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Pathological Processes * > S8-S10 Neoplasia > Flashcards

S8-S10 Neoplasia Flashcards

1
Q

What is a neoplasm?

A

An abnormal growth of cells that persists after the initial stimulus is removed

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2
Q

What is a malignant neoplasm?

A

An abnormal growth of cells that persists after the initial stimulus is removed and invades surrounding tissue with potential to spread to distant sites

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3
Q

What is a tumour?

A

Any clinically detectable lump or swelling.

A neoplasm is a type of tumour

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4
Q

What is cancer?

A

Any malignant neoplasm

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5
Q

What is a metastasis?

A

A malignant neoplasm (cancer) that has spread from it’s original location to a secondary site

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6
Q

What is dysplasia?

A

Pre-neoplastic alteration in which cells show disordered tissue organisation - this is reversible

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7
Q

What is the difference in behaviour between benign and malignant neoplasms?

A

Benign neoplasms remain confined to site of origin, don’t produce metastases.

Malignant neoplasms have the potential to metastasise

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8
Q

What is oncology?

A

The study of tumours and neoplasms

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9
Q

What does dysplasia look like under a microscope?

A

Pleomorphism (varying cells and sizes) and large hyperchromatic nuclei with a high nuclear to cytoplasmic ratio

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10
Q

What is the difference in appearance to the naked eye, between benign and malignant neoplasms?

A

Benign tumours grow in a confined local are and have pushing outer margins

Malignant tumours have an irregular outer margin and shape and may show necrosis and ulceration (if on surface)

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11
Q

What is the difference in appearance under the microscope, between benign and malignant neoplasms?

A

Benign neoplasms have cells that closely resemble parent tissues - well differentiated

Malignant neoplasms range from well to poorly differentiated, with worsening differentiation, cells have increased nuclear size, increasing nuclear to cytoplasmic ratio, increased hyperchromasia, more mitotic figures and increased variation in size and shape of cells and nuclei (pleomorphism)

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12
Q

What is anaplastic?

A

When cells have no resemblance to any tissue

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13
Q

What do clinicians use the term grade for, in terms of neoplasms?

A

To indicate the differentiation

  • high grade means poorly differentiated
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14
Q

What is neoplasia caused by?

A

Accumulation of mutations in somatic cells. Mutations caused by mutagenic agents - initiators and promotors that lead to cell proliferation

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15
Q

What are some examples of some initiators?

A 
Chemicals 
* smoking
* alcohol consumption 
* diet and obesity 
Infectious agents 
* HPV
Radiation
Inherited mutations
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16
Q

When is a collection of cells monoclonal? How does a neoplasm emerge from this group of cells?

A

If they all originated from a single founding cell

By a process called progression - accumulation of more mutations

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17
Q

Where did evidence that neoplasms are monoclonal come from?

A

Study of the x-linked gene for G6PD in tumour tissue from women.
The gene has several alleles.
In normal tissues there will be a patchwork of different types of gene.
In neoplastic tissue, there’s only one isoenzyme

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18
Q

Which genes are often altered leading to neoplasms?

A
  • proto-oncogenes - promote growth
  • tumour suppressor genes - inhibit growth
  • genes involved in regulating apoptosis
  • genes involved in DNA repair
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19
Q

What do mutations do to proto-oncogenes?

A

Activate the gene and cause an excessive increase in one or more normal functions

Gain of function mutations

Become oncogenes which encode proteins called on corporate ins that have the ability to promote cell growth in the absence of normal growth promoting signals

Oncogenes are dominant over normal counterparts

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20
Q

What do mutations do to tumour suppressor genes?

A

Loss of function mutations

Both alleles must be damaged for transformation to occur

Result in failure of growth inhibition

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21
Q

What do mutations do to DNA repair genes?

A

Loss of function mutations

Contribute indirectly - impair the ability of a cell to recognise and repair non-lethal genetic damage in other genes

So cells acquire mutations at quicker rate - mutator phenotype

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22
Q

What do mutations do to apoptosis regulating genes?

