Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecular Basis Of Disease > Cancer > Flashcards

Cancer Flashcards

1
Q

Characteristics of Cancer Cells

A
  • lack of controlled growth
  • loss of specialised functions
  • less adhesive to other cells and extra cellular matrix
  • can metastasise
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Oncogene mutations require how many mutated alleles and how does their function alter

A
  • dominant manner (only one allele needs to be mutated for pre-disposition of cancer)
  • gain of function mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Mutations in tumour suppressor genes require how many alleles to be mutated for an individual to be predisposed to cancer and how does this alter the genes functions

A
  • loss of function mutations
  • both alleles need to be mutated (two hypothesis hit) for predisposition
    (Can be acquired or inherited through somatic mutations)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Stages of metastasis

A
  1. Benign tumour in primary location, angiogenesis, proliferation
  2. Metastatic sub clone of tumour breaks through basal lamina and passes through ECM
  3. Intravasation, interacts with host lymphoid cells
  4. Tumour cells embolus
  5. Adhesion to basement membrane of endothelial cells in blood vessels
  6. Extravasation, growth at secondary site and angiogenesis occurs at new site as well
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Def: Mortality

A

death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Def: morbidity

A

disease or ill health

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is burden of disease and the equation

A

quantifies the gap between populations actual health to ideal health in a given year

= time lost due to mortality + time lost due to disability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is disability adjusted life years (DALY) and its equation

A

Years of lost life (premature mortality) + Years lost to disability (due to injury or illness)

one DALY = one year of healthy life lost due to illness/death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the association of DALY and Burden of disease

A

the higher the DALY with a particular disease/injury = the greater the burden of that disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which sex and age experiences greater burden with an associated disease

A

Males

burden increases with age (highest at 65-84)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which disease has the highest burden of disease

A

Cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

cancer incidence and mortality increases with….

A

age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the two heritable properties of cancer cells

A
  1. unrestrained growth

2. invade and colonise (like the white people)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cancer cell morphology characteristics

A
  1. large variable shaped nuclei
  2. small cytoplasmic volume
  3. variation in size and shape
  4. disorganised arrangement of cells
  5. loss of normal specialised features
  6. elevated expression of particular cell markers
  7. large number of dividing cells
  8. poorly defined tumour boundaries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the two forms of tumours

A
  1. benign (non invasive)

2. malignant (cancer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

tumour size and associated detection

A

X ray detectable
- 10^8 cells

palpable
- 10^9 cells

therefore many cells need to be cancerous before detection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does the tumour need for development and how does this occur

A

a blood supply

occurs through angiogenesis

  • vascular endothelial growth factor is released by tumour which increases blood vessel expression
  • matrix metalloproteases (MMP’s) are also released for movement of vessels through ECM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When is the earliest that cancer can be detected (cell number) and what ways is cancer detected?

A

10^8 cells (1 billion) at detection

ways:
- mammography
- X ray
- biopsy
- detection of tumour antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Treatment of cancer

A

early intervention allows for

  • surgery
  • hormone therapy
  • chemotherapy
  • targeted drug therapy
  • radiotherapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is the relationship between cancer development and genetic factors

A

mutations accumulate in different genes which increases the development of cancer gradually

  1. initiation
    - normal cell to initiated cell
  2. promotion
    - initiated cell to cancer cell (differentiated)
  3. progression
    - differentiated cancer cell to undifferentiated and invasive cancer cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the environment inside a tumour cell

A

low oxygen levels

scarce nutrients

high acidity
- due to increased lactic acid from glycolysis

natural barriers to growth
- surrounded by normal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

When do selective advantages for cancers begin

A

take years to develop and vary for each cancer and individual

examples:
- leukaemia 5-8 years
- lung cancer 10-20 years
- prostate cancer 10+ years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

CERVICAL CANCER

what is cervical cancer? main cause? symptoms?

A

WHAT:
- excess prolif of squamous epithelial cells in neck of womb (cervix)

CAUSE:
HPV is a risk factor in 90% of cases

SYMTPOMS:
early stages:
- asymptomatic
- areas of dysplasia (detectable on pap smear)
later stages:
- dysplasia becomes more advanced (may lead to malignant cervical carcinoma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

CERVICAL CANCER

detection?

