to lymphoid malignancies

3
Q

What is Fanconi’s Anaemia?

A

Inherited defect in proteins responsible for DNA repair, leading to reduced bone marrow function and congenital abnormalities.
Predisposition to cancer (most often acute myelogenous leukaemia)

4
Q

Give three examples of inherited conditions that increase susceptibility to development of certain tumours

A

Retinitis Pigmentosum
Ataxia Telangiectasia
Fanconi’s Anaemia

5
Q

What is Familial Adenomatous Polyposis?

A

Inherited defect in APC gene leading to multiple Adenomatous polyps in the large intestine. Can transform into malignant colon cancer with a mutation.

6
Q

A defect in what genes leads to inheritance of breast cancer?

A

BRCA1/2 gene

7
Q

What is Li Fraumeni Syndrome?

A

A hereditary cancer predisposition due to germ line mutations of the P53 tumour suppressor genes.
Leads to development of multiple cancers throughout life

8
Q

Define proto-oncogene

A

A gene involved in growth and differentiation, present in all normal cells, that can become an oncogene due to mutations or increased expression.

9
Q

How many alleles need to be mutated to cause neoplasia?

A

1 allele of a proto-oncogene.

2 alleles of a tumour suppressor gene.

10
Q

Give 3 examples of oncogenes, what they do and what cancers they cause

A

Ras gene: normally transmits growth-promoting signals to nucleus, mutation permanently activates it leads to continuous stimulation of cells. All cancers, especially colon and lung

C-myc gene: binds to DNA, stimulates synthesis. Overstimulation leads to breast cancer, translocation 8->14 leads to Burkitts lymphoma.

HER-2 gene: encodes growth factor receptor. Overstimulation leads to breast cancer

11
Q

Define a tumour suppressor gene

A

A gene that encodes proteins that suppress growth and therefore cancer.

12
Q

What is Knudsons 2-hit theory?

A

Both alleles of a tumour suppressor gene must be mutated to cause neoplasia, so 2 mutations are required.
Inheritance of the ‘first hit’ can lead to susceptibility to cancers

13
Q

Give 2 examples of tumour suppressor genes, what they do and what mutations cause

A

pRb gene: passage beyond the R checkpoint at the G1->S boundary is controlled by phosphorylation of pRb. Defect in both alleles leads to the cell escaping cell cycle control, retinoblastoma.

p53: ‘guardian of the genome’, encodes a nuclear protein which binds to and mediates expression of genes important for cell cycle arrest, DNA repair and apoptosis. Approx 50% of tumours

14
Q

What is the initiator stage of carcinogenesis?

A

Exposure of cells to sufficient dose of carcinogenic agents (eg. Polycyclic hydrocarbons, radiation) leads to permanent DNA damage.
Effect is modified by genetic factors.
Initiation alone is not sufficient for tumour formation.

15
Q

What is the Promotor stage of carcinogenesis?

A

Promotors (eg. Hormones, local tissue responses, immune response) can induce tumours in initiated cells.
Exposure is needed after initiation. Reversible (removing promotor returns cell to normal).

16
Q

How can radiation lead to neoplasia?

A

Causes range of damage to DNA, including single/double strand breaks and base damage. Depends on quality and dose.
Ionising: early leads to leukaemia/lymphoma, late leads to thyroid/breast cancer.
Ultraviolet leads to squamous cell carcinoma, basal cell carcinoma, malignant melanoma.

17
Q

How do carcinogens lead to neoplasia and give some examples?

A

The chemicals interact with DNA directly or require metabolic conversion to an active form.
Polycyclic aromatic hydrocarbons lead to lung/bladder/skin cancer.
Aromatic amines lead to bladder cancer.
Alkylating agents

18
Q

How can Hepatitis B lead to neoplasia?

A

Viral DNA integrates into host cell genome, causes liver cell injury, leading to regenerative hyperplasia. This increased cell division gives increased risk of genetic changes.

19
Q

How can Epstein Barr lead to neoplasia?

A

Infects epithelial cells/ B-cells leading to disregulation of normal proliferative and survival signals.
Associated with Burkitts lymphoma, hodgkins lynohoma, nasopharyngeal carcinoma.

20
Q

How can Human Papilloma virus (HPV) lead to neoplasia?

A

Disrupts normal cell cycle. Viral genes are incorporated into the host cell genome, driving proliferation.

21
Q

What cancer does asbestos cause?

A

Malignant mesothelioma or lung cancer

22
Q

What cancer can be caused by Aflatoxins?

A

Hepatocellular carcinoma

23
Q

What cancer can be caused by Schistosoma?

A

Bladder cancer

24
Q

What cancer can be caused by Helicobacter?

A

Gastric cancer and lymphoma

25
Q

List some conditions that can predispose cancer

A

Ulcerative colitis, colorectal cancer

Cirrhosis, hepatocellular carcinomas (cause of cirrhosis may be HPV)

Adenoma of colon/rectum

26
Q

Define staging

A

The extent of spread of a tumour

27
Q

What is the TNM staging system and what cancers is it used for?