A

Can acquire abnormalities that result in less cell death and enhanced survival of cells

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23
Q

What do benign and malignant neoplasm names generally end in?

A

Benign is -oma

Malignant is -carcinoma (if epithelial) or -sarcoma (if stromal)

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24
Q

What are the different polyp names? What are polyps?

A

Villous

Sessile

Tubular/pedunculated

Form in colon

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25
Q

What are names given to benign epithelial neoplasms, based on the different types of epithelia?

A
  • stratified squamous - squamous papilloma e.g. skin, buccal mucosa
  • transitional - transitional cell papilloma - bladder mucosa
  • glandular - adenoma e.g. ovary, colon
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26
Q

What name is given to a benign tumour of the colon epithelial glands?

A

Adenomatous polyp of the colon

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27
Q

What is the name given to an epithelial gland benign tumour of the ovary?

A

Cystadenoma

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28
Q

What are names given to malignant epithelial neoplasms, based on the different types of epithelia?

A
  • stratified squamous - squamous cell carcinoma e.g. skin, larynx, oesophagus, lung, etc
  • transitional - transitional cell carcinoma e.g. bladder, ureter
  • glandular - adenocarcinoma e.g. stomach, colon, lung, prostate, breast, pancreas, oesophagus, etc
  • other - basal cell carcinoma e.g. skin
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29
Q

What is a benign CT, smooth muscle neoplasm called?

A

Leiomyoma

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30
Q

What is a benign CT, fibrous tissue neoplasm called?

A

Fibroma

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31
Q

What is a benign CT, bone neoplasm called?

A

Osteoma

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32
Q

What is a benign CT, cartilage neoplasm called?

A

Chondroma

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33
Q

What is a benign CT, fat neoplasm called?

A

Lipoma

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34
Q

What is a benign CT, nerve neoplasm called?

A

Neuroma

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35
Q

What is a benign CT, nerve sheath neoplasm called?

A

Neurofibroma

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36
Q

What is a benign CT, glial cell neoplasm called?

A

Glioma

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37
Q

What is a malignant CT, smooth muscle neoplasm called?

A

Leiomyosarcoma

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38
Q

What is a malignant CT, bone neoplasm called?

A

Osteosarcoma

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39
Q

What is a malignant CT, fibrous tissue neoplasm called?

A

Fibrosarcoma

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40
Q

What is a malignant CT, cartilage neoplasm called?

A

Chondrosarcoma

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41
Q

What is a malignant CT, fat neoplasm called?

A

Liposarcoma

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42
Q

What is a malignant CT, glial cell neoplasm called?

A

Malignant glioma

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43
Q

Do you get benign blood cell, lymphoid tissue and plasma cell neoplasms?

A

No

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44
Q

What are the malignant neoplasms of blood cells, lymphoid tissue and plasma cells called?

A

Blood cells - leukaemia

Lymphoid tissue - lymphoma

Plasma cells - myeloma

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45
Q

What is the name for benign and malignant blood vessel neoplasms?

A

Benign - haemangioma

Malignant - angiosarcoma

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46
Q

What is the name for benign and malignant striated muscle neoplasms?

A

Benign - rhabdomyoma

Malignant - rhabdomyosarcoma

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47
Q

What names are given to germ cell neoplasms in the testes and ovary?

A

Testes - malignant teratoma and seminoma (malignant)

Ovary - benign teratoma

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48
Q

What is another name for a benign teratoma?

A

Dermoid cyst

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49
Q

Hat are common locations of neuroendocrine tumours? What are they derived from?

A

Gastrointestinal and respiratory systems

Endocrine cells that produce bioactive compounds hence these tumours produce excess secretory products which can cause clinical syndromes

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50
Q

What are some examples of clinical syndromes caused by neuroendocrine tumours?