A

pap smear

cervical screening test
- evidence of HPV infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Genetic changes in cancer

A

genetically unstable

- accumulate mutations and chromosomal abnormalities at higher rate than normal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Epigenetic changes in cancer

A

changes which are not in the nucleotide sequence of DNA:

  1. unusual nucleus apparence
    - histones not acetylated
    - large amount of heterochromatin
    - DNA tightly packed (no gene expression)
  2. DNA methylation
    - gene expression switched off
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How does apoptosis contribute to cancer

A

normal mechanisms to induce apoptosis are switched off

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How can stem cells give rise to cancer cells

A

mutations can occur in stem cells which can lead to cancerous stem cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are oncogenes

A

normal gene which when mutated has involvement in cancer development

oncogenes produce oncoproteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what can cause oncogenes

A
  • viruses
  • chemicals
  • radiation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What factors may result in oncogenes

A

over-expressed proteins

reduced expression of proteins

defective proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Aetiology of Rous sarcoma virus

A

RNA retrovirus

  • uses reverse transcriptase to generate DNA intermediates
  • inserts into hist genome (provirus)

gene = src
- involved in regulation of cell growth and differentiation
- becomes mutated by virus creating (v-src)
- not needed for viral replication but transforms cell leading to
cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what does src gene encode for and how does v-src alter normal functioning

A

non receptor tyrosine kinase (signalling molecule)

v-rsc = constantly activated

  • activating kinase signalling cascades
  • decreased adhesion of cell to surface
  • increased uncontrolled growth
  • loss of contact inhibition
  • increased transport of metabolites
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How does the avian leokosis virus differ in mechanisms to the Rous sarcoma virus

A

instead of creating an oncogene this virus inserts its DNA next to a proto-oncogene
- acts as a strong promotor or enhancer for the gene

proto-oncogene c-myc (DNA binding protein - transcription factor)
- increases expression of c-myc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is a class of receptors which are susceptible to mutations in cancers? what is the normal structure and function of these receptors? How does this defer when mutated?

A

RECEPTOR CLASS:
receptor tyrosine kinases (RTK’s)

NORMAL STRUCTURE:
transmembrane protein with intra and extracellular domains

NORMAL FUNCTION:
receptors for growth factors and begin signal transduction pathways once growth factors bind

MUTATED STRUCTURE/FUNCTION:
result in continually active receptors even in the absence of ligands (growth factors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Common defective receptor tyrosine kinases

A

Erb-B family (AKA EGFR)

- Her2 is part of the family and common in breast tumors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Receptor tyrosine kinase general signaling pathway

A

the receptor have tyrosine kinase domains (particular part of the intracellular portion of protein) which become phosphorylated when the ligand binds

this activates RTK allowing other intracellular signalling proteins to bind become phosphorylated and then activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What happens when Erb-B (epidermal growth factor receptor EGFR) family becomes mutated

A

the extracellular domain becomes missing due to a truncated receptor

this means that it is constitutively active

leading to uncontrolled growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what is p53 and what is its normal function

A

p53 is a tumour suppressor transcription factor

NORMAL FUNCTION:
- regulated cell cycle by activating other transcription factors and recognises DNA damage
- conserves stability of genome by preventing mutations through:
- triggering growth arrest, DNA repair or apoptosis (when cannot be
repaired)

40
Q

Normal p53 pathway

A

WHEN P53 IS NOT NEEDED:

  1. bound to Mdm2
    • Mdm2 promotes it ubiquitylation and degradation in proteasomes

WHEN P53 IS NEEDED (DNA DAMAGE):

  1. p53 becomes phosphorylated which blocks the binding of Mdm2
  2. p53 binds to regulatory region of p21 gene which stimulates its expression
  3. p21 binds to G1/S Cdk
    • G1/S Cdk allows cell to continue in cell cycle
  4. G1/S Cdk becomes inactive triggering cell cycle arrest until damage is fixed
41
Q

Mutated p53 pathway

A

p53 becomes non-functional (cannot be phosphorylated therefore stays bound to Mdm2
- this leads damaged cells to continue in cell cycle which may lead to cancer

42
Q

What is the APC protein

A

adenomatous polyposis coli

tumour supressor transcription factor

43
Q

What are APC’s 2 main roles

A
  1. inhibits myc gene (transcription factor) expression
    • myc induces expression of many genes required for cell to
      progress from G1 to S phase in cell cycle
  2. Degradation of B-catenin
    • B-catenin has 2 roles:
      - cell to cell adhesion
      - drives transcription of target genes involved in cell proliferation
    • mutations which activate B-catenin are found in many cancers
44
Q

What are the consequences of mutations in the APC protein

A

no control of myc or B-catenin expression allowing cells to continue in the cell cycle even when damaged

this can cause cancer

45
Q

COLORECTAL CANCER

what are the precancerous growths that form? where do they form?

