Neoplasia 2 Flashcards
1
Q
what are some important genes in carcinogenesis
A
- oncogenes
- tumour suppressor genes
- dna repair genes
- miRNAs
- chromosomal aberrations
- epigenetic mutations
2
Q
what are oncogenes also known as
A
accelerators
3
Q
what are accelerators of carcinogenesis
A
oncogenes
4
Q
what are brakers of carcinogenesis
A
tumour suppressor genes
5
Q
A
6
Q
A
7
Q
what can oncogenes be abnormal variants of
A
- growth factors
- growth factor receptors
- signal transducers
- control of gene expression
7
Q
what are proto oncogenes
A
normal genes which regulate cell division
7
Q
what do oncogenes produce
A
oncoproteins
8
Q
which type of tissue is more sensitive to radiation
A
those where the cells are rapidly renewed
9
Q
how do miRNA act as carcinogens
A
they have a controlling function over the rest of the genes
thousands are the target for drug development to control the development of carcinogenesis
10
Q
what are epigenetic mutations
A
changes to dna that regulate whether genes are switched on or off
caused by behaviour and environment
do not change dna sequence
reversible
11
Q
what is the most important carcinogen group
A
oncogenes
12
Q
what is the normal version of oncogenes called
A
proto oncogenes
13
Q
what forms can proto oncogenes come in
A
- growth factors
- growth factor receptors
- signal transducers
- control of gene expression
14
Q
what is the important function for proto oncogenes
A
regulation of cell division
15
Q
what happens if tight regulation of cell division is lost
A
increase in growth factor production and acting on specific cells which will divide and grow at a fast rate
often occurs if the gene is mutated
16
Q
what is the activity of oncogenes held in check by
A
tumour suppressor proteins
17
Q
what are the three mechanisms by which tight regulation of cell division is lost
A
- mutation
- excess normal product
- enhanced transcription
18
Q
what does a mutation of oncogenes lead to
A
increased activity of the product
19
Q
what can cause an excess production of normal product
A
- duplication of the gene
- viral product
20
Q
what can cause enhanced transcription of the normal product
A
translocation
chromosome rearrangement
21
Q
describe chronic myeloid leukaemia
A
- translocation can cause formation of a hybrid gene
- hybrid genes are nicknamed the philadelphia chromosome for this condition
- production of tyrosine kinase which is a growth factor that stimulates lots of pathways
22
Q
what is burketts lymphoma associated with
A
epstein barr virus
23
what is the function of tumour suppressor genes
act to inhibit cell division and suppress growth
act as anti oncogenes
requires loss of both alleles
24
what is the knudson two hit hypothesis
idea that most tumour suppressor genes require both alleles to be inactivated, either through mutations or epigenetic silencing to cause a phenotypic change
24
describe the retinoblastoma gene and how it links to the knudson two hit hypothesis
person inherits defective gene from parents and passes this to children who has both genes mutated to form a malignancy
25
describe the function of TP53
- acts just before the restriction point
- two main functions in response to damaged DNA which are to stop the cell cycle and allow dna repair
- trigger apoptosis if repair is not possible
- often inactivated in cancer through mutation or deletion or due to viral proteins
26
in how many cases of head and neck cancer are there mutations in the tp53 gene
50%
27
what is included in genetic susceptibility to cancer
- inherited cancer syndromes
- familial cancer
- defective dna repair
28
describe inherited cancer syndromes
- single mutated genes that are often tumour suppressors
- retinoblastoma and some colon cancers
29
what is an example of an inherited cancer
retinoblastoma
30
what is an example of familial cancer
breast ovary and colon
31
describe the cause of familial cancer
family clusters, genes and pattern of inheritance are not clear
32
describe defective dna repair
increased sensivity to carcinogens and general increased cancer risk if a person inherits a defective dna repair system
33
what is an example of a cancer resulting from a defective dna repair system
xeroderma pigmentosum
34
what is xeroderma pigmentosum
this is when people do not go out in the sunlight because mutations will occur and will not be repaired so they can develop many skin malignancies
35
what are some other systems affected by malignancies
- cell division control
- dna repair mechanisms
- apoptosis inhibition
- stimulation of blood vessel formation
- destructive enzymes activated
- cell motility increased
36
main differences between a cancer cell and a healthy cell
- proliferate faster
- live longer
- not fully differentiated
- invade and destroy surrounding tissues
- avoid apoptosis
- produce its own food
37
how do cancer cells proliferate
they are not dependent on growth signals coming from other areas of the body and develop their own growth signals and formation
38
what are the six basic hallmarks of a cancer
- evading apoptosis
- self sufficiency in growth signals
- insensitivity to anti growth signals
- tissue invasion and metastasis
- limitless replicative potential
- sustained angiogenesis
39
what are the modes of spread of malignant tumours
- local and then systemic
- lymphatic spread
- blood spread
- transcoelomic spread
- intraepithelial spread
40
what is haemotegenous spread
spread of maligancies through the blood
41
what is an example of a disease that spreads intraepithelially
pagets disease of the breast
42
what is metastasis
the spread of the malignant cells to distant organs forming secondary tumours
43
what is transcoelomic spread