A

Cushing’s syndrome - excess corticotrophin secretions

Zollinger Ellison syndrome - excess gastrin from pancreatic and gastric tumours

Carcinoid syndrome - excess serotonin

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51
Q

What affect can a malignant tumour of plasma cells do to the skull?

A

Can lead to raindrop skull - radiolucent regions

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52
Q

What is invasion?

A

Breach of the basement membrane with progressive infiltration and destruction of surrounding tissues

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53
Q

What is metastasis?

A

The spread of a tumour to sites that are physically discontinuous from the primary tumour

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54
Q

What is the multi-step journey of invasion and metastasis?

A
  1. Grow and invade at the primary site
  2. Enter a transport system and lodge at a secondary site
  3. Grow at the secondary site to form a new tumour (colonisation)
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55
Q

What 3 key events are involved in invasion? What does this result in, what is it called?

A
  • altered adhesion
  • stromal proteolysis
  • motility

These events create a carcinoma cell phenotype that is more like a mesenchymal cell/stromal cell than an epithelial cell (epithelial to mesenchymal transition)

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56
Q

What happens in altered adhesion?

A

Reduction in E-cadherin expression between malignant cells and changes in integrin expression between malignant cells and stromal proteins

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57
Q

What happens in stromal proteolysis?

A

The cells degrade the basement membrane and stroma and this allows for invasion

There’s altered expression of proteases e.g. of matrix metalloproteinases (MMPs)

Malignant cells take advantage of nearby non-neoplastic cells which provide growth factors and proteases - a cancer niche

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58
Q

What happens in motility?

A

Changes in the actin cytoskeleton

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59
Q

How does a metastases spread to a distant site?

A
  • blood vessels
  • lymphatic vessels
  • fluid in body cavities - transcoelomic spread
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60
Q

What is the name for the growth of malignant cells at a secondary site?

A

Colonisation

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61
Q

What is the greatest barrier to successful metastasis?

A

Failed colonisation - small clinically undetectable cell clusters that either die or fail to grow into detectable tumours - surviving microscopic deposits that fail to grow are called micrometastases - which can become cancer (dormant)

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62
Q

What determines the site of a secondary tumour?

A
  1. Regional drainage of blood, lymph or coelomic fluid

2. Seed and soil phenomenon

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63
Q

Where do lymphatic metastases drain to typically? Give an example

A

Lymph nodes

E.g. breast cancer goes to ipsilateral axillary lymph nodes

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64
Q

Where do transcoelemic spread metastases drain to typically?

A

Other areas in coelemic space/adjacent organs

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65
Q

Where do blood-borne metastases drain to typically?

A

To the next capillary bed that the malignant cells encounter

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66
Q

What is the seed and soil phenomenon

A

Explains the unpredictable distribution of blood-bone metastases

Distribution is due to interactions between malignant cells and the local tumour environment at the secondary site, is the ‘niche’ hospitable

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67
Q

What makes up a cancer niche?

A
  • stroma
  • fibroblasts
  • endothelial cells
  • inflammatory cells
68
Q

How do carcinomas and sarcomas tend to spread?

A

Carcinomas - via lymphatics first

Sarcomas - via blood stream

69
Q

What are common sites for blood borne metastasis?

A
  • lung
  • bone
  • liver
  • brain
70
Q

What are the common neoplasms that spread to bone?

A 
Osteolytic:
* breast 
* bronchus 
* kidney 
* thyroid 
Osteosclerotic:
* prostate
71
Q

Give an example of a very aggressive neoplasm and one that almost never metastasises.

A

Aggressive - small cell carcinoma of the bronchus

Never metastasise - basal cell carcinoma of the skin

72
Q

How can tumours be recognised and destroyed by immune cells?

A

Tumour antigens are presented on the cell surface of major histocompatibility complex/MHC molecules and the antigen is recognised by CD8+ cytotoxic T cells

73
Q

How can tumours avoid the immune system in immunocompetent patients?

A
  • loss or reduced expression of histocompatibility antigens
  • expression of certain factors that suppress the immune system
  • failure to produce tumour antigen
74
Q

What are the local effects of neoplasms?

A

Can be primary or secondary

  1. Direct invasion and destruction of normal tissue
  2. Ulceration at a surface leading to bleeding
  3. Compression of adjacent structures
  4. Blocking tubes and orifices
  5. Raised pressure due to tumour growth or swelling
75
Q

What are the systemic effects of neoplasms?

A

Can be burden, hormones or miscellaneous

  1. Increased tumour burden results in parasitic effect on the host
  2. Secreted factors e.g. cytokines lead to cachexia, malaise, immunosuppression and thrombosis
  3. Productive of hormones
  4. Neuropathies
  5. Skin problems e.g. pruritus or abnormal pigmentation
  6. Fever
  7. Clubbing
  8. Myositis
76
Q

What are paraneoplastic syndromes? What is an example

A

Signs and symptoms that can’t be readily explained by the anatomical distribution of the tumour or by the hormone production from the tissue the tumour arose from

Hypercalcaemia - caused by osteolysis due to bone cancer or by the production of calcaemic humoral substances e.g. tumour that secretes PTHrP (e.g. small cell lung cancer)

77
Q

What are the dominant cancer types in men and women?

A
  • prostate (men) and breast (women)
  • lung
  • bowel
  • other sites (55%)
78
Q

If considering malignant neoplasm, tailor questions to the key types…

A
  • breast - family history
  • prostate - UTI
  • lung - coughing up blood?
79
Q

What are 5 year survival rates for testicular cancer, melanoma and pancreatic cancer?

A

98%
90%
1%

80
Q

Why are survival rights higher in women than men?

A

Maybe because women are more likely to seek help earlier

81
Q

Why have chances of survival increased?

A
  • faster diagnosis - more screening, etc

* better treatments - more targeted therapies for individuals

82
Q

Which of the 3 common cancers (breast/prostate, lung, bowel), which is has the highest mortality in females and males?

A

Lung

83
Q

Which cancer has had the biggest increase in survival rates?

A

Prostate

84
Q

How do you predict someone’s outcome for survival from cancer?

A

Takes into account:

  • age
  • general health status
  • tumour site
  • tumour type
  • differentiation of tumour
  • tumour stage
  • availability of effective treatments

Not exact at all

85
Q

What is the TNM staging system of tumours?

A 
T = size of primary tumour 
N = extent of regional lymph node involvement 
M = metastatic spread via blood

Stages solid tumours, standardised across the world

86
Q

What is tumour stage a measure of?

A

Measure of the overall burden of the malignant neoplasm

It is then converted to stage 1-4

This varies for each cancer

87
Q

What are the 4 stages for cancers?

A

Stage 1 = early local disease
Stage 2 = advances local disease (N0, M0)
Stage 3 = regional metastasis (N1 or more with M0)
Stage 4 = advanced disease with distant metastasis (M1)

88
Q

What is the staging system used for lymphomas?

A

Ann Arbor staging system - based on location of nodes

  • stage 1 - in single node region
  • stage 2 - 2 nodes involved but on same side of diaphragm (above diaphragm)
  • stage 3 - multiple nodes involved, on both sides of diaphragm (above and below)
  • stage 4 - involvement of extra-lymphatic organs e.g. bone marrow or lungs
89
Q

What staging system is used for bowel cancer?

A

Dukes staging system (ABCD)

Associates stage with 5 year survival rate

  • A - 93%
  • B - 77% - larger than A
  • C - 48% - lymph node involvement
  • D - 6% - metastasis (e.g. to liver)
90
Q

What is grading? What type of cancer is this system used in?