A

polyps which form on the inside wall of the colon

46
Q

COLORECTAL CANCER

What mutations are needed for precancerous growths to become cancer? How many mutations required?

A
  1. polyps contain APC mutations
  2. if polyps undergo a Ras mutation
    - more uncontrolled cell division
  3. another mutation in p53
    • malignant carcinoma

therefore 3 MUTATIONS NEEDED

47
Q

COLORECTAL CANCER

How are the APC mutations acquired

A

INHERITED:

  1. one APC allele mutation is inherited (familial adenomatous polyposis)
  2. only one more APC mutation = formation of polyps

OTHER PATIENTS:
acquire 2 mutations during life

48
Q

What are G proteins and what are the 2 types

A 
signal transduction proteins apart of the GTPase class 
- largest class of oncoproteins

2 types:

  1. heterotrimeric complexes
  2. small monomeric GTPases (e.g. Ras)
49
Q

G proteins function pathway

A
  1. hormone binds to receptor
  2. which then binds to GDP bound G protein
  3. when bound GDP is replaced by GTP and the subunits of G proteins dissociate
  4. G protein subunit binds to adenlate cyclase
  5. Adenlyl cyclase then converts ATP to activate cAMP
50
Q

What mutation causes Ras oncoprotein?

A

a single base change in normal proto-oncogene

- changes glycine amino acid to valine

51
Q

What changes in Ras function when it becomes mutated

A

loss of GTPase activity due to:

- an increased time Ras are bound to GTP which turns signalling pathway on for a lot longer

52
Q

What is the Ras pathway

A
  1. Ras protein lies inactive on cellular membrane bound to GDP
  2. phosphorylated RTK causes binding of adaptor protein
  3. adaptor protein becomes activated allowing Ras-activating protein to bind to it
  4. Ras activating protein causes GDP to be replaced with GTP activating Ras protein
53
Q

What are the 3 main cell types found in skin

A
  1. basal cells (lower layer)
  2. squamous cells (top layer)
  3. melanocytes (produces melanin which colours skin)
54
Q

What are the 2 types of skin cancer

A
  1. melanoma of skin
    • begins in melanocytes
  2. non-melanoma skin cancer (NMSC)
    • basal cell carcinoma (BCC)
    • squamous cell carcinoma (SCC)
55
Q

NON MELANOMA SKIN CANCER

Where does basal cell carcinoma most often occur and why

A

WHERE:

  • head
  • neck
  • arms

WHY:
high UV exposure in these areas

56
Q

NON-MELANOMA SKIN CANCER

what happens cellular wise in basal cell carcinoma? What is the rate of its growth and does it spread?

A

basal cells invade the dermis (where squamous cells lie)

slow growth

usually does not spread

57
Q

NON MELANOMA SKIN CANCER

Where does squamous cell carcinoma usually occur? what is its growth rate? can it spread?

A

head, neck and arms

fast growing

can spread

58
Q

MELANOMA CANCER

exposure to ….. increases risk

A

UV

59
Q

MELANOMA

Diagnosis

A 
A - asymmetry (irregular) 
B- boarders (uneven) 
C- colour (variegated) 
D- diameter (>6mm) 
E- evolving (changing and growing over time)
60
Q

What is metastasis

A

development of secondary growths at a different site than primary tumour

61
Q

Mechanisms of metastasis

A

cancer cells secrete proteases which digest ECM

selectins on endothelial cells recognise carbohydrate groups on cancer cells allowing them to adhere to endothelial cells at new site of the body

62
Q

E-cadherin function in normal cells

A

links cells together at the side and connects to cytoskeleton within cell
- B-catenin links E-cadherin to cytoskeleton

63
Q

How does E-cadherins change in cancer cells

A

E-cadherin expression is reduced or located in cytoplasm no the membrane

this causes a breakdown in cell to cell adhesion

64
Q

What are integrins and what is their function

A

integrins enable cells to link to extracellular matrix at basal surface
- also bind to cytoskeleton

65
Q

How do integrins differ in cancer

A

reduced adhesion of cells to basal lamina

alpha5beta3 integrin have elevated expression in metastasising cells
- alpha5beta3 have a wide specificity and therefore cells can move over wider range of surfaces

66
Q

Loss of E-cadherin or integrins cause cells to become more

A

motile

67
Q

What is the role of proteases?

A

regulate composition of extracellular molecules

endopeptidases are secreted by proteases
-breaks down peptide bonds between amino acids

68
Q

What are the 2 types of proteases?

