14 - Neoplasia 3 Flashcards Preview

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Flashcards in 14 - Neoplasia 3 Deck (42)
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1
Q

What is carcinogenesis and what are the factors involved in this?

A

Extrinsic: prolonged life span

2
Q

What are the five behaviours that we undertake that can lead to cancer?

A
  • High BMI
  • Low fruit and veg intake
  • Lack of physical activity
  • Tobacco use
  • Alcohol use
3
Q

What are the categories of extrinsic carcinogens?

A
  • Infections
  • Chemicals
  • Radiation
4
Q

How is neoplasia multifactorial?

A
5
Q

What is 2-Napthylamine and what lessons does it teach us?

A
  • Chemical carcinogen used in the dye industry
    1. There is a long delay between carcinogen exposure and malignant neoplasm onset
    2. Risk of cancer depends on carcinogen dosage
    3. Carcinogens can be organ specific, e.g this carcinogen causes bladder carcinoma
6
Q

Why is it mainly roof workers that develop cancer from asbestos exposure?

A

Dosage of carcinogen highest in these populations, industrial scale

7
Q

What does the Ames test teach us about carcinogenesis?

A
  • Initiators are mutagens
  • Promoters cause prolonged proliferation

Initiators must be followed by promoters, leading to progression as there is a monoclonal expansion of mutant cells

8
Q

How can chemical carcinogens be classified?

A
9
Q

What are pro-carcinogens?

A

Chemicals that are not carcinogenic until they are converted into carcinogens by cytochrome P450 enzymes in the liver e.g nitrites

10
Q

What is a complete carcinogen?

A

Acts as both an initiator and a promoter

11
Q

What is radiation?

A

Any type of energy travelling through space.

12
Q

What are the properties of the following radiation?

  • UV radiation
  • Ionising radiation
  • Nuclear radiation
A
13
Q

Where do people’s radiation exposure come from?

A
14
Q

How does radiation damage DNA in general?

A
15
Q

How are infections carcinogenic?

A

Directly: affect genes that control cell growth

Indirectly: chronic tissue injury where the resulting regeneration acts either as a promoter for pre-existing mutations / initiator for new mutations

16
Q

How do the following pathogens act as carcinogens?

  • Human Papilloma Virus
  • Hepatitis B & C Viruses
  • Helicobacter pylori
  • Parasitic flukes
  • Human Immunodeficiency Virus
A

- HPV expresses E6 and E7 proteins which directly inhibit p53 and pRB protein function in cell proliferation (cervical carcinoma)

- Hepatitis B,C act indirectly and cause chronic liver cell injury and regeneration

- Helicobacter pylori causes chronic gastric inflammation (gastric carcinoma)

- Parasitic flukes act indirectly to cause inflammation in bile ducts and bladder mucosa (cholangio- and bladder carcinomas)

- HIV acts indirectly by lowering immunity and allowing other potentially carcinogenic infections to occur

17
Q

What is Knudson’s two hit hypothesis for carcinogenesis in sporadic and familial cases?

A
18
Q

Explain why initiation and promotion lead to neoplasms when they affect proto-oncogenes and tumour suppressor genes

A

- Tumour suppressor genes are genes which inhibit neoplastic growth – both alleles must be inactivated to allow neoplastic growth (two hits)

- Oncogenes are genes which enhance neoplastic growth and are the abnormally activated versions of normal proto-oncogenes – only one allele of each proto-oncogene needs to be activated to favour neoplastic growth

19
Q

How can the regulation point in the cell cycle be deregulated by a combination of mutations in TSG and POG?

A

⇒ The RAS proto-oncogene encodes a small G protein that relays signals into the cell & pushes the cell past the cell cycle restriction point

⇒ The mutant RAS oncogene encodes a protein that is always active, producing a constant signal to pass through the cell cycle’s restriction point

⇒ The RB gene restrains cell proliferation by inhibiting passage through the restriction point

Inactivation of both RB alleles therefore allows unrestrained passage through the restriction point

20
Q

What are some examples of protooncogenes and TSG?

A

POG:

  • GF receptors (HER2)
  • GF (PDGF)
  • Intracellular kinases (BRAF)
  • Apoptosis regulators

TSG:

- Anti-growth effect (TP53)

21
Q

What are caretaker genes?

