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Semester 2 - Mechanisms of Disease > Session 10 - NeoplasiaII > Flashcards

Session 10 - NeoplasiaII Flashcards

1
Q

Define invasion of malignant cells

A

The ability of cells to break through the basement membrane and spread

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2
Q

Where do malignant tumours invade?

A

Surrounding tissue, lymphatic and vascular channels

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3
Q

What are the steps of malignant cells invasion?

A

1) Grow and invade at primary site
2) Enter a transport system
3) Grow at the secondary site to form a new tumour

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4
Q

What is metastasis?

A

Spread of a malignant tumour to a distant non- adjacent site

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5
Q

What do malignant cells need to avoid in order to succesfully metastasise?

A

The bodies immune system
Shearing force of movement through body
Free radical damage

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6
Q

What three important alterations are required for invasion of surrounding tissue by carcinomas?

A

Altered adhesion, stromal and basement membrane proteolysis and motility.
Also need to generate new blood supply.

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7
Q

Why are the alterations required for invasion called EMT?

A

Because carcinoma becomes more like mesenchymal cell, so it is an epithelial to mesenchymal transition (EMT)
Change in phenotype, eventually undergoes MET

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8
Q

How does altered cell adhesion occur in malignant cells? (2)

A

Cell-Cell interactions
Reduced expression of cadherins, which normally bind cells together.

Cell - Stroma interactions
Reduced expression of integrins in maligant cells allows for movement

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9
Q

How do malignant cells proteolyse extracellular matrix and stroma?

A

Metastatic cells synthesise and release Matrix Metalloproteinases. These allow metastatic cells to digest ECM and move to and break through basement membrane

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10
Q

What does
MMP1 digest?
MMP2/9 digest?

A

MMP1 - Type 1 collagen

MMP2 - Type IV collagen

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11
Q

How does altered motility occur in malignant cells?

A

Changes in actin cytoskeleton, via integrin signalling.

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12
Q

Why is tumour growth halted once it reaches 1-2mm3 in volume?

A

Growth is halted due to lack of nutrients/oxygen. This alters the tumours microenvironment, making it hypoxic.

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13
Q

What does tumour hypoxia cause?

A

Upregulation of pro-angiogenesis factors such as

Angiopoietin, VEGF

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14
Q

What do angiopoietin and VEGF cause the growth of?

A

Growth of new, thin wall blood vessels that allow growth of tumour. Also provides another opportunity to enter the bloodstream.

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15
Q

How do malignant cells travel to distant sites?

A

1) Blood vessels via capillaries and venules (tumour embolisis). No elastase so no arterial movement (CVS1!)
2) Lymphatic system
3) Fluid in body (pleura, peritnoeal, pericardial and brain ventricles), which is known as transcoelomic spread.

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16
Q

What must a cell does once it reaches a secondary site?

A

Extravasation (move out of a vessel) and growth

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17
Q

What is the consequence of failed secondary site invasion?

A

Micrometastases, which are harboured by many disease free people

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18
Q

How do neoplasmic relapses occur?

A

Due to micrometastases starting to grow

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19
Q

In which type of neoplasm is metastases via lymph nodes most common? What occurs?

A

Carcinoma

Local and distant lymph nodes affected, can often involve lymphatics of the lung

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20
Q

How does transcoleomic metastases spread?

A

To other areas in coleomic space or to adjacent organs

21
Q

What is a cancer niche?

A

Interaction between malignant cells and nearby non-neoplastic cells, resulting in

22
Q

In which type of neoplasm in metastases via blood most common? What are four common sites of blood borne spread?

A

Sarcomas

Lung, bone, liver and brain

23
Q

What types of neoplasm often spread to lung?

A

Sarcomas (osteosarcoma)
Carcinomas (breast, stomach and large intestine)
Kidney (cannon ball secondary metastes)
Testis (malignant teratoma)

24
Q

What types of of neoplasm often spread to liver?

A

Carcinomas of large intestine, via portal vein

Bronchial and breast carcinoma

25
Q

What occurs in metastes to bone?

A

Can cause destruction of bone, leading to pathological fracture via carcinomas (bronchial, breast, thyroid and renal)
Can cause produce of dense bone via prostate cancer (osteosclerosis)

26
Q

What occurs in metastases to brain?

A

Causes a wide range of neurological symptoms and act as a space occupuing lesion

27
Q

What are metastasis to braince commonly from

A 
Bronchial carcinoma
Breast carcinoma
Testicular carcinoma
Testicular carcinoma
Malignant melanoma
28
Q

What is the bases of cancer staging?

A

The fact that metastasis is related to the size of the primary neoplasm

29
Q

Give an example of a very agressive neoplasm

A

Small cell bronchial carcinoma

30
Q

Give an example of a safer (relatively) carcinoma

A

Basal cell carcinoma of the skin

31
Q

What are the two wasys in which the effects of a neoplasm on a host can be classified?

A

Due to direct local effects and indirect systemic effects

32
Q

Give 3 local effects of benign neoplasms

A

Compression of adjacent structures
Blocking tubes and orifices
Ulceraton of surface mucosa
Space occupying lesion (brain)

33
Q

Give 5 local effects of malignant neoplasms

A 
Destroy surrounding tissue
Infiltration around and into nerves, blood vessels and lymphatics 
Blocking tubes and orifices 
Ulceration of surface mucosa
Space occupying lesion (brain)
34
Q

What symptoms are caused by the systemic effects of neoplasm? Why?

A 
Caused by cytokine release
Reduced appetite and weight loss (cachexia)
General discomfort (Malaise)
Fever (pyrexia)
Immunosupression 
Thrombosis
35
Q

What are the four systemic systems which are affected by systemic effects of neoplasms?

A

Haematological
Endocrine
Skin
Neuromuscular

36
Q

What are the systemic haematological repercussions of neoplasms and why do they occur?

A

Anaemia
- Due to malignant infiltration bone marrow
Low white cell and platelets
- Infiltration of bone marrow
- Consequence of treatments
Thrombosis
- Carcinoma of pancreas (secreted pro-clotting factors)

37
Q

What are the two systemic endocrine repercussions of neoplasms?

A

Excessive secretion of hormones
- due to benign and malignant neoplasms of endocrine glands
Extopic hormone secretion
- ACTH by small cell carcinoma of bronchus

38
Q

What are the four systemic skin repercussions of neoplasms?

A

Increased pigmentation
Pruritis (itching)
Fever
Dermatomyositis (inflammation of muscles and skin)

39
Q

What are five neuromuscular issues associated with neoplasms

A 
Problemas with balance
Sensory/sensorimotor neuropathies
Myopathy and mysathenia
Dysfunction of white brain matter
Not due to metastasis of braine
40
Q

What is carcinomatosis?

A

Terminal cancer

41
Q

What is embolic trauma?

A

Shearing force
Free radical damage
Immune attack

42
Q

How do cancer cells grow new blood supplies?

A

angiopoietin and VEGF recruited from cancer niche

43
Q

What is the seed and soil hypothesis of metastasis?

A

Once systemic circulation is bypassed, cancer may metastasise anywhere win the body with favourable interactions between malignant cells and local tumour environment (kidney notable in that cancers do not grow - incompatible niche)

44
Q

Where are the most likely places cancer cells will grow?

A

Bone, lung, liver, brain

45
Q

Which cancers most frequently spread to bone?

A

Breast, brain, liver, kidneys

??

46
Q

What is size of tumour proportional to?

A

Likelihood of spread

47
Q

What is paraneoplastic syndrome?

A

Effects of tumour burden, secreted hormone and other

48
Q

What are the main effects of benign tumour?

A

Local and hormonal effects

49
Q

What is erosion of epithelial surface called?

A

Ulceration

Semester 2 - Mechanisms of Disease (16 decks)

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