route of tumour metastasis across a body cavity, when a malignancy penetrates the surface of the cavity
44
describe the metastatic behaviour of carcinomas
they spread in the lymph first and later in the disease they spread in the blood
45
describe the metastatic behaviour of sarcomas
spread in the blood first and then in the lymphatics
46
describe the metastatic behaviours of lung cancer
lung to lymph node to liver bone and brain
47
describe the metastatic pathway of tongue cancer
tongue to neck nodes to lung and spine
48
what are the stages to cancer spreading through the blood into other organs and tissues
- direct spread and invasiveness
- angiogenesis
- vascular invasion and spread
- establishment of new colony
49
what happens in step one of blood spread of cancer
reduced cell to cell adhesion and invasion of the basement membrane and stroma
50
what happens in step two of cancer spreading in the blood
increased cell motility due to factors produced by tumour cells
51
what happens in step three of cancer spreading in the blood
walls of new vessels are thin and more easily invaded
cancer cells move in circulation and are packed in the capillary bed and will break out the capillaries
52
what happens in the final stage of blood spread of cancer
cells invade the surrounding tissues and proliferate and stimulate angiogenesis and spread further
53
what is tumour grading looking at
biological nature of the tumout
54
what is tumour staging looking at
the extent of the spread
55
how is the grade of a tumour studied
through histopathology
56
how is the stage of the tumour determined
clinical investigation
57
describe the process of grading tumours
histological assessment of the following factors:
- invasion into underlying tissue
- cellular atypia
58
what are some examples of cellular atypia that are looked for in histological assessment of a tumour
abnormal mitotic activity
nuclear pleomorphism
differentiation
necrosis
59
what are some methods of histological assessment when grading tumours
numerical grades
low, intermediate or high
degree of differentiation
60
what does cancer staging describe
the extent or severity of a persons cancer
knowing the stage of the disease helps when planning treatment and estimating the persons prognosis
61
what are the assessments that determine the stage of a cancer
- physical examinations
- imaging procedures
- lab tests
- pathology
- surgical reports
62
how do the staging systems of cancer differentiate
according to the organs involved
63
what is the clinical staging system for oral cancer
TNM system
64
describe the TNM staging system
T is tumour size
N is lymph node involvement
M is presence of metastasis
65
if there is metastasis, what number is used in TNM staging
M1
66
if there is no metastasis, what number is used in TNM staging
M0
67
what is the staging classification used for haemopoeitic malignancies
the ann arbor staging classification
68
what are the three stages to tumour immunology
elimination
equilibrium
escape
69
how does the immune system recognise tumour cells
tumour associated antigens
70
what are TAAs
tumour associated antigens
71
what can neoantigens also be known as
tumour associated antigens
72
what can neoantigens be made from
- products of mutated genes
- overexpressed proteins like tyrosinase
- viral proteins
- oncofetal antigens like carcinoembryonic antigens
73
why can the immune system not recognise tumour cells
because they change their antigens continuously to evade the immune system
74
what brings about the elimination stage of tumour immunology
recognition of tumour cells by immune cells, some will elicit a poor immune response and will not be destroyed
over time the malignant cells will increase the number of cells that do not cause a reaction to escape the immune system
75
elevated levels of what molecule in patient serum indicates a malignancy
carcinoembryonic antigen
76
what kind of response is elimination
cell mediated
77
what are the cells involved in the elimination stage of immune response to tumour antigens
- cytotoxic lymphocytes
- natural killer cells
- macrophages
78
what is the first line of defence against tumour cells
natural killer cells
79
describe the mechanism of action of macrophages
mechanisms similar to anti microbial killing
80
how can tumour cells evade the immune response
cells may acquire molecular changes such as
- altered tumour antigen expression, lack of t cell recognition
- activation of immunoregulatory pathways leading to t cell unresponsiveness and apoptosis
- immunosupppressive factors like cytokines which inhibit t cells
81
what is a cytokine that inhibits t cells
transforming growth factor beta
82
how does immunotherapy treat cancer
through the use of the patients own immune response to control and destroy malignant cells
83
list the types of immunotherapy
- active immunisation
- reversal of immunosuppression
- adopted cell transfer
- tumour infiltrating lymphocytes
- CAR t cell therapy
- strengthening the natural immune response
84
what is CAR T cell therapy used for
haemotological malignancies
85
summarise the haematogenous spread of cancer
step 1 - direct spread and invasiveness
- reduced cell to cell adhesion
- invasion of basement membrane and stroma
step 2 - angiogenesis
- increased cell motility
- due to factors produced by tumour cells
step 3 - vascular invasion and spread
- walls of new vessels are thin and more easily invaded
- cells move into the circulation
- cells are packed in the capillary bed and then break out of the capillaries
step 4 - establishment of a new colony
- cells invade surrounding tissues
- cells proliferate
- cells stimulate angiogenesis