A

A grade describes the degree of differentiation of a neoplasm (how much is resembles tissue of origin)

  • G1 - well differentiated
  • G2 - moderately differentiated
  • G3 - poorly differentiated
  • G4 - undifferentiated/anaplastic

Squamous cell carcinoma

91
Q

Breast cancer grading system - Bloom-Richardson score, what does it assess?

A

Tubule formation
Nuclear formation
Number of mitotic figures

There is a big survival difference between the grades

92
Q

What is the prostate cancer grading system? Why is this important?

A

Gleason’s pattern

Effects the treatment plan

93
Q

What are treatments for cancer?

A
  • surgery - most successful for remission - remove tumour with clear margins around it
  • radiotherapy
  • chemotherapy
  • hormone therapy
  • treatments targeted to specific molecular alterations
  • immunotherapy
94
Q

What is adjuvant treatment?

A

Treatment given after surgical removal of a primary tumour to eliminate subclinical disease

  1. Diagnosis
  2. Curative treatment e.g. surgery
  3. Adjuvant e.g. chemotherapy to remove any remaining metastasis
95
Q

What is neoadjuvant treatment?

A

Treatment given prior to surgical excision to reduce the size of the primary tumour

  1. Diagnosis
  2. Neoadjuvant treatment
  3. Curative treatment e.g. surgery
96
Q

What is radiation therapy?

A

Kills proliferating cells by triggering apoptosis or interfering with mitosis - kills rapidly dividing cells in G2 of cell cycle.

It causes direct or free-radical induced DNA damage that is detected by cell cycle checkpoints, this triggers apoptosis

Causes double-stranded DNA breakages which lead to damaged chromosomes that prevent M phase from completing correctly

97
Q

How is radiation therapy given?

A

In lots of small doses/fractionated doses - to minimise normal tissue damage (normal cells have time heal)

98
Q

What are the different types of chemotherapy?

A
  • antimetabolites - mimic substrates in DNA replication
  • alkylating and platinum based drugs - crosslink two strands of DNA helix
  • antibiotics - inhibit DNA topoisomerase (part of DNA synthesis) or causes double stranded DNA breaks
  • plant-derived drugs - block microtubules from assembling and interferes with mitotic spindle formation
99
Q

What are the effects of chemotherapy on the body?

A
  • hair loss
  • pain
  • mouth sores
  • trouble breathing
  • weakened immune system
  • nausea/vomiting
  • constipation/diarrhoea
  • bruising/bleeding
  • rashes
  • neuropathy

Therapy also affects normal cells that divide lots

100
Q

What is hormone therapy?

A

Common type is selective oestrogen receptor modulators (SERMs) e.g. tamoxifen - binds to oestrogen receptors and prevents oestrogen binding.
Used to treat hormone receptor positive breast cancer

101
Q

How do you target oncogenes?

A

Identify cancer specific alterations e.g. oncogene mutations and create targeted drugs that effect cancer cells only

E.g. Herceptin and Imatinib

102
Q

Most breast cancers have lots of HER2 genes, how does herceptin work on them? What is herceptin?

A

Herceptin blocks the HER2 signalling pathway - prevents growth and division of cancer cells

A monoclonal antibody that binds to the HER2 protein

103
Q

What is immunotherapy?

A

Targets the immune system to help it fight cancer by recognising and attacking cancer cells (targets points in the cancer immunity cycle)

  1. Release of cancer cells antigens
  2. Cancer antigen presentation on APCs
  3. Priming and activation of more APCs and T cells
  4. CTL cells migrate to tumours
  5. CTLs cells infiltrate tumours
  6. CTL recognise cancer cells
  7. Cytotoxic T cells (CTLs) kill cancer cells
104
Q

What are tumour markers?

A

Various substances are released by cancer cells into the circulation, these can be measured (for diagnosis, monitoring, assessing recurrence)

105
Q

What is cancer screening?

A

Screening healthy people with no symptoms - attempts to detect cancers as early as possible, so chance of cure is at its highest

e.g. breast screening and cervical screening for women of certain ages (47-73) and (25-64 every 3/5 years)

Bowel screening for men and women of certain ages (60-74) - home testing kit

  • consider lead time bias, length time bias (based on fast and slow growing tumours) and over diagnosis (would it have ever become a clinical problem for the patient?)
106
Q

What increases the risk of cancer?

A

Intrinsic host factors e.g. hereditary, age, gender

Extrinsic factors e.g. environment and behaviour - smoking, lack of physical inactivity, alcohol, etc. (85% of populations cancer risk)

107
Q

What are the 3 categories extrinsic carcinogens fall into?

A
  • chemicals
  • radiation
  • infections
108
Q

What did malignant neoplasms caused by 2-napthylamine show?

A
  • there’s a long delay between carcinogen exposure and malignant neoplasm onset
  • the risk of cancer depends on total carcinogen dosage
  • sometimes there’s organ specificity for particular carcinogens e.g. 2-napthylamine causes bladder carcinoma
109
Q

What are some other examples of industrial carcinogens?

A
  • asbestos
  • coal tars
  • vinyl chloride
110
Q

Why is the sequence in which carcinogens are administered important?

A

You have initiators and promotors.

Initiators need to be given first followed by promotors for cancer to occur

Both together lead to a monoclonal expansion of mutant cells

111
Q

What are initiators?

A

Mutagens

112
Q

What do promotors cause?

A

Prolonged proliferation in the target tissue - progression then occurs to make cells fully malignant

113
Q

How can mutagenic chemical carcinogens (initiators) be classified?

A
  • polycyclic aromatic hydrocarbons
  • aromatic amines
  • N-nitroso compounds
  • alkylating agents
  • natural products e.g. aflatoxin, asbestos
114
Q

How are pro-carcinogens converted to carcinogens?

A

Converted by cytochrome P450 enzymes in the liver

115
Q

What is the name given to carcinogens that act as both initiators and promotors?

A

Complete carcinogens

116
Q

What forms of radiation are mutagenic?

A
  • UV light

* ionising radiation e.g. x-rays and nuclear radiation

117
Q

How deep does UV light penetrate?

A

No deeper than skin

118
Q

What does ionising radiation do? What is the main exposure from?

A

It strops electrons from atoms

Nuclear radiation is made up of alpha and beta particles and gamma rays

Natural background radiation from radon (seeps from earth’s crust)

119
Q

How can radiation damage DNA generally?

A

Directly

Indirectly - generates free radicals

120
Q

What is the most important type of radiation?

A

UV as we’re exposed to it daily from sunlight - increases risk of skin cancer

121
Q

How does ionising radiation damage DNA?

A

It damages DNA bases and causes single and double strand DNA breaks

122
Q

What are carcinogenic infections? What general effects do they have?

A
  • HPV - direct
  • Hepatitis B virus - indirect (chronic tissue injury - regeneration is a promotor)
  • HIV - reduced immunity
  • H. pylori - indirect
123
Q

How does HPV cause cervical carcinoma?

A

HPV expresses E6 and E7 proteins - these inhibit p53 (E6) and pRB (E7) protein functions - these proteins are important in cell proliferation

The virus infects cells and ensures they don’t die and then hijacks it’s DNA replication machinery to make more virus particles

  • inhibiting p53 prevents apoptosis
  • RB is important as a cell cycle checkpoint
124
Q

How do hepatitis B and C viruses case cancer?

A

They cause chronic liver cell injury and regeneration

125
Q

How does Helicobacter pylori and parasitic flukes cause cancer?

A

Bacteria - It causes chronic gastric inflammation - increases the risk for gastric carcinomas

Parasites - inflammation in bile ducts and bladder mucosa - increases risk for cholangiocarcinoma and bladder carcinoma

126
Q

How does HIV cause cancer?

A

Indirectly lowers the immunity and allows other potentially carcinogenic infections to occur

127
Q

What is Knudson’s two hit hypothesis?