A
T= primary Tumour size
N= regional lymph Node involvement
M= metastasis 

Used for breast cancer and prostate cancer

28
Q

What is the staging system of breast cancer?

A

TNM system:
TIS= carcinoma in situ
T1= 5cm
T4= through the chest wall/skin

N0= no nodal involvement
N1= axillary
N2= mammary
N3= supraclavicular
M0= no metastasis
M1= presence of metastasis
29
Q

What staging system is used for colorectal cancers and how does it work?

A

Dukes staging:
A= confined to bowel wall, not extending through muscularis propria. >90% 5 year survival.
B= through the bowel wall and muscularis propria. 70% 5 year survival.
C= lymph nodes involved (C1= regional lymph nodes, C2= apical node involved) 30% 5 year survival.

30
Q

How is Hodgkin’s disease classified?

A

Ann Arbor classification:
I= one lymph node involved
II= two lymph nodes on one side of the diaphragm
III= >two lymph nodes on both sides of diaphragm
IV= multiple foci everywhere

31
Q

What is the staging system fir prostate carcinoma?

A

TNM system:
T1= tumour present but not detectable
T2= tumour can be palpated
T3= tumour has spread through prostatic capsule
T4= tumour has invaded other nearby structures

32
Q

How are tumours graded?

A

On the basis of how differentiated the tumour cells are.
Attempts to judge the extent to which tumour cells resemble their normal counterparts.
Gx= grade cannot be assessed
G1= well differentiated
G2= moderately differentiated
G3= poorly differentiated
G4= undifferentiated

33
Q

How is breast cancer graded?

A

With the Scarff-Bloom-Richardson grading system.
Looks at degree of tubule formation, the extent of nuclear variation and the number of mitoses.
G1= 85% 10 year survival
G2= 60%
G3= 15%

34
Q

How is prostate cancer graded?

A

With the Gleason grading system:

Tumour cells are scored from 2-10 (2 is most differentiated, 10 is least differentiated).

35
Q

How does Radiotherapy work?

A

Uses x-Rays or other ionising radiation to kill rapidly dividing cells. The radiation damages the DNA which is detected at cell cycle checkpoints, triggering apoptosis.

36
Q

How is damage to healthy tissue minimised in Radiotherapy?

A

The radiation is focused on the tumour, with shielding of the surrounding healthy tissue, and is given in fractionated does

37
Q

What cancers have high/fairly high sensitivity to radiotherapy?

A

High = lymphoma/leukaemia/seminoma

Fairly high = squamous carcinomas

38
Q

What cancers have moderate/low sensitivity to radiotherapy?

A

Moderate = GI, breast cancer

Low = sarcomas

39
Q

Give some examples of drugs used in chemotherapy and how they work

A

Cyclophosphamide/cisplatin: acts in cells in G1/S phase and in mitosis, cross links the 2 strands of the DNA helix

Vincristine: blocks cells entering the cell cycle and blocks mitosis by inhibiting micro tubule assembly (spindle cannot form)

Methotrexate: inhibits dihydrofolate reductase, inhibiting synthesis of new DNA.

40
Q

How does chemotherapy target cancer cells?

A

The drugs act on cells at particular stages of the cell cycle so effect rapidly diving cells

41
Q

Give 2 examples of hormone therapy

A

Tamoxifen: competes for binding to oestrogen receptors, which are expressed in 50-80% of oestrogen receptors

Since prostate cancer depends on androgens, deprive it of testosterone to treat (androgen blockade)

42
Q

Why are tumour markers useful?

A

Used in diagnosis of the tumour, monitoring of the disease and to test if there is any residual disease left after a tumour has been removed.

43
Q

Name 3 useful tumour markers

A

Carcinoembryoinc Antigen
Human Chorionic Gonadotropin
Alpha-Fetoprotein (AFP)

44
Q

What is Carcinoembryoinc Antigen and why is it a useful tumour marker?

A

It is an antigen normally expressed in embryonic tissue but is also expressed in some cancers.
Useful to see if there’s any residual disease after the tumour has been removed surgically.

45
Q

What is Human Chorionic Gonadotrophin and why is it a useful tumour marker?

A

Used in the evaluation of testicular masses: raised levels in nonseminomatous testicular tumours and in seminomas with syncytiotrophoblastic giant cells.
Used to indicate residual disease after an orchidectomy or to monitor response to therapy predict recurrence.

46
Q

What is Alpha-Fetoprotein and why is it a useful tumour marker?

A

Normally synthesised early in foetal life by the yolk sac, foetal liver & foetal GI tract.
Raised plasma levels are associated with cancer of the liver and nonseminomatous testicular cancers

47
Q

What is the point of screening?

A

It aims to detect pre-malignant, non-invasive & early invasive cancers to improve their prognosis.

48
Q

Why and when is cervical screening carried out?

A

Cytological smears are done to detect early pre-cancerous changes eg Cervical Intraepithelial Neoplasia. Treatment can then be given before invasion occurs and is curative.
First invitation at 25, 3 yearly ages 25-49 and 5 yearly ages 50-64

49
Q

Why and when is breast screening carried out?

A

Uses mammography to identify cancerous densities and calcifications before they can be felt.
Every 3 years ages 50-69