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Principles of Disease > Tumour Pathology 4 > Flashcards

Tumour Pathology 4 Flashcards

1
Q

What is mitosis?

A

Mechanism of cellular replication

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2
Q

What does mitotic division generate?

A

Two genetically identical daughter cells

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3
Q

What is a cell cycle?

A

Time interval between miotic division

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4
Q

What is the cell cycle made up of?

A

G0

G1

S

G2

M

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5
Q

What happens during G0?

A

Left cell cycle and stopped dividing

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6
Q

What happens during G1?

A

Synthesis of components needed for DNA synthesis

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7
Q

What happens during S?

A

DNA synthesis

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8
Q

What happens during G2?

A

Preparation for mitosis

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9
Q

What happens during M?

A

Mitosis and cell division

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10
Q

How much cell divisions occur per second in humans?

A

25 x 106

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11
Q

How many cells are in the body?

A

1013

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12
Q

What does quality control insure?

A

Genetic fidelity:

Each cell must recieve a full chromosome compliment

Mutations in DNA sequences must not pass on

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13
Q

What factors is the cell cycle control by?

A

External factors

Intrinsic factors

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14
Q

What external factors control the cell cycle?

A

Hormones

Growth factors

Cytokines

Stroma

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15
Q

What intrinsic factor controls the cell cycle?

A

Critical checkpoints (restriction point R)

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16
Q

What does progress before and after restriction point R depend on?

A

Prior depends on external factors

After becomes autonomous

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17
Q

Where is R?

A

At the end of G1

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18
Q

What does G1 control mechanism ensure?

A

Everything is ready for DNA synthesis

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19
Q

What does G2 control mechanism ensure?

A

Everything is ready for cell division

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20
Q

What do checkpoints in G1 check?

A

Cell size is inadequete

Nutrition supply inadequete

Essential external stimulus lacking

DNA damage detected

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21
Q

What do checkpoints in S check?

A

DNA is not replicated

Chromosome mis-alignment

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22
Q

What do checkpoints in G2 do?

A

Cell size is inadequete

DNA damage is detected

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23
Q

What are checkpoints?

A

Systems of cyclically active and inactive enzymes

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24
Q

What is a catalytic subunit activated by?

A

Regulatory subunit

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25
Q

What are cyclin dependant kinases (CDK)?

A

Catalytic subunits

26
Q

What are the catalytic subunits?

A

Cyclin-dependent kinases (CDK)

27
Q

What are cyclines?

A

Regulatory subunits

28
Q

What are the active enzyme component of checkpoints called?

A

CDK/cyclin complex

29
Q

What is the process of cyclines and cyclin dependant kinases?

A

1) Different CDKs and cyclines operate at sequential stages of the cycle
2) Active CDK/cyclin complex phosphorylates target proteins
3) Phosphorylation results in activation/inactivation
4) Substrates regulate events in the next cycle phase

30
Q

How are CDKs regulated?

A

CDKs are constitutively expressed in an inactive form, whereas cyclines accumulate and are destroyed as cycle progresses

CDKs inhibitors (CKIs)

31
Q

What are the 2 families of CKIs?

A

INK4A family

CIP/KIP family

32
Q

What do molecules of the INK4A family do?

A

Bind to CDK4 and 6 and prevent association of these with their cyclin regulatory proteins

33
Q

What are the members of the INK4A family?

A

P16INK4A

P15INK4B

P18INK4C

P19INK4D

34
Q

What is a member of the CIP/KIP family?

35
Q

What do CDK inhibitors do?

A

Bind to the cyclin/CDK complexes

36
Q

What does the Retinoblastoma gene do?

A

Encodes a 110kDa phophoprotein (pRb) which is hypophosphorylated

37
Q

What does hypophosphorylated mean?

A

Phosphorylated to a less than normal extent

38
Q

What does phosphorylation do?

A

Increases a cells progress through the cycle

39
Q

What is pRb phosphorylated by?

A

Active cyclin D/CDK complex

40
Q

What does pRb target?

A

E2F transcription factor

41
Q

What does a hypphosphorylated/active Rb do?

A

Inactivates E2F

42
Q

What does a phosphorylated/inactive Rb do?

A

Loses affinity for E2F

43
Q

When is Rb active?

A

When it is hypophosphorylated

44
Q

When is Rb inactive?

A

When it is phosphorylated

45
Q

What does E2F do?

A

It is a potent stimulator of cell cycle entry. free E2F transcription factor activates vital target genes

46
Q

What does pRb binding to E2F do to the cell cycle?

47
Q

What is carcinogenesis?

A

The initiation of cancer formation

48
Q

What is carcinogenesis caused by?

A

Mutation of genetic material that upsets the normal balance between proliferation and apoptosis

49
Q

What does uncontrolled proliferation lead to?

50
Q

Loss of the ability to control proliferation is due to mutations in genes regulating?

A

Cell division

Apoptosis

DNA

51
Q

What is carcinogenesis caused by specifically?

A

Envrionmental agents

Inherited

52
Q

What environmental agents can cause carcinogenesis?

A

Chemicals

Radiation

Oncogene viruses

53
Q

What is the process of chemical carcinogenesis?

A

1) Purine and pyrimidine bases in DNA are critically damaged by oxidising and alkylating agents

2) Chemical carcinogens or their active metabolites react with DNA forming covalent bound productes (DNA adducts)
3) Adduct formation at particular chromosome sites cause cancer

54
Q

What are critical targets for radiation damage?

A

Purines and pyrimidine bases in DNA

55
Q

What is the primary defect in cancer?

A

Uncontrolled proliferation due to cell cycle dysregulation

56
Q

What are 2 regulatory pathways that frequently cause cancer?

A

Cyclin D-pRb-E2F pathway

P53 pathway

57
Q

What genes are the cause of dysregulation at G1 to S causing most cancers?

A

Rb

CDK4

Cyclin D

P16

58
Q

What is the function of P53?

A

Maintain genetic integrity

59
Q

How do P53 levels change in damaged cells?

A

They increase

60
Q

What does the increase of P53 in damaged cells do?

A

Induces a cycle arrest at G1

Facilitates DNA repair

Severe damage of P53 leads to P53-induced apoptosis

61
Q

What happens if there is no P53 present?

A

No cell arrest

Genetically damaged cells proliferate and form malignant tumours

Principles of Disease (45 decks)

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