A

Need both alleles inactive for cancer to occur

If the cancer is familial

  • 1st hit is due to a germ line mutations and affects all cells in the body
  • 2nd hit is due to a somatic mutation

If the cancer is sporadic
* 1st hit is a somatic mutation
* 2nd hit is a somatic mutation
Both need to occur in the same cell

128
Q

What type of cancer was used to show the two hit hypothesis?

A

Retinoblastoma

129
Q

What type of genes are the one’s described in the two hit hypothesis?

A

Tumour suppressor genes as need bot alleles to be inactivated to prevent inhibition of cell growth

130
Q

What are tumour suppressor genes - normal function and abnormal function?

A

Their normal function is to stop cell proliferation

They usually result in loss of function mutations - both alleles need to be mutated

Abnormalities lead to failure of growth inhibition

131
Q

What are proto-oncogenes - normal function and abnormal function?

A

Normal function is to contribute to signalling pathways that drive proliferation

Usually result in gain of function mutations - only one allele needs to be mutated

Mutations that activate these genes and cause an excessive increase in one or more normal functions - mutations lead to oncogenes - able to promote cell growth in the absence of normal growth promoting signals - oncogenes are dominant over normal counterparts

132
Q

What was the first human oncogene to be discovered?

A

RAS - this is also the most common type of abnormality involving photo-oncogenes in human tumours

133
Q

What does the RAS proto-oncogene encode?

A

A small G protein that relays signals into the cell that eventually push the cell past the cell cycle’s restriction point. A mutated RAS protein that’s always active results in constant passage through the restriction point

134
Q

What does the RB gene do?

A

(TSG) It restrains cell proliferation by inhibiting passage through the restriction point - inactivation of both RB alleles allows unrestrained passage of cells through the restriction point

135
Q

What can pro-oncogenes encode?

A
  • growth factors e.g. PDGF
  • growth factor receptors e.g. HER2
  • plasma membrane signal transducers e.g. RAS
  • intracellular kinases e.g. BRAF
  • transcription factors e.g. MYC
  • cell cycle regulators (Cyclin D1)
  • apoptosis regulators (BCL2)
136
Q

What can tumour suppressor genes encode?

A

Encode things in the same pathways as proto-oncogenes but with antigrowth effects e.g. TP53

  • growth factors
  • growth factor receptors
  • plasma membrane signal transducers
  • intracellular kinases
  • transcription factors
  • cell cycle regulators
  • apoptosis regulators
137
Q

How does the permanent activation of RAS effect cyclin D, etc?

How does phosphorylation of Rb protein result in cell cycle proliferation?

A

Activation of RAS results in cycle D binding to CDK allowing continuance in the cell cycle

Phosphorylation allows cyclin-CDK complex to lead to continuance of the cell in the cell cycle

138
Q

Which genes prevent accumulation of DNA damage?

A

Caretaker genes

139
Q

What disease is due to mutations in DNA repeater genes? What is it’s inheritance pattern?

A

Xeroderma pigmentosum (XP) - autosomal recessive

140
Q

What is xeroderma pigmentosum due to?

A

Due to mutations in one of the seven genes that effect DNA nucleotide excision repair (NER)

141
Q

How do people with XP present?

A

They are very sensitive to UV damage and develop skin cancer at a young age

142
Q

How does hereditary non-polyposis colon cancer (HNPCC) syndrome occur? What is it’s inheritance pattern? What is it associated with?

A

A germline mutation affecting one of several DNA mismatch repair genes

Autosomal dominant

Colon carcinoma

143
Q

What genes is familial breast carcinoma associated with? What are these genes normal roles?

A

BRCA1 or BRCA2

Repairing double strand DNA breaks

Can be sporadic as well as genetic mutations

144
Q

What is the adenoma-carcinoma sequence?