A

serine proteases
- plasminogen

metalloproteinases

  • collagenase
  • stromelysin
69
Q

How does the ECM balance the function of proteases

A

protease inhibitors

70
Q

How are proteases secreted in both types

A

Both secreted as inactive forms which become activated

e. g. serine proteases
- secreted as precursor plaminogen
- becomes activated (plamin) by plaminogen activators

71
Q

How are metalloproteinases classified

A

by substrate specificity

  • collagenases (MMP1)
  • gelatinases (MMP2)
  • stromelysins (MMP3)
72
Q

Protease expression in cancer

A

penetration of basement membrane requires degradation of collagenase 4

  • collagenase 4 is produced more in metastatic cells
  • MMP3 is used for collagen 4 degradation
73
Q

Which hormones are expressed at each stage of breast development

A

puberty

  • estrogen
  • ductal elongation

sexual maturation

  • progesterone and estrogen
  • ductal branching and budding

pregnancy and post-partum lactation

  • prolactin and oxytocin
  • expansion and differentiation
74
Q

Examples of benign breast cancers

A
  • fibroadenoma

- lobular or ductal hyperplasia

75
Q

examples of malignant breast cancers

A
  • invasive lobular carcinoma (ILC)

- invasive ductal carcinoma (IDC)

76
Q

BREAST CANCER

Luminal A subtype identifiers (+-)

A

hormone receptor positive
HER2 negative
low Ki-67 (cell prolif)

77
Q

BREAST CANCER

Luminal B subtype identifiers (+ +/-)

A

Hormone receptor positive
HER2 pos/neg
high Ki67

78
Q

BREAST CANCER

Triple negative/basal-like subtype identifiers (–)

A

hormone receptor negative

HER2 negative

79
Q

BREAST CANCER

HER2 enriched subtype identifiers (-+)

A

Hormone receptor negative

HER2 positive

80
Q

BREAST CANCER

Normal like subtype identifiers (+-)

A

Hormone receptor positive

HER2 negative

81
Q

Traditional cancer treatments

A

surgery

chemo

radiation

82
Q

Systemic cancer treatment

A

angiogenesis inhibitors

immunotherapy

83
Q

Targeted cancer treatments

A

hormone therapy

monoclonal antibodies

84
Q

How does chemotherapy work and what are its effects

A

nonspecific intracellular poisons which interfere with cell division

effects:
- damage to normal cells which divide rapidly (bone marrow, digestive tract, hair follicles)

85
Q

What is radiation therapy and what are its effects

A

ionising radiation
- leads to formation of free radicals

damages DNA
- oxygen radicals

86
Q

What are the characteristics of the environment inside a tumour?

A

Low blood supply therefore deficient in O2 = hypoxic environment

87
Q

How can the the environment of the tumour be used for treatment advantage

A

hypoxia activated pro-drugs which only have effect in low oxygen environments

e.g evofosfamide (creates DNA crosslinks)

88
Q

What is the relationship between treatment and the tumour environment

A

tumour hypoxia contributes to treatment failure and relapse

- can lead to an aggressive phenotype which is resistant to both chemotherapy and radiotherapy

89
Q

CANCER TREATMENT

the drug Avastin is approved for which tumours?

A

glioblastoma and colorectal tumours

90
Q

CANCER TREATMENT

How does the drug Avastin function?

A
  1. uses recombinant human monoclonal antibodies which inhibits vascular endothelial growth factor A
  2. this blocks angiogenesis leading to lack of blood supply for the tumour
91
Q

CANCER TREATMENT

What are the adverse effects of the drug Avastin?

A

bleeding

pulmonary embolism

92
Q

BREAST CANCER TREATMENT

What are the 3 drug examples used in breast cancer?

A

Tamoxifen (TAM)

Fulvestrant (E17)

Herceptin

93
Q

BREAST CANCER TREATMENT

How does Tamoxifen (TAM) work?

A

blocks estrogen receptor (ER) activity by acting like an estrogen molecule
- antagonist

94
Q

BREAST CANCER TREATMENT

How does Fulvestrant (E17) work?

A

Binds to estrigen receptor (ER)
- down regulates ER by a functional blockage

under SERD class (selective ER degrader)

95
Q

BREAST CANCER TREATMENT

How does Herceptin work?

A

antibody based drug to treat HER2 pos breast cancer

binds to domain 4 of extracellular segment of HER2 receptor (EGF receptor)

Molecular Basis Of Disease (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions