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ESA2 Emily > MOD Neoplasia 2 > Flashcards

MOD Neoplasia 2 Flashcards

0
Q

What does altered adhesion between malignant cells and Stromal proteins cause?

A

Reduction in E Cadherin

Changes in integrin expression (which is involved in signalling of the actin cytoskeleton to alter motility)

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1
Q

What is needed for local invasion of tumour cells?

A

Altered adhesion
Stromal proteolysis
Motility

Which all lead to a carcinoma cell phenotype causing epithelial-to-mesenchymal transition (EMT)

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2
Q

Since the carcinoma must be able to degrade the basement membrane and stromal surface to invade there must be altered expression of proteases. What are they?

A

Matrix metalloproteinases
MMPs

MMP9 breaks down type 1 collagen found in basement membrane

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3
Q

Why do malignant tumours not tend to invade arterial walls?

A

They do not produce elastase to break down elastin in arterial walls. They do however produce collegenase and so can penetrate bone.

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4
Q

What is a metastasis

A

Secomdary tumour which grows separately from primary tumour and has arisen from detected, transported cells.
It can get to the n pew site via: blood, lymph, or fluid in tissue spaces

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5
Q

How are metastasises described on a chest x-Ray?

A

Coin lesions if single or cannon ball lesions if multiple.

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6
Q

How does a renal cell carcinoma grow?

A

Enters renal vein to form a plug and grows along inferior vena cava and into right heart. This is what malignant tumours often do and grow within large veins like a continuous root extension of the tumour.

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7
Q

If a metastase grows quickly, what can happen to the centre?

A

Become necrotic

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8
Q

Where do tumours which drain to the portal system metastasise to?

A

Liver

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9
Q

Where do breast carcinomas metastasise to?

A

Skelton

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10
Q

Where do bronchial carcinomas metastasise to?

A

Adrenal gland

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11
Q

What are bilateral metastatic tumours of the ovaries also known as?

A

Kruckenberg tumours

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12
Q

What do malignant cells do after penetrating lymphatics?

A

Float to next lymph node where they settle in peripheral sinus and grow

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13
Q

Describe peau d’orange

A

Carcinomas of breast tissue can permeate lymphatics of overlying skin and cause lymphatic obstruction to make the skin oedematous and puckered.

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14
Q

Why may a lymph node downstream from a tumour swell?

A

Metastasis
Or
Secondary to antigens and irritating material leaking out of tumour- especially if necrotic, ulcerated or infected.

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15
Q

Why do ascites develop?

A

Result of peritoneal seeding
Secondary factors from tumours which cause leakage of fluid from peritoneal membrane
Secondary to fluid leaking from surface of malignancy

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16
Q

When does seeding into CSF occur?

A

Tumours of CNS

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17
Q

What increases likelihood of metastasis?

A

More tumour progression
More histologically atypical
Size of primary tumour (larger)

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18
Q

Do CNS tumours metastasise?

A

Not normally

They are in an enclosed space and often kill before visceral metastases are detected.

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19
Q

Describe tumour dormancy

A

After a patient has been successfully treated there may be surviving micro deposits that fail to grow and so are called micometasteses. If a person relapses, this may be due to one of these growing.

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20
Q

Do mother to foetus metastasis occur?

A

No,

Or very very rare

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21
Q

How to invade a blood vessel:

A

Separate from tumour mass and move in right direction.
Digest way through intracellular matrix and vascular basement membrane to enter lumen of a vessel.
Escape defensive mechanisms of the blood
Survive impact and mechanical squeeze of going through a vessel small enough to metastasise
Penetrate endothelium and basement membrane and escape more dangerous cells
Multiply, induce angiogenesis and establish a tumour.

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22
Q

Is a clump of cells or a single cell likely to be better at metastising

A

Clump of approx 4

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23
Q

Describe the 5 step mechanism of metastasis

A
  1. Detachment from main tumour
  2. Invasion via release of enzymes
  3. Penetration into blood vessels (must show attachment to basement membrane, lysis by secretion of collagenase and invasion)
  4. Tumour cells are transported in the blood stream and become coated with platelets (which may help)
  5. Embolism and penetration out of vessels
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24
Q

What is the affect of prostate cancer spreading to bone?

A

Makes bone form in a disorganised, osteoscleroric, manor

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25
Q

Where do carcinomas spread to first?

A

Lymphatics

26
Q

Where do sarcomas spread to first?

A

Sarcoma- Connective tissue tumour

Blood and then from the blood to the liver, brain and bone

27
Q

Explain the seed and soil hypothesis of cancer metastasis

A 
Malignant cells (seeds) require the correct environment (soil) to establish metastasis. 
The environment is referred to as a niche because that is where it is able to metastasise to. For example: breast cancer's niche is bone marrow
28
Q

What are the local effects of tumours on the host?

A

Occlusion of a lumen if a tumour arises in a tubular or hollow structure e..g SVC occlusion, leading to blockage of blood supply to head and face becoming puffy and feeling of being strangled.

Ulceration of tumours on surface can cause bleeding and/or infection

Malignant tumours infiltrate and destroy tissues in their way, causing fistulae (abnormal communication) e.g. Between bladder and rectum.

29
Q

What is paraneoplastic syndrome?

A

Symptom complexes that accompany tumours and concern distant targets whether the mechanisms be hormonal, toxic, immunologic or unknown.

30
Q

Describe the endocrine disturbances associated with tumours.

A

Many malignant tumours perform ectopic secretion of hormones
Most common offenders are lung carcinomas e.g. Small cell carcinoma of the lung producing ADH (causing hyponatremia (abnormally low sodium levels), resulting in confusion, convulsion and coma)

Also squamous cell carcinoma of the lung producing PTH, and causing hypercalaemia, resulting in constipation, polyuria, polydipsia, vomiting, psychosis and coma.

Paraneoplastic hypercalcaemia is seen in 10-20% of cancer patients. (Meaning it is result of cancer in the body but not the direct effect of the tumour)

Neoplastic hypercalcaemia (when it is relating directly to a tumour) can be caused by: parathyroid tumour, extensive metastatic bone destruction, parathyroid-hormone-like peptide.

31
Q

What do renal cell carcinomas do to the body?

A

Produce erythropoietin, resulting in high haematocrit and symptoms related to his blood viscosity.

32
Q

Hypercoaguable state can be observed in 95% of cancer patients. Why?

A

Platelets are activated by tumour products such as ADP

tumours secrete procoagulants e.g. Tissue factor, mucin from adenocarcinomas

33
Q

What is trousseau’s syndrome?

A

An early sign of gastric, pancreatic or lung cancer

Medical sign involving episodes of vessel inflammation due to a blood clot (this is called thrombophlebitis)

34
Q

How may a tumour effect the skin?

A

Acanthosis nigricans- symmetric, brown, warty hyperpigmented skin, with hyperkeratosis of axilla region.
More than 50% occur in association with an internal malignancy especially carcinoma of the gastrointestinal tract.

Can also get pruitis (severe itching of the skin) and myositis and dermamyositis (a rash over over the eyes and fingers- often associated with malignancy)

35
Q

How does tumour cause cachexia?

A

Reduced appetite and weight loss to cause wasting of whole body because:

  • tumours cause macrophages to produce tumour necrosis factor, resulting in wasting
  • tumours cause loss of appetite and change sense of taste
  • metabolism is increased
36
Q

What is tumour lysis syndrome?

A

When a tumour with extensive, acute necrosis releases toxic amounts of potassium and Uric acid in response to X-ray or chemotherapy.
The larger the tumour the greater the danger

Often seen in Burkitts lymphoma

37
Q

How does cancer kill?

A

Infection because cancer and cancer treatment is anti inflammatory.
Haemoragging and thromboembolic phenomena- 10-20%
Cachexia 1%
Respiratory failure
Renal failure

38
Q

What are the chemical causes of cancer?

A

Soot

Tar and derivatives (aromatic amines)

39
Q

Wha percentage of cancers are due to chemicals?

A

80-90%

40
Q

Are carcinogenic molecules electrophilic or phobic?

What is the result of this?

A

Electrophilic
Seek nucleophilic sites to form Covalent bonds. E.g. DNA, RNA and proteins

Note: in their native state, few carcinogens are actually electrophilic. They are inactive and are slowly activated in the body.

41
Q

What are inactive carcinogens called?

A

Procarcinogens

42
Q

Why are carcinogens organs selective?

A

Allow activation from presence and balance of specific enzymes.

43
Q

When may alcohol promote cancer?

A

Not in itself carcinogenic, but can cause liver cirrhosis, and regenerating nodules may become neoplastic.

Also in conjunction with smoking of tobacco increases risk of oesophageal cancer

44
Q

Name some dietary carcinogens

A

Nitrosamines- produce gastric cancer
Precursor is found as a food additive in cured meat and fish to improve appearance and taste.
Also present in tobacco smoke
Can inhibit production of nitrosamines from nitrites by adding ascorbic acid to food/the diet

Aflatoxin B1- major factor in liver cancer in Africa and Asia.
Produced by a bacteria which grows on grain stored in warm, humid conditions.
Acts in conjunction with hepatitis B (which also causes liver cancer)

45
Q

Name some dietry anti carcinogens

A

Fibre
Vitamin A
Vitamin C
Certain seeds

46
Q

How may hormonal over stimulation of an organ cause malignancy?

A

Over stimulation can cause hyperplasia which can progress to benign tumours which in time can turn into malignant tumours

47
Q

How can obesity increase your risk of endometrial cancer?

A

Adipose tissue converts androgens to oestrogens, resulting in increased risk of endometrial cancer

48
Q

What cancer risk comes with the contraceptive pill?

A

Liver adenomas

49
Q

What is nulliparous and what is its relevance in cancer?

A

Having not carried a baby to 20 weeks

Increased risk of breast cancer

50
Q

What does early first pregnancy protect from?

A

Breast cancer

51
Q

What genes are associated with breast cancer genetic predisposition?

A

BRCA1 and BRCA2

52
Q

What has a person who has mesothelioma been exposed to? Is this disease benign or malignant?

A

Asbestos (Bradford hill criteria- specificity)

Malignant

53
Q

What treatment during pregnancy can actually cause cancer?

A

Diethylstilboestrol is used to stop bleeding during pregnancy, but can cause adenocarcinoma of the vagina in the foetus (if a girl)

54
Q

Can immunosuppresion cause cancer?

A

Yes

55
Q

What is the role of free radicals in cancer formation?

A

Injure DNA

Involved in carcinogenesis by ionising radiation

56
Q

What are the physical causes of tumours?

A

Ultraviolet and ionising radiation are the only two types of radiation which are carcinogenic

UV can cause squamous cell carcinoma and melanomas
Melanomas are becoming more common due to increased prevalence of sunbathing and thinning of the ozone layer
UV cases damage by forming diners and cross-links, but needs repeated stimulation

Single exposure to ionising radiation can cause cancer. Radiation injury can either cause shortened cell survival (utilised in tumour radiotherapy) or induce malignant transformation in cells

57
Q

What two viruses can cause cancer?

A

Schistosoma causes bladder cancer

Hepatocellular carcinoma is also caused by virus

58
Q

What do retroviruses do?

A

Transcribe RNA backwards into DNA using reverse transcriptase enzyme. The role of them in cancer is to steal cellular genes and turn them into cancer genes

59
Q

What is an oncogene?

A

A gene which produces cancer.

Precursors are part of normal cellular genome- proto-oncogene.

60
Q

How are proto-oncogenes activated?

A
  1. Make it encode a defective hyperactive protein

2. Make it encode too much protein

61
Q

What can Epstein Barr virus cause

A

Burkitts lymphoma and nasopharyngeal carcinoma

62
Q

What are RNA oncogenic viruses also known as and why?

A

Acute transforming proteins because they act very quickly. They can produce leukaemia in a mater of days.

ESA2 Emily (8 decks)

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