9 Neoplasia 3&4 Flashcards

1
Q

Describe multifactorial nature of neoplasia pathogenesis

A

Intrinsic factors: Heredity, Age, Sex
Extrinsic factors: Environment (chemicals, radiation, infection) , Behaviour

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2
Q

How can overweight/obesity cause cancer

A

Adipose tissues can produce hormones & inflammatory molecules that contribute to the development of hyperplasia

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3
Q

Describe the geographical variations in the incidence of malignant tumours

A

Geographical regions can either be protective or carcinogenic depending on the type of cancer

E.g.) Japanese migrants to USA; ⬆️breast cancer⬇️gastric cancer

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4
Q

Describe the mechanism of Chemical carcinogenesis

A
  1. The presence of an initiator (non-lethal) in a neoplastic clone causes mutation
  2. Monoclonal neoplastic proliferation is caused by a promtoer
  3. Expansion of a mutated pop.
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5
Q

Examples of chemical carcinogens and the common cancers they can cause

A

2-naphthylamine: seen in dye&cigarettes, Bladder cancer
Benzopyrene: seen in cigarettes
Aflatoxin: seen in fertilisers, Liver cancer
Asbestos: seen in insulators in buildings, Mesothelioma

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6
Q

How can a pro-carcinogen be converted into a carcinogen

A

Cytochrome P450

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7
Q

Carcinogens can be…

A

Both can be an initiator & promoter (tobacco)
OR
Either initiator/promoter

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8
Q

Describe the mechanism of carcinogenesis caused by radiation

A

Alpha/beta practices, gamma rays, X-rays, UV rays can damage
-DNA directly
-Indirectly by generating free radicals

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9
Q

Describe the mechanism of carcinogenesis caused by infection

A
  1. Direct effects (e.g.HPV)
  2. Indirect effects (e.g.Hep B) ➡️ chronic liver cell injury & regeneration
  3. Reduced Immunity (HIV)
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10
Q

Describe how HPV (Human Papilloma Virus) can affect genes that control cell growth

A

Associated with cervical carcinoma
-HPV makes 2 proteins (E6 & E7)

  1. Virus infects cell, causes further replication of virus particles without killing the cell
    Method: E6 inhibit p53 which prevents cell from undergoing apoptosis
  2. Interfering with Retinoblastoma protein which is important as a cell cycle checkpoint
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11
Q

Describe the functions of Proto-oncogenes
Give an example

A

Participate in signalling pathways that drive proliferation
-mutations that activate these cause an excessive increase in one/more normal functions

‘Gain-of-function’ mutations

E.g.) RAS

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12
Q

What is a RAS gene and how is it involved in neoplasia

A

-Most common type of abnormality involving proto-oncogenes in human tumours

  1. Point mutation in RAS meaning there is no need for a growth factor for RAS to bind to GTP
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13
Q

Describe the function of Tumour Suppressor Genes
Give an example

A

Stop cell proliferation

-in most instances both alleles must be damaged for transformation to occur
-abnormalities in these genes leads to failure of growth inhibition

E.g.) Retinoblastoma, p53

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14
Q

Describe the functions of DNA repair genes in neoplasia
Give an example

A

‘Caretaker genes’
-repairs DNA mutation

Some inherited cancer syndromes have germline mutations that cause malignant neoplasm

E.g.) Xeroderma Pigmentosa (autosomal recessive)
-mutation gene that affects DNA nucleotide excision repair

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15
Q

Describe the stages of carcinogenesis

A
  1. Somatic cells are exposed to env. carcinogens that are either initiators/promoters gowing in a monoclonal pop. of mutant genes.
  2. Some of the clones harbour mutations affecting a proto-oncogene/tumour suppressor gene, affecting hallmark changes
  3. During progression, the cells acquire further activated oncogenes/inactivated tumour suppressor genes
  4. This eventually results in a pop. of cells that have acquired a set of mutations that produce all of the hallmarks of cancer
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16
Q

Describe the the alterations in growth control required to achieve the stages of carcinogenesis

A
17
Q

Describe the mechanism by which Retinoblastoma genes causes Retinoblastoma

A

‘2 hit hypothesis’

  1. (40% genetic) Familial Retinoblastoma
    -1 allele present at germline
    -affect both eyes
    -only 1sporadic hit required to develop retinoblastoma
  2. (60% random) Sporadic Retinoblastoma
    -no allele present at germline
    -affects one eye
    -LOWER risk of developing retinoblastoma since it requires 2 sporadic hits
18
Q

Identify the tumours that can be inherited and describe the understanding behind this

A

Xeroderma Pigmentosa:
mutation in one of the genes that affect DNA nucleotide excision repair

Familial breast carcinoma:
BRAC1/BRAC2 genes (involved in repairing double strand DNA breaks

19
Q

Identify medical conditions that are associated with an increased risk of malignancy

A
20
Q

Occupations associated with the development of tumours

A

Demolition, asbestos removal workers, Firefighter: risk of breathing in Asbestos causing inflammation & scarring of the lungs
-Mesothelioma

Dye industry: risk of exposure to 2-napthylamine
-Bladder cancer
-Long delay between carcinogen exposure and development of a malignant problem

21
Q

Define Carcinogenesis

A

Causes of cancer

22
Q

What do initiators and promoters do in neoplasm

A

Initiator: cause mutation
Promoter: cause sustained proliferation

23
Q

What are the 6 hallmarks of cancer

A

Relevant to benign & malignant neoplasm:
1. Self-sufficiency in growth signals
2. Resistance to growth stop signals
3. No limit on the no. of times a cell can divide (cell immortalisaiton)
4. Sustained inability to induce new blood vessels (angiogenesis)
5. Resistance to apoptosis

Relevant to ONLY malignant neoplasms:
6. The ability to invade & produce metastases

24
Q

What is Germline mutation
Give examples of this

A

A detectable variation within the DNA of germ cells (sperm &ova) which can be passed on offspring
e.g.)
-Tumour suppressor genes
-Proto-oncogenes
-Genes which control DNA repair