A

Cancer progression - It can be illustrated, using colon carcinoma, to show that you need a combination of mutations in TS genes and proto-oncogenes to get a malignant neoplasms

  1. Normal epithelium
  2. APC gene mutation
  3. Early adenoma/dysplastic crypt
  4. EGFR signalling activation - KRAS gene mutation
  5. Intermediate adenoma
  6. TGF-beta response inactivation - Smad2/4
  7. Late adenoma
  8. Loss of p53 function
  9. Carcinoma
  10. Other genetic alterations
  11. Metastasis
145
Q

What are the 6 hallmarks of cancer?

A
  1. Self sufficiency in growth signals
  2. Resistance to growth stop signals e.g. TSGs
  3. Cell immortalisation - no limit to the number to times a 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 are about benign and malignant
6 is only malignant

146
Q

What is genetic instability regarded as?

A

An enabling characteristic

147
Q

What are the steps of initiation, promotion and progression to form cancer?

A
  1. Somatic cells are exposed to environmental carcinogens e.g. chemicals, radiation or infections That are either initiators or promotors
    Or have inherited mutations of germline cells
  2. A monoclonal population of mutant cells occurs
  3. Some of these clones have mutations affecting photo-oncogenes or TS genes (by chance) - the mutated proteins have roles in cell signalling pathways affecting hallmark changes
  4. During progression, the cells acquire more activated oncogenes/inactivated TS genes including ones that cause genetic instability
  5. The result over many years is a population of cells that have acquired a set of mutations that produce all the hallmarks of cancer
148
Q

What are two risk factors for hepatocellular carcinoma?

A
  • aflatoxins

* hepatitis B

149
Q

What are two risk factors for cervical cancer?

A
  • HPV

* early first pregnancy

150
Q

What is the main risk factor for colorectal carcinoma?

A
  • low fibre diet
151
Q

What are two risk factors for Burkitt’s lymphoma?

A
  • EBV

* malaria

152
Q

What are two risk factors for bladder cancer (squamous cell carcinoma) in Africa?

A
  • schistosomiasis

* catheter use, smoking, recurrent UTI, bladder stones - things that lead to chronic inflammation

153
Q

What are two risk factors for gastric adenocarcinoma?

A
  • H. pylori

* smoked and processed food

154
Q

What is malignant mesothelioma?

A

Tumour of the pleura/peritoneum/pericardium - cancer of the mesothelium

155
Q

Other than the skin, where else can malignant melanomas arise?

A

Anywhere there is mucosa/epithelium

156
Q

Which 3 types of lung cancer are associated with smoking?

A
  • squamous cell carcinoma
  • small cell carcinoma
  • adenocarcinoma
157
Q

What are the four methods of spread of lung cancer?

A
  • lymphatics
  • haematological
  • direct/local spread
  • transcoelomic
158
Q

Which tumour marker will you see in a yolk sac tumour?

A

Alpha-fetoprotein (AFP)

159
Q

Which tumour marker will you see in a choriocarcinoma?

A

Human chorionic gonadotropin (HCG)

160
Q

What types of tumour commonly occur in the testis?

A

Germ cell tumours - seminoma or non-seminomatous

161
Q

How can you tell a testicular tumour is seminomatous and not non-seminomatous?

A

Because there are no tumour markers elevated levels

162
Q

What type of cells are seen in Hodgkin’s lymphoma?

A

Reed-Sternberg cells and eosinophils (eosinophils are attracted due to factors released by reed-sternberg cells)

163
Q

What are B symptoms of Hodgkin’s lymphoma? What is their significance?

A

Non-specific system symptoms like fever, night sweats, weight loss, etc.

Indicate a worse prognosis

164
Q

How does herceptin work?

A
  1. Inhibits HER2 activation - suppression of cell growth/proliferation
  2. Helps flag tumour cells for destruction by NK cells
  3. Triggers HER2 internalisation and degradation
165
Q

Which tumour marker is used to monitor cancers of the large intestine?

A

Carcinoembryonic antigen

Pathological Processes * (10 decks)

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