A
  • Genes that maintain genetic stability, type of tumour suppressor gene
    e. g nucleotide excision repair, double strand repair
22
Q

For the following conditions, describe the type of repair system which is mutated and its overal effect on the genome:

  • Xeroderma pigmentosum
  • Hereditary non-polyposis colon cancer syndrome
  • Familial breast carcinoma
A

- Xeroderma pigmentosum: nucleotide excision repair → nucleotide instability

- HNPCC syndrome: mismatch repair → microsatellite instability

- Familial breast carcinoma: double strand break (BRCA1&2) → chromosomal instability

23
Q

What is genetic instability?

A

Genetic instability are a series of alterations in chromosome segregation during mitosis which account for the accelerated mutation rate found in malignant neoplasms

24
Q

This steady accumulation of multiple mutations is called cancer progression.

In terms of a colon carcinoma, illustrate how multiple mutations are required to make a neoplasm

A
25
Q

It is now believed that a fully evolved malignant neoplasm exhibits six hallmark signs of cancer plus one enabling feature.

What are these hallmark signs?

A

Benign: 1-5

Malignant: 1-6

26
Q

What is an enabling characteristic of malignant neoplasms?

A

Genetic instability

27
Q

Summarise the timeline of the formation of a neoplasm

A
28
Q

What are the role of the following oncogenes:

  • ras
  • c-myc
  • c-erB-2 (HER-2)
A

- RAS: normally controls the cell restriction point, activated when GF binds to receptor

- c-myc: protooncogene as it is a transcription factor

- HER2: tyrosine kinase membrane receptor that is a protooncogene

29
Q

What are some medical conditions associated with a high risk of malignancy?

A
  • Cirrhosis
  • Ulcerative colitis
  • Hashimoto’s thyroiditis
  • Chronic atrophic gastritis
30
Q

What type of tumour is normally found in the pancreas?

A
  • Normally malignant squamous cell carcinoma
  • So deadly as jaundice is the first symptom and this develops late in progression
31
Q

What is the commonest abdominal tumour to spread by transcolemic route?

A

Ovarian cancer

32
Q

What types of anaemia do you develop with cancer?

A
  • Iron deficiency due to chronic bleeding
  • Anaemia of chronic disease
  • Aplastic
  • Myelophthisic
33
Q

Why do you get cachexia with malignancy?

A
34
Q

What are the two major risk factors for the following neoplasms:

  • Hepatocellular carcinoma
  • Cervical Cancer
  • Colorectal cancer
  • Burkitt’s Lymphoma
  • African Bladder Cancer
  • Gastric adenocarcinoma
A
  • Aflatoxin, Hep B, Chronic alcohol use
  • HPV (E6 and E7), family history
  • Red meat and high fibre diet
  • EBV and Malaria
  • Schistoma (inflammation laying eggs in bladder)
  • Helicobacter Pyli (chronic inflammation)
35
Q

How does asbestos cause cancer and what cancers does it typically cause?

A
  • Fibres get inhaled into lung, invade mesothelium and set up irritation causing proliferation. 40 years later mesothelioma can occur.
  • Can absorb mutagens from cigarette smoke so double carcinogen
  • Stains blue with iron stain under microscope
  • Stomach, pharyngeal, colon, mesothelioma
36
Q

Diagnose the following malignant neoplasms of skin biopsies and discuss how they behave.

A
  1. Malignant melanoma: rapidly metastasises
  2. Squamous cell carcinoma
  3. Basal cell carcinoma: rarely metastasises but becomes invasive from in situ
37
Q

What type of genes are BRCA1 and BRCA 2 and what cancers are they associated with?

A
  • Tumour supressor genes as repair double strand breaks
  • Breast, Ovarian, Prostate, Pancreatic
38
Q

Breast cancers with BRCA1 are associated with poor differentiation and triple negative, what does this mean?

A

Negative for progesterone, oestrogen and herceptin receptors so hard to target hormone therapy and therefore poor prognosis

39
Q

What are the different lung cancers associated with smoking?

A
40
Q

What gene causes familial adenomatous polyposis (FAP)

A

APC: TSG involved in caderhins.

Hundreds of polyps in the bowel

41
Q

What is the adenoma-carcinoma sequence?

A

Step by step mutations inactivating TSG and activating oncogenes

42
Q

What are the differences between FAP and HNPCC?

A
  • HNPCC have less than 100 polyps and can quickly become cancerous, not from adenoma
  • Several gene defects in HNPCC but one in FAP